Accelerated Gray and White Matter Deterioration With Age in Schizophrenia.

PubMed

Cropley, Vanessa L; Klauser, Paul; Lenroot, Rhoshel K; Bruggemann, Jason; Sundram, Suresh; Bousman, Chad; Pereira, Avril; Di Biase, Maria A; Weickert, Thomas W; Weickert, Cynthia Shannon; Pantelis, Christos; Zalesky, Andrew

2017-03-01

Although brain changes in schizophrenia have been proposed to mirror those found with advancing age, the trajectory of gray matter and white matter changes during the disease course remains unclear. The authors sought to measure whether these changes in individuals with schizophrenia remain stable, are accelerated, or are diminished with age. Gray matter volume and fractional anisotropy were mapped in 326 individuals diagnosed with schizophrenia or schizoaffective disorder and in 197 healthy comparison subjects aged 20-65 years. Polynomial regression was used to model the influence of age on gray matter volume and fractional anisotropy at a whole-brain and voxel level. Between-group differences in gray matter volume and fractional anisotropy were regionally localized across the lifespan using permutation testing and cluster-based inference. Significant loss of gray matter volume was evident in schizophrenia, progressively worsening with age to a maximal loss of 8% in the seventh decade of life. The inferred rate of gray matter volume loss was significantly accelerated in schizophrenia up to middle age and plateaued thereafter. In contrast, significant reductions in fractional anisotropy emerged in schizophrenia only after age 35, and the rate of fractional anisotropy deterioration with age was constant and best modeled with a straight line. The slope of this line was 60% steeper in schizophrenia relative to comparison subjects, indicating a significantly faster rate of white matter deterioration with age. The rates of reduction of gray matter volume and fractional anisotropy were significantly faster in males than in females, but an interaction between sex and diagnosis was not evident. The findings suggest that schizophrenia is characterized by an initial, rapid rate of gray matter loss that slows in middle life, followed by the emergence of a deficit in white matter that progressively worsens with age at a constant rate.

Age Differentiation within Gray Matter, White Matter, and between Memory and White Matter in an Adult Life Span Cohort.

PubMed

de Mooij, Susanne M M; Henson, Richard N A; Waldorp, Lourens J; Kievit, Rogier A

2018-06-20

It is well established that brain structures and cognitive functions change across the life span. A long-standing hypothesis called "age differentiation" additionally posits that the relations between cognitive functions also change with age. To date, however, evidence for age-related differentiation is mixed, and no study has examined differentiation of the relationship between brain and cognition. Here we use multigroup structural equation models (SEMs) and SEM trees to study differences within and between brain and cognition across the adult life span (18-88 years) in a large ( N > 646, closely matched across sexes), population-derived sample of healthy human adults from the Cambridge Centre for Ageing and Neuroscience (www.cam-can.org). After factor analyses of gray matter volume (from T1- and T2-weighted MRI) and white matter organization (fractional anisotropy from diffusion-weighted MRI), we found evidence for the differentiation of gray and white matter, such that the covariance between brain factors decreased with age. However, we found no evidence for age differentiation among fluid intelligence, language, and memory, suggesting a relatively stable covariance pattern among cognitive factors. Finally, we observed a specific pattern of age differentiation between brain and cognitive factors, such that a white matter factor, which loaded most strongly on the hippocampal cingulum, became less correlated with memory performance in later life. These patterns are compatible with the reorganization of cognitive functions in the face of neural decline, and/or with the emergence of specific subpopulations in old age. SIGNIFICANCE STATEMENT The theory of age differentiation posits age-related changes in the relationships among cognitive domains, either weakening (differentiation) or strengthening (dedifferentiation), but evidence for this hypothesis is mixed. Using age-varying covariance models in a large cross-sectional adult life span sample, we found age

Ageing and brain white matter structure in 3,513 UK Biobank participants

PubMed Central

Cox, Simon R.; Ritchie, Stuart J.; Tucker-Drob, Elliot M.; Liewald, David C.; Hagenaars, Saskia P.; Davies, Gail; Wardlaw, Joanna M.; Gale, Catharine R.; Bastin, Mark E.; Deary, Ian J.

2016-01-01

Quantifying the microstructural properties of the human brain's connections is necessary for understanding normal ageing and disease. Here we examine brain white matter magnetic resonance imaging (MRI) data in 3,513 generally healthy people aged 44.64–77.12 years from the UK Biobank. Using conventional water diffusion measures and newer, rarely studied indices from neurite orientation dispersion and density imaging, we document large age associations with white matter microstructure. Mean diffusivity is the most age-sensitive measure, with negative age associations strongest in the thalamic radiation and association fibres. White matter microstructure across brain tracts becomes increasingly correlated in older age. This may reflect an age-related aggregation of systemic detrimental effects. We report several other novel results, including age associations with hemisphere and sex, and comparative volumetric MRI analyses. Results from this unusually large, single-scanner sample provide one of the most extensive characterizations of age associations with major white matter tracts in the human brain. PMID:27976682

The dimensionality of between-person differences in white matter microstructure in old age.

PubMed

Lövdén, Martin; Laukka, Erika Jonsson; Rieckmann, Anna; Kalpouzos, Grégoria; Li, Tie-Qiang; Jonsson, Tomas; Wahlund, Lars-Olof; Fratiglioni, Laura; Bäckman, Lars

2013-06-01

Between-person differences in white matter microstructure may partly generalize across the brain and partly play out differently for distinct tracts. We used diffusion-tensor imaging and structural equation modeling to investigate this issue in a sample of 260 adults aged 60-87 years. Mean fractional anisotropy and mean diffusivity of seven white matter tracts in each hemisphere were quantified. Results showed good fit of a model positing that individual differences in white matter microstructure are structured according to tracts. A general factor, although accounting for variance in the measures, did not adequately represent the individual differences. This indicates the presence of a substantial amount of tract-specific individual differences in white matter microstructure. In addition, individual differences are to a varying degree shared between tracts, indicating that general factors also affect white matter microstructure. Age-related differences in white matter microstructure were present for all tracts. Correlations among tract factors did not generally increase as a function of age, suggesting that aging is not a process with homogenous effects on white matter microstructure across the brain. These findings highlight the need for future research to examine whether relations between white matter microstructure and diverse outcomes are specific or general. Copyright © 2011 Wiley Periodicals, Inc.

White Matter Changes in Tinnitus: Is It All Age and Hearing Loss?

PubMed

Yoo, Hye Bin; De Ridder, Dirk; Vanneste, Sven

2016-02-01

Tinnitus is a condition characterized by the perception of auditory phantom sounds. It is known as the result of complex interactions between auditory and nonauditory regions. However, previous structural imaging studies on tinnitus patients showed evidence of significant white matter changes caused by hearing loss that are positively correlated with aging. Current study focused on which aspects of tinnitus pathologies affect the white matter integrity the most. We used the diffusion tensor imaging technique to acquire images that have higher contrast in brain white matter to analyze how white matter is influenced by tinnitus-related factors using voxel-based methods, region of interest analysis, and deterministic tractography. As a result, white matter integrity in chronic tinnitus patients was both directly affected by age and also mediated by the hearing loss. The most important changes in white matter regions were found bilaterally in the anterior corona radiata, anterior corpus callosum, and bilateral sagittal strata. In the tractography analysis, the white matter integrity values in tracts of right parahippocampus were correlated with the subjective tinnitus loudness.

Cerebral White Matter Integrity Mediates Adult Age Differences in Cognitive Performance

ERIC Educational Resources Information Center

Madden, David J.; Spaniol, Julia; Costello, Matthew C.; Bucur, Barbara; White, Leonard E.; Cabeza, Roberto; Davis, Simon W.; Dennis, Nancy A.; Provenzale, James M.; Huettel, Scott A.

2009-01-01

Previous research has established that age-related decline occurs in measures of cerebral white matter integrity, but the role of this decline in age-related cognitive changes is not clear. To conclude that white matter integrity has a mediating (causal) contribution, it is necessary to demonstrate that statistical control of the white…

Aging in deep gray matter and white matter revealed by diffusional kurtosis imaging.

PubMed

Gong, Nan-Jie; Wong, Chun-Sing; Chan, Chun-Chung; Leung, Lam-Ming; Chu, Yiu-Ching

2014-10-01

Diffusion tensor imaging has already been extensively used to probe microstructural alterations in white matter tracts, and scarcely, in deep gray matter. However, results in literature regarding age-related degenerative mechanisms in white matter tracts and parametric changes in the putamen are inconsistent. Diffusional kurtosis imaging is a mathematical extension of diffusion tensor imaging, which could more comprehensively mirror microstructure, particularly in isotropic tissues such as gray matter. In this study, we used the diffusional kurtosis imaging method and a white-matter model that provided metrics of explicit neurobiological interpretations in healthy participants (58 in total, aged from 25 to 84 years). Tract-based whole-brain analyses and regions-of-interest (anterior and posterior limbs of the internal capsule, cerebral peduncle, fornix, genu and splenium of corpus callosum, globus pallidus, substantia nigra, red nucleus, putamen, caudate nucleus, and thalamus) analyses were performed to examine parametric differences across regions and correlations with age. In white matter tracts, evidence was found supportive for anterior-posterior gradient and not completely supportive for retrogenesis theory. Age-related degenerations appeared to be broadly driven by axonal loss. Demyelination may also be a major driving mechanism, although confined to the anterior brain. In terms of deep gray matter, higher mean kurtosis and fractional anisotropy in the globus pallidus, substantia nigra, and red nucleus reflected higher microstructural complexity and directionality compared with the putamen, caudate nucleus, and thalamus. In particular, the unique age-related positive correlations for fractional anisotropy, mean kurtosis, and radial kurtosis in the putamen opposite to those in other regions call for further investigation of exact underlying mechanisms. In summary, the results suggested that diffusional kurtosis can provide measurements in a new dimension that

Brain white matter structure and information processing speed in healthy older age.

PubMed

Kuznetsova, Ksenia A; Maniega, Susana Muñoz; Ritchie, Stuart J; Cox, Simon R; Storkey, Amos J; Starr, John M; Wardlaw, Joanna M; Deary, Ian J; Bastin, Mark E

2016-07-01

Cognitive decline, especially the slowing of information processing speed, is associated with normal ageing. This decline may be due to brain cortico-cortical disconnection caused by age-related white matter deterioration. We present results from a large, narrow age range cohort of generally healthy, community-dwelling subjects in their seventies who also had their cognitive ability tested in youth (age 11 years). We investigate associations between older age brain white matter structure, several measures of information processing speed and childhood cognitive ability in 581 subjects. Analysis of diffusion tensor MRI data using Tract-based Spatial Statistics (TBSS) showed that all measures of information processing speed, as well as a general speed factor composed from these tests (g speed), were significantly associated with fractional anisotropy (FA) across the white matter skeleton rather than in specific tracts. Cognitive ability measured at age 11 years was not associated with older age white matter FA, except for the g speed-independent components of several individual processing speed tests. These results indicate that quicker and more efficient information processing requires global connectivity in older age, and that associations between white matter FA and information processing speed (both individual test scores and g speed), unlike some other aspects of later life brain structure, are generally not accounted for by cognitive ability measured in youth.

Genetic disorders affecting white matter in the pediatric age.

PubMed

Di Rocco, Maja; Biancheri, Roberta; Rossi, Andrea; Filocamo, Mirella; Tortori-Donati, Paolo

2004-08-15

Pediatric white matter disorders can be distinguished into well-defined leukoencephalopathies, and undefined leukoencephalopathies. The first category may be subdivided into: (a) hypomyelinating disorders; (b) dysmyelinating disorders; (c) leukodystrophies; (d) disorders related to cystic degeneration of myelin; and (e) disorders secondary to axonal damage. The second category, representing up to 50% of leukoencephalopathies in childhood, requires a multidisciplinar approach in order to define novel homogeneous subgroups of patients, possibly representing "new genetic disorders" (such as megalencephalic leukoencepahlopathy with subcortical cysts and vanishing white matter disease that have recently been identified). In the majority of cases, pediatric white matter disorders are inherited diseases. An integrated description of the clinical, neuroimaging and pathophysiological features is crucial for categorizing myelin disorders and better understanding their genetic basis. A review of the genetic disorders affecting white matter in the pediatric age, including some novel entities, is provided. Copyright 2004 Wiley-Liss, Inc.

Age-related decline in oligodendrogenesis retards white matter repair in mice.

PubMed

Miyamoto, Nobukazu; Pham, Loc-Duyen D; Hayakawa, Kazuhide; Matsuzaki, Toshinori; Seo, Ji Hae; Magnain, Caroline; Ayata, Cenk; Kim, Kyu-Won; Boas, David; Lo, Eng H; Arai, Ken

2013-09-01

Aging is one of the major risk factors for white matter injury in cerebrovascular disease. However, the effects of age on the mechanisms of injury/repair in white matter remain to be fully elucidated. Here, we ask whether, compared with young brains, white matter regions in older brains may be more vulnerable in part because of decreased rates of compensatory oligodendrogenesis after injury. A mouse model of prolonged cerebral hypoperfusion was prepared by bilateral common carotid artery stenosis in 2-month and 8-month-old mice. Matching in vitro studies were performed by subjecting oligodendrocyte precursor cells to sublethal 7-day CoCl2 treatment to induce chemical hypoxic stress. Baseline myelin density in the corpus callosum was similar in 2-month and 8-month-old mice. But after induction of prolonged cerebral hypoperfusion, older mice showed more severe white matter injury together with worse deficits in working memory. The numbers of newborn oligodendrocytes and their precursors were increased by cerebral hypoperfusion in young mice, whereas these endogenous responses were significantly dampened in older mice. Defects in cyclic AMP response element-binding protein signaling may be involved because activating cyclic AMP response element-binding protein with the type-III phosphodiesterase inhibitor cilostazol in older mice restored the differentiation of oligodendrocyte precursor cells, alleviated myelin loss, and improved cognitive dysfunction during cerebral hypoperfusion. Cell culture systems confirmed that cilostazol promoted the differentiation of oligodendrocyte precursor cells. An age-related decline in cyclic AMP response element-binding protein-mediated oligodendrogenesis may compromise endogenous white matter repair mechanisms, and therefore, drugs that activate cyclic AMP response element-binding protein signaling provide a potential therapeutic approach for treating white matter injury in aging brains.

White matter hyperintensities and normal-appearing white matter integrity in the aging brain.

PubMed

Maniega, Susana Muñoz; Valdés Hernández, Maria C; Clayden, Jonathan D; Royle, Natalie A; Murray, Catherine; Morris, Zoe; Aribisala, Benjamin S; Gow, Alan J; Starr, John M; Bastin, Mark E; Deary, Ian J; Wardlaw, Joanna M

2015-02-01

White matter hyperintensities (WMH) of presumed vascular origin are a common finding in brain magnetic resonance imaging of older individuals and contribute to cognitive and functional decline. It is unknown how WMH form, although white matter degeneration is characterized pathologically by demyelination, axonal loss, and rarefaction, often attributed to ischemia. Changes within normal-appearing white matter (NAWM) in subjects with WMH have also been reported but have not yet been fully characterized. Here, we describe the in vivo imaging signatures of both NAWM and WMH in a large group of community-dwelling older people of similar age using biomarkers derived from magnetic resonance imaging that collectively reflect white matter integrity, myelination, and brain water content. Fractional anisotropy (FA) and magnetization transfer ratio (MTR) were significantly lower, whereas mean diffusivity (MD) and longitudinal relaxation time (T1) were significantly higher, in WMH than NAWM (p < 0.0001), with MD providing the largest difference between NAWM and WMH. Receiver operating characteristic analysis on each biomarker showed that MD differentiated best between NAWM and WMH, identifying 94.6% of the lesions using a threshold of 0.747 × 10(-9) m(2)s(-1) (area under curve, 0.982; 95% CI, 0.975-0.989). Furthermore, the level of deterioration of NAWM was strongly associated with the severity of WMH, with MD and T1 increasing and FA and MTR decreasing in NAWM with increasing WMH score, a relationship that was sustained regardless of distance from the WMH. These multimodal imaging data indicate that WMH have reduced structural integrity compared with surrounding NAWM, and MD provides the best discriminator between the 2 tissue classes even within the mild range of WMH severity, whereas FA, MTR, and T1 only start reflecting significant changes in tissue microstructure as WMH become more severe. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

in vivo quantification of white matter microstructure for use in aging: A focus on two emerging techniques

PubMed Central

Lamar, Melissa; Zhou, Xiaohong Joe; Charlton, Rebecca A.; Dean, Douglas; Little, Deborah; Deoni, Sean C

2013-01-01

Human brain imaging has seen many advances in the quantification of white matter in vivo. For example, these advances have revealed the association between white matter damage and vascular disease as well as their impact on risk for and development of dementia and depression in an aging population. Current neuroimaging methods to quantify white matter damage provide a foundation for understanding such age-related neuropathology; however, these methods are not as adept at determining the underlying microstructural abnormalities signaling at risk tissue or driving white matter damage in the aging brain. This review will begin with a brief overview of the use of diffusion tensor imaging (DTI) in understanding white matter alterations in aging before focusing in more detail on select advances in both diffusion-based methods and multi-component relaxometry techniques for imaging white matter microstructural integrity within myelin sheaths and the axons they encase. While DTI greatly extended the field of white matter interrogation, these more recent technological advances will add clarity to the underlying microstructural mechanisms that contribute to white matter damage. More specifically, the methods highlighted in this review may prove more sensitive (and specific) for determining the contribution of myelin versus axonal integrity to the aging of white matter in brain. PMID:24080382

Visceral adiposity predicts subclinical white matter hyperintensities in middle-aged adults.

PubMed

Pasha, Evan P; Birdsill, Alex; Parker, Paige; Elmenshawy, Ahmed; Tanaka, Hirofumi; Haley, Andreana P

Growing prevalence of neuropathology and cognitive impairment are emerging consequences of the obesity epidemic. Adiposity indices used in examining the relationships between obesity, neuropathology, and cognition vary substantially in the literature leading to incongruent findings. Our aim was to determine the anthropometric measures most strongly associated with early white matter disease and cognitive function at midlife. Multiple adiposity indices were measured in 126 adults aged 40-62 who also completed a magnetic resonance imaging (MRI) scan to quantify white matter disease and a cognitive test battery. Anthropometric indices of obesity were compared to image-based estimates of visceral adipose tissue with dual-energy X-ray absorptiometry (DEXA) as predictors of current white matter disease and cognitive function. We also explored sex as a potential moderator of these relationships. Waist circumference (WC) was most strongly correlated with DEXA estimates of visceral adipose tissue (r=0.871, p<0.001). Increasing WC (β=0.231, p=0.034), percent body fat (β=0.230, p=0.045), and VAT (β=0.247, p=0.027) significantly predicted subclinical white matter hyperintensities in the absence of cognitive impairment after accounting for age, sex, years of education, and cardiovascular risk factors. Sex was not a significant moderator of any of the observed relationships. Of the anthropometric indices used in this study, WC, BF, and VAT successfully predicted subclinical white matter disease in cognitively normal adults at midlife. Increasing VAT may independently insidiously affect cerebral white matter prior to detectable cognitive changes, necessitating early intervention. Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Integrity of normal-appearing white matter: Influence of age, visible lesion burden and hypertension in patients with small-vessel disease.

PubMed

Muñoz Maniega, Susana; Chappell, Francesca M; Valdés Hernández, Maria C; Armitage, Paul A; Makin, Stephen D; Heye, Anna K; Thrippleton, Michael J; Sakka, Eleni; Shuler, Kirsten; Dennis, Martin S; Wardlaw, Joanna M

2017-02-01

White matter hyperintensities accumulate with age and occur in patients with stroke, but their pathogenesis is poorly understood. We measured multiple magnetic resonance imaging biomarkers of tissue integrity in normal-appearing white matter and white matter hyperintensities in patients with mild stroke, to improve understanding of white matter hyperintensities origins. We classified white matter into white matter hyperintensities and normal-appearing white matter and measured fractional anisotropy, mean diffusivity, water content (T1-relaxation time) and blood-brain barrier leakage (signal enhancement slope from dynamic contrast-enhanced magnetic resonance imaging). We studied the effects of age, white matter hyperintensities burden (Fazekas score) and vascular risk factors on each biomarker, in normal-appearing white matter and white matter hyperintensities, and performed receiver-operator characteristic curve analysis. Amongst 204 patients (34.3-90.9 years), all biomarkers differed between normal-appearing white matter and white matter hyperintensities ( P < 0.001). In normal-appearing white matter and white matter hyperintensities, mean diffusivity and T1 increased with age ( P < 0.001), all biomarkers varied with white matter hyperintensities burden ( P < 0.001; P = 0.02 signal enhancement slope), but only signal enhancement slope increased with hypertension ( P = 0.028). Fractional anisotropy showed complex age-white matter hyperintensities-tissue interactions; enhancement slope showed white matter hyperintensities-tissue interactions. Mean diffusivity distinguished white matter hyperintensities from normal-appearing white matter best at all ages. Blood-brain barrier leakage increases with hypertension and white matter hyperintensities burden at all ages in normal-appearing white matter and white matter hyperintensities, whereas water mobility and content increase as tissue damage accrues, suggesting that blood-brain barrier leakage

In vivo quantification of white matter microstructure for use in aging: a focus on two emerging techniques.

PubMed

Lamar, Melissa; Zhou, Xiaohong Joe; Charlton, Rebecca A; Dean, Douglas; Little, Deborah; Deoni, Sean C

2014-02-01

Human brain imaging has seen many advances in the quantification of white matter in vivo. For example, these advances have revealed the association between white matter damage and vascular disease as well as their impact on risk for and development of dementia and depression in an aging population. Current neuroimaging methods to quantify white matter damage provide a foundation for understanding such age-related neuropathology; however, these methods are not as adept at determining the underlying microstructural abnormalities signaling at risk tissue or driving white matter damage in the aging brain. This review will begin with a brief overview of the use of diffusion tensor imaging (DTI) in understanding white matter alterations in aging before focusing in more detail on select advances in both diffusion-based methods and multi-component relaxometry techniques for imaging white matter microstructural integrity within myelin sheaths and the axons they encase. Although DTI greatly extended the field of white matter interrogation, these more recent technological advances will add clarity to the underlying microstructural mechanisms that contribute to white matter damage. More specifically, the methods highlighted in this review may prove more sensitive (and specific) for determining the contribution of myelin versus axonal integrity to the aging of white matter in brain. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Differential vulnerability of gray matter and white matter to intrauterine growth restriction in preterm infants at 12 months corrected age.

PubMed

Padilla, Nelly; Junqué, Carme; Figueras, Francesc; Sanz-Cortes, Magdalena; Bargalló, Núria; Arranz, Angela; Donaire, Antonio; Figueras, Josep; Gratacos, Eduard

2014-01-30

Intrauterine growth restriction (IUGR) is associated with a high risk of abnormal neurodevelopment. Underlying neuroanatomical substrates are partially documented. We hypothesized that at 12 months preterm infants would evidence specific white-matter microstructure alterations and gray-matter differences induced by severe IUGR. Twenty preterm infants with IUGR (26-34 weeks of gestation) were compared with 20 term-born infants and 20 appropriate for gestational age preterm infants of similar gestational age. Preterm groups showed no evidence of brain abnormalities. At 12 months, infants were scanned sleeping naturally. Gray-matter volumes were studied with voxel-based morphometry. White-matter microstructure was examined using tract-based spatial statistics. The relationship between diffusivity indices in white matter, gray matter volumes, and perinatal data was also investigated. Gray-matter decrements attributable to IUGR comprised amygdala, basal ganglia, thalamus and insula bilaterally, left occipital and parietal lobes, and right perirolandic area. Gray-matter volumes positively correlated with birth weight exclusively. Preterm infants had reduced FA in the corpus callosum, and increased FA in the anterior corona radiata. Additionally, IUGR infants had increased FA in the forceps minor, internal and external capsules, uncinate and fronto-occipital white matter tracts. Increased axial diffusivity was observed in several white matter tracts. Fractional anisotropy positively correlated with birth weight and gestational age at birth. These data suggest that IUGR differentially affects gray and white matter development preferentially affecting gray matter. At 12 months IUGR is associated with a specific set of structural gray-matter decrements. White matter follows an unusual developmental pattern, and is apparently affected by IUGR and prematurity combined. Copyright © 2013 Elsevier B.V. All rights reserved.

Military blast exposure, ageing and white matter integrity

PubMed Central

Trotter, Benjamin B.; Robinson, Meghan E.; Milberg, William P.; McGlinchey, Regina E.

2015-01-01

Mild traumatic brain injury, or concussion, is associated with a range of neural changes including altered white matter structure. There is emerging evidence that blast exposure—one of the most pervasive causes of casualties in the recent overseas conflicts in Iraq and Afghanistan—is accompanied by a range of neurobiological events that may result in pathological changes to brain structure and function that occur independently of overt concussion symptoms. The potential effects of brain injury due to blast exposure are of great concern as a history of mild traumatic brain injury has been identified as a risk factor for age-associated neurodegenerative disease. The present study used diffusion tensor imaging to investigate whether military-associated blast exposure influences the association between age and white matter tissue structure integrity in a large sample of veterans of the recent conflicts (n = 190 blast-exposed; 59 without exposure) between the ages of 19 and 62 years. Tract-based spatial statistics revealed a significant blast exposure × age interaction on diffusion parameters with blast-exposed individuals exhibiting a more rapid cross-sectional age trajectory towards reduced tissue integrity. Both distinct and overlapping voxel clusters demonstrating the interaction were observed among the examined diffusion contrast measures (e.g. fractional anisotropy and radial diffusivity). The regions showing the effect on fractional anisotropy included voxels both within and beyond the boundaries of the regions exhibiting a significant negative association between fractional anisotropy and age in the entire cohort. The regional effect was sensitive to the degree of blast exposure, suggesting a ‘dose-response’ relationship between the number of blast exposures and white matter integrity. Additionally, there was an age-independent negative association between fractional anisotropy and years since most severe blast exposure in a subset of the blast

Sources of Disconnection in Neurocognitive Aging: Cerebral White Matter Integrity, Resting-state Functional Connectivity, and White Matter Hyperintensity Volume

PubMed Central

Madden, David J.; Parks, Emily L.; Tallman, Catherine W.; Boylan, Maria A.; Hoagey, David A.; Cocjin, Sally B.; Packard, Lauren E.; Johnson, Micah A.; Chou, Ying-hui; Potter, Guy G.; Chen, Nan-kuei; Siciliano, Rachel E.; Monge, Zachary A.; Honig, Jesse A.; Diaz, Michele T.

2017-01-01

Age-related decline in fluid cognition can be characterized as a disconnection among specific brain structures, leading to a decline in functional efficiency. The potential sources of disconnection, however, are unclear. We investigated imaging measures of cerebral white matter integrity, resting-state functional connectivity, and white matter hyperintensity (WMH) volume as mediators of the relation between age and fluid cognition, in 145 healthy, community-dwelling adults 19–79 years of age. At a general level of analysis, with a single composite measure of fluid cognition and single measures of each of the three imaging modalities, age exhibited an independent influence on the cognitive and imaging measures, and the imaging variables did not mediate the age-cognition relation. At a more specific level of analysis, resting-state functional connectivity of sensorimotor networks was a significant mediator of the age-related decline in executive function. These findings suggest that different levels of analysis lead to different models of neurocognitive disconnection, and that resting-state functional connectivity, in particular, may contribute to age-related decline in executive function. PMID:28389085

Gestational Age at Birth and Brain White Matter Development in Term-Born Infants and Children.

PubMed

Ou, X; Glasier, C M; Ramakrishnaiah, R H; Kanfi, A; Rowell, A C; Pivik, R T; Andres, A; Cleves, M A; Badger, T M

2017-12-01

Studies on infants and children born preterm have shown that adequate gestational length is critical for brain white matter development. Less is known regarding how variations in gestational age at birth in term infants and children affect white matter development, which was evaluated in this study. Using DTI tract-based spatial statistics methods, we evaluated white matter microstructures in 2 groups of term-born (≥37 weeks of gestation) healthy subjects: 2-week-old infants ( n = 44) and 8-year-old children ( n = 63). DTI parameters including fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were calculated by voxelwise and ROI methods and were correlated with gestational age at birth, with potential confounding factors such as postnatal age and sex controlled. Fractional anisotropy values, which are markers for white matter microstructural integrity, positively correlated ( P < .05, corrected) with gestational age at birth in most major white matter tracts/regions for the term infants. Mean diffusivity values, which are measures of water diffusivities in the brain, and axial and radial diffusivity values, which are markers for axonal growth and myelination, respectively, negatively correlated ( P < .05, corrected) with gestational age at birth in all major white matter tracts/regions excluding the body and splenium of the corpus callosum for the term infants. No significant correlations with gestational age were observed for any tracts/regions for the term-born 8-year-old children. Our results indicate that longer gestation during the normal term period is associated with significantly greater infant white matter development (as reflected by higher fractional anisotropy and lower mean diffusivity, axial diffusivity, and radial diffusivity values); however, similar associations were not observable in later childhood. © 2017 by American Journal of Neuroradiology.

Episodic memory function is associated with multiple measures of white matter integrity in cognitive aging

PubMed Central

Lockhart, Samuel N.; Mayda, Adriane B. V.; Roach, Alexandra E.; Fletcher, Evan; Carmichael, Owen; Maillard, Pauline; Schwarz, Christopher G.; Yonelinas, Andrew P.; Ranganath, Charan; DeCarli, Charles

2011-01-01

Previous neuroimaging research indicates that white matter injury and integrity, measured respectively by white matter hyperintensities (WMH) and fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI), differ with aging and cerebrovascular disease (CVD) and are associated with episodic memory deficits in cognitively normal older adults. However, knowledge about tract-specific relationships between WMH, FA, and episodic memory in aging remains limited. We hypothesized that white matter connections between frontal cortex and subcortical structures as well as connections between frontal and temporo-parietal cortex would be most affected. In the current study, we examined relationships between WMH, FA and episodic memory in 15 young adults, 13 elders with minimal WMH and 15 elders with extensive WMH, using an episodic recognition memory test for object-color associations. Voxel-based statistics were used to identify voxel clusters where white matter measures were specifically associated with variations in episodic memory performance, and white matter tracts intersecting these clusters were analyzed to examine white matter-memory relationships. White matter injury and integrity measures were significantly associated with episodic memory in extensive regions of white matter, located predominantly in frontal, parietal, and subcortical regions. Template based tractography indicated that white matter injury, as measured by WMH, in the uncinate and inferior longitudinal fasciculi were significantly negatively associated with episodic memory performance. Other tracts such as thalamo-frontal projections, superior longitudinal fasciculus, and dorsal cingulum bundle demonstrated strong negative associations as well. The results suggest that white matter injury to multiple pathways, including connections of frontal and temporal cortex and frontal-subcortical white matter tracts, plays a critical role in memory differences seen in older individuals. PMID:22438841

Blood Pressure Control in Aging Predicts Cerebral Atrophy Related to Small-Vessel White Matter Lesions.

PubMed

Kern, Kyle C; Wright, Clinton B; Bergfield, Kaitlin L; Fitzhugh, Megan C; Chen, Kewei; Moeller, James R; Nabizadeh, Nooshin; Elkind, Mitchell S V; Sacco, Ralph L; Stern, Yaakov; DeCarli, Charles S; Alexander, Gene E

2017-01-01

Cerebral small-vessel damage manifests as white matter hyperintensities and cerebral atrophy on brain MRI and is associated with aging, cognitive decline and dementia. We sought to examine the interrelationship of these imaging biomarkers and the influence of hypertension in older individuals. We used a multivariate spatial covariance neuroimaging technique to localize the effects of white matter lesion load on regional gray matter volume and assessed the role of blood pressure control, age and education on this relationship. Using a case-control design matching for age, gender, and educational attainment we selected 64 participants with normal blood pressure, controlled hypertension or uncontrolled hypertension from the Northern Manhattan Study cohort. We applied gray matter voxel-based morphometry with the scaled subprofile model to (1) identify regional covariance patterns of gray matter volume differences associated with white matter lesion load, (2) compare this relationship across blood pressure groups, and (3) relate it to cognitive performance. In this group of participants aged 60-86 years, we identified a pattern of reduced gray matter volume associated with white matter lesion load in bilateral temporal-parietal regions with relative preservation of volume in the basal forebrain, thalami and cingulate cortex. This pattern was expressed most in the uncontrolled hypertension group and least in the normotensives, but was also more evident in older and more educated individuals. Expression of this pattern was associated with worse performance in executive function and memory. In summary, white matter lesions from small-vessel disease are associated with a regional pattern of gray matter atrophy that is mitigated by blood pressure control, exacerbated by aging, and associated with cognitive performance.

Synergistic Effects of Age on Patterns of White and Gray Matter Volume across Childhood and Adolescence1,2,3

PubMed Central

Krongold, Mark; Cooper, Cassandra; Lebel, Catherine

2015-01-01

Abstract 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. PMID:26464999

Dopamine transporter availability in clinically normal aging is associated with individual differences in white matter integrity.

PubMed

Rieckmann, Anna; Hedden, Trey; Younger, Alayna P; Sperling, Reisa A; Johnson, Keith A; Buckner, Randy L

2016-02-01

Aging-related differences in white matter integrity, the presence of amyloid plaques, and density of biomarkers indicative of dopamine functions can be detected and quantified with in vivo human imaging. The primary aim of the present study was to investigate whether these imaging-based measures constitute independent imaging biomarkers in older adults, which would speak to the hypothesis that the aging brain is characterized by multiple independent neurobiological cascades. We assessed MRI-based markers of white matter integrity and PET-based marker of dopamine transporter density and amyloid deposition in the same set of 53 clinically normal individuals (age 65-87). A multiple regression analysis demonstrated that dopamine transporter availability is predicted by white matter integrity, which was detectable even after controlling for chronological age. Further post-hoc exploration revealed that dopamine transporter availability was further associated with systolic blood pressure, mirroring the established association between cardiovascular health and white matter integrity. Dopamine transporter availability was not associated with the presence of amyloid burden. Neurobiological correlates of dopamine transporter measures in aging are therefore likely unrelated to Alzheimer's disease but are aligned with white matter integrity and cardiovascular risk. More generally, these results suggest that two common imaging markers of the aging brain that are typically investigated separately do not reflect independent neurobiological processes. Hum Brain Mapp 37:621-631, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Brain white matter damage in aging and cognitive ability in youth and older age.

PubMed

Valdés Hernández, Maria Del C; Booth, Tom; Murray, Catherine; Gow, Alan J; Penke, Lars; Morris, Zoe; Maniega, Susana Muñoz; Royle, Natalie A; Aribisala, Benjamin S; Bastin, Mark E; Starr, John M; Deary, Ian J; Wardlaw, Joanna M

2013-12-01

Cerebral white matter hyperintensities (WMH) reflect accumulating white matter damage with aging and impair cognition. The role of childhood intelligence is rarely considered in associations between cognitive impairment and WMH. We studied community-dwelling older people all born in 1936, in whom IQ had been assessed at age 11 years. We assessed medical histories, current cognitive ability and quantified WMH on MR imaging. Among 634 participants, mean age 72.7 (SD 0.7), age 11 IQ was the strongest predictor of late life cognitive ability. After accounting for age 11 IQ, greater WMH load was significantly associated with lower late life general cognitive ability (β = -0.14, p < 0.01) and processing speed (β = -0.19, p < 0.001). WMH were also associated independently with lower age 11 IQ (β = -0.08, p < 0.05) and hypertension. In conclusion, having more WMH is significantly associated with lower cognitive ability, after accounting for prior ability, age 11IQ. Early-life IQ also influenced WMH in later life. Determining how lower IQ in youth leads to increasing brain damage with aging is important for future successful cognitive aging. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Gestational age at birth and brain white matter development in term-born infants and children

USDA-ARS?s Scientific Manuscript database

Studies on infants and children born preterm have shown that adequate gestational length is critical for brain white matter development. Less is known regarding how variations in gestational age at birth in term infants and children affect white matter development, which was evaluated in this study....

White Matter Lipids as a Ketogenic Fuel Supply in Aging Female Brain: Implications for Alzheimer's Disease.

PubMed

Klosinski, Lauren P; Yao, Jia; Yin, Fei; Fonteh, Alfred N; Harrington, Michael G; Christensen, Trace A; Trushina, Eugenia; Brinton, Roberta Diaz

2015-12-01

White matter degeneration is a pathological hallmark of neurodegenerative diseases including Alzheimer's. Age remains the greatest risk factor for Alzheimer's and the prevalence of age-related late onset Alzheimer's is greatest in females. We investigated mechanisms underlying white matter degeneration in an animal model consistent with the sex at greatest Alzheimer's risk. Results of these analyses demonstrated decline in mitochondrial respiration, increased mitochondrial hydrogen peroxide production and cytosolic-phospholipase-A2 sphingomyelinase pathway activation during female brain aging. Electron microscopic and lipidomic analyses confirmed myelin degeneration. An increase in fatty acids and mitochondrial fatty acid metabolism machinery was coincident with a rise in brain ketone bodies and decline in plasma ketone bodies. This mechanistic pathway and its chronologically phased activation, links mitochondrial dysfunction early in aging with later age development of white matter degeneration. The catabolism of myelin lipids to generate ketone bodies can be viewed as a systems level adaptive response to address brain fuel and energy demand. Elucidation of the initiating factors and the mechanistic pathway leading to white matter catabolism in the aging female brain provides potential therapeutic targets to prevent and treat demyelinating diseases such as Alzheimer's and multiple sclerosis. Targeting stages of disease and associated mechanisms will be critical.

White Matter Lipids as a Ketogenic Fuel Supply in Aging Female Brain: Implications for Alzheimer's Disease

PubMed Central

Klosinski, Lauren P.; Yao, Jia; Yin, Fei; Fonteh, Alfred N.; Harrington, Michael G.; Christensen, Trace A.; Trushina, Eugenia; Brinton, Roberta Diaz

2015-01-01

White matter degeneration is a pathological hallmark of neurodegenerative diseases including Alzheimer's. Age remains the greatest risk factor for Alzheimer's and the prevalence of age-related late onset Alzheimer's is greatest in females. We investigated mechanisms underlying white matter degeneration in an animal model consistent with the sex at greatest Alzheimer's risk. Results of these analyses demonstrated decline in mitochondrial respiration, increased mitochondrial hydrogen peroxide production and cytosolic-phospholipase-A2 sphingomyelinase pathway activation during female brain aging. Electron microscopic and lipidomic analyses confirmed myelin degeneration. An increase in fatty acids and mitochondrial fatty acid metabolism machinery was coincident with a rise in brain ketone bodies and decline in plasma ketone bodies. This mechanistic pathway and its chronologically phased activation, links mitochondrial dysfunction early in aging with later age development of white matter degeneration. The catabolism of myelin lipids to generate ketone bodies can be viewed as a systems level adaptive response to address brain fuel and energy demand. Elucidation of the initiating factors and the mechanistic pathway leading to white matter catabolism in the aging female brain provides potential therapeutic targets to prevent and treat demyelinating diseases such as Alzheimer's and multiple sclerosis. Targeting stages of disease and associated mechanisms will be critical. PMID:26844268

The effect of ageing on grey and white matter reductions in schizophrenia.

PubMed

Bose, Subrata K; Mackinnon, Toby; Mehta, Mitul A; Turkheimer, Federico E; Howes, Oliver D; Selvaraj, Sudhakar; Kempton, Matthew J; Grasby, Paul M

2009-07-01

Total brain volume and, in particular gray matter (GM) volume is reduced in patients with schizophrenia and recent studies suggest there is greater progressive loss of brain volume in the patients with schizophrenia than in normal controls. However, as the longitudinal studies do not include life-long follow-up, it is not clear if this occurs across the lifespan or only in the early phase of the illness. In this study we investigated this by studying the effects of age on brain tissue volumes in schizophrenia (n=34, age range=27-65 years)to test the prediction that there is a progressive loss in grey matter volume with increasing age in patients compared to healthy controls (n=33, age range=18-73 years). The results showed there was diminished relative GM volume loss with age in patients with schizophrenia compared to controls--in contrast to our prediction. However, there was increased relative white matter (WM) loss with age in schizophrenia. The results also replicated previous findings that patients with schizophrenia have significantly lower total (1509 versus 1596 mm(3)) and regional GM volume (755 versus 822 mm(3)) and increased cerebrospinal fluid (CSF) volume when compared to matched healthy volunteers. Overall these findings indicate that the proportion of grey matter in schizophrenia is reduced compared to controls early in the illness, and this difference diminishes with age; the corresponding effect in the proportion of WM is an increase with age compared to controls. This suggests that illness related factors may differentially affect grey and white matter, with implications for understanding the pathophysiology of schizophrenia and related psychotic disorders.

Age-related decline in task switching is linked to both global and tract-specific changes in white matter microstructure.

PubMed

Jolly, Todd A D; Cooper, Patrick S; Rennie, Jaime L; Levi, Christopher R; Lenroot, Rhoshel; Parsons, Mark W; Michie, Patricia T; Karayanidis, Frini

2017-03-01

Task-switching performance relies on a broadly distributed frontoparietal network and declines in older adults. In this study, they investigated whether this age-related decline in task switching performance was mediated by variability in global or regional white matter microstructural health. Seventy cognitively intact adults (43-87 years) completed a cued-trials task switching paradigm. Microstructural white matter measures were derived using diffusion tensor imaging (DTI) analyses on the diffusion-weighted imaging (DWI) sequence. Task switching performance decreased with increasing age and radial diffusivity (RaD), a measure of white matter microstructure that is sensitive to myelin structure. RaD mediated the relationship between age and task switching performance. However, the relationship between RaD and task switching performance remained significant when controlling for age and was stronger in the presence of cardiovascular risk factors. Variability in error and RT mixing cost were associated with RaD in global white matter and in frontoparietal white matter tracts, respectively. These findings suggest that age-related increase in mixing cost may result from both global and tract-specific disruption of cerebral white matter linked to the increased incidence of cardiovascular risks in older adults. Hum Brain Mapp 38:1588-1603, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain

PubMed Central

Al-Mashhadi, Sufana; Simpson, Julie E.; Heath, Paul R.; Dickman, Mark; Forster, Gillian; Matthews, Fiona E.; Brayne, Carol; Ince, Paul G.; Wharton, Stephen B.

2016-01-01

White matter lesions (WML) are common in brain aging and are associated with dementia. We aimed to investigate whether oxidative DNA damage and occur in WML and in apparently normal white matter in cases with lesions. Tissue from WML and control white matter from brains with lesions (controls lesional) and without lesions (controls non-lesional) were obtained, using post-mortem magnetic resonance imaging-guided sampling, from the Medical Research Council Cognitive Function and Ageing Study. Oxidative damage was assessed by immunohistochemistry to 8-hydroxy-2′-deoxoguanosine (8-OHdG) and Western blotting for malondialdehyde. DNA response was assessed by phosphorylated histone H2AX (γH2AX), p53, senescence markers and by quantitative Reverse transcription polymerase chain reaction (RT-PCR) panel for candidate DNA damage-associated genes. 8-OHdG was expressed in glia and endothelium, with increased expression in both WML and controls lesional compared with controls non-lesional (P < 0.001). γH2Ax showed a similar, although attenuated difference among groups (P = 0.03). Expression of senescence-associated β-galactosidase and p16 suggested induction of senescence mechanisms in glia. Oxidative DNA damage and a DNA damage response are features of WML pathogenesis and suggest candidate mechanisms for glial dysfunction. Their expression in apparently normal white matter in cases with WML suggests that white matter dysfunction is not restricted to lesions. The role of this field-effect lesion pathogenesis and cognitive impairment are areas to be defined. PMID:25311358

Predictors of Memory in Healthy Aging: Polyunsaturated Fatty Acid Balance and Fornix White Matter Integrity.

PubMed

Zamroziewicz, Marta K; Paul, Erick J; Zwilling, Chris E; Barbey, Aron K

2017-07-01

Recent evidence demonstrates that age and disease-related decline in cognition depends not only upon degeneration in brain structure and function, but also on dietary intake and nutritional status. Memory, a potential preclinical marker of Alzheimer's disease, is supported by white matter integrity in the brain and dietary patterns high in omega-3 and omega-6 polyunsaturated fatty acids. However, the extent to which memory is supported by specific omega-3 and omega-6 polyunsaturated fatty acids, and the degree to which this relationship is reliant upon microstructure of particular white matter regions is not known. This study therefore examined the cross-sectional relationship between empirically-derived patterns of omega-3 and omega-6 polyunsaturated fatty acids (represented by nutrient biomarker patterns), memory, and regional white matter microstructure in healthy, older adults. We measured thirteen plasma phospholipid omega-3 and omega-6 polyunsaturated fatty acids, memory, and regional white matter microstructure in 94 cognitively intact older adults (65 to 75 years old). A three-step mediation analysis was implemented using multivariate linear regressions, adjusted for age, gender, education, income, depression status, and body mass index. The mediation analysis revealed that a mixture of plasma phospholipid omega-3 and omega-6 polyunsaturated fatty acids is linked to memory and that white matter microstructure of the fornix fully mediates the relationship between this pattern of plasma phospholipid polyunsaturated fatty acids and memory. These results suggest that memory may be optimally supported by a balance of plasma phospholipid omega-3 and omega-6 polyunsaturated fatty acids through the preservation of fornix white matter microstructure in cognitively intact older adults. This report provides novel evidence for the benefits of plasma phospholipid omega-3 and omega-6 polyunsaturated fatty acid balance on memory and underlying white matter microstructure.

Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain.

PubMed

Al-Mashhadi, Sufana; Simpson, Julie E; Heath, Paul R; Dickman, Mark; Forster, Gillian; Matthews, Fiona E; Brayne, Carol; Ince, Paul G; Wharton, Stephen B

2015-09-01

White matter lesions (WML) are common in brain aging and are associated with dementia. We aimed to investigate whether oxidative DNA damage and occur in WML and in apparently normal white matter in cases with lesions. Tissue from WML and control white matter from brains with lesions (controls lesional) and without lesions (controls non-lesional) were obtained, using post-mortem magnetic resonance imaging-guided sampling, from the Medical Research Council Cognitive Function and Ageing Study. Oxidative damage was assessed by immunohistochemistry to 8-hydroxy-2'-deoxoguanosine (8-OHdG) and Western blotting for malondialdehyde. DNA response was assessed by phosphorylated histone H2AX (γH2AX), p53, senescence markers and by quantitative Reverse transcription polymerase chain reaction (RT-PCR) panel for candidate DNA damage-associated genes. 8-OHdG was expressed in glia and endothelium, with increased expression in both WML and controls lesional compared with controls non-lesional (P < 0.001). γH2Ax showed a similar, although attenuated difference among groups (P = 0.03). Expression of senescence-associated β-galactosidase and p16 suggested induction of senescence mechanisms in glia. Oxidative DNA damage and a DNA damage response are features of WML pathogenesis and suggest candidate mechanisms for glial dysfunction. Their expression in apparently normal white matter in cases with WML suggests that white matter dysfunction is not restricted to lesions. The role of this field-effect lesion pathogenesis and cognitive impairment are areas to be defined. © 2014 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

White matter correlates of cognitive domains in normal aging with diffusion tensor imaging.

PubMed

Sasson, Efrat; Doniger, Glen M; Pasternak, Ofer; Tarrasch, Ricardo; Assaf, Yaniv

2013-01-01

The ability to perform complex as well as simple cognitive tasks engages a network of brain regions that is mediated by the white matter fiber bundles connecting them. Different cognitive tasks employ distinctive white matter fiber bundles. The temporal lobe and its projections subserve a variety of key functions known to deteriorate during aging. In a cohort of 52 healthy subjects (ages 25-82 years), we performed voxel-wise regression analysis correlating performance in higher-order cognitive domains (executive function, information processing speed, and memory) with white matter integrity, as measured by diffusion tensor imaging (DTI) fiber tracking in the temporal lobe projections [uncinate fasciculus (UF), fornix, cingulum, inferior longitudinal fasciculus (ILF), and superior longitudinal fasciculus (SLF)]. The fiber tracts were spatially registered and statistical parametric maps were produced to spatially localize the significant correlations. Results showed that performance in the executive function domain is correlated with DTI parameters in the left SLF and right UF; performance in the information processing speed domain is correlated with fractional anisotropy (FA) in the left cingulum, left fornix, right and left ILF and SLF; and the memory domain shows significant correlations with DTI parameters in the right fornix, right cingulum, left ILF, left SLF and right UF. These findings suggest that DTI tractography enables anatomical definition of region of interest (ROI) for correlation of behavioral parameters with diffusion indices, and functionality can be correlated with white matter integrity.

White matter tracts associated with set-shifting in healthy aging.

PubMed

Perry, Michele E; McDonald, Carrie R; Hagler, Donald J; Gharapetian, Lusineh; Kuperman, Joshua M; Koyama, Alain K; Dale, Anders M; McEvoy, Linda K

2009-11-01

Attentional set-shifting ability, commonly assessed with the Trail Making Test (TMT), decreases with increasing age in adults. Since set-shifting performance relies on activity in widespread brain regions, deterioration of the white matter tracts that connect these regions may underlie the age-related decrease in performance. We used an automated fiber tracking method to investigate the relationship between white matter integrity in several cortical association tracts and TMT performance in a sample of 24 healthy adults, 21-80 years. Diffusion tensor images were used to compute average fractional anisotropy (FA) for five cortical association tracts, the corpus callosum (CC), and the corticospinal tract (CST), which served as a control. Results showed that advancing age was associated with declines in set-shifting performance and with decreased FA in the CC and in association tracts that connect frontal cortex to more posterior brain regions, including the inferior fronto-occipital fasciculus (IFOF), uncinate fasciculus (UF), and superior longitudinal fasciculus (SLF). Declines in average FA in these tracts, and in average FA of the right inferior longitudinal fasciculus (ILF), were associated with increased time to completion on the set-shifting subtask of the TMT but not with the simple sequencing subtask. FA values in these tracts were strong mediators of the effect of age on set-shifting performance. Automated tractography methods can enhance our understanding of the fiber systems involved in performance of specific cognitive tasks and of the functional consequences of age-related changes in those systems.

Nogo receptor blockade overcomes remyelination failure after white matter stroke and stimulates functional recovery in aged mice

PubMed Central

Sozmen, Elif G.; Rosenzweig, Shira; Llorente, Irene L.; DiTullio, David J.; Machnicki, Michal; Vinters, Harry V.; Havton, Lief A.; Giger, Roman J.; Hinman, Jason D.

2016-01-01

White matter stroke is a distinct stroke subtype, accounting for up to 25% of stroke and constituting the second leading cause of dementia. The biology of possible tissue repair after white matter stroke has not been determined. In a mouse stroke model, white matter ischemia causes focal damage and adjacent areas of axonal myelin disruption and gliosis. In these areas of only partial damage, local white matter progenitors respond to injury, as oligodendrocyte progenitors (OPCs) proliferate. However, OPCs fail to mature into oligodendrocytes (OLs) even in regions of demyelination with intact axons and instead divert into an astrocytic fate. Local axonal sprouting occurs, producing an increase in unmyelinated fibers in the corpus callosum. The OPC maturation block after white matter stroke is in part mediated via Nogo receptor 1 (NgR1) signaling. In both aged and young adult mice, stroke induces NgR1 ligands and down-regulates NgR1 inhibitors during the peak OPC maturation block. Nogo ligands are also induced adjacent to human white matter stroke in humans. A Nogo signaling blockade with an NgR1 antagonist administered after stroke reduces the OPC astrocytic transformation and improves poststroke oligodendrogenesis in mice. Notably, increased white matter repair in aged mice is translated into significant poststroke motor recovery, even when NgR1 blockade is provided during the chronic time points of injury. These data provide a perspective on the role of NgR1 ligand function in OPC fate in the context of a specific and common type of stroke and show that it is amenable to systemic intervention to promote recovery. PMID:27956620

Nogo receptor blockade overcomes remyelination failure after white matter stroke and stimulates functional recovery in aged mice.

PubMed

Sozmen, Elif G; Rosenzweig, Shira; Llorente, Irene L; DiTullio, David J; Machnicki, Michal; Vinters, Harry V; Havton, Lief A; Giger, Roman J; Hinman, Jason D; Carmichael, S Thomas

2016-12-27

White matter stroke is a distinct stroke subtype, accounting for up to 25% of stroke and constituting the second leading cause of dementia. The biology of possible tissue repair after white matter stroke has not been determined. In a mouse stroke model, white matter ischemia causes focal damage and adjacent areas of axonal myelin disruption and gliosis. In these areas of only partial damage, local white matter progenitors respond to injury, as oligodendrocyte progenitors (OPCs) proliferate. However, OPCs fail to mature into oligodendrocytes (OLs) even in regions of demyelination with intact axons and instead divert into an astrocytic fate. Local axonal sprouting occurs, producing an increase in unmyelinated fibers in the corpus callosum. The OPC maturation block after white matter stroke is in part mediated via Nogo receptor 1 (NgR1) signaling. In both aged and young adult mice, stroke induces NgR1 ligands and down-regulates NgR1 inhibitors during the peak OPC maturation block. Nogo ligands are also induced adjacent to human white matter stroke in humans. A Nogo signaling blockade with an NgR1 antagonist administered after stroke reduces the OPC astrocytic transformation and improves poststroke oligodendrogenesis in mice. Notably, increased white matter repair in aged mice is translated into significant poststroke motor recovery, even when NgR1 blockade is provided during the chronic time points of injury. These data provide a perspective on the role of NgR1 ligand function in OPC fate in the context of a specific and common type of stroke and show that it is amenable to systemic intervention to promote recovery.

Monotonic non-linear transformations as a tool to investigate age-related effects on brain white matter integrity: A Box-Cox investigation.

PubMed

Morozova, Maria; Koschutnig, Karl; Klein, Elise; Wood, Guilherme

2016-01-15

Non-linear effects of age on white matter integrity are ubiquitous in the brain and indicate that these effects are more pronounced in certain brain regions at specific ages. Box-Cox analysis is a technique to increase the log-likelihood of linear relationships between variables by means of monotonic non-linear transformations. Here we employ Box-Cox transformations to flexibly and parsimoniously determine the degree of non-linearity of age-related effects on white matter integrity by means of model comparisons using a voxel-wise approach. Analysis of white matter integrity in a sample of adults between 20 and 89years of age (n=88) revealed that considerable portions of the white matter in the corpus callosum, cerebellum, pallidum, brainstem, superior occipito-frontal fascicle and optic radiation show non-linear effects of age. Global analyses revealed an increase in the average non-linearity from fractional anisotropy to radial diffusivity, axial diffusivity, and mean diffusivity. These results suggest that Box-Cox transformations are a useful and flexible tool to investigate more complex non-linear effects of age on white matter integrity and extend the functionality of the Box-Cox analysis in neuroimaging. Copyright © 2015 Elsevier Inc. All rights reserved.

Lifespan Trajectories of White Matter Changes in Rhesus Monkeys.

PubMed

Kubicki, M; Baxi, M; Pasternak, O; Tang, Y; Karmacharya, S; Chunga, N; Lyall, A E; Rathi, Y; Eckbo, R; Bouix, S; Mortazavi, F; Papadimitriou, G; Shenton, M E; Westin, C F; Killiany, R; Makris, N; Rosene, D L

2018-04-26

Progress in neurodevelopmental brain research has been achieved through the use of animal models. Such models not only help understanding biological changes that govern brain development, maturation and aging, but are also essential for identifying possible mechanisms of neurodevelopmental and age-related chronic disorders, and to evaluate possible interventions with potential relevance to human disease. Genetic relationship of rhesus monkeys to humans makes those animals a great candidate for such models. With the typical lifespan of 25 years, they undergo cognitive maturation and aging that is similar to this observed in humans. Quantitative structural neuroimaging has been proposed as one of the candidate in vivo biomarkers for tracking white matter brain maturation and aging. While lifespan trajectories of white matter changes have been mapped in humans, such knowledge is not available for nonhuman primates. Here, we analyze and model lifespan trajectories of white matter microstructure using in vivo diffusion imaging in a sample of 44 rhesus monkeys. We report quantitative parameters (including slopes and peaks) of lifespan trajectories for 8 individual white matter tracts. We show different trajectories for cellular and extracellular microstructural imaging components that are associated with white matter maturation and aging, and discuss similarities and differences between those in humans and rhesus monkeys, the importance of our findings, and future directions for the field.Significance Statement: Quantitative structural neuroimaging has been proposed as one of the candidate in vivo biomarkers for tracking brain maturation and aging. While lifespan trajectories of structural white matter changes have been mapped in humans, such knowledge is not available for rhesus monkeys. We present here results of the analysis and modeling of the lifespan trajectories of white matter microstructure using in vivo diffusion imaging in a sample of 44 rhesus monkeys (age 4

Cortical grey matter and subcortical white matter brain microstructural changes in schizophrenia are localised and age independent: a case-control diffusion tensor imaging study.

PubMed

Chiapponi, Chiara; Piras, Fabrizio; Piras, Federica; Fagioli, Sabrina; Caltagirone, Carlo; Spalletta, Gianfranco

2013-01-01

It is still unknown whether the structural brain impairments that characterize schizophrenia (SZ) worsen during the lifetime. Here, we aimed to describe age-related microstructural brain changes in cortical grey matter and subcortical white matter of patients affected by SZ. In this diffusion tensor imaging study, we included 69 patients diagnosed with SZ and 69 healthy control (HC) subjects, age and gender matched. We carried out analyses of covariance, with diagnosis as fixed factor and brain diffusion-related parameters as dependent variables, and controlled for the effect of education. White matter fractional anisotropy decreased in the entire age range spanned (18-65 years) in both SZ and HC and was significantly lower in younger patients with SZ, with no interaction (age by diagnosis) effect in fiber tracts including corpus callosum, corona radiata, thalamic radiations and external capsule. Also, grey matter mean diffusivity increased in the entire age range in both SZ and HC and was significantly higher in younger patients, with no age by diagnosis interaction in the left frontal operculum cortex, left insula and left planum polare and in the right temporal pole and right intracalcarine cortex. In individuals with SZ we found that localized brain cortical and white matter subcortical microstructural impairments appear early in life but do not worsen in the 18-65 year age range.

On describing human white matter anatomy: the white matter query language.

PubMed

Wassermann, Demian; Makris, Nikos; Rathi, Yogesh; Shenton, Martha; Kikinis, Ron; Kubicki, Marek; Westin, Carl-Fredrik

2013-01-01

The main contribution of this work is the careful syntactical definition of major white matter tracts in the human brain based on a neuroanatomist's expert knowledge. We present a technique to formally describe white matter tracts and to automatically extract them from diffusion MRI data. The framework is based on a novel query language with a near-to-English textual syntax. This query language allows us to construct a dictionary of anatomical definitions describing white matter tracts. The definitions include adjacent gray and white matter regions, and rules for spatial relations. This enables automated coherent labeling of white matter anatomy across subjects. We use our method to encode anatomical knowledge in human white matter describing 10 association and 8 projection tracts per hemisphere and 7 commissural tracts. The technique is shown to be comparable in accuracy to manual labeling. We present results applying this framework to create a white matter atlas from 77 healthy subjects, and we use this atlas in a proof-of-concept study to detect tract changes specific to schizophrenia.

Normative development of white matter tracts: similarities and differences in relation to age, gender, and intelligence.

PubMed

Clayden, Jonathan D; Jentschke, Sebastian; Muñoz, Mónica; Cooper, Janine M; Chadwick, Martin J; Banks, Tina; Clark, Chris A; Vargha-Khadem, Faraneh

2012-08-01

The white matter of the brain undergoes a range of structural changes throughout development; from conception to birth, in infancy, and onwards through childhood and adolescence. Several studies have used diffusion magnetic resonance imaging (dMRI) to investigate these changes, but a consensus has not yet emerged on which white matter tracts undergo changes in the later stages of development or what the most important driving factors are behind these changes. In this study of typically developing 8- to 16-year-old children, we use a comprehensive data-driven approach based on principal components analysis to identify effects of age, gender, and brain volume on dMRI parameters, as well as their relative importance. We also show that secondary components of these parameters predict full-scale IQ, independently of the age- and gender-related effects. This overarching assessment of the common factors and gender differences in normal white matter tract development will help to advance understanding of this process in late childhood and adolescence.

Brain white matter damage in aging and cognitive ability in youth and older age☆

PubMed Central

Valdés Hernández, Maria del C.; Booth, Tom; Murray, Catherine; Gow, Alan J.; Penke, Lars; Morris, Zoe; Maniega, Susana Muñoz; Royle, Natalie A.; Aribisala, Benjamin S.; Bastin, Mark E.; Starr, John M.; Deary, Ian J.; Wardlaw, Joanna M.

2013-01-01

Cerebral white matter hyperintensities (WMH) reflect accumulating white matter damage with aging and impair cognition. The role of childhood intelligence is rarely considered in associations between cognitive impairment and WMH. We studied community-dwelling older people all born in 1936, in whom IQ had been assessed at age 11 years. We assessed medical histories, current cognitive ability and quantified WMH on MR imaging. Among 634 participants, mean age 72.7 (SD 0.7), age 11 IQ was the strongest predictor of late life cognitive ability. After accounting for age 11 IQ, greater WMH load was significantly associated with lower late life general cognitive ability (β = −0.14, p < 0.01) and processing speed (β = −0.19, p < 0.001). WMH were also associated independently with lower age 11 IQ (β = −0.08, p < 0.05) and hypertension. In conclusion, having more WMH is significantly associated with lower cognitive ability, after accounting for prior ability, age 11IQ. Early-life IQ also influenced WMH in later life. Determining how lower IQ in youth leads to increasing brain damage with aging is important for future successful cognitive aging. PMID:23850341

Diffusion tensor imaging detects age related white matter change over a 2 year follow-up which is associated with working memory decline.

PubMed

Charlton, R A; Schiavone, F; Barrick, T R; Morris, R G; Markus, H S

2010-01-01

Diffusion tensor imaging (DTI) is a sensitive method for detecting white matter damage, and in cross sectional studies DTI measures correlate with age related cognitive decline. However, there are few data on whether DTI can detect age related changes over short time periods and whether such change correlates with cognitive function. In a community sample of 84 middle-aged and elderly adults, MRI and cognitive testing were performed at baseline and after 2 years. Changes in DTI white matter histograms, white matter hyperintensity (WMH) volume and brain volume were determined. Change over time in performance on tests of executive function, working memory and information processing speed were also assessed. Significant change in all MRI measures was detected. For cognition, change was detected for working memory and this correlated with change in DTI only. In a stepwise regression, with change in working memory as the dependent variable, a DTI histogram measure explained 10.8% of the variance in working memory. Change in WMH or brain volume did not contribute to the model. DTI is sensitive to age related change in white matter ultrastructure and appears useful for monitoring age related white matter change even over short time periods.

White matter tract covariance patterns predict age-declining cognitive abilities.

PubMed

Gazes, Yunglin; Bowman, F DuBois; Razlighi, Qolamreza R; O'Shea, Deirdre; Stern, Yaakov; Habeck, Christian

2016-01-15

Previous studies investigating the relationship of white matter (WM) integrity to cognitive abilities and aging have either focused on a global measure or a few selected WM tracts. Ideally, contribution from all of the WM tracts should be evaluated at the same time. However, the high collinearity among WM tracts precludes systematic examination of WM tracts simultaneously without sacrificing statistical power due to stringent multiple-comparison corrections. Multivariate covariance techniques enable comprehensive simultaneous examination of all WM tracts without being penalized for high collinearity among observations. In this study, Scaled Subprofile Modeling (SSM) was applied to the mean integrity of 18 major WM tracts to extract covariance patterns that optimally predicted four cognitive abilities (perceptual speed, episodic memory, fluid reasoning, and vocabulary) in 346 participants across ages 20 to 79years old. Using expression of the covariance patterns, age-independent effects of white matter integrity on cognition and the indirect effect of WM integrity on age-related differences in cognition were tested separately, but inferences from the indirect analyses were cautiously made given that cross-sectional data set was used in the analysis. A separate covariance pattern was identified that significantly predicted each cognitive ability after controlling for age except for vocabulary, but the age by WM covariance pattern interaction was not significant for any of the three abilities. Furthermore, each of the patterns mediated the effect of age on the respective cognitive ability. A distinct set of WM tracts was most influential in each of the three patterns. The WM covariance pattern accounting for fluid reasoning showed the most number of influential WM tracts whereas the episodic memory pattern showed the least number. Specific patterns of WM tracts make significant contributions to the age-related differences in perceptual speed, episodic memory, and

Roflumilast promotes memory recovery and attenuates white matter injury in aged rats subjected to chronic cerebral hypoperfusion.

PubMed

Santiago, Amanda; Soares, Lígia Mendes; Schepers, Melissa; Milani, Humberto; Vanmierlo, Tim; Prickaerts, Jos; Weffort de Oliveira, Rúbia M

2018-06-19

Chronic cerebral hypoperfusion (CCH) has been associated with aging-related vascular dementia, including Alzheimer's disease. It can be induced by the four-vessel occlusion/internal carotid artery (4VO/ICA) model in aged rats, resulting in persistent memory deficits, white matter injury, and significant neuronal loss in the hippocampus and cerebral cortex. The phosphodiesterase type 4 inhibitor (PDE4-I) roflumilast has been reported to have pro-cognitive effects in several behavioral paradigms. The present study evaluated the effects of repeated roflumilast treatment in aged rats that were subjected to CCH. After surgery, roflumilast (0.003 and 0.01 mg/kg) was administered intraperitoneally once per day for 29 days. Memory performance was assessed in the aversive radial maze (AvRM) 7, 14, and 21 days after CCH. The effects of roflumilast on hippocampal neurodegeneration and white matter injury were investigated using Nissl and Kluver-Barrera staining, respectively. Western blot and RT-qPCR were used to explore microglial polarization using M1 (Iba-1 and iNOS) and M2 (Arginase-1) markers. Chronic cerebral hypoperfusion caused persistent memory deficits, hippocampal neurodegeneration, and vacuolization and fiber disarrangement in white matter. Repeated roflumilast treatment restored CCH-induced cognitive impairments in aged rats but in the absence of the rescue of hippocampal neurons. Attenuation of white matter injury was detected in the optic tract in aged CCH rats that were treated with roflumilast. In vitro, roflumilast increased Arg-1 gene expression in myelin-laden primary microglia. The present data suggest that roflumilast might be useful for the treatment of cognitive sequelae associated with CCH. Copyright © 2018. Published by Elsevier Ltd.

Age-related effects in the neocortical organization of chimpanzees: gray and white matter volume, cortical thickness, and gyrification.

PubMed

Autrey, Michelle M; Reamer, Lisa A; Mareno, Mary Catherine; Sherwood, Chet C; Herndon, James G; Preuss, Todd; Schapiro, Steve J; Hopkins, William D

2014-11-01

Among primates, humans exhibit the most profound degree of age-related brain volumetric decline in particular regions, such as the hippocampus and the frontal lobe. Recent studies have shown that our closest living relatives, the chimpanzees, experience little to no volumetric decline in gray and white matter over the adult lifespan. However, these previous studies were limited with a small sample of chimpanzees of the most advanced ages. In the present study, we sought to further test for potential age-related decline in cortical organization in chimpanzees by expanding the sample size of aged chimpanzees. We used the BrainVisa software to measure total brain volume, gray and white matter volumes, gray matter thickness, and gyrification index in a cross-sectional sample of 219 captive chimpanzees (8-53 years old), with 38 subjects being 40 or more years of age. Mean depth and cortical fold opening of 11 major sulci of the chimpanzee brains were also measured. We found that chimpanzees showed increased gyrification with age and a cubic relationship between age and white matter volume. For the association between age and sulcus depth and width, the results were mostly non-significant with the exception of one negative correlation between age and the fronto-orbital sulcus. In short, results showed that chimpanzees exhibit few age-related changes in global cortical organization, sulcus folding and sulcus width. These findings support previous studies and the theory that the age-related changes in the human brain is due to an extended lifespan. Copyright © 2014 Elsevier Inc. All rights reserved.

Retinal microvasculature and white matter microstructure: The Rotterdam Study.

PubMed

Mutlu, Unal; Cremers, Lotte G M; de Groot, Marius; Hofman, Albert; Niessen, Wiro J; van der Lugt, Aad; Klaver, Caroline C W; Ikram, M Arfan; Vernooij, Meike W; Ikram, M Kamran

2016-09-06

To investigate whether retinal microvascular damage is related to normal-appearing white matter microstructure on diffusion tensor MRI. We included 2,436 participants (age ≥45 years) from the population-based Rotterdam Study (2005-2009) who had gradable retinal images and brain MRI scans. Retinal arteriolar and venular calibers were measured semiautomatically on fundus photographs. White matter microstructure was assessed using diffusion tensor MRI. We used linear regression models to investigate the associations of retinal vascular calibers with markers of normal-appearing white matter microstructure, adjusting for age, sex, the fellow vascular caliber, and additionally for structural MRI markers and cardiovascular risk factors. Narrower arterioles and wider venules were associated with poor white matter microstructure: adjusted difference in fractional anisotropy per SD decrease in arteriolar caliber -0.061 (95% confidence interval -0.106 to -0.016), increase in venular caliber -0.054 (-0.096 to -0.011), adjusted difference in mean diffusivity per SD decrease in arteriolar caliber 0.048 (0.007-0.088), and increase in venular caliber 0.047 (0.008-0.085). The associations for venules were more prominent in women. Retinal vascular calibers are related to normal-appearing white matter microstructure. This suggests that microvascular damage in the white matter is more widespread than visually detectable as white matter lesions. © 2016 American Academy of Neurology.

Long-term white matter tract reorganization following prolonged febrile seizures.

PubMed

Pujar, Suresh S; Seunarine, Kiran K; Martinos, Marina M; Neville, Brian G R; Scott, Rod C; Chin, Richard F M; Clark, Chris A

2017-05-01

Diffusion magnetic resonance imaging (MRI) studies have demonstrated acute white matter changes following prolonged febrile seizures (PFS), but their longer-term evolution is unknown. We investigated a population-based cohort to determine white matter diffusion properties 8 years after PFS. We used diffusion tensor imaging (DTI) and applied Tract-Based Spatial Statistics for voxel-wise comparison of white matter microstructure between 26 children with PFS and 27 age-matched healthy controls. Age, gender, handedness, and hippocampal volumes were entered as covariates for voxel-wise analysis. Mean duration between the episode of PFS and follow-up was 8.2 years (range 6.7-9.6). All children were neurologically normal, and had normal conventional neuroimaging. On voxel-wise analysis, compared to controls, the PFS group had (1) increased fractional anisotropy in early maturing central white matter tracts, (2) increased mean and axial diffusivity in several peripheral white matter tracts and late-maturing central white matter tracts, and (3) increased radial diffusivity in peripheral white matter tracts. None of the tracts had reduced fractional anisotropy or diffusivity indices in the PFS group. In this homogeneous, population-based sample, we found increased fractional anisotropy in early maturing central white matter tracts and increased mean and axial diffusivity with/without increased radial diffusivity in several late-maturing peripheral white matter tracts 8 years post-PFS. We propose disruption in white matter maturation secondary to seizure-induced axonal injury, with subsequent neuroplasticity and microstructural reorganization as a plausible explanation. © 2017 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

Abnormal white matter properties in adolescent girls with anorexia nervosa

PubMed Central

Travis, Katherine E.; Golden, Neville H.; Feldman, Heidi M.; Solomon, Murray; Nguyen, Jenny; Mezer, Aviv; Yeatman, Jason D.; Dougherty, Robert F.

2015-01-01

Anorexia nervosa (AN) is a serious eating disorder that typically emerges during adolescence and occurs most frequently in females. To date, very few studies have investigated the possible impact of AN on white matter tissue properties during adolescence, when white matter is still developing. The present study evaluated white matter tissue properties in adolescent girls with AN using diffusion MRI with tractography and T1 relaxometry to measure R1 (1/T1), an index of myelin content. Fifteen adolescent girls with AN (mean age = 16.6 years ± 1.4) were compared to fifteen age-matched girls with normal weight and eating behaviors (mean age = 17.1 years ± 1.3). We identified and segmented 9 bilateral cerebral tracts (18) and 8 callosal fiber tracts in each participant's brain (26 total). Tract profiles were generated by computing measures for fractional anisotropy (FA) and R1 along the trajectory of each tract. Compared to controls, FA in the AN group was significantly decreased in 4 of 26 white matter tracts and significantly increased in 2 of 26 white matter tracts. R1 was significantly decreased in the AN group compared to controls in 11 of 26 white matter tracts. Reduced FA in combination with reduced R1 suggests that the observed white matter differences in AN are likely due to reductions in myelin content. For the majority of tracts, group differences in FA and R1 did not occur within the same tract. The present findings have important implications for understanding the neurobiological factors underlying white matter changes associated with AN and invite further investigations examining associations between white matter properties and specific physiological, cognitive, social, or emotional functions affected in AN. PMID:26740918

Age-Related Changes in Axonal and Mitochondrial Ultrastructure and Function in White Matter

PubMed Central

Stahon, Katharine E.; Bastian, Chinthasagar; Griffith, Shelby; Kidd, Grahame J.; Brunet, Sylvain

2016-01-01

The impact of aging on CNS white matter (WM) is of general interest because the global effects of aging on myelinated nerve fibers are more complex and profound than those in cortical gray matter. It is important to distinguish between axonal changes created by normal aging and those caused by neurodegenerative diseases, including multiple sclerosis, stroke, glaucoma, Alzheimer's disease, and traumatic brain injury. Using three-dimensional electron microscopy, we show that in mouse optic nerve, which is a pure and fully myelinated WM tract, aging axons are larger, have thicker myelin, and are characterized by longer and thicker mitochondria, which are associated with altered levels of mitochondrial shaping proteins. These structural alterations in aging mitochondria correlate with lower ATP levels and increased generation of nitric oxide, protein nitration, and lipid peroxidation. Moreover, mitochondria–smooth endoplasmic reticulum interactions are compromised due to decreased associations and decreased levels of calnexin and calreticulin, suggesting a disruption in Ca2+ homeostasis and defective unfolded protein responses in aging axons. Despite these age-related modifications, axon function is sustained in aging WM, which suggests that age-dependent changes do not lead to irreversible functional decline under normal conditions, as is observed in neurodegenerative diseases. SIGNIFICANCE STATEMENT Aging is a common risk factor for a number of neurodegenerative diseases, including stroke. Mitochondrial dysfunction and oxidative damage with age are hypothesized to increase risk for stroke. We compared axon–myelin–node–mitochondrion–smooth endoplasmic reticulum (SER) interactions in white matter obtained at 1 and 12 months. We show that aging axons have enlarged volume, thicker myelin, and elongated and thicker mitochondria. Furthermore, there are reduced SER connections to mitochondria that correlate with lower calnexin and calreticulin levels. Despite a

Cortical gray and subcortical white matter associations in Parkinson's disease.

PubMed

Sterling, Nicholas W; Du, Guangwei; Lewis, Mechelle M; Swavely, Steven; Kong, Lan; Styner, Martin; Huang, Xuemei

2017-01-01

Cortical atrophy has been documented in both Parkinson's disease (PD) and healthy aging, but its relationship to changes in subcortical white matter is unknown. This was investigated by obtaining T1- and diffusion-weighted images from 76 PD and 70 controls at baseline and 18 and 36 months, from which cortical volumes and underlying subcortical white matter axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) were determined. Twelve of 69 cortical subregions had significant group differences, and for these, underlying subcortical white matter was explored. At baseline, higher cortical volumes were significantly correlated with lower underlying subcortical white matter AD, RD, and higher FA (ps ≤ 0.017) in PD. Longitudinally, higher rates of cortical atrophy in PD were associated with increased rates of change in AD RD, and FA values (ps ≤ 0.0013) in 2 subregions explored. The significant gray-white matter associations were not found in controls. Thus, unlike healthy aging, cortical atrophy and subcortical white matter changes may not be independent events in PD. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of estrogen replacement therapy on the myelin sheath ultrastructure of myelinated fibers in the white matter of middle-aged ovariectomized rats.

PubMed

He, Qi; Luo, Yanmin; Lv, Fulin; Xiao, Qian; Chao, Fenglei; Qiu, Xuan; Zhang, Lei; Gao, Yuan; Xiu, Yun; Huang, Chunxia; Tang, Yong

2018-04-01

The effects of estrogen replacement therapy (ORT) on white matter and the myelin sheath ultrastructure in the white matter of middle-aged ovariectomized (OVX) rats were investigated in this study. Middle-aged rats were ovariectomized and divided into a placebo replacement (OVX + O) group and an estrogen replacement (OVX + E) group. Then, the Morris water maze, electron microscope techniques, and stereological methods were used to investigate the effects of ORT on spatial learning capacity, white matter volume and the myelin sheath ultrastructure in the white matter. We found that the spatial learning capacity of the OVX + E rats was significantly improved compared with that of the OVX + O rats. When compared with that of OVX + O rats, the total volume of the myelin sheaths in the white matter of the OVX + E rats was significantly increased by 27%, and the difference between the outer perimeter and inner perimeter of the myelin sheaths of the white matter in the OVX + E rats increased significantly by 12.6%. The myelinated fibers with mean diameters of 1.2-1.4 μm were significantly longer (46.1%) in the OVX + E rats; the difference between the mean diameter of myelinated fibers and the mean diameter of axons (0-0.4 μm) was significantly increased by 21.6% in the OVX + E rats. These results suggested that ORT had positive protective effects on the spatial learning ability and on the myelin sheath ultrastructure in the white matter of middle-aged OVX rats. © 2017 Wiley Periodicals, Inc.

Age-related changes in the topological organization of the white matter structural connectome across the human lifespan.

PubMed

Zhao, Tengda; Cao, Miao; Niu, Haijing; Zuo, Xi-Nian; Evans, Alan; He, Yong; Dong, Qi; Shu, Ni

2015-10-01

Lifespan is a dynamic process with remarkable changes in brain structure and function. Previous neuroimaging studies have indicated age-related microstructural changes in specific white matter tracts during development and aging. However, the age-related alterations in the topological architecture of the white matter structural connectome across the human lifespan remain largely unknown. Here, a cohort of 113 healthy individuals (ages 9-85) with both diffusion and structural MRI acquisitions were examined. For each participant, the high-resolution white matter structural networks were constructed by deterministic fiber tractography among 1024 parcellation units and were quantified with graph theoretical analyses. The global network properties, including network strength, cost, topological efficiency, and robustness, followed an inverted U-shaped trajectory with a peak age around the third decade. The brain areas with the most significantly nonlinear changes were located in the prefrontal and temporal cortices. Different brain regions exhibited heterogeneous trajectories: the posterior cingulate and lateral temporal cortices displayed prolonged maturation/degeneration compared with the prefrontal cortices. Rich-club organization was evident across the lifespan, whereas hub integration decreased linearly with age, especially accompanied by the loss of frontal hubs and their connections. Additionally, age-related changes in structural connections were predominantly located within and between the prefrontal and temporal modules. Finally, based on the graph metrics of structural connectome, accurate predictions of individual age were obtained (r = 0.77). Together, the data indicated a dynamic topological organization of the brain structural connectome across human lifespan, which may provide possible structural substrates underlying functional and cognitive changes with age. © 2015 Wiley Periodicals, Inc.

GENETICS OF WHITE MATTER DEVELOPMENT: A DTI STUDY OF 705 TWINS AND THEIR SIBLINGS AGED 12 TO 29

PubMed Central

Chiang, Ming-Chang; McMahon, Katie L.; de Zubicaray, Greig I.; Martin, Nicholas G.; Hickie, Ian; Toga, Arthur W.; Wright, Margaret J.; Thompson, Paul M.

2011-01-01

White matter microstructure is under strong genetic control, yet it is largely unknown how genetic influences change from childhood into adulthood. In one of the largest brain mapping studies ever performed, we determined whether the genetic control over white matter architecture depends on age, sex, socioeconomic status (SES), and intelligence quotient (IQ). We assessed white matter integrity voxelwise using diffusion tensor imaging at high magnetic field (4-Tesla), in 705 twins and their siblings (age range 12–29; 290 M/415 F). White matter integrity was quantified using a widely accepted measure, fractional anisotropy (FA). We fitted gene-environment interaction models pointwise, to visualize brain regions where age, sex, SES and IQ modulate heritability of fiber integrity. We hypothesized that environmental factors would start to outweigh genetic factors during late childhood and adolescence. Genetic influences were greater in adolescence versus adulthood, and greater in males than in females. Socioeconomic status significantly interacted with genes that affect fiber integrity: heritability was higher in those with higher SES. In people with above-average IQ, genetic factors explained over 800% of the observed FA variability in the thalamus, genu, posterior internal capsule, and superior corona radiata. In those with below-average IQ, however, only around 40% FA variability in the same regions was attributable to genetic factors. Genes affect fiber integrity, but their effects vary with age, sex, SES and IQ. Gene-environment interactions are vital to consider in the search for specific genetic polymorphisms that affect brain integrity and connectivity. PMID:20950689

Age-related delay in visual and auditory evoked responses is mediated by white- and grey-matter differences.

PubMed

Price, D; Tyler, L K; Neto Henriques, R; Campbell, K L; Williams, N; Treder, M S; Taylor, J R; Henson, R N A

2017-06-09

Slowing is a common feature of ageing, yet a direct relationship between neural slowing and brain atrophy is yet to be established in healthy humans. We combine magnetoencephalographic (MEG) measures of neural processing speed with magnetic resonance imaging (MRI) measures of white and grey matter in a large population-derived cohort to investigate the relationship between age-related structural differences and visual evoked field (VEF) and auditory evoked field (AEF) delay across two different tasks. Here we use a novel technique to show that VEFs exhibit a constant delay, whereas AEFs exhibit delay that accumulates over time. White-matter (WM) microstructure in the optic radiation partially mediates visual delay, suggesting increased transmission time, whereas grey matter (GM) in auditory cortex partially mediates auditory delay, suggesting less efficient local processing. Our results demonstrate that age has dissociable effects on neural processing speed, and that these effects relate to different types of brain atrophy.

Age-related delay in visual and auditory evoked responses is mediated by white- and grey-matter differences

PubMed Central

Price, D.; Tyler, L. K.; Neto Henriques, R.; Campbell, K. L.; Williams, N.; Treder, M.S.; Taylor, J. R.; Brayne, Carol; Bullmore, Edward T.; Calder, Andrew C.; Cusack, Rhodri; Dalgleish, Tim; Duncan, John; Matthews, Fiona E.; Marslen-Wilson, William D.; Rowe, James B.; Shafto, Meredith A.; Cheung, Teresa; Davis, Simon; Geerligs, Linda; Kievit, Rogier; McCarrey, Anna; Mustafa, Abdur; Samu, David; Tsvetanov, Kamen A.; van Belle, Janna; Bates, Lauren; Emery, Tina; Erzinglioglu, Sharon; Gadie, Andrew; Gerbase, Sofia; Georgieva, Stanimira; Hanley, Claire; Parkin, Beth; Troy, David; Auer, Tibor; Correia, Marta; Gao, Lu; Green, Emma; Allen, Jodie; Amery, Gillian; Amunts, Liana; Barcroft, Anne; Castle, Amanda; Dias, Cheryl; Dowrick, Jonathan; Fair, Melissa; Fisher, Hayley; Goulding, Anna; Grewal, Adarsh; Hale, Geoff; Hilton, Andrew; Johnson, Frances; Johnston, Patricia; Kavanagh-Williamson, Thea; Kwasniewska, Magdalena; McMinn, Alison; Norman, Kim; Penrose, Jessica; Roby, Fiona; Rowland, Diane; Sargeant, John; Squire, Maggie; Stevens, Beth; Stoddart, Aldabra; Stone, Cheryl; Thompson, Tracy; Yazlik, Ozlem; Barnes, Dan; Dixon, Marie; Hillman, Jaya; Mitchell, Joanne; Villis, Laura; Henson, R. N. A.

2017-01-01

Slowing is a common feature of ageing, yet a direct relationship between neural slowing and brain atrophy is yet to be established in healthy humans. We combine magnetoencephalographic (MEG) measures of neural processing speed with magnetic resonance imaging (MRI) measures of white and grey matter in a large population-derived cohort to investigate the relationship between age-related structural differences and visual evoked field (VEF) and auditory evoked field (AEF) delay across two different tasks. Here we use a novel technique to show that VEFs exhibit a constant delay, whereas AEFs exhibit delay that accumulates over time. White-matter (WM) microstructure in the optic radiation partially mediates visual delay, suggesting increased transmission time, whereas grey matter (GM) in auditory cortex partially mediates auditory delay, suggesting less efficient local processing. Our results demonstrate that age has dissociable effects on neural processing speed, and that these effects relate to different types of brain atrophy. PMID:28598417

The white matter query language: a novel approach for describing human white matter anatomy

PubMed Central

Makris, Nikos; Rathi, Yogesh; Shenton, Martha; Kikinis, Ron; Kubicki, Marek; Westin, Carl-Fredrik

2016-01-01

We have developed a novel method to describe human white matter anatomy using an approach that is both intuitive and simple to use, and which automatically extracts white matter tracts from diffusion MRI volumes. Further, our method simplifies the quantification and statistical analysis of white matter tracts on large diffusion MRI databases. This work reflects the careful syntactical definition of major white matter fiber tracts in the human brain based on a neuroanatomist’s expert knowledge. The framework is based on a novel query language with a near-to-English textual syntax. This query language makes it possible to construct a dictionary of anatomical definitions that describe white matter tracts. The definitions include adjacent gray and white matter regions, and rules for spatial relations. This novel method makes it possible to automatically label white matter anatomy across subjects. After describing this method, we provide an example of its implementation where we encode anatomical knowledge in human white matter for ten association and 15 projection tracts per hemisphere, along with seven commissural tracts. Importantly, this novel method is comparable in accuracy to manual labeling. Finally, we present results applying this method to create a white matter atlas from 77 healthy subjects, and we use this atlas in a small proof-of-concept study to detect changes in association tracts that characterize schizophrenia. PMID:26754839

The white matter query language: a novel approach for describing human white matter anatomy.

PubMed

Wassermann, Demian; Makris, Nikos; Rathi, Yogesh; Shenton, Martha; Kikinis, Ron; Kubicki, Marek; Westin, Carl-Fredrik

2016-12-01

We have developed a novel method to describe human white matter anatomy using an approach that is both intuitive and simple to use, and which automatically extracts white matter tracts from diffusion MRI volumes. Further, our method simplifies the quantification and statistical analysis of white matter tracts on large diffusion MRI databases. This work reflects the careful syntactical definition of major white matter fiber tracts in the human brain based on a neuroanatomist's expert knowledge. The framework is based on a novel query language with a near-to-English textual syntax. This query language makes it possible to construct a dictionary of anatomical definitions that describe white matter tracts. The definitions include adjacent gray and white matter regions, and rules for spatial relations. This novel method makes it possible to automatically label white matter anatomy across subjects. After describing this method, we provide an example of its implementation where we encode anatomical knowledge in human white matter for ten association and 15 projection tracts per hemisphere, along with seven commissural tracts. Importantly, this novel method is comparable in accuracy to manual labeling. Finally, we present results applying this method to create a white matter atlas from 77 healthy subjects, and we use this atlas in a small proof-of-concept study to detect changes in association tracts that characterize schizophrenia.

White matter involvement in sporadic Creutzfeldt-Jakob disease

PubMed Central

Mandelli, Maria Luisa; DeArmond, Stephen J.; Hess, Christopher P.; Vitali, Paolo; Papinutto, Nico; Oehler, Abby; Miller, Bruce L.; Lobach, Irina V.; Bastianello, Stefano; Geschwind, Michael D.; Henry, Roland G.

2014-01-01

Sporadic Creutzfeldt-Jakob disease is considered primarily a disease of grey matter, although the extent of white matter involvement has not been well described. We used diffusion tensor imaging to study the white matter in sporadic Creutzfeldt-Jakob disease compared to healthy control subjects and to correlated magnetic resonance imaging findings with histopathology. Twenty-six patients with sporadic Creutzfeldt-Jakob disease and nine age- and gender-matched healthy control subjects underwent volumetric T1-weighted and diffusion tensor imaging. Six patients had post-mortem brain analysis available for assessment of neuropathological findings associated with prion disease. Parcellation of the subcortical white matter was performed on 3D T1-weighted volumes using Freesurfer. Diffusion tensor imaging maps were calculated and transformed to the 3D-T1 space; the average value for each diffusion metric was calculated in the total white matter and in regional volumes of interest. Tract-based spatial statistics analysis was also performed to investigate the deeper white matter tracts. There was a significant reduction of mean (P = 0.002), axial (P = 0.0003) and radial (P = 0.0134) diffusivities in the total white matter in sporadic Creutzfeldt-Jakob disease. Mean diffusivity was significantly lower in most white matter volumes of interest (P < 0.05, corrected for multiple comparisons), with a generally symmetric pattern of involvement in sporadic Creutzfeldt-Jakob disease. Mean diffusivity reduction reflected concomitant decrease of both axial and radial diffusivity, without appreciable changes in white matter anisotropy. Tract-based spatial statistics analysis showed significant reductions of mean diffusivity within the white matter of patients with sporadic Creutzfeldt-Jakob disease, mainly in the left hemisphere, with a strong trend (P = 0.06) towards reduced mean diffusivity in most of the white matter bilaterally. In contrast, by visual assessment there was no white

Major Superficial White Matter Abnormalities in Huntington's Disease

PubMed Central

Phillips, Owen R.; Joshi, Shantanu H.; Squitieri, Ferdinando; Sanchez-Castaneda, Cristina; Narr, Katherine; Shattuck, David W.; Caltagirone, Carlo; Sabatini, Umberto; Di Paola, Margherita

2016-01-01

Background: The late myelinating superficial white matter at the juncture of the cortical gray and white matter comprising the intracortical myelin and short-range association fibers has not received attention in Huntington's disease. It is an area of the brain that is late myelinating and is sensitive to both normal aging and neurodegenerative disease effects. Therefore, it may be sensitive to Huntington's disease processes. Methods: Structural MRI data from 25 Pre-symptomatic subjects, 24 Huntington's disease patients and 49 healthy controls was run through a cortical pattern-matching program. The surface corresponding to the white matter directly below the cortical gray matter was then extracted. Individual subject's Diffusion Tensor Imaging (DTI) data was aligned to their structural MRI data. Diffusivity values along the white matter surface were then sampled at each vertex point. DTI measures with high spatial resolution across the superficial white matter surface were then analyzed with the General Linear Model to test for the effects of disease. Results: There was an overall increase in the axial and radial diffusivity across much of the superficial white matter (p < 0.001) in Pre-symptomatic subjects compared to controls. In Huntington's disease patients increased diffusivity covered essentially the whole brain (p < 0.001). Changes are correlated with genotype (CAG repeat number) and disease burden (p < 0.001). Conclusions: This study showed broad abnormalities in superficial white matter even before symptoms are present in Huntington's disease. Since, the superficial white matter has a unique microstructure and function these abnormalities suggest it plays an important role in the disease. PMID:27242403

White matter neuroanatomical differences in young children who stutter

PubMed Central

Zhu, David C.; Choo, Ai Leen; Angstadt, Mike

2015-01-01

The ability to express thoughts through fluent speech production is a most human faculty, one that is often taken for granted. Stuttering, which disrupts the smooth flow of speech, affects 5% of preschool-age children and 1% of the general population, and can lead to significant communication difficulties and negative psychosocial consequences throughout one’s lifetime. Despite the fact that symptom onset typically occurs during early childhood, few studies have yet examined the possible neural bases of developmental stuttering during childhood. Here we present a diffusion tensor imaging study that examined white matter measures reflecting neuroanatomical connectivity (fractional anisotropy) in 77 children [40 controls (20 females), 37 who stutter (16 females)] between 3 and 10 years of age. We asked whether previously reported anomalous white matter measures in adults and older children who stutter that were found primarily in major left hemisphere tracts (e.g. superior longitudinal fasciculus) are also present in younger children who stutter. All children exhibited normal speech, language, and cognitive development as assessed through a battery of assessments. The two groups were matched in chronological age and socioeconomic status. Voxel-wise whole brain comparisons using tract-based spatial statistics and region of interest analyses of fractional anisotropy were conducted to examine white matter changes associated with stuttering status, age, sex, and stuttering severity. Children who stutter exhibited significantly reduced fractional anisotropy relative to controls in white matter tracts that interconnect auditory and motor structures, corpus callosum, and in tracts interconnecting cortical and subcortical areas. In contrast to control subjects, fractional anisotropy changes with age were either stagnant or showed dissociated development among major perisylvian brain areas in children who stutter. These results provide first glimpses into the

Mapping White Matter Microstructure in the One Month Human Brain.

PubMed

Dean, D C; Planalp, E M; Wooten, W; Adluru, N; Kecskemeti, S R; Frye, C; Schmidt, C K; Schmidt, N L; Styner, M A; Goldsmith, H H; Davidson, R J; Alexander, A L

2017-08-29

White matter microstructure, essential for efficient and coordinated transmission of neural communications, undergoes pronounced development during the first years of life, while deviations to this neurodevelopmental trajectory likely result in alterations of brain connectivity relevant to behavior. Hence, systematic evaluation of white matter microstructure in the normative brain is critical for a neuroscientific approach to both typical and atypical early behavioral development. However, few studies have examined the infant brain in detail, particularly in infants under 3 months of age. Here, we utilize quantitative techniques of diffusion tensor imaging and neurite orientation dispersion and density imaging to investigate neonatal white matter microstructure in 104 infants. An optimized multiple b-value diffusion protocol was developed to allow for successful acquisition during non-sedated sleep. Associations between white matter microstructure measures and gestation corrected age, regional asymmetries, infant sex, as well as newborn growth measures were assessed. Results highlight changes of white matter microstructure during the earliest periods of development and demonstrate differential timing of developing regions and regional asymmetries. Our results contribute to a growing body of research investigating the neurobiological changes associated with neurodevelopment and suggest that characteristics of white matter microstructure are already underway in the weeks immediately following birth.

Framework for shape analysis of white matter fiber bundles.

PubMed

Glozman, Tanya; Bruckert, Lisa; Pestilli, Franco; Yecies, Derek W; Guibas, Leonidas J; Yeom, Kristen W

2018-02-15

Diffusion imaging coupled with tractography algorithms allows researchers to image human white matter fiber bundles in-vivo. These bundles are three-dimensional structures with shapes that change over time during the course of development as well as in pathologic states. While most studies on white matter variability focus on analysis of tissue properties estimated from the diffusion data, e.g. fractional anisotropy, the shape variability of white matter fiber bundle is much less explored. In this paper, we present a set of tools for shape analysis of white matter fiber bundles, namely: (1) a concise geometric model of bundle shapes; (2) a method for bundle registration between subjects; (3) a method for deformation estimation. Our framework is useful for analysis of shape variability in white matter fiber bundles. We demonstrate our framework by applying our methods on two datasets: one consisting of data for 6 normal adults and another consisting of data for 38 normal children of age 11 days to 8.5 years. We suggest a robust and reproducible method to measure changes in the shape of white matter fiber bundles. We demonstrate how this method can be used to create a model to assess age-dependent changes in the shape of specific fiber bundles. We derive such models for an ensemble of white matter fiber bundles on our pediatric dataset and show that our results agree with normative human head and brain growth data. Creating these models for a large pediatric longitudinal dataset may improve understanding of both normal development and pathologic states and propose novel parameters for the examination of the pediatric brain. Copyright © 2017 Elsevier Inc. All rights reserved.

Frontal white matter hyperintensities, clasmatodendrosis and gliovascular abnormalities in ageing and post-stroke dementia

PubMed Central

Chen, Aiqing; Akinyemi, Rufus O.; Hase, Yoshiki; Firbank, Michael J.; Ndung’u, Michael N.; Foster, Vincent; Craggs, Lucy J. L.; Washida, Kazuo; Okamoto, Yoko; Thomas, Alan J.; Polvikoski, Tuomo M.; Allan, Louise M.; Oakley, Arthur E.; O’Brien, John T.; Horsburgh, Karen; Ihara, Masafumi

2016-01-01

Abstract White matter hyperintensities as seen on brain T 2 -weighted magnetic resonance imaging are associated with varying degrees of cognitive dysfunction in stroke, cerebral small vessel disease and dementia. The pathophysiological mechanisms within the white matter accounting for cognitive dysfunction remain unclear. With the hypothesis that gliovascular interactions are impaired in subjects with high burdens of white matter hyperintensities, we performed clinicopathological studies in post-stroke survivors, who had exhibited greater frontal white matter hyperintensities volumes that predicted shorter time to dementia onset. Histopathological methods were used to identify substrates in the white matter that would distinguish post-stroke demented from post-stroke non-demented subjects. We focused on the reactive cell marker glial fibrillary acidic protein (GFAP) to study the incidence and location of clasmatodendrosis, a morphological attribute of irreversibly injured astrocytes. In contrast to normal appearing GFAP+ astrocytes, clasmatodendrocytes were swollen and had vacuolated cell bodies. Other markers such as aldehyde dehydrogenase 1 family, member L1 (ALDH1L1) showed cytoplasmic disintegration of the astrocytes. Total GFAP+ cells in both the frontal and temporal white matter were not greater in post-stroke demented versus post-stroke non-demented subjects. However, the percentage of clasmatodendrocytes was increased by >2-fold in subjects with post-stroke demented compared to post-stroke non-demented subjects ( P = 0.026) and by 11-fold in older controls versus young controls ( P < 0.023) in the frontal white matter. High ratios of clasmotodendrocytes to total astrocytes in the frontal white matter were consistent with lower Mini-Mental State Examination and the revised Cambridge Cognition Examination scores in post-stroke demented subjects. Double immunofluorescent staining showed aberrant co-localization of aquaporin 4 (AQP4) in retracted GFAP

Frontal white matter hyperintensities, clasmatodendrosis and gliovascular abnormalities in ageing and post-stroke dementia.

PubMed

Chen, Aiqing; Akinyemi, Rufus O; Hase, Yoshiki; Firbank, Michael J; Ndung'u, Michael N; Foster, Vincent; Craggs, Lucy J L; Washida, Kazuo; Okamoto, Yoko; Thomas, Alan J; Polvikoski, Tuomo M; Allan, Louise M; Oakley, Arthur E; O'Brien, John T; Horsburgh, Karen; Ihara, Masafumi; Kalaria, Raj N

2016-01-01

White matter hyperintensities as seen on brain T2-weighted magnetic resonance imaging are associated with varying degrees of cognitive dysfunction in stroke, cerebral small vessel disease and dementia. The pathophysiological mechanisms within the white matter accounting for cognitive dysfunction remain unclear. With the hypothesis that gliovascular interactions are impaired in subjects with high burdens of white matter hyperintensities, we performed clinicopathological studies in post-stroke survivors, who had exhibited greater frontal white matter hyperintensities volumes that predicted shorter time to dementia onset. Histopathological methods were used to identify substrates in the white matter that would distinguish post-stroke demented from post-stroke non-demented subjects. We focused on the reactive cell marker glial fibrillary acidic protein (GFAP) to study the incidence and location of clasmatodendrosis, a morphological attribute of irreversibly injured astrocytes. In contrast to normal appearing GFAP+ astrocytes, clasmatodendrocytes were swollen and had vacuolated cell bodies. Other markers such as aldehyde dehydrogenase 1 family, member L1 (ALDH1L1) showed cytoplasmic disintegration of the astrocytes. Total GFAP+ cells in both the frontal and temporal white matter were not greater in post-stroke demented versus post-stroke non-demented subjects. However, the percentage of clasmatodendrocytes was increased by >2-fold in subjects with post-stroke demented compared to post-stroke non-demented subjects (P = 0.026) and by 11-fold in older controls versus young controls (P < 0.023) in the frontal white matter. High ratios of clasmotodendrocytes to total astrocytes in the frontal white matter were consistent with lower Mini-Mental State Examination and the revised Cambridge Cognition Examination scores in post-stroke demented subjects. Double immunofluorescent staining showed aberrant co-localization of aquaporin 4 (AQP4) in retracted GFAP+ astrocytes with

Exploring the multiple-hit hypothesis of preterm white matter damage using diffusion MRI.

PubMed

Barnett, Madeleine L; Tusor, Nora; Ball, Gareth; Chew, Andrew; Falconer, Shona; Aljabar, Paul; Kimpton, Jessica A; Kennea, Nigel; Rutherford, Mary; David Edwards, A; Counsell, Serena J

2018-01-01

Preterm infants are at high risk of diffuse white matter injury and adverse neurodevelopmental outcome. The multiple hit hypothesis suggests that the risk of white matter injury increases with cumulative exposure to multiple perinatal risk factors. Our aim was to test this hypothesis in a large cohort of preterm infants using diffusion weighted magnetic resonance imaging (dMRI). We studied 491 infants (52% male) without focal destructive brain lesions born at < 34 weeks, who underwent structural and dMRI at a specialist Neonatal Imaging Centre. The median (range) gestational age (GA) at birth was 30 + 1 (23 + 2 -33 + 5 ) weeks and median postmenstrual age at scan was 42 + 1 (38-45) weeks. dMRI data were analyzed using tract based spatial statistics and the relationship between dMRI measures in white matter and individual perinatal risk factors was assessed. We tested the hypothesis that increased exposure to perinatal risk factors was associated with lower fractional anisotropy (FA), and higher radial, axial and mean diffusivity (RD, AD, MD) in white matter. Neurodevelopmental performance was investigated using the Bayley Scales of Infant and Toddler Development, Third Edition (BSITD-III) in a subset of 381 infants at 20 months corrected age. We tested the hypothesis that lower FA and higher RD, AD and MD in white matter were associated with poorer neurodevelopmental performance. Identified risk factors for diffuse white matter injury were lower GA at birth, fetal growth restriction, increased number of days requiring ventilation and parenteral nutrition, necrotizing enterocolitis and male sex. Clinical chorioamnionitis and patent ductus arteriosus were not associated with white matter injury. Multivariate analysis demonstrated that fetal growth restriction, increased number of days requiring ventilation and parenteral nutrition were independently associated with lower FA values. Exposure to cumulative risk factors was associated with reduced white matter FA

[Research on brain white matter network in cerebral palsy infant].

PubMed

Li, Jun; Yang, Cheng; Wang, Yuanjun; Nie, Shengdong

2017-10-01

Present study used diffusion tensor image and tractography to construct brain white matter networks of 15 cerebral palsy infants and 30 healthy infants that matched for age and gender. After white matter network analysis, we found that both cerebral palsy and healthy infants had a small-world topology in white matter network, but cerebral palsy infants exhibited abnormal topological organization: increased shortest path length but decreased normalize clustering coefficient, global efficiency and local efficiency. Furthermore, we also found that white matter network hub regions were located in the left cuneus, precuneus, and left posterior cingulate gyrus. However, some abnormal nodes existed in the frontal, temporal, occipital and parietal lobes of cerebral palsy infants. These results indicated that the white matter networks for cerebral palsy infants were disrupted, which was consistent with previous studies about the abnormal brain white matter areas. This work could help us further study the pathogenesis of cerebral palsy infants.

Developmental differences in white matter architecture between boys and girls.

PubMed

Schmithorst, Vincent J; Holland, Scott K; Dardzinski, Bernard J

2008-06-01

Previous studies have found developmental differences between males and females in brain structure. During childhood and adolescence, relative white matter volume increases faster in boys than in girls. Sex differences in the development of white matter microstructure were investigated in a cohort of normal children ages 5-18 in a cross-sectional diffusion tensor imaging (DTI) study. Greater fractional anisotropy (FA) in boys was shown in associative white matter regions (including the frontal lobes), while greater FA in girls was shown in the splenium of the corpus callosum. Greater mean diffusivity (MD) in boys was shown in the corticospinal tract and in frontal white matter in the right hemisphere; greater MD in girls was shown in occipito-parietal regions and the most superior aspect of the corticospinal tract in the right hemisphere. Significant sex-age interactions on FA and MD were also shown. Girls displayed a greater rate of fiber density increase with age when compared with boys in associative regions (reflected in MD values). However, girls displayed a trend toward increased organization with age (reflected in FA values) only in the right hemisphere, while boys displayed this trend only in the left hemisphere. These results indicate differing developmental trajectories in white matter for boys and girls and the importance of taking sex into account in developmental DTI studies. The results also may have implications for the study of the relationship of brain architecture with intelligence. Copyright 2007 Wiley-Liss, Inc.

Chronic Kidney Disease Is Associated With White Matter Hyperintensity Volume

PubMed Central

Khatri, Minesh; Wright, Clinton B.; Nickolas, Thomas L.; Yoshita, Mitsuhiro; Paik, Myunghee C.; Kranwinkel, Grace; Sacco, Ralph L.; DeCarli, Charles

2010-01-01

Background and Purpose White matter hyperintensities have been associated with increased risk of stroke, cognitive decline, and dementia. Chronic kidney disease is a risk factor for vascular disease and has been associated with inflammation and endothelial dysfunction, which have been implicated in the pathogenesis of white matter hyperintensities. Few studies have explored the relationship between chronic kidney disease and white matter hyperintensities. Methods The Northern Manhattan Study is a prospective, community-based cohort of which a subset of stroke-free participants underwent MRIs. MRIs were analyzed quantitatively for white matter hyperintensities volume, which was log-transformed to yield a normal distribution (log-white matter hyperintensity volume). Kidney function was modeled using serum creatinine, the Cockcroft-Gault formula for creatinine clearance, and the Modification of Diet in Renal Disease formula for estimated glomerular filtration rate. Creatinine clearance and estimated glomerular filtration rate were trichotomized to 15 to 60 mL/min, 60 to 90 mL/min, and >90 mL/min (reference). Linear regression was used to measure the association between kidney function and log-white matter hyperintensity volume adjusting for age, gender, race–ethnicity, education, cardiac disease, diabetes, homocysteine, and hypertension. Results Baseline data were available on 615 subjects (mean age 70 years, 60% women, 18% whites, 21% blacks, 62% Hispanics). In multivariate analysis, creatinine clearance 15 to 60 mL/min was associated with increased log-white matter hyperintensity volume (β 0.322; 95% CI, 0.095 to 0.550) as was estimated glomerular filtration rate 15 to 60 mL/min (β 0.322; 95% CI, 0.080 to 0.564). Serum creatinine, per 1-mg/dL increase, was also positively associated with log-white matter hyperintensity volume (β 1.479; 95% CI, 1.067 to 2.050). Conclusions The association between moderate–severe chronic kidney disease and white matter

White matter organization in cervical spinal cord relates differently to age and control of grip force in healthy subjects.

PubMed

Lindberg, Påvel G; Feydy, Antoine; Maier, Marc A

2010-03-17

Diffusion tensor imaging (DTI) can be used to elucidate relations between CNS structure and function. We hypothesized that the degree of spinal white matter organization relates to the accuracy of control of grip force. Healthy subjects of different age were studied using DTI and visuomotor tracking of precision grip force. The latter is a prime component of manual dexterity. A regional analysis of spinal white matter [fractional anisotropy (FA)] across multiple cervical levels (C2-C3, C4-C5, and C6-C7) and in different regions of interest (left and right lateral or medial spinal cord) was performed. FA was highest at the C2-C3 level, higher on the right than the left side, and higher in the lateral than in the medial spinal cord (p < 0.001). FA of whole cervical spinal cord (C2-C7) was lower in subjects with high tracking error (r = -0.56, p = 0.004) and decreased with age (r = -0.63, p = 0.001). A multiple regression analysis revealed an independent contribution of each predictor (semipartial correlations: age, r = -0.55, p < 0.001; tracking error, r = -0.49, p = 0.003). The closest relation between FA and tracking error was found at the C6-C7 level in the lateral spinal cord, in which the corticospinal tract innervates spinal circuitry controlling hand and digit muscles. FA of the medial spinal cord correlated consistently with age across all cervical levels, whereas FA of the lateral spinal cord did not. The results suggest (1) a functionally relevant specialization of lateral spinal cord white matter and (2) an increased sensitivity to age-related decline in medial spinal cord white matter in healthy subjects.

White Matter Injury in Ischemic Stroke

PubMed Central

Wang, Yuan; Liu, Gang; Hong, Dandan; Chen, Fenghua; Ji, Xunming; Cao, Guodong

2017-01-01

Stroke is one of the major causes of disability and mortality worldwide. It is well known that ischemic stroke can cause gray matter injury. However, stroke also elicits profound white matter injury, a risk factor for higher stroke incidence and poor neurological outcomes. The majority of damage caused by stroke is located in subcortical regions and, remarkably, white matter occupies nearly half of the average infarct volume. Indeed, white matter is exquisitely vulnerable to ischemia and is often injured more severely than gray matter. Clinical symptoms related to white matter injury include cognitive dysfunction, emotional disorders, sensorimotor impairments, as well as urinary incontinence and pain, all of which are closely associated with destruction and remodeling of white matter connectivity. White matter injury can be noninvasively detected by MRI, which provides a three-dimensional assessment of its morphology, metabolism, and function. There is an urgent need for novel white matter therapies, as currently available strategies are limited to preclinical animal studies. Optimal protection against ischemic stroke will need to encompass the fortification of both gray and white matter. In this review, we discuss white matter injury after ischemic stroke, focusing on clinical features and tools, such as imaging, manifestation, and potential treatments. We also briefly discuss the pathophysiology of WMI and future research directions. PMID:27090751

White Matter Development during Adolescence as Shown by Diffusion MRI

ERIC Educational Resources Information Center

Schmithorst, Vincent J.; Yuan, Weihong

2010-01-01

Previous volumetric developmental MRI studies of the brain have shown white matter development continuing through adolescence and into adulthood. This review presents current findings regarding white matter development and organization from diffusion MRI studies. The general trend during adolescence (age 12-18 years) is towards increasing…

Testing the hypothesis of accelerated cerebral white matter aging in schizophrenia and major depression

PubMed Central

Kochunov, P.; Glahn, D.C.; Rowland, L.M.; Olvera, R.L.; Winkler, A; Yang, Y.H.; Sampath, H.; Carpenter, W.T.; Dugarrila, R.; Curran, J.; Blangero, J.; Hong, L.E.

2012-01-01

Introduction Elevated rate of aging-related biological and functional decline, termed accelerated aging, is reported in patients with schizophrenia (SCZ) and major depressive disorder (MDD). We used diffusion tensor imaging (DTI) derived fractional anisotropy (FA) as biomarkers of aging-related decline in white matter (WM) integrity to test the hypotheses of accelerated aging in SCZ and MDD. Methods The SCZ cohort was composed of 58/60 SCZ patients/controls (age=20–60years). MDD cohort was composed of 136/351 MDD patients/controls (age=20–79years). Main outcome measures were the diagnosis-by-age interaction on whole-brain-averaged WM FA values and FA values from twelve major WM tracts. Results Diagnosis-by-age interaction for the whole-brain average FA was significant for the SCZ (p=0.04) but not in MDD cohort (p=0.80). Diagnosis-by-age interaction was nominally significant (p<0.05) for five WM tracts for SCZ and for none of the tracts in the MDD cohort. Tract-specific heterochronicity of the onset of age-related decline in SCZ demonstrated strong negative correlations with the age-of- peak myelination and the rates of age-related decline obtained from normative sample (r=−0.61 and −0.80, p<0.05, respectively). No such trends existed for MDD cohort. Conclusion Cerebral WM showed accelerated aging in SCZ but not in MDD, suggesting some difference in the pathophysiology underlying their WM aging changes. Tract-specific heterochronicity of WM development modulated presentation of accelerated aging in SCZ: white matter tracts that matured later in life appeared more sensitive to the pathophysiology of SCZ and demonstrated more susceptibility to disorder-related accelerated decline in FA values with age. This trend was not observed in MDD cohort. PMID:23200529

The relationship between white matter brain metabolites and cognition in normal aging: the GENIE study.

PubMed

Charlton, R A; McIntyre, D J O; Howe, F A; Morris, R G; Markus, H S

2007-08-20

Magnetic resonance spectroscopy (MRS) has demonstrated age-related changes in brain metabolites that may underlie micro-structural brain changes, but few studies have examined their relationship with cognitive decline. We performed a cross-sectional study of brain metabolism and cognitive function in 82 healthy adults (aged 50-90) participating in the GENIE (St GEorge's Neuropsychology and Imaging in the Elderly) study. Absolute metabolite concentrations were measured by proton chemical shift imaging within voxels placed in the centrum semiovale white matter. Cognitive abilities assessed were executive function, working memory, information processing speed, long-term memory and fluid intelligence. Correlations showed that all cognitive domains declined with age. Total creatine (tCr) concentration increased with age (r=0.495, p<0.001). Regression analyses were performed for each cognitive variable, including estimated intelligence and the metabolites, with age then added as a final step. A significant relationship was observed between tCr and executive function, long-term memory, and fluid intelligence, although these relationships did not remain significant after age was added as a final step in the regression. The regression analysis also demonstrated a significant relationship between N-acetylaspartate (NAA) and executive function. As there was no age-related decline in NAA, this argues against axonal loss with age; however the relationship between NAA and executive function independent of age and estimated intelligence is consistent with white matter axonal integrity having an important role in executive function in normal individuals.

Atypical Frontal-Striatal-Thalamic Circuit White Matter Development in Pediatric Obsessive Compulsive Disorder

PubMed Central

Fitzgerald, Kate D.; Liu, Yanni; Reamer, Elyse N.; Taylor, Stephan F.; Welsh, Robert C.

2015-01-01

Objective Atypical development of frontal-striatal-thalamic circuitry (FSTC) has been hypothesized to underlie the early course of obsessive-compulsive disorder (OCD); however, the development of FSTC white matter tracts remains to be studied in young patients. Method To address this gap, we scanned 36 patients with pediatric OCD compared to 27 healthy controls, aged 8 to 19 years, with diffusion tensor imaging (DTI) to measure fractional anisotropy (FA), an index of white matter coherence. Tract-based spatial statistics (TBSS) were used to test differential effects of age on FA, across the whole brain, in those with OCD compared to healthy youth, followed by analyses in a priori regions of interest (anterior corpus callosum, anterior cingulum bundle and anterior limb of the internal capsule [ALIC]) to further characterize developmental differences between groups. Results Patients with OCD showed more pronounced age-related increases in FA than controls in regions of interest, as well as several other white matter tracts. In patients, greater FA in anterior cingulum bundle correlated with more severe symptoms after controlling for age. Conclusions Our findings support theories of atypical FSTC maturation in pediatric OCD by providing the first evidence for altered trajectories of white matter development in anterior corpus callosum, anterior cingulum bundle, and ALIC in young patients. Steeper age-related increases of FA in these and other select white matter tracts in OCD, compared to healthy controls, may derive from an early delay in white matter development and/or prolonged white matter growth, but confirmation of these possibilities awaits longitudinal work. PMID:25440312

Coupled changes in brain white matter microstructure and fluid intelligence in later life.

PubMed

Ritchie, Stuart J; Bastin, Mark E; Tucker-Drob, Elliot M; Maniega, Susana Muñoz; Engelhardt, Laura E; Cox, Simon R; Royle, Natalie A; Gow, Alan J; Corley, Janie; Pattie, Alison; Taylor, Adele M; Valdés Hernández, Maria Del C; Starr, John M; Wardlaw, Joanna M; Deary, Ian J

2015-06-03

Understanding aging-related cognitive decline is of growing importance in aging societies, but relatively little is known about its neural substrates. Measures of white matter microstructure are known to correlate cross-sectionally with cognitive ability measures, but only a few small studies have tested for longitudinal relations among these variables. We tested whether there were coupled changes in brain white matter microstructure indexed by fractional anisotropy (FA) and three broad cognitive domains (fluid intelligence, processing speed, and memory) in a large cohort of human participants with longitudinal diffusion tensor MRI and detailed cognitive data taken at ages 73 years (n = 731) and 76 years (n = 488). Longitudinal changes in white matter microstructure were coupled with changes in fluid intelligence, but not with processing speed or memory. Individuals with higher baseline white matter FA showed less subsequent decline in processing speed. Our results provide evidence for a longitudinal link between changes in white matter microstructure and aging-related cognitive decline during the eighth decade of life. They are consistent with theoretical perspectives positing that a corticocortical "disconnection" partly explains cognitive aging. Copyright © 2015 Ritchie et al.

The Role of White Matter Hyperintensities and Medial Temporal Lobe Atrophy in Age-Related Executive Dysfunctioning

ERIC Educational Resources Information Center

Oosterman, Joukje M.; Vogels, Raymond L. C.; van Harten, Barbera; Gouw, Alida A.; Scheltens, Philip; Poggesi, Anna; Weinstein, Henry C.; Scherder, Erik J. A.

2008-01-01

Various studies support an association between white matter hyperintensities (WMH) and deficits in executive function in nondemented ageing. Studies examining executive functions and WMH have generally adopted executive function as a phrase including various functions such as flexibility, inhibition, and working memory. However, these functions…

The Impact of Sex, Puberty, and Hormones on White Matter Microstructure in Adolescents

PubMed Central

Herting, Megan M.; Maxwell, Emily C.; Irvine, Christy

2012-01-01

Background: During adolescence, numerous factors influence the organization of the brain. It is unclear what influence sex and puberty have on white matter microstructure, as well as the role that rapidly increasing sex steroids play. Methods: White matter microstructure was examined in 77 adolescents (ages 10–16) using diffusion tensor imaging. Multiple regression analyses were performed to examine the relationships between fractional anisotropy (FA) and mean diffusivity (MD) and sex, puberty, and their interaction, controlling for age. Follow-up analyses determined if sex steroids predicted microstructural characteristics in sexually dimorphic and pubertal-related white matter regions, as well as in whole brain. Results: Boys had higher FA in white matter carrying corticospinal, long-range association, and cortico-subcortical fibers, and lower MD in frontal and temporal white matter compared with girls. Pubertal development was related to higher FA in the insula, while a significant sex-by-puberty interaction was seen in superior frontal white matter. In boys, testosterone predicted white matter integrity in sexually dimorphic regions as well as whole brain FA, whereas estradiol showed a negative relationship with FA in girls. Conclusions: Sex differences and puberty uniquely relate to white matter microstructure in adolescents, which can partially be explained by sex steroids. PMID:22002939

White matter microstructure integrity in relation to reading proficiency☆.

PubMed

Nikki Arrington, C; Kulesz, Paulina A; Juranek, Jenifer; Cirino, Paul T; Fletcher, Jack M

2017-11-01

Components of reading proficiency such asaccuracy, fluency, and comprehension require the successful coordination of numerous, yet distinct, cortical regions. Underlying white matter tracts allow for communication among these regions. This study utilized unique residualized tract - based spatial statistics methodology to identify the relations of white matter microstructure integrity to three components of reading proficiency in 49 school - aged children with typically developing phonological decoding skills and 27 readers with poor decoders. Results indicated that measures of white matter integrity were differentially associated with components of reading proficiency. In both typical and poor decoders, reading comprehension correlated with measures of integrity of the right uncinate fasciculus; reading comprehension was also related to the left inferior longitudinal fasciculus in poor decoders. Also in poor decoders, word reading fluency was related to the right uncinate and left inferior fronto - occipital fasciculi. Word reading was unrelated to white matter integrity in either group. These findings expand our knowledge of the association between white matter integrity and different elements of reading proficiency. Copyright © 2017 Elsevier Inc. All rights reserved.

White Matter Integrity, Substance Use, and Risk Taking in Adolescence

PubMed Central

Jacobus, Joanna; Thayer, Rachel E.; Trim, Ryan S.; Bava, Sunita; Frank, Lawrence R.; Tapert, Susan F.

2012-01-01

White matter development is important for efficient communication between brain regions, higher order cognitive functioning, and complex behaviors. Adolescents have a higher propensity for engaging in risky behaviors, yet few studies have explored associations between white matter integrity and risk taking directly. Altered white matter integrity in mid-adolescence was hypothesized to predict subsequent risk taking behaviors 1.5 years later. Adolescent substance users (predominantly alcohol and marijuana, n=47) and demographically similar non-users (n=49) received diffusion tensor imaging at baseline (ages 16–19), and risk taking measures at both baseline and an 18-month follow-up (i.e., at ages 17–20). Brain regions of interest were: fornix, superior corona radiata, superior longitudinal fasciculus, and superior fronto-occipital fasciculus. In substance using youth (n=47), lower white matter integrity at baseline in the fornix and superior corona radiata predicted follow-up substance use (ΔR2 =10–12%, ps < .01), and baseline fornix integrity predicted follow-up delinquent behaviors (ΔR2 = 10%, p < .01) 1.5 years later. Poorer fronto-limbic white matter integrity was linked to a greater propensity for future risk taking behaviors among youth who initiated heavy substance use by mid-adolescence. Most notable were relationships between projection and limbic system fibers and future substance use frequency. Subcortical white matter coherence along with an imbalance between the maturation levels in cognitive control and reward systems may disadvantage the resistance to engage in risk taking behaviors during adolescence. PMID:22564204

White matter integrity, substance use, and risk taking in adolescence.

PubMed

Jacobus, Joanna; Thayer, Rachel E; Trim, Ryan S; Bava, Sunita; Frank, Lawrence R; Tapert, Susan F

2013-06-01

White matter development is important for efficient communication between brain regions, higher order cognitive functioning, and complex behaviors. Adolescents have a higher propensity for engaging in risky behaviors, yet few studies have explored associations between white matter integrity and risk taking directly. Altered white matter integrity in mid-adolescence was hypothesized to predict subsequent risk taking behaviors 1.5 years later. Adolescent substance users (predominantly alcohol and marijuana, n = 47) and demographically similar nonusers (n = 49) received diffusion tensor imaging at baseline (ages 16-19), and risk taking measures at both baseline and an 18-month follow-up (i.e., at ages 17-20). Brain regions of interest were the fornix, superior corona radiata, superior longitudinal fasciculus, and superior fronto-occipital fasciculus. In substance-using youth (n = 47), lower white matter integrity at baseline in the fornix and superior corona radiata predicted follow-up substance use (ΔR2 = 10-12%, ps < .01), and baseline fornix integrity predicted follow-up delinquent behaviors (ΔR2 = 10%, p < .01) 1.5 years later. Poorer fronto-limbic white matter integrity was linked to a greater propensity for future risk taking behaviors among youth who initiated heavy substance use by mid-adolescence. Most notable were relationships between projection and limbic-system fibers and future substance-use frequency. Subcortical white matter coherence, along with an imbalance between the maturation levels in cognitive control and reward systems, may disadvantage the resistance to engage in risk taking behaviors during adolescence. 2013 APA, all rights reserved

Global versus Tract-Specific Components of Cerebral White Matter Integrity: Relation to Adult Age and Perceptual-Motor Speed

PubMed Central

Johnson, Micah A.; Diaz, Michele T.; Madden, David J.

2014-01-01

Although age-related differences in white matter have been well documented, the degree to which regional, tract-specific effects can be distinguished from global, brain-general effects is not yet clear. Similarly, the manner in which global and regional differences in white matter integrity contribute to age-related differences in cognition has not been well established. To address these issues, we analyzed diffusion tensor imaging measures from 52 younger adults (18–28) and 64 older adults (60–85). We conducted principal component analysis on each diffusion measure, using data from eight individual tracts. Two components were observed for fractional anisotropy: The first comprised high loadings from the superior longitudinal fasciculi and corticospinal tracts, and the second comprised high loadings from the optic radiations. In contrast, variation in axial, radial, and mean diffusivities yielded a single-component solution in each case, with high loadings from most or all tracts. For fractional anisotropy, the complementary results of multiple components and variability in component loadings across tracts suggest regional variation. However, for the diffusivity indices, the single component with high loadings from most or all of the tracts suggests primarily global, brain-general variation. Further analyses indicated that age was a significant mediator of the relation between each component and perceptual-motor speed. These data suggest that individual differences in white matter integrity, and their relation to age-related differences in perceptual-motor speed, represent influences that are beyond the level of individual tracts, but the extent to which regional or global effects predominate may differ between anisotropy and diffusivity measures. PMID:24972959

An MRI study of white matter tract integrity in regular cannabis users: effects of cannabis use and age.

PubMed

Jakabek, David; Yücel, Murat; Lorenzetti, Valentina; Solowij, Nadia

2016-10-01

Conflicting evidence exists on the effects of cannabis use on brain white matter integrity. The extant literature has exclusively focused on younger cannabis users, with no studies sampling older cannabis users. We recruited a sample with a broad age range to examine the integrity of major white matter tracts in association with cannabis use parameters and neurodevelopmental stage. Regular cannabis users (n = 56) and non-users (n = 20) with a mean age of 32 (range 18-55 years) underwent structural and diffusion MRI scans. White matter was examined using voxel-based statistics and via probabilistic tract reconstruction. The integrity of tracts was assessed using average fractional anisotropy, axial diffusivity and radial diffusivity. Diffusion measures were compared between users and non-users and as group-by-age interactions. Correlations between diffusion measures and age of onset, duration, frequency and dose of current cannabis use were examined. Cannabis users overall had lower fractional anisotropy than healthy non-users in the forceps minor tract only (p = .015, partial eta = 0.07), with no voxel-wise differences observed. Younger users showed predominantly reduced axial diffusivity, whereas older users had higher radial diffusivity in widespread tracts. Higher axial diffusivity was associated with duration of cannabis use in the cingulum angular bundle (beta = 5.00 × 10(-5), p = .003). Isolated higher AD in older cannabis users was also observed. The findings suggest that exogenous cannabinoids alter normal brain maturation, with differing effects at various neurodevelopmental stages of life. These age-related differences are posited to account for the disparate results described in the literature.

Higher prevalence of cerebral white matter hyperintensities in homozygous APOE-ɛ4 allele carriers aged 45-75: Results from the ALFA study.

PubMed

Rojas, Santiago; Brugulat-Serrat, Anna; Bargalló, Nuria; Minguillón, Carolina; Tucholka, Alan; Falcon, Carles; Carvalho, Andreia; Morán, Sebastian; Esteller, Manel; Gramunt, Nina; Fauria, Karine; Camí, Jordi; Molinuevo, José L; Gispert, Juan D

2018-02-01

Cerebral white matter hyperintensities are believed the consequence of small vessel disease and are associated with risk and progression of Alzheimer's disease. The ɛ4 allele of the APOE gene is the major factor accountable for Alzheimer's disease heritability. However, the relationship between white matter hyperintensities and APOE genotype in healthy subjects remains controversial. We investigated the association between APOE-ɛ4 and vascular risk factors with white matter hyperintensities, and explored their interactions, in a cohort of cognitively healthy adults (45-75 years). White matter hyperintensities were assessed with the Fazekas Scale from magnetic resonance images (575 participants: 74 APOE-ɛ4 homozygotes, 220 heterozygotes and 281 noncarriers) and classified into normal (Fazekas < 2) and pathological (≥2). Stepwise logistic regression was used to study the association between pathological Fazekas and APOE genotype after correcting for cardiovascular and sociodemographic factors. APOE-ɛ4 homozygotes, but not heterozygotes, bear a significantly higher risk (OR 3.432; 95% CI [1.297-9.082]; p = 0.013) of displaying pathological white matter hyperintensities. As expected, aging, hypertension and cardiovascular and dementia risk scales were also positively associated to pathological white matter hyperintensities, but these did not modulate the effect of APOE-ɛ4/ɛ4. In subjects at genetic risk of developing Alzheimer's disease, the control of modifiable risk factors of white matter hyperintensities is of particular relevance to reduce or delay dementia's onset.

White matter microstructure mediates the relationship between cardiorespiratory fitness and spatial working memory in older adults.

PubMed

Oberlin, Lauren E; Verstynen, Timothy D; Burzynska, Agnieszka Z; Voss, Michelle W; Prakash, Ruchika Shaurya; Chaddock-Heyman, Laura; Wong, Chelsea; Fanning, Jason; Awick, Elizabeth; Gothe, Neha; Phillips, Siobhan M; Mailey, Emily; Ehlers, Diane; Olson, Erin; Wojcicki, Thomas; McAuley, Edward; Kramer, Arthur F; Erickson, Kirk I

2016-05-01

White matter structure declines with advancing age and has been associated with a decline in memory and executive processes in older adulthood. Yet, recent research suggests that higher physical activity and fitness levels may be associated with less white matter degeneration in late life, although the tract-specificity of this relationship is not well understood. In addition, these prior studies infrequently associate measures of white matter microstructure to cognitive outcomes, so the behavioral importance of higher levels of white matter microstructural organization with greater fitness levels remains a matter of speculation. Here we tested whether cardiorespiratory fitness (VO2max) levels were associated with white matter microstructure and whether this relationship constituted an indirect pathway between cardiorespiratory fitness and spatial working memory in two large, cognitively and neurologically healthy older adult samples. Diffusion tensor imaging was used to determine white matter microstructure in two separate groups: Experiment 1, N=113 (mean age=66.61) and Experiment 2, N=154 (mean age=65.66). Using a voxel-based regression approach, we found that higher VO2max was associated with higher fractional anisotropy (FA), a measure of white matter microstructure, in a diverse network of white matter tracts, including the anterior corona radiata, anterior internal capsule, fornix, cingulum, and corpus callosum (PFDR-corrected<.05). This effect was consistent across both samples even after controlling for age, gender, and education. Further, a statistical mediation analysis revealed that white matter microstructure within these regions, among others, constituted a significant indirect path between VO2max and spatial working memory performance. These results suggest that greater aerobic fitness levels are associated with higher levels of white matter microstructural organization, which may, in turn, preserve spatial memory performance in older adulthood

Neuropathology of White Matter Lesions, Blood-Brain Barrier Dysfunction, and Dementia.

PubMed

Hainsworth, Atticus H; Minett, Thais; Andoh, Joycelyn; Forster, Gillian; Bhide, Ishaan; Barrick, Thomas R; Elderfield, Kay; Jeevahan, Jamuna; Markus, Hugh S; Bridges, Leslie R

2017-10-01

We tested whether blood-brain barrier dysfunction in subcortical white matter is associated with white matter abnormalities or risk of clinical dementia in older people (n=126; mean age 86.4, SD: 7.7 years) in the MRC CFAS (Medical Research Council Cognitive Function and Ageing Study). Using digital pathology, we quantified blood-brain barrier dysfunction (defined by immunohistochemical labeling for the plasma marker fibrinogen). This was assessed within subcortical white matter tissue samples harvested from postmortem T 2 magnetic resonance imaging (MRI)-detected white matter hyperintensities, from normal-appearing white matter (distant from coexistent MRI-defined hyperintensities), and from equivalent areas in MRI normal brains. Histopathologic lesions were defined using a marker for phagocytic microglia (CD68, clone PGM1). Extent of fibrinogen labeling was not significantly associated with white matter abnormalities defined either by MRI (odds ratio, 0.90; 95% confidence interval, 0.79-1.03; P =0.130) or by histopathology (odds ratio, 0.93; 95% confidence interval, 0.77-1.12; P =0.452). Among participants with normal MRI (no detectable white matter hyperintensities), increased fibrinogen was significantly related to decreased risk of clinical dementia (odds ratio, 0.74; 95% confidence interval, 0.58-0.94; P =0.013). Among participants with histological lesions, increased fibrinogen was related to increased risk of dementia (odds ratio, 2.26; 95% confidence interval, 1.25-4.08; P =0.007). Our data suggest that some degree of blood-brain barrier dysfunction is common in older people and that this may be related to clinical dementia risk, additional to standard MRI biomarkers. © 2017 American Heart Association, Inc.

Three-year changes in leisure activities are associated with concurrent changes in white matter microstructure and perceptual speed in individuals aged 80 years and older.

PubMed

Köhncke, Ylva; Laukka, Erika J; Brehmer, Yvonne; Kalpouzos, Grégoria; Li, Tie-Qiang; Fratiglioni, Laura; Bäckman, Lars; Lövdén, Martin

2016-05-01

Accumulating evidence suggests that engagement in leisure activities is associated with favorable trajectories of cognitive aging, but little is known about brain changes related to both activities and cognition. White matter microstructure shows experience-dependent plasticity and declines in aging. Therefore, we investigated the role of change in white matter microstructure in the activities-cognition link. We used repeated assessments of engagement, perceptual speed, and white matter microstructure (probed with diffusion tensor imaging) in a population-based sample of individuals over 80 years without dementia (n = 442, Mage = 85.1; n = 70 for diffusion tensor imaging; 2 occasions 3 years apart). Using multivariate latent change modeling, we observed positive correlations among changes in predominantly social activities, white matter microstructure, and perceptual speed. Interindividual differences in change in white matter microstructure statistically accounted for the association between change in leisure activities and change in perceptual speed. However, as analyses are based on observational data from 2 measurement occasions, causality remains unclear. Copyright © 2016 Elsevier Inc. All rights reserved.

Growth of White Matter in the Adolescent Brain: Myelin or Axon?

ERIC Educational Resources Information Center

Paus, Tomas

2010-01-01

White matter occupies almost half of the human brain. It contains axons connecting spatially segregated modules and, as such, it is essential for the smooth flow of information in functional networks. Structural maturation of white matter continues during adolescence, as reflected in age-related changes in its volume, as well as in its…

White Matter Volume Predicts Language Development in Congenital Heart Disease.

PubMed

Rollins, Caitlin K; Asaro, Lisa A; Akhondi-Asl, Alireza; Kussman, Barry D; Rivkin, Michael J; Bellinger, David C; Warfield, Simon K; Wypij, David; Newburger, Jane W; Soul, Janet S

2017-02-01

To determine whether brain volume is reduced at 1 year of age and whether these volumes are associated with neurodevelopment in biventricular congenital heart disease (CHD) repaired in infancy. Infants with biventricular CHD (n = 48) underwent brain magnetic resonance imaging (MRI) and neurodevelopmental testing with the Bayley Scales of Infant Development-II and the MacArthur-Bates Communicative Development Inventories at 1 year of age. A multitemplate based probabilistic segmentation algorithm was applied to volumetric MRI data. We compared volumes with those of 13 healthy control infants of comparable ages. In the group with CHD, we measured Spearman correlations between neurodevelopmental outcomes and the residuals from linear regression of the volumes on corrected chronological age at MRI and sex. Compared with controls, infants with CHD had reductions of 54 mL in total brain (P = .009), 40 mL in cerebral white matter (P <.001), and 1.2 mL in brainstem (P = .003) volumes. Within the group with CHD, brain volumes were not correlated with Bayley Scales of Infant Development-II scores but did correlate positively with MacArthur-Bates Communicative Development Inventory language development. Infants with biventricular CHD show total brain volume reductions at 1 year of age, driven by differences in cerebral white matter. White matter volume correlates with language development, but not broader developmental indices. These findings suggest that abnormalities in white matter development detected months after corrective heart surgery may contribute to language impairment. ClinicalTrials.gov: NCT00006183. Copyright © 2016 Elsevier Inc. All rights reserved.

Vulnerability of white matter tracts and cognition to the SOD2 polymorphism: A preliminary study of antioxidant defense genes in brain aging.

PubMed

Salminen, Lauren E; Schofield, Peter R; Pierce, Kerrie D; Bruce, Steven E; Griffin, Michael G; Tate, David F; Cabeen, Ryan P; Laidlaw, David H; Conturo, Thomas E; Bolzenius, Jacob D; Paul, Robert H

2017-06-30

Oxidative stress is a key mechanism of the aging process that can cause damage to brain white matter and cognitive functions. Polymorphisms in the superoxide dismutase 2 (SOD2) and catalase (CAT) genes have been associated with abnormalities in antioxidant enzyme activity in the aging brain, suggesting a risk for enhanced oxidative damage to white matter and cognition among older individuals with these genetic variants. The present study compared differences in white matter microstructure and cognition among 96 older adults with and without genetic risk factors of SOD2 (rs4880) and CAT (rs1001179). Results revealed higher radial diffusivity in the anterior thalamic radiation among SOD2 CC genotypes compared to CT/TT genotypes. Further, the CC genotype moderated the relationship between the hippocampal cingulum and processing speed, though this did not survive multiple test correction. The CAT polymorphism was not associated with brain outcomes in this cohort. These results suggest that the CC genotype of SOD2 is an important genetic marker of suboptimal brain aging in healthy individuals. Copyright © 2017 Elsevier B.V. All rights reserved.

Altered white matter development in children born very preterm.

PubMed

Young, Julia M; Vandewouw, Marlee M; Morgan, Benjamin R; Smith, Mary Lou; Sled, John G; Taylor, Margot J

2018-06-01

Children born very preterm (VPT) at less than 32 weeks' gestational age (GA) are prone to disrupted white matter maturation and impaired cognitive development. The aims of the present study were to identify differences in white matter microstructure and connectivity of children born VPT compared to term-born children, as well as relations between white matter measures with cognitive outcomes and early brain injury. Diffusion images and T1-weighted anatomical MR images were acquired along with developmental assessments in 31 VPT children (mean GA: 28.76 weeks) and 28 term-born children at 4 years of age. FSL's tract-based spatial statistics was used to create a cohort-specific template and mean fractional anisotropy (FA) skeleton that was applied to each child's DTI data. Whole brain deterministic tractography was performed and graph theoretical measures of connectivity were calculated based on the number of streamlines between cortical and subcortical nodes derived from the Desikan-Killiany atlas. Between-group analyses included FSL Randomise for voxel-wise statistics and permutation testing for connectivity analyses. Within-group analyses between FA values and graph measures with IQ, language and visual-motor scores as well as history of white matter injury (WMI) and germinal matrix/intraventricular haemorrhage (GMH/IVH) were performed. In the children born VPT, FA values within major white matter tracts were reduced compared to term-born children. Reduced measures of local strength, clustering coefficient, local and global efficiency were present in the children born VPT within nodes in the lateral frontal, middle and superior temporal, cingulate, precuneus and lateral occipital regions. Within-group analyses revealed associations in term-born children between FA, Verbal IQ, Performance IQ and Full scale IQ within regions of the superior longitudinal fasciculus, inferior fronto-occipital fasciculus, forceps minor and forceps major. No associations with outcome

White matter and cognition: making the connection

PubMed Central

Fields, R. Douglas

2016-01-01

Whereas the cerebral cortex has long been regarded by neuroscientists as the major locus of cognitive function, the white matter of the brain is increasingly recognized as equally critical for cognition. White matter comprises half of the brain, has expanded more than gray matter in evolution, and forms an indispensable component of distributed neural networks that subserve neurobehavioral operations. White matter tracts mediate the essential connectivity by which human behavior is organized, working in concert with gray matter to enable the extraordinary repertoire of human cognitive capacities. In this review, we present evidence from behavioral neurology that white matter lesions regularly disturb cognition, consider the role of white matter in the physiology of distributed neural networks, develop the hypothesis that white matter dysfunction is relevant to neurodegenerative disorders, including Alzheimer's disease and the newly described entity chronic traumatic encephalopathy, and discuss emerging concepts regarding the prevention and treatment of cognitive dysfunction associated with white matter disorders. Investigation of the role of white matter in cognition has yielded many valuable insights and promises to expand understanding of normal brain structure and function, improve the treatment of many neurobehavioral disorders, and disclose new opportunities for research on many challenging problems facing medicine and society. PMID:27512019

Lifelong Bilingualism Contributes to Cognitive Reserve against White Matter Integrity Declines in Aging

PubMed Central

Gold, Brian T.; Johnson, Nathan F.; Powell, David K.

2013-01-01

Recent evidence suggests that lifelong bilingualism may contribute to cognitive reserve (CR) in normal aging. However, there is currently no neuroimaging evidence to suggest that lifelong bilinguals can retain normal cognitive functioning in the face of age-related neurodegeneration. Here we explored this issue by comparing white matter (WM) integrity and gray matter (GM) volumetric patterns of older adult lifelong bilinguals (N = 20) and monolinguals (N = 20). The groups were matched on a range of relevant cognitive test scores and on the established CR variables of education, socioeconomic status and intelligence. Participants underwent high-resolution structural imaging for assessment of GM volume and diffusion tensor imaging (DTI) for assessment of WM integrity. Results indicated significantly lower microstructural integrity in the bilingual group in several WM tracts. In particular, compared to their monolingual peers, the bilingual group showed lower fractional anisotropy and/or higher radial diffusivity in the inferior longitudinal fasciculus/inferior fronto-occipital fasciculus bilaterally, the fornix, and multiple portions of the corpus callosum. There were no group differences in GM volume. Our results suggest that lifelong bilingualism contributes to CR against WM integrity declines in aging. PMID:24103400

An augmented aging process in brain white matter in HIV.

PubMed

Kuhn, Taylor; Kaufmann, Tobias; Doan, Nhat Trung; Westlye, Lars T; Jones, Jacob; Nunez, Rodolfo A; Bookheimer, Susan Y; Singer, Elyse J; Hinkin, Charles H; Thames, April D

2018-06-01

HIV infection and aging are both associated with neurodegeneration. However, whether the aging process alone or other factors associated with advanced age account for the progression of neurodegeneration in the aging HIV-positive (HIV+) population remains unclear. HIV+ (n = 70) and HIV-negative (HIV-, n = 34) participants underwent diffusion tensor imaging (DTI) and metrics of microstructural properties were extracted from regions of interest (ROIs). A support vector regression model was trained on two independent datasets of healthy adults across the adult life-span (n = 765, Cam-CAN = 588; UiO = 177) to predict participant age from DTI metrics, and applied to the HIV dataset. Predicted brain age gap (BAG) was computed as the difference between predicted age and chronological age, and statistically compared between HIV groups. Regressions assessed the relationship between BAG and HIV severity/medical comorbidities. Finally, correlation analyses tested for associations between BAG and cognitive performance. BAG was significantly higher in the HIV+ group than the HIV- group F (1, 103) = 12.408, p = .001). HIV RNA viral load was significantly associated with BAG, particularly in older HIV+ individuals (R 2  = 0.29, F(7, 70) = 2.66, p = .021). Further, BAG was negatively correlated with domain-level cognitive function (learning: r = -0.26, p = .008; memory: r = -0.21, p = .034). HIV infection is associated with augmented white matter aging, and greater brain aging is associated with worse cognitive performance in multiple domains. © 2018 Wiley Periodicals, Inc.

White Matter Changes and Confrontation Naming in Retired Aging National Football League Athletes.

PubMed

Strain, Jeremy F; Didehbani, Nyaz; Spence, Jeffrey; Conover, Heather; Bartz, Elizabeth K; Mansinghani, Sethesh; Jeroudi, Myrtle K; Rao, Neena K; Fields, Lindy M; Kraut, Michael A; Cullum, C Munro; Hart, John; Womack, Kyle B

2017-01-15

Using diffusion tensor imaging (DTI), we assessed the relationship of white matter integrity and performance on the Boston Naming Test (BNT) in a group of retired professional football players and a control group. We examined correlations between fractional anisotropy (FA) and mean diffusivity (MD) with BNT T-scores in an unbiased voxelwise analysis processed with tract-based spatial statistics (TBSS). We also analyzed the DTI data by grouping voxels together as white matter tracts and testing each tract's association with BNT T-scores. Significant voxelwise correlations between FA and BNT performance were only seen in the retired football players (p < 0.02). Two tracts had mean FA values that significantly correlated with BNT performance: forceps minor and forceps major. White matter integrity is important for distributed cognitive processes, and disruption correlates with diminished performance in athletes exposed to concussive and subconcussive brain injuries, but not in controls without such exposure.

White matter integrity as a marker for cognitive plasticity in aging.

PubMed

de Lange, Ann-Marie Glasø; Bråthen, Anne Cecilie Sjøli; Grydeland, Håkon; Sexton, Claire; Johansen-Berg, Heidi; Andersson, Jesper L R; Rohani, Darius A; Nyberg, Lars; Fjell, Anders M; Walhovd, Kristine B

2016-11-01

Age-related differences in white matter (WM) integrity are substantial, but it is unknown whether between-subject variability in WM integrity influences the capacity for cognitive improvement. We investigated the effects of memory training related to active and passive control conditions in older adults and tested whether WM integrity at baseline was predictive of training benefits. We hypothesized that (1) memory improvement would be restricted to the training group, (2) widespread areas would show greater mean diffusivity (MD) and lower fractional anisotropy in older adults relative to young adults, and (3) within these areas, variability in WM microstructure in the older group would be predictive of training gains. The results showed that only the group receiving training improved their memory. Significant age differences in MD and fractional anisotropy were found in widespread areas. Within these areas, voxelwise analyses showed a negative relationship between MD and memory improvement in 3 clusters, indicating that WM integrity could serve as a marker for the ability to adapt in response to cognitive challenges in aging. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

White matter of the brain

MedlinePlus

White matter is found in the deeper tissues of the brain (subcortical). It contains nerve fibers (axons), which are ... or covering called myelin. Myelin gives the white matter its color. It also protects the nerve fibers ...

Spatial coherence of oriented white matter microstructure: Applications to white matter regions associated with genetic similarity.

PubMed

Hallgrímsson, Haraldur T; Cieslak, Matthew; Foschini, Luca; Grafton, Scott T; Singh, Ambuj K

2018-05-15

We present a method to discover differences between populations with respect to the spatial coherence of their oriented white matter microstructure in arbitrarily shaped white matter regions. This method is applied to diffusion MRI scans of a subset of the Human Connectome Project dataset: 57 pairs of monozygotic and 52 pairs of dizygotic twins. After controlling for morphological similarity between twins, we identify 3.7% of all white matter as being associated with genetic similarity (35.1 k voxels, p<10 -4 , false discovery rate 1.5%), 75% of which spatially clusters into twenty-two contiguous white matter regions. Furthermore, we show that the orientation similarity within these regions generalizes to a subset of 47 pairs of non-twin siblings, and show that these siblings are on average as similar as dizygotic twins. The regions are located in deep white matter including the superior longitudinal fasciculus, the optic radiations, the middle cerebellar peduncle, the corticospinal tract, and within the anterior temporal lobe, as well as the cerebellum, brain stem, and amygdalae. These results extend previous work using undirected fractional anisotrophy for measuring putative heritable influences in white matter. Our multidirectional extension better accounts for crossing fiber connections within voxels. This bottom up approach has at its basis a novel measurement of coherence within neighboring voxel dyads between subjects, and avoids some of the fundamental ambiguities encountered with tractographic approaches to white matter analysis that estimate global connectivity. Copyright © 2018 Elsevier Inc. All rights reserved.

Association of schizophrenia onset age and white matter integrity with treatment effect of D-cycloserine: a randomized placebo-controlled double-blind crossover study.

PubMed

Takiguchi, Kazuo; Uezato, Akihito; Itasaka, Michio; Atsuta, Hidenori; Narushima, Kenji; Yamamoto, Naoki; Kurumaji, Akeo; Tomita, Makoto; Oshima, Kazunari; Shoda, Kosaku; Tamaru, Mai; Nakataki, Masahito; Okazaki, Mitsutoshi; Ishiwata, Sayuri; Ishiwata, Yasuyoshi; Yasuhara, Masato; Arima, Kunimasa; Ohmori, Tetsuro; Nishikawa, Toru

2017-07-12

It has been reported that drugs which promote the N-Methyl-D-aspartate-type glutamate receptor function by stimulating the glycine modulatory site in the receptor improve negative symptoms and cognitive dysfunction in schizophrenia patients being treated with antipsychotic drugs. We performed a placebo-controlled double-blind crossover study involving 41 schizophrenia patients in which D-cycloserine 50 mg/day was added-on, and the influence of the onset age and association with white matter integrity on MR diffusion tensor imaging were investigated for the first time. The patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Brief Assessment of Cognition in Schizophrenia (BACS), and other scales. D-cycloserine did not improve positive or negative symptoms or cognitive dysfunction in schizophrenia. The investigation in consideration of the onset age suggests that D-cycloserine may aggravate negative symptoms of early-onset schizophrenia. The better treatment effect of D-cycloserine on BACS was observed when the white matter integrity of the sagittal stratum/ cingulum/fornix stria terminalis/genu of corpus callosum/external capsule was higher, and the better treatment effect on PANSS general psychopathology (PANSS-G) was observed when the white matter integrity of the splenium of corpus callosum was higher. In contrast, the better treatment effect of D-cycloserine on PANSS-G and SANS-IV were observed when the white matter integrity of the posterior thalamic radiation (left) was lower. It was suggested that response to D-cycloserine is influenced by the onset age and white matter integrity. UMIN Clinical Trials Registry (number UMIN000000468 ). Registered 18 August 2006.

Total Homocysteine Is Associated With White Matter Hyperintensity Volume

PubMed Central

Wright, Clinton B.; Paik, Myunghee C.; Brown, Truman R.; Stabler, Sally P.; Allen, Robert H.; Sacco, Ralph L.; DeCarli, Charles

2005-01-01

Background Total homocysteine (tHcy) has been implicated as a risk factor for stroke and dementia, but the mechanism is unclear. White matter hyperintensities may be a risk factor for both, but studies of the relationship between tHcy and quantitative measures of white matter hyperintensity volume (WMHV) are lacking, especially in minority populations. Methods A community-based sample of 259 subjects with baseline tHcy levels underwent pixel-based quantitative measurement of WMHV. We examined the relationship between tHcy and WMHV adjusting for age, sociodemographics, vascular risk factors, and B12 deficiency. Results Higher levels of tHcy were associated with WMHV adjusting for sociodemographics and vascular risk factors. Conclusions These cross-sectional data provide evidence that tHcy is a risk factor for white matter damage. PMID:15879345

The effect of lifelong bilingualism on regional grey and white matter volume.

PubMed

Olsen, Rosanna K; Pangelinan, Melissa M; Bogulski, Cari; Chakravarty, M Mallar; Luk, Gigi; Grady, Cheryl L; Bialystok, Ellen

2015-07-01

Lifelong bilingualism is associated with the delayed diagnosis of dementia, suggesting bilingual experience is relevant to brain health in aging. While the effects of bilingualism on cognitive functions across the lifespan are well documented, less is known about the neural substrates underlying differential behaviour. It is clear that bilingualism affects brain regions that mediate language abilities and that these regions are at least partially overlapping with those that exhibit age-related decline. Moreover, the behavioural advantages observed in bilingualism are generally found in executive function performance, suggesting that the frontal lobes may also be sensitive to bilingualism, which exhibit volume reductions with age. The current study investigated structural differences in the brain of lifelong bilingual older adults (n=14, mean age=70.4) compared with older monolinguals (n=14, mean age=70.6). We employed two analytic approaches: 1) we examined global differences in grey and white matter volumes; and, 2) we examined local differences in volume and cortical thickness of specific regions of interest previously implicated in bilingual/monolingual comparisons (temporal pole) or in aging (entorhinal cortex and hippocampus). We expected bilinguals would exhibit greater volume of the frontal lobe and temporal lobe (grey and white matter), given the importance of these regions in executive and language functions, respectively. We further hypothesized that regions in the medial temporal lobe, which demonstrate early changes in aging and exhibit neural pathology in dementia, would be more preserved in the bilingual group. As predicted, bilinguals exhibit greater frontal lobe white matter compared with monolinguals. Moreover, increasing age was related to decreasing temporal pole cortical thickness in the monolingual group, but no such relationship was observed for bilinguals. Finally, Stroop task performance was positively correlated with frontal lobe white

Novel white matter tract integrity metrics sensitive to Alzheimer disease progression.

PubMed

Fieremans, E; Benitez, A; Jensen, J H; Falangola, M F; Tabesh, A; Deardorff, R L; Spampinato, M V S; Babb, J S; Novikov, D S; Ferris, S H; Helpern, J A

2013-01-01

Along with cortical abnormalities, white matter microstructural changes such as axonal loss and myelin breakdown are implicated in the pathogenesis of Alzheimer disease. Recently, a white matter model was introduced that relates non-Gaussian diffusional kurtosis imaging metrics to characteristics of white matter tract integrity, including the axonal water fraction, the intra-axonal diffusivity, and the extra-axonal axial and radial diffusivities. This study reports these white matter tract integrity metrics in subjects with amnestic mild cognitive impairment (n = 12), Alzheimer disease (n = 14), and age-matched healthy controls (n = 15) in an effort to investigate their sensitivity, diagnostic accuracy, and associations with white matter changes through the course of Alzheimer disease. With tract-based spatial statistics and region-of-interest analyses, increased diffusivity in the extra-axonal space (extra-axonal axial and radial diffusivities) in several white matter tracts sensitively and accurately discriminated healthy controls from those with amnestic mild cognitive impairment (area under the receiver operating characteristic curve = 0.82-0.95), while widespread decreased axonal water fraction discriminated amnestic mild cognitive impairment from Alzheimer disease (area under the receiver operating characteristic curve = 0.84). Additionally, these white matter tract integrity metrics in the body of the corpus callosum were strongly correlated with processing speed in amnestic mild cognitive impairment (r = |0.80-0.82|, P < .001). These findings have implications for the course and spatial progression of white matter degeneration in Alzheimer disease, suggest the mechanisms by which these changes occur, and demonstrate the viability of these white matter tract integrity metrics as potential neuroimaging biomarkers of the earliest stages of Alzheimer disease and disease progression.

Age-Related Gray and White Matter Changes in Normal Adult Brains

PubMed Central

Farokhian, Farnaz; Yang, Chunlan; Beheshti, Iman; Matsuda, Hiroshi; Wu, Shuicai

2017-01-01

Normal aging is associated with both structural changes in many brain regions and functional declines in several cognitive domains with advancing age. Advanced neuroimaging techniques enable explorative analyses of structural alterations that can be used as assessments of such age-related changes. Here we used voxel-based morphometry (VBM) to investigate regional and global brain volume differences among four groups of healthy adults from the IXI Dataset: older females (OF, mean age 68.35 yrs; n=69), older males (OM, 68.43 yrs; n=66), young females (YF, 27.09 yrs; n=71), and young males (YM, 27.91 yrs; n=71), using 3D T1-weighted MRI data. At the global level, we investigated the influence of age and gender on brain volumes using a two-way analysis of variance. With respect to gender, we used the Pearson correlation to investigate global brain volume alterations due to age in the older and young groups. At the regional level, we used a flexible factorial statistical test to compare the means of gray matter (GM) and white matter (WM) volume alterations among the four groups. We observed different patterns in both the global and regional GM and WM alterations in the young and older groups with respect to gender. At the global level, we observed significant influences of age and gender on global brain volumes. At the regional level, the older subjects showed a widespread reduction in GM volume in regions of the frontal, insular, and cingulate cortices compared to the young subjects in both genders. Compared to the young subjects, the older subjects showed a widespread WM decline prominently in the thalamic radiations, in addition to increased WM in pericentral and occipital areas. Knowledge of these observed brain volume differences and changes may contribute to the elucidation of mechanisms underlying aging as well as age-related brain atrophy and disease. PMID:29344423

ADRB2, brain white matter integrity and cognitive ageing in the Lothian Birth Cohort 1936.

PubMed

Lyall, Donald M; Lopez, Lorna M; Bastin, Mark E; Maniega, Susana Muñoz; Penke, Lars; Valdés Hernández, Maria del C; Royle, Natalie A; Starr, John M; Porteous, David J; Wardlaw, Joanna M; Deary, Ian J

2013-01-01

The non-synonymous mutations arg16gly (rs1042713) and gln27glu (rs1042714) in the adrenergic β-2 receptor gene (ADRB2) have been associated with cognitive function and brain white matter integrity. The current study aimed to replicate these findings and expand them to a broader range of cognitive and brain phenotypes. The sample used is a community-dwelling group of older people, the Lothian Birth Cohort 1936. They had been assessed cognitively at age 11 years, and undertook further cognitive assessments and brain diffusion MRI tractography in older age. The sample size range for cognitive function variables was N = 686-765, and for neuroimaging variables was N = 488-587. Previously-reported findings with these genetic variants did not replicate in this cohort. Novel, nominally significant associations were observed; notably, the integrity of the left arcuate fasciculus mediated the association between rs1042714 and the Digit Symbol Coding test of information processing speed. No significant associations of cognitive and brain phenotypes with ADRB2 variants survived correction for false discovery rate. Previous findings may therefore have been subject to type 1 error. Further study into links between ADRB2, cognitive function and brain white matter integrity is required.

Impaired empathic abilities and reduced white matter integrity in schizophrenia.

PubMed

Fujino, Junya; Takahashi, Hidehiko; Miyata, Jun; Sugihara, Genichi; Kubota, Manabu; Sasamoto, Akihiko; Fujiwara, Hironobu; Aso, Toshihiko; Fukuyama, Hidenao; Murai, Toshiya

2014-01-03

Empathic abilities are impaired in schizophrenia. Although the pathology of schizophrenia is thought to involve disrupted white matter integrity, the relationship between empathic disabilities and altered white matter in the disorder remains unclear. The present study tested associations between empathic disabilities and white matter integrity in order to investigate the neural basis of impaired empathy in schizophrenia. Sixty-nine patients with schizophrenia and 69 age-, gender-, handedness-, education- and IQ level-matched healthy controls underwent diffusion-weighted imaging. Empathic abilities were assessed using the Interpersonal Reactivity Index (IRI). Using tract-based spatial statistics (TBSS), the associations between empathic abilities and white matter fractional anisotropy (FA), a measure of white matter integrity, were examined in the patient group within brain areas that showed a significant FA reduction compared with the controls. The patients with schizophrenia reported lower perspective taking and higher personal distress according to the IRI. The patients showed a significant FA reduction in bilateral deep white matter in the frontal, temporal, parietal and occipital lobes, a large portion of the corpus callosum, and the corona radiata. In schizophrenia patients, fantasy subscales positively correlated with FA in the left inferior fronto-occipital fasciculi and anterior thalamic radiation, and personal distress subscales negatively correlated with FA in the splenium of the corpus callosum. These results suggest that disrupted white matter integrity in these regions constitutes a pathology underpinning specific components of empathic disabilities in schizophrenia, highlighting that different aspects of empathic impairments in the disorder would have, at least partially, distinct neuropathological bases. © 2013.

The effects of puberty on white matter development in boys.

PubMed

Menzies, Lara; Goddings, Anne-Lise; Whitaker, Kirstie J; Blakemore, Sarah-Jayne; Viner, Russell M

2015-02-01

Neuroimaging studies demonstrate considerable changes in white matter volume and microstructure during adolescence. Most studies have focused on age-related effects, whilst puberty-related changes are not well understood. Using diffusion tensor imaging and tract-based spatial statistics, we investigated the effects of pubertal status on white matter mean diffusivity (MD) and fractional anisotropy (FA) in 61 males aged 12.7-16.0 years. Participants were grouped into early-mid puberty (≤Tanner Stage 3 in pubic hair and gonadal development; n=22) and late-post puberty (≥Tanner Stage 4 in pubic hair or gonadal development; n=39). Salivary levels of pubertal hormones (testosterone, DHEA and oestradiol) were also measured. Pubertal stage was significantly related to MD in diverse white matter regions. No relationship was observed between pubertal status and FA. Regression modelling of MD in the significant regions demonstrated that an interaction model incorporating puberty, age and puberty×age best explained our findings. In addition, testosterone was correlated with MD in these pubertally significant regions. No relationship was observed between oestradiol or DHEA and MD. In conclusion, pubertal status was significantly related to MD, but not FA, and this relationship cannot be explained by changes in chronological age alone. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

The effects of puberty on white matter development in boys

PubMed Central

Menzies, Lara; Goddings, Anne-Lise; Whitaker, Kirstie J.; Blakemore, Sarah-Jayne; Viner, Russell M.

2015-01-01

Neuroimaging studies demonstrate considerable changes in white matter volume and microstructure during adolescence. Most studies have focused on age-related effects, whilst puberty-related changes are not well understood. Using diffusion tensor imaging and tract-based spatial statistics, we investigated the effects of pubertal status on white matter mean diffusivity (MD) and fractional anisotropy (FA) in 61 males aged 12.7–16.0 years. Participants were grouped into early-mid puberty (≤Tanner Stage 3 in pubic hair and gonadal development; n = 22) and late-post puberty (≥Tanner Stage 4 in pubic hair or gonadal development; n = 39). Salivary levels of pubertal hormones (testosterone, DHEA and oestradiol) were also measured. Pubertal stage was significantly related to MD in diverse white matter regions. No relationship was observed between pubertal status and FA. Regression modelling of MD in the significant regions demonstrated that an interaction model incorporating puberty, age and puberty × age best explained our findings. In addition, testosterone was correlated with MD in these pubertally significant regions. No relationship was observed between oestradiol or DHEA and MD. In conclusion, pubertal status was significantly related to MD, but not FA, and this relationship cannot be explained by changes in chronological age alone. PMID:25454416

White Matter Hyperintensities Improve Ischemic Stroke Recurrence Prediction.

PubMed

Andersen, Søren Due; Larsen, Torben Bjerregaard; Gorst-Rasmussen, Anders; Yavarian, Yousef; Lip, Gregory Y H; Bach, Flemming W

2017-01-01

Nearly one in 5 patients with ischemic stroke will invariably experience a second stroke within 5 years. Stroke risk stratification schemes based solely on clinical variables perform only modestly in non-atrial fibrillation (AF) patients and improvement of these schemes will enhance their clinical utility. Cerebral white matter hyperintensities are associated with an increased risk of incident ischemic stroke in the general population, whereas their association with the risk of ischemic stroke recurrence is more ambiguous. In a non-AF stroke cohort, we investigated the association between cerebral white matter hyperintensities and the risk of recurrent ischemic stroke, and we evaluated the predictive performance of the CHA2DS2VASc score and the Essen Stroke Risk Score (clinical scores) when augmented with information on white matter hyperintensities. In a registry-based, observational cohort study, we included 832 patients (mean age 59.6 (SD 13.9); 42.0% females) with incident ischemic stroke and no AF. We assessed the severity of white matter hyperintensities using MRI. Hazard ratios stratified by the white matter hyperintensities score and adjusted for the components of the CHA2DS2VASc score were calculated based on the Cox proportional hazards analysis. Recalibrated clinical scores were calculated by adding one point to the score for the presence of moderate to severe white matter hyperintensities. The discriminatory performance of the scores was assessed with the C-statistic. White matter hyperintensities were significantly associated with the risk of recurrent ischemic stroke after adjusting for clinical risk factors. The hazard ratios ranged from 1.65 (95% CI 0.70-3.86) for mild changes to 5.28 (95% CI 1.98-14.07) for the most severe changes. C-statistics for the prediction of recurrent ischemic stroke were 0.59 (95% CI 0.51-0.65) for the CHA2DS2VASc score and 0.60 (95% CI 0.53-0.68) for the Essen Stroke Risk Score. The recalibrated clinical scores showed

White Matter Volume Predicts Language Development in Congenital Heart Disease

PubMed Central

Rollins, Caitlin K.; Asaro, Lisa A.; Akhondi-Asl, Alireza; Kussman, Barry D.; Rivkin, Michael J.; Bellinger, David C.; Warfield, Simon K.; Wypij, David; Newburger, Jane W.; Soul, Janet S.

2016-01-01

Objective To determine whether brain volume is reduced at one year and whether these volumes are associated with neurodevelopment in biventricular congenital heart disease (CHD) repaired in infancy. Study design Infants with biventricular CHD (n = 48) underwent brain magnetic resonance imaging (MRI) and neurodevelopmental testing with the Bayley Scales of Infant Development-II (BSID-II) and the MacArthur-Bates Communicative Development Inventories (CDI) at one year. A multi-template based probabilistic segmentation algorithm was applied to volumetric MRI data. We compared volumes with those of 13 healthy control infants of comparable ages. In the CHD group, we measured Spearman correlations between neurodevelopmental outcomes and the residuals from linear regression of the volumes on corrected chronological age at MRI and sex. Results Compared with controls, CHD infant had reductions of 54 mL in total brain (P = 0.009), 40 mL in cerebral white matter (P < 0.001), and 1.2 mL in brainstem (P = 0.003) volumes. Within the CHD group, brain volumes were not correlated with BSID-II scores but did correlate positively with CDI language development. Conclusion Infants with biventricular CHD show total brain volume reductions at one year of age, driven by differences in cerebral white matter. White matter volume correlates with language development, but not broader developmental indices. These findings suggest that abnormalities in white matter development detected months after corrective heart surgery may contribute to language impairment. Trial registration ClinicalTrials.gov: NCT00006183 PMID:27837950

Cognitive correlates of white matter lesion load and brain atrophy

PubMed Central

Dong, Chuanhui; Nabizadeh, Nooshin; Caunca, Michelle; Cheung, Ying Kuen; Rundek, Tatjana; Elkind, Mitchell S.V.; DeCarli, Charles; Sacco, Ralph L.; Stern, Yaakov

2015-01-01

Objective: We investigated white matter lesion load and global and regional brain volumes in relation to domain-specific cognitive performance in the stroke-free Northern Manhattan Study (NOMAS) population. Methods: We quantified white matter hyperintensity volume (WMHV), total cerebral volume (TCV), and total lateral ventricular (TLV) volume, as well as hippocampal and cortical gray matter (GM) lobar volumes in a subgroup. We used general linear models to examine MRI markers in relation to domain-specific cognitive performance, adjusting for key covariates. Results: MRI and cognitive data were available for 1,163 participants (mean age 70 ± 9 years; 60% women; 66% Hispanic, 17% black, 15% white). Across the entire sample, those with greater WMHV had worse processing speed. Those with larger TLV volume did worse on episodic memory, processing speed, and semantic memory tasks, and TCV did not explain domain-specific variability in cognitive performance independent of other measures. Age was an effect modifier, and stratified analysis showed that TCV and WMHV explained variability in some domains above age 70. Smaller hippocampal volume was associated with worse performance across domains, even after adjusting for APOE ε4 and vascular risk factors, whereas smaller frontal lobe volumes were only associated with worse executive function. Conclusions: In this racially/ethnically diverse, community-based sample, white matter lesion load was inversely associated with cognitive performance, independent of brain atrophy. Lateral ventricular, hippocampal, and lobar GM volumes explained domain-specific variability in cognitive performance. PMID:26156514

Persistence of abnormalities in white matter in children with type 1 diabetes.

PubMed

Fox, Larry A; Hershey, Tamara; Mauras, Nelly; Arbeláez, Ana Maria; Tamborlane, William V; Buckingham, Bruce; Tsalikian, Eva; Englert, Kim; Raman, Mira; Jo, Booil; Shen, Hanyang; Reiss, Allan; Mazaika, Paul

2018-07-01

Prior studies suggest white matter growth is reduced and white matter microstructure is altered in the brains of young children with type 1 diabetes when compared with brains of non-diabetic children, due in part to adverse effects of hyperglycaemia. This longitudinal observational study examines whether dysglycaemia alters the developmental trajectory of white matter microstructure over time in young children with type 1 diabetes. One hundred and eighteen children, aged 4 to <10 years old with type 1 diabetes and 58 age-matched, non-diabetic children were studied at baseline and 18 months, at five Diabetes Research in Children Network clinical centres. We analysed longitudinal trajectories of white matter using diffusion tensor imaging. Continuous glucose monitoring profiles and HbA 1c levels were obtained every 3 months. Axial diffusivity was lower in children with diabetes at baseline (p = 0.022) and at 18 months (p = 0.015), indicating that differences in white matter microstructure persist over time in children with diabetes. Within the diabetes group, lower exposure to hyperglycaemia, averaged over the time since diagnosis, was associated with higher fractional anisotropy (p = 0.037). Fractional anisotropy was positively correlated with performance (p < 0.002) and full-scale IQ (p < 0.02). These results suggest that hyperglycaemia is associated with altered white matter development, which may contribute to the mild cognitive deficits in this population.

Selective white matter pathology induces a specific impairment in spatial working memory.

PubMed

Coltman, Robin; Spain, Aisling; Tsenkina, Yanina; Fowler, Jill H; Smith, Jessica; Scullion, Gillian; Allerhand, Mike; Scott, Fiona; Kalaria, Rajesh N; Ihara, Masafumi; Daumas, Stephanie; Deary, Ian J; Wood, Emma; McCulloch, James; Horsburgh, Karen

2011-12-01

The integrity of the white matter is critical in regulating efficient neuronal communication and maintaining cognitive function. Damage to brain white matter putatively contributes to age-related cognitive decline. There is a growing interest in animal models from which the mechanistic basis of white matter pathology in aging can be elucidated but to date there has been a lack of systematic behavior and pathology in the same mice. Anatomically widespread, diffuse white matter damage was induced, in 3 different cohorts of C57Bl/6J mice, by chronic hypoperfusion produced by bilateral carotid stenosis. A comprehensive assessment of spatial memory (spatial reference learning and memory; cohort 1) and serial spatial learning and memory (cohort 2) using the water maze, and spatial working memory (cohort 3) using the 8-arm radial arm maze, was conducted. In parallel, a systematic assessment of white matter components (myelin, axon, glia) was conducted using immunohistochemical markers (myelin-associated glycoprotein [MAG], degraded myelin basic protein [dMBP], anti-amyloid precursor protein [APP], anti-ionized calcium-binding adapter molecule [Iba-1]). Ischemic neuronal perikarya damage, assessed using histology (hematoxylin and eosin; H&E), was absent in all shams but was present in some hypoperfused mice (2/11 in cohort 1, 4/14 in cohort 2, and 17/24 in cohort 3). All animals with neuronal perikaryal damage were excluded from further study. Diffuse white matter damage occurred, throughout the brain, in all hypoperfused mice in each cohort and was essentially absent in sham-operated controls. There was a selective impairment in spatial working memory, with all other measures of spatial memory remaining intact, in hypoperfused mice with selective white matter damage. The results demonstrate that diffuse white matter pathology, in the absence of gray matter damage, induces a selective impairment of spatial working memory. This highlights the importance of assessing

Correlation Between White Matter Lesions and Intelligence Quotient in Patients With Congenital Cytomegalovirus Infection.

PubMed

Inaba, Yuji; Motobayashi, Mitsuo; Nishioka, Makoto; Kaneko, Tomoki; Yamauchi, Shoko; Kawasaki, Yoichiro; Shiba, Naoko; Nishio, Shin-ya; Moteki, Hideaki; Miyagawa, Maiko; Takumi, Yutaka; Usami, Shin-ichi; Koike, Kenichi

2016-02-01

It is well known that congenital cytomegalovirus infection exhibits white matter and other types of lesions in magnetic resonance imaging (MRI), but little is known on the clinical significance of white matter lesions because they are also present in asymptomatic congenital cytomegalovirus infection. We investigated for relationships among white matter lesions, intelligence quotient, and other neurodevelopmental features. Nine children (five boys and four girls; mean age: 87.4 months, range: 63-127 months) with sensorineural hearing loss (five bilateral and four unilateral) had been diagnosed as having congenital cytomegalovirus infection by positive polymerase chain reaction findings of dried umbilical cords. They were evaluated for the presence of autistic features, tested using Wechsler Intelligence Scale for Children-Fourth Edition for intelligence quotient, and underwent brain MRI to measure white matter lesion localization and volume. At the time of MRI examination (mean age: 69.4 months, range: 19-92 months), white matter lesions were detected in eight of nine patients. Five subjects were diagnosed as having autism spectrum disorders. We observed increased white matter lesion volume was associated with lower intelligence quotient scores (R(2) = 0.533, P = 0.026) but not with autism spectrum disorders. In individuals with congenital cytomegalovirus, an increased white matter lesion volume is associated with lower intelligence quotient scores but not with an increased likelihood of autistic behavior. Copyright © 2016 Elsevier Inc. All rights reserved.

White matter hyperintensities and headache: A population-based imaging study (HUNT MRI).

PubMed

Honningsvåg, Lasse-Marius; Håberg, Asta Kristine; Hagen, Knut; Kvistad, Kjell Arne; Stovner, Lars Jacob; Linde, Mattias

2018-01-01

Objective To examine the relationship between white matter hyperintensities and headache. Methods White matter hyperintensities burden was assessed semi-quantitatively using Fazekas and Scheltens scales, and by manual and automated volumetry of MRI in a sub-study of the general population-based Nord-Trøndelag Health Study (HUNT MRI). Using validated questionnaires, participants were categorized into four cross-sectional headache groups: Headache-free (n = 551), tension-type headache (n = 94), migraine (n = 91), and unclassified headache (n = 126). Prospective questionnaire data was used to further categorize participants into groups according to the evolution of headache during the last 12 years: Stable headache-free, past headache, new onset headache, and persistent headache. White matter hyperintensities burden was compared across headache groups using adjusted multivariate regression models. Results Individuals with tension-type headache were more likely to have extensive white matter hyperintensities than headache-free subjects, with this being the case across all methods of white matter hyperintensities assessment (Scheltens scale: Odds ratio, 2.46; 95% CI, 1.44-4.20). Migraine or unclassified headache did not influence the odds of having extensive white matter hyperintensities. Those with new onset headache were more likely to have extensive white matter hyperintensities than those who were stable headache-free (Scheltens scale: Odds ratio, 2.24; 95% CI, 1.13-4.44). Conclusions Having tension-type headache or developing headache in middle age was linked to extensive white matter hyperintensities. These results were similar across all methods of assessing white matter hyperintensities. If white matter hyperintensities treatment strategies emerge in the future, this association should be taken into consideration.

Effects of exercise on capillaries in the white matter of transgenic AD mice.

PubMed

Zhang, Yi; Chao, Feng-Lei; Zhou, Chun-Ni; Jiang, Lin; Zhang, Lei; Chen, Lin-Mu; Luo, Yan-Min; Xiao, Qian; Tang, Yong

2017-09-12

Previous studies have shown that exercise can prevent white matter atrophy in APP/PS1 transgenic Alzheimer's disease (AD) mice. However, the mechanism of this protective effect remains unknown. To further understand this issue, we investigated the effects of exercise on the blood supply of white matter in transgenic AD mice. Six-month-old male APP/PS1 mice were randomly divided into a control group and a running group, and age-matched non-transgenic littermates were used as a wild-type control group. Mice in the running group ran on a treadmill at low intensity for four months. Then, spatial learning and memory abilities, white matter and white matter capillaries were examined in all mice. The 10-month-old AD mice exhibited deficits in cognitive function, and 4 months of exercise improved these deficits. The white matter volume and the total length, total volume and total surface area of the white matter capillaries were decreased in the 10-month-old AD mice, and 4 months of exercise dramatically delayed the changes in these parameters in the AD mice. Our results demonstrate that even low-intensity running exercise can improve spatial learning and memory abilities, delay white matter atrophy and protect white matter capillaries in early-stage AD mice. Protecting capillaries might be an important structural basis for the exercise-induced protection of the structural integrity of white matter in AD.

White-matter functional networks changes in patients with schizophrenia.

PubMed

Jiang, Yuchao; Luo, Cheng; Li, Xuan; Li, Yingjia; Yang, Hang; Li, Jianfu; Chang, Xin; Li, Hechun; Yang, Huanghao; Wang, Jijun; Duan, Mingjun; Yao, Dezhong

2018-04-13

Resting-state functional MRI (rsfMRI) is a useful technique for investigating the functional organization of human gray-matter in neuroscience and neuropsychiatry. Nevertheless, most studies have demonstrated the functional connectivity and/or task-related functional activity in the gray-matter. White-matter functional networks have been investigated in healthy subjects. Schizophrenia has been hypothesized to be a brain disorder involving insufficient or ineffective communication associated with white-matter abnormalities. However, previous studies have mainly examined the structural architecture of white-matter using MRI or diffusion tensor imaging and failed to uncover any dysfunctional connectivity within the white-matter on rsfMRI. The current study used rsfMRI to evaluate white-matter functional connectivity in a large cohort of ninety-seven schizophrenia patients and 126 healthy controls. Ten large-scale white-matter networks were identified by a cluster analysis of voxel-based white-matter functional connectivity and classified into superficial, middle and deep layers of networks. Evaluation of the spontaneous oscillation of white-matter networks and the functional connectivity between them showed that patients with schizophrenia had decreased amplitudes of low-frequency oscillation and increased functional connectivity in the superficial perception-motor networks. Additionally, we examined the interactions between white-matter and gray-matter networks. The superficial perception-motor white-matter network had decreased functional connectivity with the cortical perception-motor gray-matter networks. In contrast, the middle and deep white-matter networks had increased functional connectivity with the superficial perception-motor white-matter network and the cortical perception-motor gray-matter network. Thus, we presumed that the disrupted association between the gray-matter and white-matter networks in the perception-motor system may be compensated for

Bootstrapping white matter segmentation, Eve++

NASA Astrophysics Data System (ADS)

Plassard, Andrew; Hinton, Kendra E.; Venkatraman, Vijay; Gonzalez, Christopher; Resnick, Susan M.; Landman, Bennett A.

2015-03-01

Multi-atlas labeling has come in wide spread use for whole brain labeling on magnetic resonance imaging. Recent challenges have shown that leading techniques are near (or at) human expert reproducibility for cortical gray matter labels. However, these approaches tend to treat white matter as essentially homogeneous (as white matter exhibits isointense signal on structural MRI). The state-of-the-art for white matter atlas is the single-subject Johns Hopkins Eve atlas. Numerous approaches have attempted to use tractography and/or orientation information to identify homologous white matter structures across subjects. Despite success with large tracts, these approaches have been plagued by difficulties in with subtle differences in course, low signal to noise, and complex structural relationships for smaller tracts. Here, we investigate use of atlas-based labeling to propagate the Eve atlas to unlabeled datasets. We evaluate single atlas labeling and multi-atlas labeling using synthetic atlases derived from the single manually labeled atlas. On 5 representative tracts for 10 subjects, we demonstrate that (1) single atlas labeling generally provides segmentations within 2mm mean surface distance, (2) morphologically constraining DTI labels within structural MRI white matter reduces variability, and (3) multi-atlas labeling did not improve accuracy. These efforts present a preliminary indication that single atlas labels with correction is reasonable, but caution should be applied. To purse multi-atlas labeling and more fully characterize overall performance, more labeled datasets would be necessary.

Maternal adiposity negatively influences infant brain white matter development.

PubMed

Ou, Xiawei; Thakali, Keshari M; Shankar, Kartik; Andres, Aline; Badger, Thomas M

2015-05-01

To study potential effects of maternal body composition on central nervous system (CNS) development of newborn infants. Diffusion tensor imaging (DTI) was used to evaluate brain white matter development in 2-week-old, full-term, appropriate for gestational age (AGA) infants from uncomplicated pregnancies of normal-weight (BMI < 25 at conception) or obese ( BMI = 30 at conception) and otherwise healthy mothers. Tract-based spatial statistics (TBSS) analyses were used for voxel-wise group comparison of fractional anisotropy (FA), a sensitive measure of white matter integrity. DNA methylation analyses of umbilical cord tissue focused on genes known to be important in CNS development were also performed. Newborns from obese women had significantly lower FA values in multiple white matter regions than those born of normal-weight mothers. Global and regional FA values negatively correlated (P < 0.05) with maternal fat mass percentage. Linear regression analysis followed by gene ontology enrichment showed that methylation status of 68 CpG sites representing 57 genes with GO terms related to CNS development was significantly associated with maternal adiposity status. These results suggest a negative association between maternal adiposity and white matter development in offspring. © 2015 The Obesity Society.

ApoE influences regional white-matter axonal density loss in Alzheimer's disease.

PubMed

Slattery, Catherine F; Zhang, Jiaying; Paterson, Ross W; Foulkes, Alexander J M; Carton, Amelia; Macpherson, Kirsty; Mancini, Laura; Thomas, David L; Modat, Marc; Toussaint, Nicolas; Cash, David M; Thornton, John S; Henley, Susie M D; Crutch, Sebastian J; Alexander, Daniel C; Ourselin, Sebastien; Fox, Nick C; Zhang, Hui; Schott, Jonathan M

2017-09-01

Mechanisms underlying phenotypic heterogeneity in young onset Alzheimer disease (YOAD) are poorly understood. We used diffusion tensor imaging and neurite orientation dispersion and density imaging (NODDI) with tract-based spatial statistics to investigate apolipoprotein (APOE) ε4 modulation of white-matter damage in 37 patients with YOAD (22, 59% APOE ε4 positive) and 23 age-matched controls. Correlation between neurite density index (NDI) and neuropsychological performance was assessed in 4 white-matter regions of interest. White-matter disruption was more widespread in ε4+ individuals but more focal (posterior predominant) in the absence of an ε4 allele. NODDI metrics indicate fractional anisotropy changes are underpinned by combinations of axonal loss and morphological change. Regional NDI in parieto-occipital white matter correlated with visual object and spatial perception battery performance (right and left, both p = 0.02), and performance (nonverbal) intelligence (WASI matrices, right, p = 0.04). NODDI provides tissue-specific microstructural metrics of white-matter tract damage in YOAD, including NDI which correlates with focal cognitive deficits, and APOEε4 status is associated with different patterns of white-matter neurodegeneration. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Joint source based morphometry identifies linked gray and white matter group differences.

PubMed

Xu, Lai; Pearlson, Godfrey; Calhoun, Vince D

2009-02-01

We present a multivariate approach called joint source based morphometry (jSBM), to identify linked gray and white matter regions which differ between groups. In jSBM, joint independent component analysis (jICA) is used to decompose preprocessed gray and white matter images into joint sources and statistical analysis is used to determine the significant joint sources showing group differences and their relationship to other variables of interest (e.g. age or sex). The identified joint sources are groupings of linked gray and white matter regions with common covariation among subjects. In this study, we first provide a simulation to validate the jSBM approach. To illustrate our method on real data, jSBM is then applied to structural magnetic resonance imaging (sMRI) data obtained from 120 chronic schizophrenia patients and 120 healthy controls to identify group differences. JSBM identified four joint sources as significantly associated with schizophrenia. Linked gray-white matter regions identified in each of the joint sources included: 1) temporal--corpus callosum, 2) occipital/frontal--inferior fronto-occipital fasciculus, 3) frontal/parietal/occipital/temporal--superior longitudinal fasciculus and 4) parietal/frontal--thalamus. Age effects on all four joint sources were significant, but sex effects were significant only for the third joint source. Our findings demonstrate that jSBM can exploit the natural linkage between gray and white matter by incorporating them into a unified framework. This approach is applicable to a wide variety of problems to study linked gray and white matter group differences.

Joint source based morphometry identifies linked gray and white matter group differences

PubMed Central

Xu, Lai; Pearlson, Godfrey; Calhoun, Vince D.

2009-01-01

We present a multivariate approach called joint source based morphometry (jSBM), to identify linked gray and white matter regions which differ between groups. In jSBM, joint independent component analysis (jICA) is used to decompose preprocessed gray and white matter images into joint sources and statistical analysis is used to determine the significant joint sources showing group differences and their relationship to other variables of interest (e.g. age or sex). The identified joint sources are groupings of linked gray and white matter regions with common covariation among subjects. In this study, we first provide a simulation to validate the jSBM approach. To illustrate our method on real data, jSBM is then applied to structural magnetic resonance imaging (sMRI) data obtained from 120 chronic schizophrenia patients and 120 healthy controls to identify group differences. JSBM identified four joint sources as significantly associated with schizophrenia. Linked gray–white matter regions identified in each of the joint sources included: 1) temporal — corpus callosum, 2) occipital/frontal — inferior fronto-occipital fasciculus, 3) frontal/parietal/occipital/temporal —superior longitudinal fasciculus and 4) parietal/frontal — thalamus. Age effects on all four joint sources were significant, but sex effects were significant only for the third joint source. Our findings demonstrate that jSBM can exploit the natural linkage between gray and white matter by incorporating them into a unified framework. This approach is applicable to a wide variety of problems to study linked gray and white matter group differences. PMID:18992825

Frontotemporal white matter changes in amyotrophic lateral sclerosis.

PubMed

Abrahams, Sharon; Goldstein, Laura H; Suckling, John; Ng, Virginia; Simmons, Andy; Chitnis, Xavier; Atkins, Louise; Williams, Steve C R; Leigh, P N

2005-03-01

Cognitive dysfunction can occur in some patients with amyotrophic lateral sclerosis (ALS) who are not suffering from dementia. The most striking and consistent cognitive deficit has been found using tests of verbal fluency. ALS patients with verbal fluency deficits have shown functional imaging abnormalities predominantly in frontotemporal regions using positron emission tomography (PET). This study used automated volumetric voxel-based analysis of grey and white matter densities of structural magnetic resonance imaging (MRI) scans to explore the underlying pattern of structural cerebral change in nondemented ALS patients with verbal fluency deficits. Two groups of ALS patients, defined by the presence or absence of cognitive impairment on the basis of the Written Verbal Fluency Test (ALSi, cognitively impaired, n=11; ALSu, cognitively unimpaired n=12) were compared with healthy age matched controls (n=12). A comparison of the ALSi group with controls revealed significantly (p<0.002) reduced white matter volume in extensive motor and non-motor regions, including regions corresponding to frontotemporal association fibres. These patients demonstrated a corresponding cognitive profile of executive and memory dysfunction. Less extensive white matter reductions were revealed in the comparison of the ALSu and control groups in regions corresponding to frontal association fibres. White matter volumes were also found to correlate with performance on memory tests. There were no significant reductions in grey matter volume in the comparison of either patient group with controls. The structural white matter abnormalities in frontal and temporal regions revealed here may underlie the cognitive and functional imaging abnormalities previously reported in non-demented ALS patients. The results also suggest that extra-motor structural abnormalities may be present in ALS patients with no evidence of cognitive change. The findings support the hypothesis of a continuum of extra

New daily persistent headache: A lack of an association with white matter abnormalities on neuroimaging.

PubMed

Rozen, Todd D

2016-09-01

To provide results from the largest study of new daily persistent headache patients to date and specifically evaluate if patients with primary new daily persistent headache develop white matter abnormalities or infarct-like lesions on neuroimaging. Retrospective analysis of patient medical records utilizing an electronic medical record system. All patients were seen at a headache specialty clinic by a single headache neurologist and diagnosed with primary new daily persistent headache during the time period of January 2009 to January 2013. Altogether, 97 patients were diagnosed with primary new daily persistent headache (65 women and 32 men). The mean average age of onset was slightly younger in women than men: 32.4 years vs. 35.8 years. In total, 84 of the 97 new daily persistent headache patients had no white matter abnormalities or infarct-like lesions on magnetic resonance imaging with a gender distribution of 56 women and 28 men. The mean age of onset of this white matter negative subgroup was 31.1 years. Of these individuals, 36% had cardiovascular/cerebrovascular risk factors and 44% had a history of migraine. Only 13 new daily persistent headache patients (nine women, four men) demonstrated white matter abnormalities on magnetic resonance imaging. None had infarct-like lesions. The mean age of onset of this white matter positive subgroup was 54.2 years, significantly older than the white matter negative population (p < .05). All new daily persistent headache patients in the white matter positive subgroup had cardiovascular/cerebrovascular risk factors and dual risk factors were noted in seven of 13 patients. Only 23% had a migraine history. Almost 40% of the patients in the white matter negative group were imaged 3 years after headache onset and at least six patients were imaged at least 9 years or more after onset of new daily persistent headache. Triggering events in both white matter lesion positive and negative populations were typical of the new

Deep versus periventricular white matter lesions and cognitive function in a community sample of middle-aged participants.

PubMed

Soriano-Raya, Juan José; Miralbell, Júlia; López-Cancio, Elena; Bargalló, Núria; Arenillas, Juan Francisco; Barrios, Maite; Cáceres, Cynthia; Toran, Pere; Alzamora, Maite; Dávalos, Antoni; Mataró, Maria

2012-09-01

The association of cerebral white matter lesions (WMLs) with cognitive status is not well understood in middle-aged individuals. Our aim was to determine the specific contribution of periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs) to cognitive function in a community sample of asymptomatic participants aged 50 to 65 years. One hundred stroke- and dementia-free adults completed a comprehensive neuropsychological battery and brain MRI protocol. Participants were classified according to PVH and DWMH scores (Fazekas scale). We dichotomized our sample into low grade WMLs (participants without or with mild lesions) and high grade WMLs (participants with moderate or severe lesions). Analyses were performed separately in PVH and DWMH groups. High grade DWMHs were associated with significantly lower scores in executive functioning (-0.45 standard deviations [SD]), attention (-0.42 SD), verbal fluency (-0.68 SD), visual memory (-0.52 SD), visuospatial skills (-0.79 SD), and psychomotor speed (-0.46 SD). Further analyses revealed that high grade DWMHs were also associated with a three- to fourfold increased risk of impaired scores (i.e.,<1.5 SD) in executive functioning, verbal fluency, visuospatial skills, and psychomotor speed. Our findings suggest that only DWMHs, not PVHs, are related to diminished cognitive function in middle-aged individuals. (JINS, 2012, 18, 1-12).

Microstructural White Matter Alterations in the Corpus Callosum of Girls With Conduct Disorder.

PubMed

Menks, Willeke Martine; Furger, Reto; Lenz, Claudia; Fehlbaum, Lynn Valérie; Stadler, Christina; Raschle, Nora Maria

2017-03-01

Diffusion tensor imaging (DTI) studies in adolescent conduct disorder (CD) have demonstrated white matter alterations of tracts connecting functionally distinct fronto-limbic regions, but only in boys or mixed-gender samples. So far, no study has investigated white matter integrity in girls with CD on a whole-brain level. Therefore, our aim was to investigate white matter alterations in adolescent girls with CD. We collected high-resolution DTI data from 24 girls with CD and 20 typically developing control girls using a 3T magnetic resonance imaging system. Fractional anisotropy (FA) and mean diffusivity (MD) were analyzed for whole-brain as well as a priori-defined regions of interest, while controlling for age and intelligence, using a voxel-based analysis and an age-appropriate customized template. Whole-brain findings revealed white matter alterations (i.e., increased FA) in girls with CD bilaterally within the body of the corpus callosum, expanding toward the right cingulum and left corona radiata. The FA and MD results in a priori-defined regions of interest were more widespread and included changes in the cingulum, corona radiata, fornix, and uncinate fasciculus. These results were not driven by age, intelligence, or attention-deficit/hyperactivity disorder comorbidity. This report provides the first evidence of white matter alterations in female adolescents with CD as indicated through white matter reductions in callosal tracts. This finding enhances current knowledge about the neuropathological basis of female CD. An increased understanding of gender-specific neuronal characteristics in CD may influence diagnosis, early detection, and successful intervention strategies. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Effects of exercise on capillaries in the white matter of transgenic AD mice

PubMed Central

Zhang, Yi; Chao, Feng-Lei; Zhou, Chun-Ni; Jiang, Lin; Zhang, Lei; Chen, Lin-Mu; Luo, Yan-Min; Xiao, Qian; Tang, Yong

2017-01-01

Previous studies have shown that exercise can prevent white matter atrophy in APP/PS1 transgenic Alzheimer’s disease (AD) mice. However, the mechanism of this protective effect remains unknown. To further understand this issue, we investigated the effects of exercise on the blood supply of white matter in transgenic AD mice. Six-month-old male APP/PS1 mice were randomly divided into a control group and a running group, and age-matched non-transgenic littermates were used as a wild-type control group. Mice in the running group ran on a treadmill at low intensity for four months. Then, spatial learning and memory abilities, white matter and white matter capillaries were examined in all mice. The 10-month-old AD mice exhibited deficits in cognitive function, and 4 months of exercise improved these deficits. The white matter volume and the total length, total volume and total surface area of the white matter capillaries were decreased in the 10-month-old AD mice, and 4 months of exercise dramatically delayed the changes in these parameters in the AD mice. Our results demonstrate that even low-intensity running exercise can improve spatial learning and memory abilities, delay white matter atrophy and protect white matter capillaries in early-stage AD mice. Protecting capillaries might be an important structural basis for the exercise-induced protection of the structural integrity of white matter in AD. PMID:29029478

Some guidelines for structural equation modelling in cognitive neuroscience: the case of Charlton et al.'s study on white matter integrity and cognitive ageing.

PubMed

Penke, Lars; Deary, Ian J

2010-09-01

Charlton et al. (2008) (Charlton, R.A., Landua, S., Schiavone, F., Barrick, T.R., Clark, C.A., Markus, H.S., Morris, R.G.A., 2008. Structural equation modelling investigation of age-related variance in executive function and DTI-measured white matter change. Neurobiol. Aging 29, 1547-1555) presented a model that suggests a specific age-related effect of white matter integrity on working memory. We illustrate potential pitfalls of structural equation modelling by criticizing their model for (a) its neglect of latent variables, (b) its complexity, (c) its questionable causal assumptions, (d) the use of empirical model reduction, (e) the mix-up of theoretical perspectives, and (f) the failure to compare alternative models. We show that a more parsimonious model, based solely on the well-established general factor of cognitive ability, fits their data at least as well. Importantly, when modelled this way there is no support for a role of white matter integrity in cognitive aging in this sample, indicating that their conclusion is strongly dependent on how the data are analysed. We suggest that evidence from more conclusive study designs is needed. Copyright 2009 Elsevier Inc. All rights reserved.

White Matter Integrity Reductions in Intermittent Explosive Disorder

PubMed Central

Lee, Royce; Arfanakis, Konstantinos; Evia, Arnold M; Fanning, Jennifer; Keedy, Sarah; Coccaro, Emil F

2016-01-01

Intermittent explosive disorder (IED), as described in DSM-5, is the categorical expression of pathological impulsive aggression. Previous work has identified neurobiological correlates of the disorder in patterns of frontal-limbic brain activity and dysregulation of serotonergic neurotransmission. Given the importance of short- and-long range white matter connections of the brain in social and emotional behavior, studies of white matter connectivity in impulsive aggression are warranted. Diffusion tensor imaging (DTI) studies in the related conditions of antisocial and borderline personality disorder have produced preliminary evidence of disturbed white matter connectivity in these disorders, but to date there have been no DTI studies in IED. A total of 132 male and female adults between the ages of 18 and 55 years underwent Turboprop-DTI on a 3-Tesla MRI scanner. Of these, 42 subjects had IED, 40 were normal controls, and 50 were clinical psychiatric controls with psychiatric disorders without IED. All subjects were free of alcohol, psychotropic medications, or drugs of abuse. The diffusion tensor was calculated in each voxel and maps of fractional anisotropy (FA) were generated. Tract-based spatial statistics (TBSS) were used to compare FA along the white matter skeleton among the three subject groups. IED was associated with lower FA in two clusters located in the superior longitudinal fasciculus (SLF) when compared with the psychiatric and healthy controls. Impulsive aggression and borderline personality disorder, but not psychopathy or antisocial personality disorder, was associated with lower FA in the two clusters within the SLF. In conclusion, IED was associated with lower white matter integrity in long-range connections between the frontal and temporoparietal regions. PMID:27206265

White Matter Integrity Reductions in Intermittent Explosive Disorder.

PubMed

Lee, Royce; Arfanakis, Konstantinos; Evia, Arnold M; Fanning, Jennifer; Keedy, Sarah; Coccaro, Emil F

2016-10-01

Intermittent explosive disorder (IED), as described in DSM-5, is the categorical expression of pathological impulsive aggression. Previous work has identified neurobiological correlates of the disorder in patterns of frontal-limbic brain activity and dysregulation of serotonergic neurotransmission. Given the importance of short- and-long range white matter connections of the brain in social and emotional behavior, studies of white matter connectivity in impulsive aggression are warranted. Diffusion tensor imaging (DTI) studies in the related conditions of antisocial and borderline personality disorder have produced preliminary evidence of disturbed white matter connectivity in these disorders, but to date there have been no DTI studies in IED. A total of 132 male and female adults between the ages of 18 and 55 years underwent Turboprop-DTI on a 3-Tesla MRI scanner. Of these, 42 subjects had IED, 40 were normal controls, and 50 were clinical psychiatric controls with psychiatric disorders without IED. All subjects were free of alcohol, psychotropic medications, or drugs of abuse. The diffusion tensor was calculated in each voxel and maps of fractional anisotropy (FA) were generated. Tract-based spatial statistics (TBSS) were used to compare FA along the white matter skeleton among the three subject groups. IED was associated with lower FA in two clusters located in the superior longitudinal fasciculus (SLF) when compared with the psychiatric and healthy controls. Impulsive aggression and borderline personality disorder, but not psychopathy or antisocial personality disorder, was associated with lower FA in the two clusters within the SLF. In conclusion, IED was associated with lower white matter integrity in long-range connections between the frontal and temporoparietal regions.

White matter alterations in narcolepsy patients with cataplexy: tract-based spatial statistics.

PubMed

Park, Yun K; Kwon, Oh-Hun; Joo, Eun Yeon; Kim, Jae-Hun; Lee, Jong M; Kim, Sung T; Hong, Seung B

2016-04-01

Functional imaging studies and voxel-based morphometry analysis of brain magnetic resonance imaging showed abnormalities in the hypothalamus-thalamus-orbitofrontal pathway, demonstrating altered hypocretin pathway in narcolepsy. Those distinct morphometric changes account for problems in wake-sleep control, attention and memory. It also raised the necessity to evaluate white matter changes. To investigate brain white matter alterations in drug-naïve narcolepsy patients with cataplexy and to explore relationships between white matter changes and patient clinical characteristics, drug-naïve narcolepsy patients with cataplexy (n = 22) and healthy age- and gender-matched controls (n = 26) were studied. Fractional anisotropy and mean diffusivity images were obtained from whole-brain diffusion tensor imaging, and tract-based spatial statistics were used to localize white matter abnormalities. Compared with controls, patients showed significant decreases in fractional anisotropy of white matter of the bilateral anterior cingulate, fronto-orbital area, frontal lobe, anterior limb of the internal capsule and corpus callosum, as well as the left anterior and medial thalamus. Patients and controls showed no differences in mean diffusivity. Among patients, mean diffusivity values of white matter in the bilateral superior frontal gyri, bilateral fronto-orbital gyri and right superior parietal gyrus were positively correlated with depressive mood. This tract-based spatial statistics study demonstrated that drug-naïve patients with narcolepsy had reduced fractional anisotropy of white matter in multiple brain areas and significant relationship between increased mean diffusivity of white matter in frontal/cingulate and depression. It suggests the widespread disruption of white matter integrity and prevalent brain degeneration of frontal lobes according to a depressive symptom in narcolepsy. © 2015 European Sleep Research Society.

White Matter Integrity and Pictorial Reasoning in High-Functioning Children with Autism

PubMed Central

Sahyoun, Chérif P.; Belliveau, John W.; Mody, Maria

2010-01-01

The current study investigated the neurobiological role of white matter in visuospatial versus linguistic processing abilities in autism using diffusion tensor imaging. We examined differences in white matter integrity between high-functioning children with autism (HFA) and typically developing controls (CTRL), in relation to the groups’ response times (RT) on a pictorial reasoning task under three conditions: visuospatial, V, semantic, S, and V+S, a hybrid condition allowing language use to facilitate visuospatial transformations. Diffusion-weighted images were collected from HFA and CTRL participants, matched on age and IQ, and significance maps were computed for group differences in fractional anisotropy (FA) and in RT-FA association for each condition. Typically developing children showed increased FA within frontal white matter and the superior longitudinal fasciculus (SLF). HFA showed increased FA within peripheral white matter, including the ventral temporal lobe. Additionally, RT-FA relationships in the semantic condition (S) implicated white matter near the STG and in the SLF within the temporal and frontal lobes to a greater extent in CTRL. Performance in visuospatial reasoning (V, V+S), in comparison, was related to peripheral parietal and superior precentral white matter in HFA, but to the SLF, callosal, and frontal white matter in CTRL. Our results appear to support a preferential use of linguistically-mediated pathways in reasoning by typically-developing children, whereas autistic cognition may rely more on visuospatial processing networks. PMID:20542370

Are APOE ɛ genotype and TOMM40 poly-T repeat length associations with cognitive ageing mediated by brain white matter tract integrity?

PubMed

Lyall, D M; Harris, S E; Bastin, M E; Muñoz Maniega, S; Murray, C; Lutz, M W; Saunders, A M; Roses, A D; Valdés Hernández, M del C; Royle, N A; Starr, J M; Porteous, D J; Wardlaw, J M; Deary, I J

2014-09-23

Genetic polymorphisms in the APOE ɛ and TOMM40 '523' poly-T repeat gene loci have been associated with significantly increased risk of Alzheimer's disease. This study investigated the independent effects of these polymorphisms on human cognitive ageing, and the extent to which nominally significant associations with cognitive ageing were mediated by previously reported genetic associations with brain white matter tract integrity in this sample. Most participants in the Lothian Birth Cohort 1936 completed a reasoning-type intelligence test at age 11 years, and detailed cognitive/physical assessments and structural diffusion tensor brain magnetic resonance imaging at a mean age of 72.70 years (s.d.=0.74). Participants were genotyped for APOE ɛ2/ɛ3/ɛ4 status and TOMM40 523 poly-T repeat length. Data were available from 758-814 subjects for cognitive analysis, and 522-543 for mediation analysis with brain imaging data. APOE genotype was significantly associated with performance on several different tests of cognitive ability, including general factors of intelligence, information processing speed and memory (raw P-values all<0.05), independently of childhood IQ and vascular disease history. Formal tests of mediation showed that several significant APOE-cognitive ageing associations--particularly those related to tests of information processing speed--were partially mediated by white matter tract integrity. TOMM40 523 genotype was not associated with cognitive ageing. A range of brain phenotypes are likely to form the anatomical basis for significant associations between APOE genotype and cognitive ageing, including white matter tract microstructural integrity.

Are APOE ɛ genotype and TOMM40 poly-T repeat length associations with cognitive ageing mediated by brain white matter tract integrity?

PubMed Central

Lyall, D M; Harris, S E; Bastin, M E; Muñoz Maniega, S; Murray, C; Lutz, M W; Saunders, A M; Roses, A D; Valdés Hernández, M del C; Royle, N A; Starr, J M; Porteous, D J; Wardlaw, J M; Deary, I J

2014-01-01

Genetic polymorphisms in the APOE ɛ and TOMM40 ‘523' poly-T repeat gene loci have been associated with significantly increased risk of Alzheimer's disease. This study investigated the independent effects of these polymorphisms on human cognitive ageing, and the extent to which nominally significant associations with cognitive ageing were mediated by previously reported genetic associations with brain white matter tract integrity in this sample. Most participants in the Lothian Birth Cohort 1936 completed a reasoning-type intelligence test at age 11 years, and detailed cognitive/physical assessments and structural diffusion tensor brain magnetic resonance imaging at a mean age of 72.70 years (s.d.=0.74). Participants were genotyped for APOE ɛ2/ɛ3/ɛ4 status and TOMM40 523 poly-T repeat length. Data were available from 758–814 subjects for cognitive analysis, and 522–543 for mediation analysis with brain imaging data. APOE genotype was significantly associated with performance on several different tests of cognitive ability, including general factors of intelligence, information processing speed and memory (raw P-values all<0.05), independently of childhood IQ and vascular disease history. Formal tests of mediation showed that several significant APOE-cognitive ageing associations—particularly those related to tests of information processing speed—were partially mediated by white matter tract integrity. TOMM40 523 genotype was not associated with cognitive ageing. A range of brain phenotypes are likely to form the anatomical basis for significant associations between APOE genotype and cognitive ageing, including white matter tract microstructural integrity. PMID:25247594

Biofidelic white matter heterogeneity decreases computational model predictions of white matter strains during rapid head rotations.

PubMed

Maltese, Matthew R; Margulies, Susan S

2016-11-01

The finite element (FE) brain model is used increasingly as a design tool for developing technology to mitigate traumatic brain injury. We developed an ultra high-definition FE brain model (>4 million elements) from CT and MRI scans of a 2-month-old pre-adolescent piglet brain, and simulated rapid head rotations. Strain distributions in the thalamus, coronal radiata, corpus callosum, cerebral cortex gray matter, brainstem and cerebellum were evaluated to determine the influence of employing homogeneous brain moduli, or distinct experimentally derived gray and white matter property representations, where some white matter regions are stiffer and others less stiff than gray matter. We find that constitutive heterogeneity significantly lowers white matter deformations in all regions compared with homogeneous properties, and should be incorporated in FE model injury prediction.

White-matter microstructure and hearing acuity in older adults: a population-based cross-sectional DTI study.

PubMed

Rigters, Stephanie C; Cremers, Lotte G M; Ikram, M Arfan; van der Schroeff, Marc P; de Groot, Marius; Roshchupkin, Gennady V; Niessen, Wiro J N; Baatenburg de Jong, Robert J; Goedegebure, André; Vernooij, Meike W

2018-01-01

To study the relation between the microstructure of white matter in the brain and hearing function in older adults we carried out a population-based, cross-sectional study. In 2562 participants of the Rotterdam Study, we conducted diffusion tensor imaging to determine the microstructure of the white-matter tracts. We performed pure-tone audiogram and digit-in-noise tests to quantify hearing acuity. Poorer white-matter microstructure, especially in the association tracts, was related to poorer hearing acuity. After differentiating the separate white-matter tracts in the left and right hemisphere, poorer white-matter microstructure in the right superior longitudinal fasciculus and the right uncinate fasciculus remained significantly associated with worse hearing. These associations did not significantly differ between middle-aged (51-69 years old) and older (70-100 years old) participants. Progressing age was thus not found to be an effect modifier. In a voxel-based analysis no voxels in the white matter were significantly associated with hearing impairment. Copyright © 2017 Elsevier Inc. All rights reserved.

Adolescent engagement in dangerous behaviors is associated with increased white matter maturity of frontal cortex.

PubMed

Berns, Gregory S; Moore, Sara; Capra, C Monica

2009-08-26

Myelination of white matter in the brain continues throughout adolescence and early adulthood. This cortical immaturity has been suggested as a potential cause of dangerous and impulsive behaviors in adolescence. We tested this hypothesis in a group of healthy adolescents, age 12-18 (N = 91), who underwent diffusion tensor imaging (DTI) to delineate cortical white matter tracts. As a measure of real-world risk taking, participants completed the Adolescent Risk Questionnaire (ARQ) which measures engagement in dangerous activities. After adjusting for age-related changes in both DTI and ARQ, engagement in dangerous behaviors was found to be positively correlated with fractional anisotropy and negatively correlated with transverse diffusivity in frontal white matter tracts, indicative of increased myelination and/or density of fibers (ages 14-18, N = 60). The direction of correlation suggests that rather than having immature cortices, adolescents who engage in dangerous activities have frontal white matter tracts that are more adult in form than their more conservative peers.

Impaired language abilities and white matter abnormalities in children born very preterm and/or very low birth weight

PubMed Central

Reidy, Natalie; Morgan, Angela; Thompson, Deanne K; Inder, Terrie E.; Doyle, Lex W; Anderson, Peter J

2012-01-01

Objectives To investigate language abilities in children born very preterm (VPT; <32 weeks’ gestational age (GA)) or very low birth weight (VLBW; <1500 g) at 7 years of age and compare their performances with children born at term, and to determine whether group differences could be explained by cerebral white matter abnormality on neonatal MRI. Study design A cohort of 198 children born <30 weeks’ GA and/or <1250 g, and 70 term controls were examined. White matter abnormalities were rated quantitatively on brain MRI at term-equivalent age. Language was assessed at age 7 years using standardized language tests. Differences between groups were tested in the five language sub-domains of phonological awareness, semantics, grammar, discourse, and pragmatics. A mediation effect was tested between birth group, white matter abnormality, and language sub-domains. Results The VPT/VLBW group performed significantly worse than controls on all language sub-domains (all p <.001). White matter abnormality mediated the effect of group differences on phonological awareness, and partly mediated this effect for semantics, grammar and discourse. White matter abnormality was not significantly associated with pragmatics (p = .13). Conclusions Language is an important area of concern in children born VPT/VLBW. Neonatal white matter abnormality is an important predictor of outcome; however, different language abilities are differentially associated with neonatal white matter abnormality. PMID:23158026

White matter maturation profiles through early childhood predict general cognitive ability.

PubMed

Deoni, Sean C L; O'Muircheartaigh, Jonathan; Elison, Jed T; Walker, Lindsay; Doernberg, Ellen; Waskiewicz, Nicole; Dirks, Holly; Piryatinsky, Irene; Dean, Doug C; Jumbe, N L

2016-03-01

Infancy and early childhood are periods of rapid brain development, during which brain structure and function mature alongside evolving cognitive ability. An important neurodevelopmental process during this postnatal period is the maturation of the myelinated white matter, which facilitates rapid communication across neural systems and networks. Though prior brain imaging studies in children (4 years of age and above), adolescents, and adults have consistently linked white matter development with cognitive maturation and intelligence, few studies have examined how these processes are related throughout early development (birth to 4 years of age). Here, we show that the profile of white matter myelination across the first 5 years of life is strongly and specifically related to cognitive ability. Using a longitudinal design, coupled with advanced magnetic resonance imaging, we demonstrate that children with above-average ability show differential trajectories of myelin development compared to average and below average ability children, even when controlling for socioeconomic status, gestation, and birth weight. Specifically, higher ability children exhibit slower but more prolonged early development, resulting in overall increased myelin measures by ~3 years of age. These results provide new insight into the early neuroanatomical correlates of cognitive ability, and suggest an early period of prolonged maturation with associated protracted white matter plasticity may result in strengthened neural networks that can better support later development. Further, these results reinforce the necessity of a longitudinal perspective in investigating typical or suspected atypical cognitive maturation.

Effects of white matter lesions on brain perfusion in patients with mild cognitive impairment.

PubMed

Ishibashi, Masato; Kimura, Noriyuki; Aso, Yasuhiro; Matsubara, Etsuro

2018-05-01

To evaluate the effects of white matter lesions on regional cerebral blood flow in subjects with amnestic mild cognitive impairment. Seventy-five subjects with mild cognitive impairment (36 men and 39 women; mean age, 78.1 years) were included in the study. We used the Mini-Mental State Examination to assess cognitive function. All subjects underwent brain magnetic resonance imaging and 99m Tc ethylcysteinate dimer single photon emission computed tomography. Subjects were stratified based on the presence or absence of white matter lesions on magnetic resonance imaging. Statistical parametric mapping of differences in regional cerebral blood flow between the two groups were assessed by voxel-by-voxel group analysis using SPM8. Of all 75 subjects with mild cognitive impairment, 46 (61.3%) had mild to moderate white matter lesions. The prevalence of hypertension tended to be higher in subjects with white matter lesions than in those without white matter lesions. Mini-Mental State Examination scores were significantly lower in subjects with white matter lesions than in those without white matter lesions. Subjects with white matter lesions had decreased regional cerebral blood flow mainly in the frontal, parietal, and medial temporal lobes, as well as the putamen, compared to those without white matter lesions. In subjects with mild cognitive impairment, white matter lesions were associated with cognitive impairment and mainly frontal lobe brain function. Copyright © 2018 Elsevier B.V. All rights reserved.

Quantitative susceptibility mapping as a biomarker for evaluating white matter alterations in Parkinson's disease.

PubMed

Guan, Xiaojun; Huang, Peiyu; Zeng, Qiaoling; Liu, Chunlei; Wei, Hongjiang; Xuan, Min; Gu, Quanquan; Xu, Xiaojun; Wang, Nian; Yu, Xinfeng; Luo, Xiao; Zhang, Minming

2018-02-07

Myelinated white matter showing diamagnetic susceptibility is important for information transfer in the brain. In Parkinson's disease (PD), the white matter is also suffering degenerative alterations. Quantitative susceptibility mapping (QSM) is a novel technique for noninvasive assessment of regional white matter ultrastructure, and provides different information of white matter in addition to standard diffusion tensor imaging (DTI). In this study, we used QSM to detect spatial white matter alterations in PD patients (n = 65) and age- and sex-matched normal controls (n = 46). Voxel-wise tract-based spatial statistics were performed to analyze QSM and DTI data. QSM showed extensive white matter involvement-including regions adjacent to the frontal, parietal, and temporal lobes-in PD patients, which was more widespread than that observed using DTI. Both QSM and DTI showed similar alterations in the left inferior longitudinal fasciculus and right cerebellar hemisphere. Further, alterations in the white matter were correlated with motor impairment and global disease severity in PD patients. We suggest that QSM may provide a novel approach for detecting white matter alterations and underlying network disruptions in PD. Further, the combination of QSM and DTI would provide a more complete evaluation of the diseased brain by analyzing different biological tissue properties.

Experience-dependent plasticity in white matter microstructure: reasoning training alters structural connectivity

PubMed Central

Mackey, Allyson P.; Whitaker, Kirstie J.; Bunge, Silvia A.

2012-01-01

Diffusion tensor imaging (DTI) techniques have made it possible to investigate white matter plasticity in humans. Changes in DTI measures, principally increases in fractional anisotropy (FA), have been observed following training programs as diverse as juggling, meditation, and working memory. Here, we sought to test whether three months of reasoning training could alter white matter microstructure. We recruited participants (n = 23) who were enrolled in a course to prepare for the Law School Admission Test (LSAT), a test that places strong demands on reasoning skills, as well as age- and IQ-matched controls planning to take the LSAT in the future (n = 22). DTI data were collected at two scan sessions scheduled three months apart. In trained participants but not controls, we observed decreases in radial diffusivity (RD) in white matter connecting frontal cortices, and in mean diffusivity (MD) within frontal and parietal lobe white matter. Further, participants exhibiting larger gains on the LSAT exhibited greater decreases in MD in the right internal capsule. In summary, reasoning training altered multiple measures of white matter structure in young adults. While the cellular underpinnings are unknown, these results provide evidence of experience-dependent white matter changes that may not be limited to myelination. PMID:22936899

DTI-measured white matter abnormalities in adolescents with Conduct Disorder

PubMed Central

Haney-Caron, Emily; Caprihan, Arvind; Stevens, Michael C.

2013-01-01

Emerging research suggests that antisocial behavior in youth is linked to abnormal brain white matter microstructure, but the extent of such anatomical connectivity abnormalities remain largely untested because previous Conduct Disorder (CD) studies typically have selectively focused on specific frontotemporal tracts. This study aimed to replicate and extend previous frontotemporal diffusion tensor imaging (DTI) findings to determine whether noncomorbid CD adolescents have white matter microstructural abnormalities in major white matter tracts across the whole brain. Seventeen CD-diagnosed adolescents recruited from the community were compared to a group of 24 non-CD youth which did not differ in average age (12–18) or gender proportion. Tract-based spatial statistics (TBSS) fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) measurements were compared between groups using FSL nonparametric two-sample t test, clusterwise whole-brain corrected, p<.05. CD FA and AD deficits were widespread, but unrelated to gender, verbal ability, or CD age of onset. CD adolescents had significantly lower FA and AD values in frontal lobe and temporal lobe regions, including frontal lobe anterior/superior corona radiata, and inferior longitudinal and fronto-occpital fasciculi passing through the temporal lobe. The magnitude of several CD FA deficits was associated with number of CD symptoms. Because AD, but not RD, differed between study groups, abnormalities of axonal microstructure in CD rather than myelination are suggested. This study provides evidence that adolescent antisocial disorder is linked to abnormal white matter microstructure in more than just the uncinate fasciulcus as identified in previous DTI studies, or frontotemporal brain structures as suggested by functional neuroimaging studies. Instead, neurobiological risk specific to antisociality in adolescence is linked to microstructural abnormality in numerous long-range white matter

Development of the Cell Population in the Brain White Matter of Young Children.

PubMed

Sigaard, Rasmus Krarup; Kjær, Majken; Pakkenberg, Bente

2016-01-01

While brain gray matter is primarily associated with sensorimotor processing and cognition, white matter modulates the distribution of action potentials, coordinates communication between different brain regions, and acts as a relay for input/output signals. Previous studies have described morphological changes in gray and white matter during childhood and adolescence, which are consistent with cellular genesis and maturation, but corresponding events in infants are poorly documented. In the present study, we estimated the total number of cells (neurons, oligodendrocytes, astrocytes, and microglia) in the cerebral white matter of 9 infants aged 0-33 months, using design-based stereological methods to obtain quantitative data about brain development. There were linear increases with age in the numbers of oligodendrocytes (7-28 billion) and astrocytes (1.5-6.7 billion) during the first 3 years of life, thus attaining two-thirds of the corresponding numbers in adults. The numbers of neurons (0.7 billion) and microglia (0.2 billion) in the white matter did not increase during the first 3 years of life, but showed large biological variation. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Multifractal analysis of white matter structural changes on 3D magnetic resonance imaging between normal aging and early Alzheimer’s disease

NASA Astrophysics Data System (ADS)

Ni, Huang-Jing; Zhou, Lu-Ping; Zeng, Peng; Huang, Xiao-Lin; Liu, Hong-Xing; Ning, Xin-Bao

2015-07-01

Applications of multifractal analysis to white matter structure changes on magnetic resonance imaging (MRI) have recently received increasing attentions. Although some progresses have been made, there is no evident study on applying multifractal analysis to evaluate the white matter structural changes on MRI for Alzheimer’s disease (AD) research. In this paper, to explore multifractal analysis of white matter structural changes on 3D MRI volumes between normal aging and early AD, we not only extend the traditional box-counting multifractal analysis (BCMA) into the 3D case, but also propose a modified integer ratio based BCMA (IRBCMA) algorithm to compensate for the rigid division rule in BCMA. We verify multifractal characteristics in 3D white matter MRI volumes. In addition to the previously well studied multifractal feature, Δα, we also demonstrated Δf as an alternative and effective multifractal feature to distinguish NC from AD subjects. Both Δα and Δf are found to have strong positive correlation with the clinical MMSE scores with statistical significance. Moreover, the proposed IRBCMA can be an alternative and more accurate algorithm for 3D volume analysis. Our findings highlight the potential usefulness of multifractal analysis, which may contribute to clarify some aspects of the etiology of AD through detection of structural changes in white matter. Project supported by the National Natural Science Foundation of China (Grant No. 61271079), the Vice Chancellor Research Grant in University of Wollongong, and the Priority Academic Program Development of Jiangsu Higher Education Institutions, China.

Associations Between White Matter Microstructure and Infants’ Working Memory

PubMed Central

Short, Sarah J.; Elison, Jed T.; Goldman, Barbara Davis; Styner, Martin; Gu, Hongbin; Connelly, Mark; Maltbie, Eric; Woolson, Sandra; Lin, Weili; Gerig, Guido; Reznick, J. Steven; Gilmore, John H.

2013-01-01

Working memory emerges in infancy and plays a privileged role in subsequent adaptive cognitive development. The neural networks important for the development of working memory during infancy remain unknown. We used diffusion tensor imaging (DTI) and deterministic fiber tracking to characterize the microstructure of white matter fiber bundles hypothesized to support working memory in 12-month-old infants (n=73). Here we show robust associations between infants’ visuospatial working memory performance and microstructural characteristics of widespread white matter. Significant associations were found for white matter tracts that connect brain regions known to support working memory in older children and adults (genu, anterior and superior thalamic radiations, anterior cingulum, arcuate fasciculus, and the temporal-parietal segment). Better working memory scores were associated with higher FA and lower RD values in these selected white matter tracts. These tract-specific brain-behavior relationships accounted for a significant amount of individual variation above and beyond infants’ gestational age and developmental level, as measured with the Mullen Scales of Early Learning. Working memory was not associated with global measures of brain volume, as expected, and few associations were found between working memory and control white matter tracts. To our knowledge, this study is among the first demonstrations of brain-behavior associations in infants using quantitative tractography. The ability to characterize subtle individual differences in infant brain development associated with complex cognitive functions holds promise for improving our understanding of normative development, biomarkers of risk, experience-dependent learning and neuro-cognitive periods of developmental plasticity. PMID:22989623

Decreased frontal white-matter volume in chronic substance abuse.

PubMed

Schlaepfer, Thomas E; Lancaster, Eric; Heidbreder, Rebecca; Strain, Eric C; Kosel, Markus; Fisch, Hans-Ulrich; Pearlson, Godfrey D

2006-04-01

There is quite a body of work assessing functional brain changes in chronic substance abuse, much less is known about structural brain abnormalities in this patient population. In this study we used magnetic resonance imaging (MRI) to determine if structural brain differences exist in patients abusing illicit drugs compared to healthy controls. Sixteen substance abusers who abused heroin, cocaine and cannabis but not alcohol and 16 age-, sex- and race-matched controls were imaged on a MRI scanner. Contiguous, 5-mm-thick axial slices were acquired with simultaneous T2 and proton density sequences. Volumes were estimated for total grey and white matter, frontal grey and white matter, ventricles, and CSF using two different methods: a conventional segmentation and a stereological method based on the Cavalieri principle. Overall brain volume differences were corrected for by expressing the volumes of interest as a percentage of total brain volume. Volume measures obtained with the two methods were highly correlated (r=0.65, p<0.001). Substance abusers had significantly less frontal white-matter volume percentage than controls. There were no significant differences in any of the other brain volumes measured. This difference in frontal lobe white matter might be explained by a direct neurotoxic effect of drug use on white matter, a pre-existing abnormality in the development of the frontal lobe or a combination of both effects. This last explanation might be compelling based on the fact that newer concepts on shared aspects of some neuropsychiatric disorders focus on the promotion and inhibition of the process of myelination throughout brain development and subsequent degeneration.

Spaceflight Effect on White Matter Structural Integrity

NASA Technical Reports Server (NTRS)

Lee, Jessica K.; Kopplemans, Vincent; Paternack, Ofer; Bloomberg, Jacob J.; Mulavara, Ajitkumar P.; Seidler, Rachael D.

2017-01-01

Recent reports of elevated brain white matter hyperintensity (WMH) counts and volume in postflight astronaut MRIs suggest that further examination of spaceflight's impact on the microstructure of brain white matter is warranted. To this end, retrospective longitudinal diffusion-weighted MRI scans obtained from 15 astronauts were evaluated. In light of the recent reports of microgravity-induced cephalad fluid shift and gray matter atrophy seen in astronauts, we applied a technique to estimate diffusion tensor imaging (DTI) metrics corrected for free water contamination. This approach enabled the analysis of white matter tissue-specific alterations that are unrelated to fluid shifts, occurring from before spaceflight to after landing. After spaceflight, decreased fractional anisotropy (FA) values were detected in an area encompassing the superior and inferior longitudinal fasciculi and the inferior fronto-occipital fasciculus. Increased radial diffusivity (RD) and decreased axial diffusivity (AD) were also detected within overlapping regions. In addition, FA values in the corticospinal tract decreased and RD measures in the precentral gyrus white matter increased from before to after flight. The results show disrupted structural connectivity of white matter in tracts involved in visuospatial processing, vestibular function, and movement control as a result of spaceflight. The findings may help us understand the structural underpinnings of the extensive spaceflight-induced sensorimotor remodeling. Prospective longitudinal assessment of the white matter integrity in astronauts is needed to characterize the evolution of white matter microstructural changes associated with spaceflight, their behavioral consequences, and the time course of recovery. Supported by a grant from the National Space Biomedical Research Institute, NASA NCC 9-58.

DTI and VBM reveal white matter changes without associated gray matter changes in patients with idiopathic restless legs syndrome

PubMed Central

Belke, Marcus; Heverhagen, Johannes T; Keil, Boris; Rosenow, Felix; Oertel, Wolfgang H; Stiasny-Kolster, Karin; Knake, Susanne; Menzler, Katja

2015-01-01

Background and Purpose We evaluated cerebral white and gray matter changes in patients with iRLS in order to shed light on the pathophysiology of this disease. Methods Twelve patients with iRLS were compared to 12 age- and sex-matched controls using whole-head diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) techniques. Evaluation of the DTI scans included the voxelwise analysis of the fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). Results Diffusion tensor imaging revealed areas of altered FA in subcortical white matter bilaterally, mainly in temporal regions as well as in the right internal capsule, the pons, and the right cerebellum. These changes overlapped with changes in RD. Voxel-based morphometry did not reveal any gray matter alterations. Conclusions We showed altered diffusion properties in several white matter regions in patients with iRLS. White matter changes could mainly be attributed to changes in RD, a parameter thought to reflect altered myelination. Areas with altered white matter microstructure included areas in the internal capsule which include the corticospinal tract to the lower limbs, thereby supporting studies that suggest changes in sensorimotor pathways associated with RLS. PMID:26442748

White matter hyperintensities of presumed vascular origin: a population-based study in rural Ecuador (The Atahualpa Project).

PubMed

Del Brutto, Oscar H; Mera, Robertino M; Del Brutto, Victor J; Zambrano, Mauricio; Lama, Julio

2015-04-01

Cerebral small vessel disease is probably one of the most common pathogenetic mechanisms underlying stroke in Latin America. However, the importance of silent markers of small vessel disease, including white matter hyperintensities of presumed vascular origin, has not been assessed so far. The study aims to evaluate prevalence and correlates of white matter hyperintensities in community-dwelling elders living in Atahualpa (rural Ecuador). Atahualpa residents aged ≥ 60 years were identified during a door-to-door survey and invited to undergo brain magnetic resonance imaging for identification and grading white matter hyperintensities and other markers of small vessel disease. Using multivariate logistic regression models, we evaluated whether white matter hyperintensities is associated with demographics, cardiovascular health status, stroke, cerebral microbleeds, and cortical atrophy, after adjusting for the other variables. Out of 258 enrolled persons (mean age, 70 ± 8 years; 59% women), 172 (67%) had white matter hyperintensities, which were moderate to severe in 63. Analyses showed significant associations of white matter hyperintensities presence and severity with age and cardiovascular health status, as well as with overt and silent strokes, and a trend for association with cerebral microbleeds and cortical atrophy. Prevalence and correlates of white matter hyperintensities in elders living in rural Ecuador is almost comparable with that reported from industrialized nations, reinforcing the concept that the burden of small vessel disease is on the rise in underserved Latin American populations. © 2014 World Stroke Organization.

White Matter Injury and Recovery after Hypertensive Intracerebral Hemorrhage

PubMed Central

Zuo, Shilun; Pan, Pengyu; Li, Qiang

2017-01-01

Hypertensive intracerebral hemorrhage (ICH) could very probably trigger white matter injury in patients. Through the continuous study of white matter injury after hypertensive ICH, we achieve a more profound understanding of the pathophysiological mechanism of its occurrence and development. At the same time, we found a series of drugs and treatment methods for the white matter repair. In the current reality, the research paradigm of white matter injury after hypertensive ICH is relatively obsolete or incomplete, and there are still lots of deficiencies in the research. In the face of the profound changes of stroke research perspective, we believe that the combination of the lenticulostriate artery, nerve nuclei of the hypothalamus-thalamus-basal ganglia, and the white matter fibers located within the capsula interna will be beneficial to the research of white matter injury and repair. This paper has classified and analyzed the study of white matter injury and repair after hypertensive ICH and also rethought the shortcomings of the current research. We hope that it could help researchers further explore and study white matter injury and repair after hypertensive ICH. PMID:28680884

Characteristics of early MRI in children and adolescents with vanishing white matter.

PubMed

van der Lei, Hannemieke D; Steenweg, Marjan E; Barkhof, Frederik; de Grauw, Ton; d'Hooghe, Marc; Morton, Richard; Shah, Siddharth; Wolf, Nicole; van der Knaap, Marjo S

2012-02-01

MRI in vanishing white matter typically shows diffuse abnormality of the cerebral white matter, which becomes increasingly rarefied and cystic. We investigated the MRI characteristics preceding this stage. In a retrospective observational study, we evaluated all available MRIs in our database of DNA-confirmed VWM patients and selected MRIs without diffuse cerebral white matter abnormalities and without signs of rarefaction or cystic degeneration in patients below 20 years of age. A previously established scoring list was used to evaluate the MRIs. An MRI of seven patients fulfilled the criteria. All had confluent and symmetrical abnormalities in the periventricular and bordering deep white matter. In young patients, myelination was delayed. The inner rim of the corpus callosum was affected in all patients. In early stages of VWM, MRI does not necessarily display diffuse cerebral white matter involvement and rarefaction or cystic degeneration. If the MRI abnormalities do not meet the criteria for VWM, it helps to look at the corpus callosum. If the inner rim (the callosal-septal interface) is affected, VWM should be considered. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A probabilistic atlas of the cerebellar white matter.

PubMed

van Baarsen, K M; Kleinnijenhuis, M; Jbabdi, S; Sotiropoulos, S N; Grotenhuis, J A; van Cappellen van Walsum, A M

2016-01-01

Imaging of the cerebellar cortex, deep cerebellar nuclei and their connectivity are gaining attraction, due to the important role the cerebellum plays in cognition and motor control. Atlases of the cerebellar cortex and nuclei are used to locate regions of interest in clinical and neuroscience studies. However, the white matter that connects these relay stations is of at least similar functional importance. Damage to these cerebellar white matter tracts may lead to serious language, cognitive and emotional disturbances, although the pathophysiological mechanism behind it is still debated. Differences in white matter integrity between patients and controls might shed light on structure-function correlations. A probabilistic parcellation atlas of the cerebellar white matter would help these studies by facilitating automatic segmentation of the cerebellar peduncles, the localization of lesions and the comparison of white matter integrity between patients and controls. In this work a digital three-dimensional probabilistic atlas of the cerebellar white matter is presented, based on high quality 3T, 1.25mm resolution diffusion MRI data from 90 subjects participating in the Human Connectome Project. The white matter tracts were estimated using probabilistic tractography. Results over 90 subjects were symmetrical and trajectories of superior, middle and inferior cerebellar peduncles resembled the anatomy as known from anatomical studies. This atlas will contribute to a better understanding of cerebellar white matter architecture. It may eventually aid in defining structure-function correlations in patients with cerebellar disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

White matter disease in midlife is heritable, related to hypertension, and shares some genetic influence with systolic blood pressure.

PubMed

Fennema-Notestine, Christine; McEvoy, Linda K; Notestine, Randy; Panizzon, Matthew S; Yau, Wai-Ying Wendy; Franz, Carol E; Lyons, Michael J; Eyler, Lisa T; Neale, Michael C; Xian, Hong; McKenzie, Ruth E; Kremen, William S

2016-01-01

White matter disease in the brain increases with age and cardiovascular disease, emerging in midlife, and these associations may be influenced by both genetic and environmental factors. We examined the frequency, distribution, and heritability of abnormal white matter and its association with hypertension in 395 middle-aged male twins (61.9 ± 2.6 years) from the Vietnam Era Twin Study of Aging, 67% of whom were hypertensive. A multi-channel segmentation approach estimated abnormal regions within the white matter. Using multivariable regression models, we characterized the frequency distribution of abnormal white matter in midlife and investigated associations with hypertension and Apolipoprotein E- ε4 status and the impact of duration and control of hypertension. Then, using the classical twin design, we estimated abnormal white matter heritability and the extent of shared genetic overlap with blood pressure. Abnormal white matter was predominantly located in periventricular and deep parietal and frontal regions; associated with age ( t  = 1.9, p  = 0.05) and hypertension ( t  = 2.9, p  = 0.004), but not Apolipoprotein ε4 status; and was greater in those with uncontrolled hypertension relative to controlled ( t  = 3.0, p  = 0.003) and normotensive ( t  = 4.0, p  = 0.0001) groups, suggesting that abnormal white matter may reflect currently active cerebrovascular effects. Abnormal white matter was highly heritable (a 2  = 0.81) and shared some genetic influences with systolic blood pressure (r A  = 0.26), although there was evidence for distinct genetic contributions and unique environmental influences. Future longitudinal research will shed light on factors impacting white matter disease presentation, progression, and potential recovery.

White matter injury detection in neonatal MRI

NASA Astrophysics Data System (ADS)

Cheng, Irene; Hajari, Nasim; Firouzmanesh, Amirhossein; Shen, Rui; Miller, Steven; Poskitt, Ken; Basu, Anup

2013-02-01

Early detection of white matter injury in premature newborns can facilitate timely clinical treatments reducing the potential risk of later developmental deficits. It was reported that there were more than 5% premature newborns in British Columbia, Canada, among which 5-10% exhibited major motor deficits and 25-50% exhibited significant developmental and visual deficits. With the advancement of computer assisted detection systems, it is possible to automatically identify white matter injuries, which are found inside the grey matter region of the brain. Atlas registration has been suggested in the literature to distinguish grey matter from the soft tissues inside the skull. However, our subjects are premature newborns delivered at 24 to 32 weeks of gestation. During this period, the grey matter undergoes rapid changes and differs significantly from one to another. Besides, not all detected white spots represent injuries. Additional neighborhood information and expert input are required for verification. In this paper, we propose a white matter feature identification system for premature newborns, which is composed of several steps: (1) Candidate white matter segmentation; (2) Feature extraction from candidates; (3) Validation with data obtained at a later stage on the children; and (4) Feature confirmation for automated detection. The main challenge of this work lies in segmenting white matter injuries from noisy and low resolution data. Our approach integrates image fusion and contrast enhancement together with a fuzzy segmentation technique to achieve promising results. Other applications, such as brain tumor and intra-ventricular haemorrhage detection can also benefit from our approach.

Tryptophan Metabolism and White Matter Integrity in Schizophrenia

PubMed Central

Chiappelli, Joshua; Postolache, Teodor T; Kochunov, Peter; Rowland, Laura M; Wijtenburg, S Andrea; Shukla, Dinesh K; Tagamets, Malle; Du, Xiaoming; Savransky, Anya; Lowry, Christopher A; Can, Adem; Fuchs, Dietmar; Hong, L Elliot

2016-01-01

Schizophrenia is associated with abnormalities in the structure and functioning of white matter, but the underlying neuropathology is unclear. We hypothesized that increased tryptophan degradation in the kynurenine pathway could be associated with white matter microstructure and biochemistry, potentially contributing to white matter abnormalities in schizophrenia. To test this, fasting plasma samples were obtained from 37 schizophrenia patients and 38 healthy controls and levels of total tryptophan and its metabolite kynurenine were assessed. The ratio of kynurenine to tryptophan was used as an index of tryptophan catabolic activity in this pathway. White matter structure and function were assessed by diffusion tensor imaging (DTI) and 1H magnetic resonance spectroscopy (MRS). Tryptophan levels were significantly lower (p<0.001), and kynurenine/tryptophan ratios were correspondingly higher (p=0.018) in patients compared with controls. In patients, lower plasma tryptophan levels corresponded to lower structural integrity (DTI fractional anisotropy) (r=0.347, p=0.038). In both patients and controls, the kynurenine/tryptophan ratio was inversely correlated with frontal white matter glutamate level (r=−0.391 and −0.350 respectively, p=0.024 and 0.036). These results provide initial evidence implicating abnormal tryptophan/kynurenine pathway activity in changes to white matter integrity and white matter glutamate in schizophrenia. PMID:27143602

Tract-specific fractional anisotropy predicts cognitive outcome in a community sample of middle-aged participants with white matter lesions

PubMed Central

Soriano-Raya, Juan José; Miralbell, Júlia; López-Cancio, Elena; Bargalló, Núria; Arenillas, Juan Francisco; Barrios, Maite; Cáceres, Cynthia; Toran, Pere; Alzamora, Maite; Dávalos, Antoni; Mataró, Maria

2014-01-01

Cerebral white matter lesions (WMLs) have been consistently related to cognitive dysfunction but the role of white matter (WM) damage in cognitive impairment is not fully determined. Diffusion tensor imaging is a promising tool to explain impaired cognition related to WMLs. We investigated the separate association of high-grade periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs) with fractional anisotropy (FA) in middle-aged individuals. We also assessed the predictive value to cognition of FA within specific WM tracts associated with high-grade WMLs. One hundred participants from the Barcelona-AsIA Neuropsychology Study were divided into groups based on low- and high-grade WMLs. Voxel-by-voxel FA were compared between groups, with separate analyses for high-grade PVHs and DWMHs. The mean FA within areas showing differences between groups was extracted in each tract for linear regression analyses. Participants with high-grade PVHs and participants with high-grade DWMHs showed lower FA in different areas of specific tracts. Areas showing decreased FA in high-grade DWMHs predicted lower cognition, whereas areas with decreased FA in high-grade PVHs did not. The predictive value to cognition of specific WM tracts supports the involvement of cortico-subcortical circuits in cognitive deficits only in DWMHs. PMID:24549185

Tract-specific fractional anisotropy predicts cognitive outcome in a community sample of middle-aged participants with white matter lesions.

PubMed

Soriano-Raya, Juan José; Miralbell, Júlia; López-Cancio, Elena; Bargalló, Núria; Arenillas, Juan Francisco; Barrios, Maite; Cáceres, Cynthia; Toran, Pere; Alzamora, Maite; Dávalos, Antoni; Mataró, Maria

2014-05-01

Cerebral white matter lesions (WMLs) have been consistently related to cognitive dysfunction but the role of white matter (WM) damage in cognitive impairment is not fully determined. Diffusion tensor imaging is a promising tool to explain impaired cognition related to WMLs. We investigated the separate association of high-grade periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs) with fractional anisotropy (FA) in middle-aged individuals. We also assessed the predictive value to cognition of FA within specific WM tracts associated with high-grade WMLs. One hundred participants from the Barcelona-AsIA Neuropsychology Study were divided into groups based on low- and high-grade WMLs. Voxel-by-voxel FA were compared between groups, with separate analyses for high-grade PVHs and DWMHs. The mean FA within areas showing differences between groups was extracted in each tract for linear regression analyses. Participants with high-grade PVHs and participants with high-grade DWMHs showed lower FA in different areas of specific tracts. Areas showing decreased FA in high-grade DWMHs predicted lower cognition, whereas areas with decreased FA in high-grade PVHs did not. The predictive value to cognition of specific WM tracts supports the involvement of cortico-subcortical circuits in cognitive deficits only in DWMHs.

Deficits in Neurite Density Underlie White Matter Structure Abnormalities in First-Episode Psychosis.

PubMed

Rae, Charlotte L; Davies, Geoff; Garfinkel, Sarah N; Gabel, Matt C; Dowell, Nicholas G; Cercignani, Mara; Seth, Anil K; Greenwood, Kathryn E; Medford, Nick; Critchley, Hugo D

2017-11-15

Structural abnormalities across multiple white matter tracts are recognized in people with early psychosis, consistent with dysconnectivity as a neuropathological account of symptom expression. We applied advanced neuroimaging techniques to characterize microstructural white matter abnormalities for a deeper understanding of the developmental etiology of psychosis. Thirty-five first-episode psychosis patients, and 19 healthy controls, participated in a quantitative neuroimaging study using neurite orientation dispersion and density imaging, a multishell diffusion-weighted magnetic resonance imaging technique that distinguishes white matter fiber arrangement and geometry from changes in neurite density. Fractional anisotropy (FA) and mean diffusivity images were also derived. Tract-based spatial statistics compared white matter structure between patients and control subjects and tested associations with age, symptom severity, and medication. Patients with first-episode psychosis had lower regional FA in multiple commissural, corticospinal, and association tracts. These abnormalities predominantly colocalized with regions of reduced neurite density, rather than aberrant fiber bundle arrangement (orientation dispersion index). There was no direct relationship with active symptoms. FA decreased and orientation dispersion index increased with age in patients, but not control subjects, suggesting accelerated effects of white matter geometry change. Deficits in neurite density appear fundamental to abnormalities in white matter integrity in early psychosis. In the first application of neurite orientation dispersion and density imaging in psychosis, we found that processes compromising axonal fiber number, density, and myelination, rather than processes leading to spatial disruption of fiber organization, are implicated in the etiology of psychosis. This accords with a neurodevelopmental origin of aberrant brain-wide structural connectivity predisposing individuals to

Disrupted white matter integrity in heroin dependence: a controlled study utilizing diffusion tensor imaging.

PubMed

Liu, Haihong; Li, Lin; Hao, Yihui; Cao, Dong; Xu, Lin; Rohrbaugh, Robert; Xue, Zhimin; Hao, Wei; Shan, Baoci; Liu, Zhening

2008-01-01

Fractional anisotropy (FA) via diffusion tensor imaging (DTI) can quantify the white matter integrity. Exposure to addictive drugs, such as alcohol, cocaine, methamphetamine, marijuana, and nicotine has been shown to alter FA. White matter abnormalities have been shown, but it remains unclear whether the white matter FA is altered in heroin dependence. Utilizing DTI, we investigated the FA difference between heroin-dependent and control subjects by a voxel-based strategy. The FA values of the identified regions were calculated from the FA image of each subject and were correlated with clinical features including months of heroin use, age, education, and dose of methadone. Reduced FA among 16 heroin dependent subjects was located in the bilateral frontal sub-gyral regions, right precentral and left cingulate gyrus. FA in the right frontal sub-gyral was negatively correlated with duration of heroin use. The disrupted white matter integrity in right frontal white matter may occur in continuous heroin abuse.

White matter lesions and the cholinergic deficit in aging and mild cognitive impairment.

PubMed

Richter, Nils; Michel, Anne; Onur, Oezguer A; Kracht, Lutz; Dietlein, Markus; Tittgemeyer, Marc; Neumaier, Bernd; Fink, Gereon R; Kukolja, Juraj

2017-05-01

In Alzheimer's disease (AD), white matter lesions (WMLs) are associated with an increased risk of progression from mild cognitive impairment (MCI) to dementia, while memory deficits have, at least in part, been linked to a cholinergic deficit. We investigated the relationship between WML load assessed with the Scheltens scale, cerebral acetylcholinesterase (AChE) activity measured with [ 11 C]N-methyl-4-piperidyl acetate PET, and neuropsychological performance in 17 patients with MCI due to AD and 18 cognitively normal older participants. Only periventricular, not nonperiventricular, WML load negatively correlated with AChE activity in both groups. Memory performance depended on periventricular and total WML load across groups. Crucially, AChE activity predicted memory function better than WML load, gray matter atrophy, or age. The effects of WML load on memory were fully mediated by AChE activity. Data suggest that the contribution of WML to the dysfunction of the cholinergic system in MCI due to AD depends on WML distribution. Pharmacologic studies are warranted to explore whether this influences the response to cholinergic treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Altered tract-specific white matter microstructure is related to poorer cognitive performance: The Rotterdam Study.

PubMed

Cremers, Lotte G M; de Groot, Marius; Hofman, Albert; Krestin, Gabriel P; van der Lugt, Aad; Niessen, Wiro J; Vernooij, Meike W; Ikram, M Arfan

2016-03-01

White matter microstructural integrity has been related to cognition. Yet, the potential role of specific white matter tracts on top of a global white matter effect remains unclear, especially when considering specific cognitive domains. Therefore, we determined the tract-specific effect of white matter microstructure on global cognition and specific cognitive domains. In 4400 nondemented and stroke-free participants (mean age 63.7 years, 55.5% women), we obtained diffusion magnetic resonance imaging parameters (fractional anisotropy and mean diffusivity) in 14 white matter tracts using probabilistic tractography and assessed cognitive performance with a cognitive test battery. Tract-specific white matter microstructure in all supratentorial tracts was associated with poorer global cognition. Lower fractional anisotropy in association tracts, primarily the inferior fronto-occipital fasciculus, and higher mean diffusivity in projection tracts, in particular the posterior thalamic radiation, most strongly related to poorer cognition. Altered white matter microstructure related to poorer information processing speed, executive functioning, and motor speed, but not to memory. Tract-specific microstructural changes may aid in better understanding the mechanism of cognitive impairment and neurodegenerative diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Astrocytes and Developmental White Matter Disorders

ERIC Educational Resources Information Center

Sen, Ellora; Levison, Steven W.

2006-01-01

There is an increasing awareness that the astrocytes in the immature periventricular white matter are vulnerable to ischemia and respond to inflammation. Here we provide a synopsis of the articles that have evaluated the causes and consequences of developmental brain injuries to white matter astrocytes as well as the consequences of several…

Maternal adiposity negatively influences infant brain white matter development

USDA-ARS?s Scientific Manuscript database

Objective: To study potential effects of maternal body composition on central nervous system (CNS) development of newborn infants. Methods: Diffusion tensor imaging was used to evaluate brain white matter development in 2-week-old, full-term, appropriate for gestational age infants from uncomplicat...

Evidence for Functional Networks within the Human Brain's White Matter.

PubMed

Peer, Michael; Nitzan, Mor; Bick, Atira S; Levin, Netta; Arzy, Shahar

2017-07-05

Investigation of the functional macro-scale organization of the human cortex is fundamental in modern neuroscience. Although numerous studies have identified networks of interacting functional modules in the gray-matter, limited research was directed to the functional organization of the white-matter. Recent studies have demonstrated that the white-matter exhibits blood oxygen level-dependent signal fluctuations similar to those of the gray-matter. Here we used these signal fluctuations to investigate whether the white-matter is organized as functional networks by applying a clustering analysis on resting-state functional MRI (RSfMRI) data from white-matter voxels, in 176 subjects (of both sexes). This analysis indicated the existence of 12 symmetrical white-matter functional networks, corresponding to combinations of white-matter tracts identified by diffusion tensor imaging. Six of the networks included interhemispheric commissural bridges traversing the corpus callosum. Signals in white-matter networks correlated with signals from functional gray-matter networks, providing missing knowledge on how these distributed networks communicate across large distances. These findings were replicated in an independent subject group and were corroborated by seed-based analysis in small groups and individual subjects. The identified white-matter functional atlases and analysis codes are available at http://mind.huji.ac.il/white-matter.aspx Our results demonstrate that the white-matter manifests an intrinsic functional organization as interacting networks of functional modules, similarly to the gray-matter, which can be investigated using RSfMRI. The discovery of functional networks within the white-matter may open new avenues of research in cognitive neuroscience and clinical neuropsychiatry. SIGNIFICANCE STATEMENT In recent years, functional MRI (fMRI) has revolutionized all fields of neuroscience, enabling identifications of functional modules and networks in the human

White matter compromise predicts poor intellectual outcome in survivors of pediatric low-grade glioma.

PubMed

Liu, Fang; Scantlebury, Nadia; Tabori, Uri; Bouffet, Eric; Laughlin, Suzanne; Strother, Douglas; McConnell, Dina; Hukin, Juliette; Fryer, Chris; Brière, Marie-Eve; Montour-Proulx, Isabelle; Keene, Daniel; Wang, Frank; Mabbott, Donald J

2015-04-01

While the impact of cranial radiation on white matter following treatment for pediatric brain tumor has been the focus of many recent studies, the effect of treatment in the absence of radiation has received little attention. The relations between white matter and cognitive outcome have not been explored in patients who have undergone radiation-free treatment. As most patients treated without cranial radiation survive long after their diagnosis, it is critical to identify factors that may impact structural and neurocognitive outcomes. Using diffusion tensor imaging, we examined white matter structure in 32 patients with pediatric low-grade glioma (PLGG) (19 with subtentorial location and 13 with supratentorial location) and 32 healthy participants. Indices of intellectual functioning were also evaluated. Radiation was not used to treat this cohort, aged 8-19 years. We detected evidence of deficits in IQ and compromised supra- and subtentorial white matter in patients relative to healthy children (P < .05). Compromise of supratentorial white matter mediated the impact of treatment for PLGG on IQ. Greater white matter compromise was observed in patients who presented without multiple symptoms, were treated with biopsy/no surgery, had positive neurofibromatosis 1 status, were younger age at diagnosis, and whose parents had lower levels of education (P < .05). Our findings provide evidence of increased risk of intellectual and white matter compromise in patients treated for PLGG without radiation. We identify a neural origin of cognitive deficit useful for predicting outcome and mitigating long-term adverse effects in pediatric brain tumor patients treated without cranial radiation. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Neonatal White Matter Abnormalities an Important Predictor of Neurocognitive Outcome for Very Preterm Children

PubMed Central

Woodward, Lianne J.; Clark, Caron A. C.; Bora, Samudragupta; Inder, Terrie E.

2012-01-01

Background Cerebral white matter abnormalities on term MRI are a strong predictor of motor disability in children born very preterm. However, their contribution to cognitive impairment is less certain. Objective Examine relationships between the presence and severity of cerebral white matter abnormalities on neonatal MRI and a range of neurocognitive outcomes assessed at ages 4 and 6 years. Design/Methods The study sample consisted of a regionally representative cohort of 104 very preterm (≤32 weeks gestation) infants born from 1998–2000 and a comparison group of 107 full-term infants. At term equivalent, all preterm infants underwent a structural MRI scan that was analyzed qualitatively for the presence and severity of cerebral white matter abnormalities, including cysts, signal abnormalities, loss of white matter volume, ventriculomegaly, and corpus callosal thinning/myelination. At corrected ages 4 and 6 years, all children underwent a comprehensive neurodevelopmental assessment that included measures of general intellectual ability, language development, and executive functioning. Results At 4 and 6 years, very preterm children without cerebral white matter abnormalities showed no apparent neurocognitive impairments relative to their full-term peers on any of the domain specific measures of intelligence, language, and executive functioning. In contrast, children born very preterm with mild and moderate-to-severe white matter abnormalities were characterized by performance impairments across all measures and time points, with more severe cerebral abnormalities being associated with increased risks of cognitive impairment. These associations persisted after adjustment for gender, neonatal medical risk factors, and family social risk. Conclusions Findings highlight the importance of cerebral white matter connectivity for later intact cognitive functioning amongst children born very preterm. Preterm born children without cerebral white matter abnormalities on

White matter lesions in Parkinson disease

PubMed Central

Bohnen, Nicolaas I.; Albin, Roger L.

2013-01-01

Pure vascular parkinsonism without evidence of nigral Lewy body pathology may occur as a distinct clinicopathological entity, but a much more frequent occurrence is the comorbid presence of age-associated white matter lesions (WMLs) in idiopathic Parkinson disease (PD). WMLs are associated with motor and cognitive symptoms in otherwise normal elderly individuals. Comorbid WMLs are, therefore, expected to contribute to clinical symptoms in PD. Studies of WMLs in PD differ with regard to methods of assessment of WML burden and the patient populations selected for analysis, but converging evidence suggests that postural stability and gait motor functions are predominantly affected. WMLs are described to contribute to dementia in Alzheimer disease, and emerging but inconclusive evidence indicates similar effects in PD. In this article, we review the literature addressing the occurrence and impact of WMLs in PD, and suggest that WMLs may exacerbate or contribute to some motor and cognitive deficits associated with PD. We review existing and emerging methods for studying white matter pathology in vivo, and propose future research directions. PMID:21343896

White matter structural network abnormalities underlie executive dysfunction in amyotrophic lateral sclerosis.

PubMed

Dimond, Dennis; Ishaque, Abdullah; Chenji, Sneha; Mah, Dennell; Chen, Zhang; Seres, Peter; Beaulieu, Christian; Kalra, Sanjay

2017-03-01

Research in amyotrophic lateral sclerosis (ALS) suggests that executive dysfunction, a prevalent cognitive feature of the disease, is associated with abnormal structural connectivity and white matter integrity. In this exploratory study, we investigated the white matter constructs of executive dysfunction, and attempted to detect structural abnormalities specific to cognitively impaired ALS patients. Eighteen ALS patients and 22 age and education matched healthy controls underwent magnetic resonance imaging on a 4.7 Tesla scanner and completed neuropsychometric testing. ALS patients were categorized into ALS cognitively impaired (ALSci, n = 9) and ALS cognitively competent (ALScc, n = 5) groups. Tract-based spatial statistics and connectomics were used to compare white matter integrity and structural connectivity of ALSci and ALScc patients. Executive function performance was correlated with white matter FA and network metrics within the ALS group. Executive function performance in the ALS group correlated with global and local network properties, as well as FA, in regions throughout the brain, with a high predilection for the frontal lobe. ALSci patients displayed altered local connectivity and structural integrity in these same frontal regions that correlated with executive dysfunction. Our results suggest that executive dysfunction in ALS is related to frontal network disconnectivity, which potentially mediates domain-specific, or generalized cognitive impairment, depending on the degree of global network disruption. Furthermore, reported co-localization of decreased network connectivity and diminished white matter integrity suggests white matter pathology underlies this topological disruption. We conclude that executive dysfunction in ALSci is associated with frontal and global network disconnectivity, underlined by diminished white matter integrity. Hum Brain Mapp 38:1249-1268, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Concurrent white matter bundles and grey matter networks using independent component analysis.

PubMed

O'Muircheartaigh, Jonathan; Jbabdi, Saad

2018-04-15

Developments in non-invasive diffusion MRI tractography techniques have permitted the investigation of both the anatomy of white matter pathways connecting grey matter regions and their structural integrity. In parallel, there has been an expansion in automated techniques aimed at parcellating grey matter into distinct regions based on functional imaging. Here we apply independent component analysis to whole-brain tractography data to automatically extract brain networks based on their associated white matter pathways. This method decomposes the tractography data into components that consist of paired grey matter 'nodes' and white matter 'edges', and automatically separates major white matter bundles, including known cortico-cortical and cortico-subcortical tracts. We show how this framework can be used to investigate individual variations in brain networks (in terms of both nodes and edges) as well as their associations with individual differences in behaviour and anatomy. Finally, we investigate correspondences between tractography-based brain components and several canonical resting-state networks derived from functional MRI. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Ischemic tolerance in pre-myelinated white matter: the role of astrocyte glycogen in brain pathology.

PubMed

Fern, Robert

2015-06-01

In isolated white matter, ischemic tolerance changes dramatically in the period immediately before the onset of myelination. In the absence of an extrinsic energy source, postnatal day 0 to 2 (P0 to P2) white matter axons are here shown to maintain excitability for over twice as long as axons >P2, a differential that was dependent on glycogen metabolism. Prolonged withdrawal of extrinsic energy supply tended to spare axons in zones around astrocytes, which are shown to be the sole repository for glycogen particles in developing white matter. Analysis of mitochondrial volume fraction revealed that neither axons nor astrocytes had a low metabolic rate in neonatal white matter, while oligodendroglia at older ages had an elevated metabolism. The astrocyte population is established early in neural development, and exhibits reduced cell density as maturation progresses and white matter expands. The findings show that this event establishes the necessary conditions for ischemia sensitivity in white matter and indicates that astrocyte proximity may be significant for the survival of neuronal elements in conditions associated with compromised energy supply.

Linking white matter and deep gray matter alterations in premanifest Huntington disease.

PubMed

Faria, Andreia V; Ratnanather, J Tilak; Tward, Daniel J; Lee, David Soobin; van den Noort, Frieda; Wu, Dan; Brown, Timothy; Johnson, Hans; Paulsen, Jane S; Ross, Christopher A; Younes, Laurent; Miller, Michael I

2016-01-01

Huntington disease (HD) is a fatal progressive neurodegenerative disorder for which only symptomatic treatment is available. A better understanding of the pathology, and identification of biomarkers will facilitate the development of disease-modifying treatments. HD is potentially a good model of a neurodegenerative disease for development of biomarkers because it is an autosomal-dominant disease with complete penetrance, caused by a single gene mutation, in which the neurodegenerative process can be assessed many years before onset of signs and symptoms of manifest disease. Previous MRI studies have detected abnormalities in gray and white matter starting in premanifest stages. However, the understanding of how these abnormalities are related, both in time and space, is still incomplete. In this study, we combined deep gray matter shape diffeomorphometry and white matter DTI analysis in order to provide a better mapping of pathology in the deep gray matter and subcortical white matter in premanifest HD. We used 296 MRI scans from the PREDICT-HD database. Atrophy in the deep gray matter, thalamus, hippocampus, and nucleus accumbens was analyzed by surface based morphometry, and while white matter abnormalities were analyzed in (i) regions of interest surrounding these structures, using (ii) tractography-based analysis, and using (iii) whole brain atlas-based analysis. We detected atrophy in the deep gray matter, particularly in putamen, from early premanifest stages. The atrophy was greater both in extent and effect size in cases with longer exposure to the effects of the CAG expansion mutation (as assessed by greater CAP-scores), and preceded detectible abnormalities in the white matter. Near the predicted onset of manifest HD, the MD increase was widespread, with highest indices in the deep and posterior white matter. This type of in-vivo macroscopic mapping of HD brain abnormalities can potentially indicate when and where therapeutics could be targeted to delay

White matter tract integrity predicts visual search performance in young and older adults.

PubMed

Bennett, Ilana J; Motes, Michael A; Rao, Neena K; Rypma, Bart

2012-02-01

Functional imaging research has identified frontoparietal attention networks involved in visual search, with mixed evidence regarding whether different networks are engaged when the search target differs from distracters by a single (elementary) versus multiple (conjunction) features. Neural correlates of visual search, and their potential dissociation, were examined here using integrity of white matter connecting the frontoparietal networks. The effect of aging on these brain-behavior relationships was also of interest. Younger and older adults performed a visual search task and underwent diffusion tensor imaging (DTI) to reconstruct 2 frontoparietal (superior and inferior longitudinal fasciculus; SLF and ILF) and 2 midline (genu, splenium) white matter tracts. As expected, results revealed age-related declines in conjunction, but not elementary, search performance; and in ILF and genu tract integrity. Importantly, integrity of the superior longitudinal fasciculus, ILF, and genu tracts predicted search performance (conjunction and elementary), with no significant age group differences in these relationships. Thus, integrity of white matter tracts connecting frontoparietal attention networks contributes to search performance in younger and older adults. Copyright © 2012 Elsevier Inc. All rights reserved.

White Matter Tract Integrity Predicts Visual Search Performance in Young and Older Adults

PubMed Central

Bennett, Ilana J.; Motes, Michael A.; Rao, Neena K.; Rypma, Bart

2011-01-01

Functional imaging research has identified fronto-parietal attention networks involved in visual search, with mixed evidence regarding whether different networks are engaged when the search target differs from distracters by a single (elementary) versus multiple (conjunction) features. Neural correlates of visual search, and their potential dissociation, were examined here using integrity of white matter connecting the fronto-parietal networks. The effect of aging on these brain-behavior relationships was also of interest. Younger and older adults performed a visual search task and underwent diffusion tensor imaging (DTI) to reconstruct two fronto-parietal (superior and inferior longitudinal fasciculus, SLF and ILF) and two midline (genu, splenium) white matter tracts. As expected, results revealed age-related declines in conjunction, but not elementary, search performance; and in ILF and genu tract integrity. Importantly, integrity of the SLF, ILF, and genu tracts predicted search performance (conjunction and elementary), with no significant age group differences in these relationships. Thus, integrity of white matter tracts connecting fronto-parietal attention networks contributes to search performance in younger and older adults. PMID:21402431

Longitudinal changes in white matter microstructure after heavy cannabis use

PubMed Central

Becker, Mary P.; Collins, Paul F.; Lim, Kelvin O.; Muetzel, R.L.; Luciana, M.

2015-01-01

Diffusion tensor imaging (DTI) studies of cannabis users report alterations in brain white matter microstructure, primarily based on cross-sectional research, and etiology of the alterations remains unclear. We report findings from longitudinal voxelwise analyses of DTI data collected at baseline and at a 2-year follow-up on 23 young adult (18-20 years old at baseline) regular cannabis users and 23 age-, sex-, and IQ-matched non-using controls with limited substance use histories. Onset of cannabis use was prior to age 17. Cannabis users displayed reduced longitudinal growth in fractional anisotropy in the central and parietal regions of the right and left superior longitudinal fasciculus, in white matter adjacent to the left superior frontal gyrus, in the left corticospinal tract, and in the right anterior thalamic radiation lateral to the genu of the corpus callosum, along with less longitudinal reduction of radial diffusion in the right central/posterior superior longitudinal fasciculus, corticospinal tract, and posterior cingulum. Greater amounts of cannabis use were correlated with reduced longitudinal growth in FA as was relatively impaired performance on a measure of verbal learning. These findings suggest that continued heavy cannabis use during adolescence and young adulthood alters ongoing development of white matter microstructure, contributing to functional impairment. PMID:26602958

Age-related white matter microstructural differences partly mediate age-related decline in processing speed but not cognition.

PubMed

Salami, Alireza; Eriksson, Johan; Nilsson, Lars-Göran; Nyberg, Lars

2012-03-01

Aging is associated with declining cognitive performance as well as structural changes in brain gray and white matter (WM). The WM deterioration contributes to a disconnection among distributed brain networks and may thus mediate age-related cognitive decline. The present diffusion tensor imaging (DTI) study investigated age-related differences in WM microstructure and their relation to cognition (episodic memory, visuospatial processing, fluency, and speed) in a large group of healthy subjects (n=287) covering 6 decades of the human life span. Age related decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were observed across the entire WM skeleton as well as in specific WM tracts, supporting the WM degeneration hypothesis. The anterior section of the corpus callosum was more susceptible to aging compared to the posterior section, lending support to the anterior-posterior gradient of WM integrity in the corpus callosum. Finally, and of critical interest, WM integrity differences were found to mediate age-related reductions in processing speed but no significant mediation was found for episodic memory, visuospatial ability, or fluency. These findings suggest that compromised WM integrity is not a major contributing factor to declining cognitive performance in normal aging. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease. Copyright © 2011 Elsevier B.V. All rights reserved.

APOL1 renal-risk variants associate with reduced cerebral white matter lesion volume and increased gray matter volume.

PubMed

Freedman, Barry I; Gadegbeku, Crystal A; Bryan, R Nick; Palmer, Nicholette D; Hicks, Pamela J; Ma, Lijun; Rocco, Michael V; Smith, S Carrie; Xu, Jianzhao; Whitlow, Christopher T; Wagner, Benjamin C; Langefeld, Carl D; Hawfield, Amret T; Bates, Jeffrey T; Lerner, Alan J; Raj, Dominic S; Sadaghiani, Mohammad S; Toto, Robert D; Wright, Jackson T; Bowden, Donald W; Williamson, Jeff D; Sink, Kaycee M; Maldjian, Joseph A; Pajewski, Nicholas M; Divers, Jasmin

2016-08-01

To assess apolipoprotein L1 gene (APOL1) renal-risk-variant effects on the brain, magnetic resonance imaging (MRI)-based cerebral volumes and cognitive function were assessed in 517 African American-Diabetes Heart Study (AA-DHS) Memory IN Diabetes (MIND) and 2568 hypertensive African American Systolic Blood Pressure Intervention Trial (SPRINT) participants without diabetes. Within these cohorts, 483 and 197 had cerebral MRI, respectively. AA-DHS participants were characterized as follows: 60.9% female, mean age of 58.6 years, diabetes duration 13.1 years, estimated glomerular filtration rate of 88.2 ml/min/1.73 m(2), and a median spot urine albumin to creatinine ratio of 10.0 mg/g. In additive genetic models adjusting for age, sex, ancestry, scanner, intracranial volume, body mass index, hemoglobin A1c, statins, nephropathy, smoking, hypertension, and cardiovascular disease, APOL1 renal-risk-variants were positively associated with gray matter volume (β = 3.4 × 10(-3)) and negatively associated with white matter lesion volume (β = -0.303) (an indicator of cerebral small vessel disease) and cerebrospinal fluid volume (β= -30707) (all significant), but not with white matter volume or cognitive function. Significant associations corresponding to adjusted effect sizes (β/SE) were observed with gray matter volume (0.16) and white matter lesion volume (-0.208), but not with cerebrospinal fluid volume (-0.251). Meta-analysis results with SPRINT Memory and Cognition in Decreased Hypertension (MIND) participants who had cerebral MRI were confirmatory. Thus, APOL1 renal-risk-variants are associated with larger gray matter volume and lower white matter lesion volume suggesting lower intracranial small vessel disease. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Correlation between white matter damage and gray matter lesions in multiple sclerosis patients.

PubMed

Han, Xue-Mei; Tian, Hong-Ji; Han, Zheng; Zhang, Ce; Liu, Ying; Gu, Jie-Bing; Bakshi, Rohit; Cao, Xia

2017-05-01

We observed the characteristics of white matter fibers and gray matter in multiple sclerosis patients, to identify changes in diffusion tensor imaging fractional anisotropy values following white matter fiber injury. We analyzed the correlation between fractional anisotropy values and changes in whole-brain gray matter volume. The participants included 20 patients with relapsing-remitting multiple sclerosis and 20 healthy volunteers as controls. All subjects underwent head magnetic resonance imaging and diffusion tensor imaging. Our results revealed that fractional anisotropy values decreased and gray matter volumes were reduced in the genu and splenium of corpus callosum, left anterior thalamic radiation, hippocampus, uncinate fasciculus, right corticospinal tract, bilateral cingulate gyri, and inferior longitudinal fasciculus in multiple sclerosis patients. Gray matter volumes were significantly different between the two groups in the right frontal lobe (superior frontal, middle frontal, precentral, and orbital gyri), right parietal lobe (postcentral and inferior parietal gyri), right temporal lobe (caudate nucleus), right occipital lobe (middle occipital gyrus), right insula, right parahippocampal gyrus, and left cingulate gyrus. The voxel sizes of atrophic gray matter positively correlated with fractional anisotropy values in white matter association fibers in the patient group. These findings suggest that white matter fiber bundles are extensively injured in multiple sclerosis patients. The main areas of gray matter atrophy in multiple sclerosis are the frontal lobe, parietal lobe, caudate nucleus, parahippocampal gyrus, and cingulate gyrus. Gray matter atrophy is strongly associated with white matter injury in multiple sclerosis patients, particularly with injury to association fibers.

Influence of cerebral white matter hyperintensities on cognitive impairment in elderly medical patients.

PubMed

Shibata, Koichi; Nishimura, Yoshiko; Otsuka, Kuniaki; Sakura, Hiroshi

2017-10-01

We investigated the characteristics of elderly medical patients with white matter hyperintensities on magnetic resonance imaging. A total of 213 patients (123 men and 90 women; mean age 74.8 years) reported their history of hypertension, diabetes, dyslipidemia, previous stroke, coronary heart disease and chronic kidney disease (CKD). All patients completed the Mini-Mental State Examination and Geriatric Depression Scale. White matter hyperintensities were evaluated for the periventricular region, basal ganglia (BGH), deep white matter and infratentorial region, and brain atrophy was calculated as bicaudate ratios. Patients with cognitive impairment (Mini-Mental State Examination score < 24) were significantly older (P = 0.001), had periventricular region hyperintensities (P = 0.029) and BGH (P = 0.0015), and showed atrophy (P < 0.0001). Logistic regression showed that cognitive impairment was predicted by stroke (OR 2.5, 95% CI 0.033-0.894, P = 0.036) and atrophy (OR 8.43, 95% CI 5.71-37.0, P = 0.0109). Multiple regressions showed that BGH was associated with CKD (β = 0.213; P = 0.003), and infratentorial region was associated with stroke (β = 0.157; P =0.035) and CKD (β = 0.172; P = 0.016). Periventricular region was associated with age (β = 0.2; P = 0.011) and Geriatric Depression Scale (β = 0.151; P = 0.037), and deep white matter hyperintensities with age (β = 0.189; P = 0.016). Although cognitive impairment in elderly medical patients is associated with stroke and brain atrophy, white matter hyperintensities, especially BGH and infratentorial region, are associated with cognitive decline in relation to CKD. Geriatr Gerontol Int 2017; 17: 1488-1493. © 2016 Japan Geriatrics Society.

Visual White Matter Integrity in Schizophrenia

PubMed Central

Butler, Pamela D.; Hoptman, Matthew J.; Nierenberg, Jay; Foxe, John J.; Javitt, Daniel C.; Lim, Kelvin O.

2007-01-01

Objective Patients with schizophrenia have visual-processing deficits. This study examines visual white matter integrity as a potential mechanism for these deficits. Method Diffusion tensor imaging was used to examine white matter integrity at four levels of the visual system in 17 patients with schizophrenia and 21 comparison subjects. The levels examined were the optic radiations, the striate cortex, the inferior parietal lobule, and the fusiform gyrus. Results Schizophrenia patients showed a significant decrease in fractional anisotropy in the optic radiations but not in any other region. Conclusions This finding indicates that white matter integrity is more impaired at initial input, rather than at higher levels of the visual system, and supports the hypothesis that visual-processing deficits occur at the early stages of processing. PMID:17074957

Structural white matter changes in adolescents and young adults with maple syrup urine disease.

PubMed

Klee, D; Thimm, E; Wittsack, H J; Schubert, D; Primke, R; Pentang, G; Schaper, J; Mödder, U; Antoch, A; Wendel, U; Cohnen, M

2013-11-01

To get insight into the nature of magnetic resonance (MR) white matter abnormalities of patients with classic maple syrup urine disease (MSUD) under diet control. Ten patients with classic MSUD and one with a severe MSUD variant (mean age 21.5 ± 5.1 years) on diet and 11 age and sex-matched healthy subjects were enrolled. Apart from standard MR sequences, diffusion weighted images (DWI), diffusion tensor images (DTI), and magnetization transfer images (MT) were obtained and comparatively analyzed for apparent diffusion coefficient (ADC), tensor fractional anisotropy (FA) and MT maps in 11 regions of interest (ROI) within the white matter. In MSUD patients DWI, DTI and FA showed distinct signal changes in the cerebral hemispheres, the dorsal limb of internal capsule, the brain stem and the central cerebellum. Signal intensity was increased in DWI with a reduced ADC and decreased values for FA. MT did not reveal differences between patients and control subjects. Signal abnormalities in the white matter of adolescents and young adults under diet control may be interpreted as consequence of structural alterations like dysmyelination. The reduced ADC and FA in the white matter with preserved MT indicate a reduction in fiber tracks.

Superficial white matter damage in anti-NMDA receptor encephalitis.

PubMed

Phillips, Owen Robert; Joshi, Shantanu H; Narr, Katherine L; Shattuck, David W; Singh, Manpreet; Di Paola, Margherita; Ploner, Christoph J; Prüss, Harald; Paul, Friedemann; Finke, Carsten

2018-05-01

Clinical brain MRI is normal in the majority of patients with anti- N -methyl-D-aspartate receptor (NMDAR) encephalitis. However, extensive deep white matter damage wasrecently identifiedin these patients using diffusion weighted imaging. Here, our aim was to study a particularly vulnerable brain compartment, the late myelinating superficial white matter. Forty-six patients with anti-NMDAR encephalitis were included. Ten out of these were considered neurologically recovered (modified Rankin scale of zero), while 36 patients were non-recovered. In addition, 30 healthy controls were studied. MRI data were collected from all subjects and superficial white matter mean diffusivity derived from diffusion tensor imaging was compared between groups in whole brain, lobar and vertex-based analyses. Patients underwent comprehensive cognitive testing, and correlation analyses were performed between cognitive performance and superficial white matter integrity. Non-recovered patients showed widespread superficial white matter damage in comparison to recovered patients and healthy controls. Vertex-based analyses revealed that damage predominated in frontal and temporal lobes. In contrast, the superficial white matter was intact in recovered patients. Importantly, persistent cognitive impairments in working memory, verbal memory, visuospatial memory and attention significantly correlated with damage of the superficial white matter in patients. Anti-NMDAR encephalitis is associated with extensive superficial white matter damage in patients with incomplete recovery. The strong association with impairment in several cognitive domains highlights the clinical relevance of white matter damage in this disorder and warrants investigations of the underlying pathophysiological mechanisms. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

White Matter and Development in Children with an Autism Spectrum Disorder

ERIC Educational Resources Information Center

Mak-Fan, Kathleen M.; Morris, Drew; Vidal, Julie; Anagnostou, Evdokia; Roberts, Wendy; Taylor, Margot J.

2013-01-01

Recent research suggests that brain development follows an abnormal trajectory in children with autism spectrum disorders (ASD). The current study examined changes in diffusivity with age within defined white matter tracts in a group of typically developing children and a group of children with an ASD, aged 6 to 14 years. Age by group interactions…

Quantitative ultrasonography of the periventricular white and grey matter of the developing brain.

PubMed

Mullaart, R A; Thijssen, J M; Rotteveel, J J; Valckx, F M; van Geemen, A J

1999-05-01

This study addresses the value of operator-independent computer processing of ultrasonograms of the developing brain. With this aim, routine cranial ultrasonograms obtained from 39 term and preterm infants without clinical or sonographic evidence of brain damage were analyzed by five observers. The procedure, respectively, included: 1. the definition of four regions of interest (ROI), one white matter and one grey matter area on each side of the brain; 2. digitization of the sonogram data within these ROIs; 3. correction for the equipment settings, using data from a tissue-mimicking phantom as a reference; and 4. calculation of four sonogram characteristics (i.e., mean echo level, MEAN, signal-to-noise ratio, SNR, and axial and lateral correlation, CORAX and CORLAT, of the echo level co-occurrence matrix). Significant differences between both sides of the brain or a significant influence of ROI size were not found. The interobserver spread was considerable, but less than the intersubject spread. Two sonogram characteristics seemed strongly correlated in white and grey matter (CORAX and CORLAT) and another only in white matter (SNR with CORAX and CORLAT). MEAN seemed not to be correlated with any other characteristic. Furthermore, it was found that maturation equally decreases white and grey matter MEAN and, thus, hardly affects the ratio between the two. An effect on the other sonogram characteristics was only found in the white matter (i.e., an increase of SNR and a decrease of CORAX and CORLAT). Except for MEAN, the grey matter sonogram characteristics seem hardly affected by maturation. In view of these findings, we conclude that quantitative ultrasonography reveals white and grey matter maturation and, furthermore, provides a conceptional-age-independent reference (MEAN white:grey matter ratio) that might be found to facilitate the detection of pathologic brain alterations.

White matter lesions relate to tract-specific reductions in functional connectivity.

PubMed

Langen, Carolyn D; Zonneveld, Hazel I; White, Tonya; Huizinga, Wyke; Cremers, Lotte G M; de Groot, Marius; Ikram, Mohammad Arfan; Niessen, Wiro J; Vernooij, Meike W

2017-03-01

White matter lesions play a role in cognitive decline and dementia. One presumed pathway is through disconnection of functional networks. Little is known about location-specific effects of lesions on functional connectivity. This study examined location-specific effects within anatomically-defined white matter tracts in 1584 participants of the Rotterdam Study, aged 50-95. Tracts were delineated from diffusion magnetic resonance images using probabilistic tractography. Lesions were segmented on fluid-attenuated inversion recovery images. Functional connectivity was defined across each tract on resting-state functional magnetic resonance images by using gray matter parcellations corresponding to the tract ends and calculating the correlation of the mean functional activity between the gray matter regions. A significant relationship between both local and brain-wide lesion load and tract-specific functional connectivity was found in several tracts using linear regressions, also after Bonferroni correction. Indirect connectivity analyses revealed that tract-specific functional connectivity is affected by lesions in several tracts simultaneously. These results suggest that local white matter lesions can decrease tract-specific functional connectivity, both in direct and indirect connections. Copyright © 2016 Elsevier Inc. All rights reserved.

Longitudinal Study of White Matter Development and Outcomes in Children Born Very Preterm.

PubMed

Young, Julia M; Morgan, Benjamin R; Whyte, Hilary E A; Lee, Wayne; Smith, Mary Lou; Raybaud, Charles; Shroff, Manohar M; Sled, John G; Taylor, Margot J

2017-08-01

Identifying trajectories of early white matter development is important for understanding atypical brain development and impaired functional outcomes in children born very preterm (<32 weeks gestational age [GA]). In this study, 161 diffusion images were acquired in children born very preterm (median GA: 29 weeks) shortly following birth (75), term-equivalent (39), 2 years (18), and 4 years of age (29). Diffusion tensors were computed to obtain measures of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), which were aligned and averaged. A paediatric atlas was applied to obtain diffusion metrics within 12 white matter tracts. Developmental trajectories across time points demonstrated age-related changes which plateaued between term-equivalent and 2 years of age in the majority of posterior tracts and between 2 and 4 years of age in anterior tracts. Between preterm and term-equivalent scans, FA rates of change were slower in anterior than posterior tracts. Partial least squares analyses revealed associations between slower MD and RD rates of change within the external and internal capsule with lower intelligence quotients and language scores at 4 years of age. These results uniquely demonstrate early white matter development and its linkage to cognitive functions. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

White Matter Structural Connectivity and Episodic Memory in Early Childhood

PubMed Central

Ngo, Chi T.; Alm, Kylie H.; Metoki, Athanasia; Hampton, William; Riggins, Tracy; Newcombe, Nora S.; Olson, Ingrid R.

2018-01-01

Episodic memory undergoes dramatic improvement in early childhood; the reason for this is poorly understood. In adults, episodic memory relies on a distributed neural network. Key brain regions that supporting these processes include the hippocampus, portions of the parietal cortex, and portions of prefrontal cortex, each of which shows different developmental profiles. Here we asked whether developmental differences in the axonal pathways connecting these regions may account for the robust gains in episodic memory in young children. Using diffusion weighted imaging, we examined whether white matter connectivity between brain regions implicated in episodic memory differed with age, and were associated with memory performance differences in 4- and 6-year-old children. Results revealed that white matter connecting the hippocampus to the inferior parietal lobule significantly predicted children’s performance on episodic memory tasks. In contrast, variation in the white matter connecting the hippocampus to the medial prefrontal cortex did not relate to memory performance. These findings suggest that structural connectivity between the hippocampus and lateral parietal regions is relevant to the development of episodic memory PMID:29175538

Astrocyte pathology in the ventral prefrontal white matter in depression.

PubMed

Rajkowska, Grazyna; Legutko, Beata; Moulana, Mohadetheh; Syed, Maryam; Romero, Damian G; Stockmeier, Craig A; Miguel-Hidalgo, Jose Javier

2018-04-07

Astrocyte functions in white matter are less well understood than in gray matter. Our recent study of white matter in ventral prefrontal cortex (vPFC) revealed alterations in expression of myelin-related genes in major depressive disorder (MDD). Since white matter astrocytes maintain myelin, we hypothesized that morphometry of these cells will be altered in MDD in the same prefrontal white matter region in which myelin-related genes are altered. White matter adjacent to vPFC was examined in 25 MDD and 21 control subjects. Density and size of GFAP-immunoreactive (-ir) astrocyte cell bodies was measured. The area fraction of GFAP-ir astrocytes (cell bodies + processes) was also estimated. GFAP mRNA expression was determined using qRT-PCR. The density of GFAP-ir astrocytes was also measured in vPFC white matter of rats subjected to chronic unpredictable stress (CUS) and control animals. Fibrous and smooth GFAP-ir astrocytes were distinguished in human white matter. The density of both types of astrocytes was significantly decreased in MDD. Area fraction of GFAP immunoreactivity was significantly decreased in MDD, but mean soma size remained unchanged. Expression of GFAP mRNA was significantly decreased in MDD. In CUS rats there was a significant decrease in astrocyte density in prefrontal white matter. The decrease in density and area fraction of white matter astrocytes and GFAP mRNA in MDD may be linked to myelin pathology previously noted in these subjects. Astrocyte pathology may contribute to axon disturbances in axon integrity reported by neuroimaging studies in MDD and interfere with signal conduction in the white matter. Copyright © 2018. Published by Elsevier Ltd.

Substance-use initiation moderates the effect of stress on white-matter microstructure in adolescents.

PubMed

Zhai, Zu Wei; Yip, Sarah W; Morie, Kristen P; Sinha, Rajita; Mayes, Linda C; Potenza, Marc N

2018-04-01

While childhood stress may contribute risk to substance-use initiation and differences in brain white-matter development, understanding of the potential impact of substance-use initiation on the relationship between experienced stress and white-matter microstructure remains limited. This study examined whether substance-use initiation moderated the effect of perceived stress on white-matter differences using measures of primary white-matter fiber anisotropy. Forty adolescents (age 14.75 ± .87 years) were assessed on the Perceived Stress Scale, and 50% were determined to have presence of substance-use initiation. White-matter microstructure was examined using primary-fiber orientations anisotropy, which may reflect white-matter integrity, modeled separately from other fiber orientations in the same voxels. Analyses were conducted on regions of interest previously associated with childhood stress and substance use. Lower perceived stress and presence of substance-use initiation were related to greater right cingulum primary-fiber measures. Substance-use-initiation status moderated the association between perceived stress and right cingulum primary-fiber measures, such that higher perceived stress was associated with lower right cingulum primary-fiber anisotropy in adolescents without substance-use initiation, but not in those with substance-use initiation. Findings in primary-fiber anisotropy suggest differences in right cingulum white-matter integrity is associated with substance-use initiation in higher-stress adolescents. This reflects a possible pre-existing risk factor, an impact of early substance use, or a combination thereof. Examination of potential markers associated with substance-use initiation in white-matter microstructure among stress-exposed youth warrant additional investigation as such biomarkers may inform efforts relating to tailored interventions. (Am J Addict 2018;27:217-224). © 2018 American Academy of Addiction Psychiatry.

Atypical age-dependency of executive function and white matter microstructure in children and adolescents with autism spectrum disorders.

PubMed

Martínez, Kenia; Merchán-Naranjo, Jessica; Pina-Camacho, Laura; Alemán-Gómez, Yasser; Boada, Leticia; Fraguas, David; Moreno, Carmen; Arango, Celso; Janssen, Joost; Parellada, Mara

2017-11-01

Executive function (EF) performance is associated with measurements of white matter microstructure (WMS) in typical individuals. Impaired EF is a hallmark symptom of autism spectrum disorders (ASD) but it is unclear how impaired EF relates to variability in WMS. Twenty-one male youth (8-18 years) with ASD and without intellectual disability and twenty-one typical male participants (TP) matched for age, intelligence quotient, handedness, race and parental socioeconomic status were recruited. Five EF domains were assessed and several DTI-based measurements of WMS [fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD)] were estimated for eighteen white matter tracts. The ASD group had lower scores for attention (F = 8.37, p = 0.006) and response inhibition (F = 13.09, p = 0.001). Age-dependent changes of EF performance and WMS measurements were present in TP but attenuated in the ASD group. The strongest diagnosis-by-age effect was found for forceps minor, left anterior thalamic radiation and left cingulum angular bundle (all p's ≤ 0.002). In these tracts subjects with ASD tended to have equal or increased FA and/or reduced MD and/or RD at younger ages while controls had increased FA and/or reduced MD and/or RD thereafter. Only for TP individuals, increased FA in the left anterior thalamic radiation was associated with better response inhibition, while reduced RD in forceps minor and left cingulum angular bundle was related to better problem solving and working memory performance respectively. These findings provide novel insight into the age-dependency of EF performance and WMS in ASD, which can be instructive to cognitive training programs.

Sex differences in white matter development during adolescence: a DTI study.

PubMed

Wang, Yingying; Adamson, Chris; Yuan, Weihong; Altaye, Mekibib; Rajagopal, Akila; Byars, Anna W; Holland, Scott K

2012-10-10

Adolescence is a complex transitional period in human development, composing physical maturation, cognitive and social behavioral changes. The objective of this study is to investigate sex differences in white matter development and the associations between intelligence and white matter microstructure in the adolescent brain using diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS). In a cohort of 16 typically-developing adolescents aged 13 to 17 years, longitudinal DTI data were recorded from each subject at two time points that were one year apart. We used TBSS to analyze the diffusion indices including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Our results suggest that boys (13-18 years) continued to demonstrate white matter maturation, whereas girls appeared to reach mature levels earlier. In addition, we identified significant positive correlations between FA and full-scale intelligence quotient (IQ) in the right inferior fronto-occipital fasciculus when both sexes were looked at together. Only girls showed significant positive correlations between FA and verbal IQ in the left cortico-spinal tract and superior longitudinal fasciculus. The preliminary evidence presented in this study supports that boys and girls have different developmental trajectories in white matter microstructure. Copyright © 2012 Elsevier B.V. All rights reserved.

A challenging issue: Detection of white matter hyperintensities in neonatal brain MRI.

PubMed

Morel, Baptiste; Yongchao Xu; Virzi, Alessio; Geraud, Thierry; Adamsbaum, Catherine; Bloch, Isabelle

2016-08-01

The progress of magnetic resonance imaging (MRI) allows for a precise exploration of the brain of premature infants at term equivalent age. The so-called DEHSI (diffuse excessive high signal intensity) of the white matter of premature brains remains a challenging issue in terms of definition, and thus of interpretation. We propose a semi-automatic detection and quantification method of white matter hyperintensities in MRI relying on morphological operators and max-tree representations, which constitutes a powerful tool to help radiologists to improve their interpretation. Results show better reproducibility and robustness than interactive segmentation.

White matter structure changes as adults learn a second language.

PubMed

Schlegel, Alexander A; Rudelson, Justin J; Tse, Peter U

2012-08-01

Traditional models hold that the plastic reorganization of brain structures occurs mainly during childhood and adolescence, leaving adults with limited means to learn new knowledge and skills. Research within the last decade has begun to overturn this belief, documenting changes in the brain's gray and white matter as healthy adults learn simple motor and cognitive skills [Lövdén, M., Bodammer, N. C., Kühn, S., Kaufmann, J., Schütze, H., Tempelmann, C., et al. Experience-dependent plasticity of white-matter microstructure extends into old age. Neuropsychologia, 48, 3878-3883, 2010; Taubert, M., Draganski, B., Anwander, A., Müller, K., Horstmann, A., Villringer, A., et al. Dynamic properties of human brain structure: Learning-related changes in cortical areas and associated fiber connections. The Journal of Neuroscience, 30, 11670-11677, 2010; Scholz, J., Klein, M. C., Behrens, T. E. J., & Johansen-Berg, H. Training induces changes in white-matter architecture. Nature Neuroscience, 12, 1370-1371, 2009; Draganski, B., Gaser, C., Busch, V., Schuirer, G., Bogdahn, U., & May, A. Changes in grey matter induced by training. Nature, 427, 311-312, 2004]. Although the significance of these changes is not fully understood, they reveal a brain that remains plastic well beyond early developmental periods. Here we investigate the role of adult structural plasticity in the complex, long-term learning process of foreign language acquisition. We collected monthly diffusion tensor imaging scans of 11 English speakers who took a 9-month intensive course in written and spoken Modern Standard Chinese as well as from 16 control participants who did not study a language. We show that white matter reorganizes progressively across multiple sites as adults study a new language. Language learners exhibited progressive changes in white matter tracts associated with traditional left hemisphere language areas and their right hemisphere analogs. Surprisingly, the most significant changes

White Matter Structure in Older Adults Moderates the Benefit of Sleep Spindles on Motor Memory Consolidation.

PubMed

Mander, Bryce A; Zhu, Alyssa H; Lindquist, John R; Villeneuve, Sylvia; Rao, Vikram; Lu, Brandon; Saletin, Jared M; Ancoli-Israel, Sonia; Jagust, William J; Walker, Matthew P

2017-11-29

Sleep spindles promote the consolidation of motor skill memory in young adults. Older adults, however, exhibit impoverished sleep-dependent motor memory consolidation. The underlying pathophysiological mechanism(s) explaining why motor memory consolidation in older adults fails to benefit from sleep remains unclear. Here, we demonstrate that male and female older adults show impoverished overnight motor skill memory consolidation relative to young adults, with the extent of impairment being associated with the degree of reduced frontal fast sleep spindle density. The magnitude of the loss of frontal fast sleep spindles in older adults was predicted by the degree of reduced white matter integrity throughout multiple white matter tracts known to connect subcortical and cortical brain regions. We further demonstrate that the structural integrity of selective white matter fiber tracts, specifically within right posterior corona radiata, right tapetum, and bilateral corpus callosum, statistically moderates whether sleep spindles promoted overnight consolidation of motor skill memory. Therefore, white matter integrity within tracts known to connect cortical sensorimotor control regions dictates the functional influence of sleep spindles on motor skill memory consolidation in the elderly. The deterioration of white matter fiber tracts associated with human brain aging thus appears to be one pathophysiological mechanism influencing subcortical-cortical propagation of sleep spindles and their related memory benefits. SIGNIFICANCE STATEMENT Numerous studies have shown that sleep spindle expression is reduced and sleep-dependent motor memory is impaired in older adults. However, the mechanisms underlying these alterations have remained unknown. The present study reveals that age-related degeneration of white matter within select fiber tracts is associated with reduced sleep spindles in older adults. We further demonstrate that, within these same fiber tracts, the degree of

White Matter Structure in Older Adults Moderates the Benefit of Sleep Spindles on Motor Memory Consolidation

PubMed Central

Zhu, Alyssa H.; Lindquist, John R.; Villeneuve, Sylvia; Rao, Vikram; Lu, Brandon; Ancoli-Israel, Sonia

2017-01-01

Sleep spindles promote the consolidation of motor skill memory in young adults. Older adults, however, exhibit impoverished sleep-dependent motor memory consolidation. The underlying pathophysiological mechanism(s) explaining why motor memory consolidation in older adults fails to benefit from sleep remains unclear. Here, we demonstrate that male and female older adults show impoverished overnight motor skill memory consolidation relative to young adults, with the extent of impairment being associated with the degree of reduced frontal fast sleep spindle density. The magnitude of the loss of frontal fast sleep spindles in older adults was predicted by the degree of reduced white matter integrity throughout multiple white matter tracts known to connect subcortical and cortical brain regions. We further demonstrate that the structural integrity of selective white matter fiber tracts, specifically within right posterior corona radiata, right tapetum, and bilateral corpus callosum, statistically moderates whether sleep spindles promoted overnight consolidation of motor skill memory. Therefore, white matter integrity within tracts known to connect cortical sensorimotor control regions dictates the functional influence of sleep spindles on motor skill memory consolidation in the elderly. The deterioration of white matter fiber tracts associated with human brain aging thus appears to be one pathophysiological mechanism influencing subcortical–cortical propagation of sleep spindles and their related memory benefits. SIGNIFICANCE STATEMENT Numerous studies have shown that sleep spindle expression is reduced and sleep-dependent motor memory is impaired in older adults. However, the mechanisms underlying these alterations have remained unknown. The present study reveals that age-related degeneration of white matter within select fiber tracts is associated with reduced sleep spindles in older adults. We further demonstrate that, within these same fiber tracts, the degree of

Cortex Parcellation Associated Whole White Matter Parcellation in Individual Subjects.

PubMed

Schiffler, Patrick; Tenberge, Jan-Gerd; Wiendl, Heinz; Meuth, Sven G

2017-01-01

The investigation of specific white matter areas is a growing field in neurological research and is typically achieved through the use of atlases. However, the definition of anatomically based regions remains challenging for the white matter and thus hinders region-specific analysis in individual subjects. In this article, we focus on creating a whole white matter parcellation method for individual subjects where these areas can be associated to cortex regions. This is done by combining cortex parcellation and fiber tracking data. By tracking fibers out of each cortex region and labeling the fibers according to their origin, we populate a candidate image. We then derive the white matter parcellation by classifying each white matter voxel according to the distribution of labels in the corresponding voxel from the candidate image. The parcellation of the white matter with the presented method is highly reliable and is not as dependent on registration as with white matter atlases. This method allows for the parcellation of the whole white matter into individual cortex region associated areas and, therefore, associates white matter alterations to cortex regions. In addition, we compare the results from the presented method to existing atlases. The areas generated by the presented method are not as sharply defined as the areas in most existing atlases; however, they are computed directly in the DWI space of the subject and, therefore, do not suffer from distortion caused by registration. The presented approach might be a promising tool for clinical and basic research to investigate modalities or system specific micro structural alterations of white matter areas in a quantitative manner.

Cortex Parcellation Associated Whole White Matter Parcellation in Individual Subjects

PubMed Central

Schiffler, Patrick; Tenberge, Jan-Gerd; Wiendl, Heinz; Meuth, Sven G.

2017-01-01

The investigation of specific white matter areas is a growing field in neurological research and is typically achieved through the use of atlases. However, the definition of anatomically based regions remains challenging for the white matter and thus hinders region-specific analysis in individual subjects. In this article, we focus on creating a whole white matter parcellation method for individual subjects where these areas can be associated to cortex regions. This is done by combining cortex parcellation and fiber tracking data. By tracking fibers out of each cortex region and labeling the fibers according to their origin, we populate a candidate image. We then derive the white matter parcellation by classifying each white matter voxel according to the distribution of labels in the corresponding voxel from the candidate image. The parcellation of the white matter with the presented method is highly reliable and is not as dependent on registration as with white matter atlases. This method allows for the parcellation of the whole white matter into individual cortex region associated areas and, therefore, associates white matter alterations to cortex regions. In addition, we compare the results from the presented method to existing atlases. The areas generated by the presented method are not as sharply defined as the areas in most existing atlases; however, they are computed directly in the DWI space of the subject and, therefore, do not suffer from distortion caused by registration. The presented approach might be a promising tool for clinical and basic research to investigate modalities or system specific micro structural alterations of white matter areas in a quantitative manner. PMID:28729829

White matter abnormalities of microstructure and physiological noise in schizophrenia.

PubMed

Cheng, Hu; Newman, Sharlene D; Kent, Jerillyn S; Bolbecker, Amanda; Klaunig, Mallory J; O'Donnell, Brian F; Puce, Aina; Hetrick, William P

2015-12-01

White matter abnormalities in schizophrenia have been revealed by many imaging techniques and analysis methods. One of the findings by diffusion tensor imaging is a decrease in fractional anisotropy (FA), which is an indicator of white matter integrity. On the other hand, elevation of metabolic rate in white matter was observed from positron emission tomography (PET) studies. In this report, we aim to compare the two structural and functional effects on the same subjects. Our comparison is based on the hypothesis that signal fluctuation in white matter is associated with white matter functional activity. We examined the variance of the signal in resting state fMRI and found significant differences between individuals with schizophrenia and non-psychiatric controls specifically in white matter tissue. Controls showed higher temporal signal-to-noise ratios clustered in regions including temporal, frontal, and parietal lobes, cerebellum, corpus callosum, superior longitudinal fasciculus, and other major white matter tracts. These regions with higher temporal signal-to-noise ratio agree well with those showing higher metabolic activity reported by studies using PET. The results suggest that individuals with schizophrenia tend to have higher functional activity in white matter in certain brain regions relative to healthy controls. Despite some overlaps, the distinct regions for physiological noise are different from those for FA derived from diffusion tensor imaging, and therefore provide a unique angle to explore potential mechanisms to white matter abnormality.

Profiles of White Matter Tract Pathology in Frontotemporal Dementia

PubMed Central

Mahoney, Colin J; Ridgway, Gerard R; Malone, Ian B; Downey, Laura E; Beck, Jonathan; Kinnunen, Kirsi M; Schmitz, Nicole; Golden, Hannah L; Rohrer, Jonathan D; Schott, Jonathan M; Rossor, Martin N; Ourselin, Sebastien; Mead, Simon; Fox, Nick C; Warren, Jason D

2014-01-01

Despite considerable interest in improving clinical and neurobiological characterisation of frontotemporal dementia and in defining the role of brain network disintegration in its pathogenesis, information about white matter pathway alterations in frontotemporal dementia remains limited. Here we investigated white matter tract damage using an unbiased, template-based diffusion tensor imaging (DTI) protocol in a cohort of 27 patients with the behavioral variant of frontotemporal dementia (bvFTD) representing both major genetic and sporadic forms, in relation both to healthy individuals and to patients with Alzheimer's disease. Widespread white matter tract pathology was identified in the bvFTD group compared with both healthy controls and Alzheimer's disease group, with prominent involvement of uncinate fasciculus, cingulum bundle and corpus callosum. Relatively discrete and distinctive white matter profiles were associated with genetic subgroups of bvFTD associated with MAPT and C9ORF72 mutations. Comparing diffusivity metrics, optimal overall separation of the bvFTD group from the healthy control group was signalled using radial diffusivity, whereas optimal overall separation of the bvFTD group from the Alzheimer's disease group was signalled using fractional anisotropy. Comparing white matter changes with regional grey matter atrophy (delineated using voxel based morphometry) in the bvFTD cohort revealed co-localisation between modalities particularly in the anterior temporal lobe, however white matter changes extended widely beyond the zones of grey matter atrophy. Our findings demonstrate a distributed signature of white matter alterations that is likely to be core to the pathophysiology of bvFTD and further suggest that this signature is modulated by underlying molecular pathologies. PMID:24510641

Alcohol Use and Cerebral White Matter Compromise in Adolescence

PubMed Central

Elofson, Jonathan; Gongvatana, Win; Carey, Kate B.

2013-01-01

Alcohol use is typically initiated during adolescence, a period known to be critical in neurodevelopment. The adolescent brain may be particularly susceptible to the harmful effects of alcohol. While the cognitive deficits associated with alcohol use during adolescence have been well-documented, the neural substrates underlying these effects remain inadequately understood. Cerebral white matter has been suggested as a primary site of alcohol-related damage and diffusion tensor imaging (DTI) allows for the quantification of white matter integrity in vivo. This review summarizes results from both cross-sectional and longitudinal studies employing DTI that indicate that white matter tracts, particularly those thought to be involved in executive functioning, continue to develop throughout adolescence and into adulthood. Numerous DTI studies reveal a positive correlation between white matter integrity and neurocognitive performance and, in adults, the detrimental effects of prolonged alcohol-dependence on white matter integrity. We provide a comprehensive review of the DTI studies exploring the relationship between alcohol use and white matter integrity in adolescents. Results from most of these studies suggest that alcohol use is associated with reduced white matter integrity, particularly in the superior longitudinal fasciculus (SLF), and some evidence suggests that this relationship may be influenced by sex. We conclude by highlighting confounds and limitations of the available research and suggesting directions for future research. PMID:23583835

A COMPREHENSIVE EXAMINATION OF WHITE MATTER TRACTS AND CONNECTOMETRY IN MAJOR DEPRESSIVE DISORDER

PubMed Central

Delaparte, Lauren; Yeh, Fang‐Cheng; DeLorenzo, Christine; McGrath, Patrick J.; Weissman, Myrna M.; Adams, Phillip; Fava, Maurizio; Deckersbach, Thilo; McInnis, Melvin G.; Carmody, Thomas J.; Cooper, Crystal M.; Kurian, Benji T.; Lu, Hanzhang; Toups, Marisa S.; Trivedi, Madhukar H.; Parsey, Ramin V.

2015-01-01

Background Major depressive disorder (MDD) is a debilitating disorder characterized by widespread brain abnormalities. The literature is mixed as to whether or not white matter abnormalities are associated with MDD. This study sought to examine fractional anisotropy (FA) in white matter tracts in individuals with MDD using diffusion tensor imaging (DTI). Methods 139 participants with MDD and 39 healthy controls (HC) in a multisite study were included. DTI scans were acquired in 64 directions and FA was determined in the brain using four methods: region of interest (ROI), tract‐based spatial statistics (TBSS), and diffusion tractography. Diffusion connectometry was used to identify white matter pathways associated with MDD. Results There were no significant differences when comparing FA in MDD and HC groups using any method. In the MDD group, there was a significant relationship between depression severity and FA in the right medial orbitofrontal cortex, and between age of onset of MDD and FA in the right caudal anterior cingulate cortex using the ROI method. There was a significant relationship between age of onset and connectivity in the thalamocortical radiation, inferior longitudinal fasciculus, and cerebellar tracts using diffusion connectometry. Conclusions The lack of group differences in FA and connectometry analysis may result from the clinically heterogenous nature of MDD. However, the relationship between FA and depression severity may suggest a state biomarker of depression that should be investigated as a potential indicator of response. Age of onset may also be a significant clinical feature to pursue when studying white matter tracts. PMID:26477532

Severe cerebral white matter involvement in a case of dentatorubropallidoluysian atrophy studied at autopsy.

PubMed

Muñoz, Esteban; Campdelacreu, Jaume; Ferrer, Isidre; Rey, María J; Cardozo, Adriana; Gómez, Beatriz; Tolosa, Eduardo

2004-06-01

The pathophysiology of white matter involvement in dentatorubropallidoluysian atrophy (DRPLA) is controversial. Moreover, the clinical repercussions and evolution of these lesions have not been well documented. To describe a case of DRPLA with severe cerebellar white matter involvement. Case report. Patient A 62-year-old woman with DRPLA. When the genetic diagnosis was made, the patient manifested severe ataxia, slight dysarthria, and subcortical cognitive impairment. Cranial magnetic resonance imaging showed atrophy of the cerebellum and brainstem and moderate high-intensity signal alterations in the periventricular cerebral white matter in T2-weighted sequences. In the following 5 years, she developed uncontrolled head movements associated with severe bruxism and tetraparesis, and became deeply demented. New magnetic resonance imaging showed severe diffuse cerebral white matter alterations in T2 sequences with only slight progression of brainstem and cerebellar atrophy. After her death at 67 years of age, the autopsy study showed diffuse myelin pallor, axonal preservation, and reactive astrogliosis in the cerebral white matter, with only mild atherosclerotic changes, and moderate neuronal loss in the cerebellum and brainstem. Leukoencephalopathy could be a prominent finding in some patients with DRPLA, explaining, at least in part, their clinical evolution. In our case, the disproportion between the severity of white matter damage and vascular changes does not support a cardinal role for ischemic mechanisms in leukoencephalopathy.

White Matter Disruptions in Schizophrenia Are Spatially Widespread and Topologically Converge on Brain Network Hubs

PubMed Central

Baker, Simon T.; Cropley, Vanessa L.; Bousman, Chad; Fornito, Alex; Cocchi, Luca; Fullerton, Janice M.; Rasser, Paul; Schall, Ulrich; Henskens, Frans; Michie, Patricia T.; Loughland, Carmel; Catts, Stanley V.; Mowry, Bryan; Weickert, Thomas W.; Shannon Weickert, Cynthia; Carr, Vaughan; Lenroot, Rhoshel; Pantelis, Christos; Zalesky, Andrew

2017-01-01

Abstract White matter abnormalities associated with schizophrenia have been widely reported, although the consistency of findings across studies is moderate. In this study, neuroimaging was used to investigate white matter pathology and its impact on whole-brain white matter connectivity in one of the largest samples of patients with schizophrenia. Fractional anisotropy (FA) and mean diffusivity (MD) were compared between patients with schizophrenia or schizoaffective disorder (n = 326) and age-matched healthy controls (n = 197). Between-group differences in FA and MD were assessed using voxel-based analysis and permutation testing. Automated whole-brain white matter fiber tracking and the network-based statistic were used to characterize the impact of white matter pathology on the connectome and its rich club. Significant reductions in FA associated with schizophrenia were widespread, encompassing more than 40% (234ml) of cerebral white matter by volume and involving all cerebral lobes. Significant increases in MD were also widespread and distributed similarly. The corpus callosum, cingulum, and thalamic radiations exhibited the most extensive pathology according to effect size. More than 50% of cortico-cortical and cortico-subcortical white matter fiber bundles comprising the connectome were disrupted in schizophrenia. Connections between hub regions comprising the rich club were disproportionately affected. Pathology did not differ between patients with schizophrenia and schizoaffective disorder and was not mediated by medication. In conclusion, although connectivity between cerebral hubs is most extensively disturbed in schizophrenia, white matter pathology is widespread, affecting all cerebral lobes and the cerebellum, leading to disruptions in the majority of the brain’s fiber bundles. PMID:27535082

Connectivity-driven white matter scaling and folding in primate cerebral cortex

PubMed Central

Herculano-Houzel, Suzana; Mota, Bruno; Kaas, Jon H.

2010-01-01

Larger brains have an increasingly folded cerebral cortex whose white matter scales up faster than the gray matter. Here we analyze the cellular composition of the subcortical white matter in 11 primate species, including humans, and one Scandentia, and show that the mass of the white matter scales linearly across species with its number of nonneuronal cells, which is expected to be proportional to the total length of myelinated axons in the white matter. This result implies that the average axonal cross-section area in the white matter, a, does not scale significantly with the number of neurons in the gray matter, N. The surface area of the white matter increases with N0.87, not N1.0. Because this surface can be defined as the product of N, a, and the fraction n of cortical neurons connected through the white matter, we deduce that connectivity decreases in larger cerebral cortices as a slowly diminishing fraction of neurons, which varies with N−0.16, sends myelinated axons into the white matter. Decreased connectivity is compatible with previous suggestions that neurons in the cerebral cortex are connected as a small-world network and should slow down the increase in global conduction delay in cortices with larger numbers of neurons. Further, a simple model shows that connectivity and cortical folding are directly related across species. We offer a white matter-based mechanism to account for increased cortical folding across species, which we propose to be driven by connectivity-related tension in the white matter, pulling down on the gray matter. PMID:20956290

The energetics of central nervous system white matter

PubMed Central

Harris, Julia J.; Attwell, David

2012-01-01

The energetics of CNS white matter are poorly understood. We derive a signalling energy budget for rodent white matter (based on data from the optic nerve and corpus callosum) which can be compared to previous energy budgets for the grey matter regions of the brain, perform a cost-benefit analysis of the energetics of myelination, and assess mechanisms for energy production and glucose supply in myelinated axons. We show that white matter synapses consume ≤0.5% of the energy of grey matter synapses and that this, rather than more energy-efficient action potentials, is the main reason why CNS white matter uses less energy than grey matter. Surprisingly, while the energetic cost of building myelin could be repaid within months by the reduced ATP cost of neuronal action potentials, the energetic cost of maintaining the oligodendrocyte resting potential usually outweighs the saving on action potentials. Thus, although it dramatically speeds action potential propagation, myelination need not save energy. Finally, we show that mitochondria in optic nerve axons could sustain measured firing rates with a plausible density of glucose transporters in the nodal membrane, without the need for energy transfer from oligodendrocytes. PMID:22219296

Neonatal deep white matter venous infarction and liquefaction: a pseudo-abscess lesion.

PubMed

Ruess, Lynne; Dent, Carly M; Tiarks, Hailey J; Yoshida, Michelle A; Rusin, Jerome A

2014-11-01

Deep white matter hemorrhagic venous infarction with subsequent cavitation due to necrosis and liquefaction has been described in neonates and may be associated with infection and meningitis. In our experience, the MRI pattern of these lesions is confused with the pattern seen with cerebral abscesses. The purpose of our study was to characterize the MRI findings of post infarction necrosis and liquefaction after hemorrhagic deep white matter venous infarction in infants and to distinguish these lesions from cerebral abscesses. An institutional review board approved a retrospective review of imaging records to identify all patients with cerebral venous infarction at a children's hospital during a 10-year period. Nine infants had deep white matter hemorrhagic venous infarction with white matter fluid signal cavitary lesions. A diagnosis of cerebral abscess was considered in all. The imaging and laboratory findings in these patients are reviewed and compared to descriptions of abscesses found in the literature. There were six female and three male infants. The mean age at presentation was 20 days (range: 0-90 days), while the corrected age at presentation was less than 30 days for all patients. Seven patients presented with seizures and signs of infection; one infant presented with lethargy and later proved to have protein C deficiency. MRI was performed 0-12 days from presentation in these eight patients. Another patient with known protein C deficiency underwent MRI at 30 days for follow-up of screening US abnormalities. There were a total of 38 deep cerebral white matter fluid signal cavitary lesions: 25 frontal, 9 parietal, 2 temporal, 2 occipital. Larger lesions had dependent debris. All lesions had associated hemorrhage and many lesions had evidence of adjacent small vessel venous thrombosis. Lesions imaged after gadolinium showed peripheral enhancement. Three lesions increased in size on follow-up imaging. Three patients, two with meningitis confirmed via

White Matter Glia Pathology in Autism

DTIC Science & Technology

2013-09-01

www.ncbi.nlm.nih.gov/pubmed/21078227 5 . Sundaram SK, Kumar A, Makki MI, Behen ME, Chugani HT , Chugani DC. Diffusion tensor imaging of frontal lobe in autism ...AD_________________ Award Number: W81XWH-12-1-0302 TITLE: White matter glia pathology in autism PRINCIPAL INVESTIGATOR...COVERED 01 September 2012 – 31 August 2013 4. TITLE AND SUBTITLE White matter glia pathology in autism 5a. CONTRACT NUMBER W81XWH-12-1-0302 5b

Structure-Specific Statistical Mapping of White Matter Tracts

PubMed Central

Yushkevich, Paul A.; Zhang, Hui; Simon, Tony; Gee, James C.

2008-01-01

We present a new model-based framework for the statistical analysis of diffusion imaging data associated with specific white matter tracts. The framework takes advantage of the fact that several of the major white matter tracts are thin sheet-like structures that can be effectively modeled by medial representations. The approach involves segmenting major tracts and fitting them with deformable geometric medial models. The medial representation makes it possible to average and combine tensor-based features along directions locally perpendicular to the tracts, thus reducing data dimensionality and accounting for errors in normalization. The framework enables the analysis of individual white matter structures, and provides a range of possibilities for computing statistics and visualizing differences between cohorts. The framework is demonstrated in a study of white matter differences in pediatric chromosome 22q11.2 deletion syndrome. PMID:18407524

Severe retinopathy of prematurity predicts delayed white matter maturation and poorer neurodevelopment.

PubMed

Glass, Torin J A; Chau, Vann; Gardiner, Jane; Foong, Justin; Vinall, Jillian; Zwicker, Jill G; Grunau, Ruth E; Synnes, Anne; Poskitt, Kenneth J; Miller, Steven P

2017-11-01

To determine whether severe retinopathy of prematurity (ROP) is associated with (1) abnormal white matter maturation and (2) neurodevelopmental outcomes at 18 months' corrected age (CA) compared with neonates without severe ROP. We conducted a prospective longitudinal cohort of extremely preterm neonates born 24-28 weeks' gestational age recruited between 2006 and 2013 with brain MRIs obtained both early in life and at term-equivalent age. Severe ROP was defined as ROP treated with retinal laser photocoagulation. Using diffusion tensor imaging and tract-based spatial statistics (TBSS), white matter maturation was assessed by mean fractional anisotropy (FA) in seven predefined regions of interest. Neurodevelopmental outcomes were assessed with Bayley Scales of Infant and Toddler Development-III (Bayley-III) composite scores at 18 months' CA. Subjects were compared using Fisher's exact, Kruskal-Wallis and generalised estimating equations. Families were recruited from the neonatal intensive care unit at BC Women's Hospital. Of 98 extremely preterm neonates (median: 26.0 weeks) assessed locally for ROP, 19 (19%) had severe ROP and 83 (85%) were assessed at 18 months' CA. Severe ROP was associated with lower FA in the posterior white matter, and with decreased measures of brain maturation in the optic radiations, posterior limb of the internal capsule (PLIC) and external capsule on TBSS. Bayley-III cognitive and motor scores were lower in infants with severe ROP. Severe ROP is associated with maturational delay in the optic radiations, PLIC, external capsule and posterior white matter, housing the primary visual and motor pathways, and is associated with poorer cognitive and motor outcomes at 18 months' CA. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Whole-brain grey matter density predicts balance stability irrespective of age and protects older adults from falling.

PubMed

Boisgontier, Matthieu P; Cheval, Boris; van Ruitenbeek, Peter; Levin, Oron; Renaud, Olivier; Chanal, Julien; Swinnen, Stephan P

2016-03-01

Functional and structural imaging studies have demonstrated the involvement of the brain in balance control. Nevertheless, how decisive grey matter density and white matter microstructural organisation are in predicting balance stability, and especially when linked to the effects of ageing, remains unclear. Standing balance was tested on a platform moving at different frequencies and amplitudes in 30 young and 30 older adults, with eyes open and with eyes closed. Centre of pressure variance was used as an indicator of balance instability. The mean density of grey matter and mean white matter microstructural organisation were measured using voxel-based morphometry and diffusion tensor imaging, respectively. Mixed-effects models were built to analyse the extent to which age, grey matter density, and white matter microstructural organisation predicted balance instability. Results showed that both grey matter density and age independently predicted balance instability. These predictions were reinforced when the level of difficulty of the conditions increased. Furthermore, grey matter predicted balance instability beyond age and at least as consistently as age across conditions. In other words, for balance stability, the level of whole-brain grey matter density is at least as decisive as being young or old. Finally, brain grey matter appeared to be protective against falls in older adults as age increased the probability of losing balance in older adults with low, but not moderate or high grey matter density. No such results were observed for white matter microstructural organisation, thereby reinforcing the specificity of our grey matter findings. Copyright © 2016 Elsevier B.V. All rights reserved.

Increased white matter metabolic rates in autism spectrum disorder and schizophrenia.

PubMed

Mitelman, Serge A; Buchsbaum, Monte S; Young, Derek S; Haznedar, M Mehmet; Hollander, Eric; Shihabuddin, Lina; Hazlett, Erin A; Bralet, Marie-Cecile

2017-11-22

Both autism spectrum disorder (ASD) and schizophrenia are often characterized as disorders of white matter integrity. Multimodal investigations have reported elevated metabolic rates, cerebral perfusion and basal activity in various white matter regions in schizophrenia, but none of these functions has previously been studied in ASD. We used 18 fluorodeoxyglucose positron emission tomography to compare white matter metabolic rates in subjects with ASD (n = 25) to those with schizophrenia (n = 41) and healthy controls (n = 55) across a wide range of stereotaxically placed regions-of-interest. Both subjects with ASD and schizophrenia showed increased metabolic rates across the white matter regions assessed, including internal capsule, corpus callosum, and white matter in the frontal and temporal lobes. These increases were more pronounced, more widespread and more asymmetrical in subjects with ASD than in those with schizophrenia. The highest metabolic increases in both disorders were seen in the prefrontal white matter and anterior limb of the internal capsule. Compared to normal controls, differences in gray matter metabolism were less prominent and differences in adjacent white matter metabolism were more prominent in subjects with ASD than in those with schizophrenia. Autism spectrum disorder and schizophrenia are associated with heightened metabolic activity throughout the white matter. Unlike in the gray matter, the vector of white matter metabolic abnormalities appears to be similar in ASD and schizophrenia, may reflect inefficient functional connectivity with compensatory hypermetabolism, and may be a common feature of neurodevelopmental disorders.

Sex differences in adolescent white matter architecture.

PubMed

Bava, Sunita; Boucquey, Veronique; Goldenberg, Diane; Thayer, Rachel E; Ward, Megan; Jacobus, Joanna; Tapert, Susan F

2011-02-23

Sex-specific trajectories in white matter development during adolescence may help explain cognitive and behavioral divergences between males and females. Knowledge of sex differences in typically developing adolescents can provide a basis for interpreting sexual dimorphisms in abilities and actions. We examined 58 healthy adolescents (12-14years of age) with diffusion tensor imaging (DTI). Diffusion parameters fractional anisotropy (FA), and mean (MD), radial (RD), and axial diffusivities (AD) were subjected to whole-brain voxel-wise group comparisons using tract-based spatial statistics. Sex differences in white matter microstructure were examined in relation to pubertal development. Early adolescent females (n=29) evidenced higher FA in the right superior corona radiata, higher FA and AD in bilateral corticospinal tracts (≥164μl, p<.01), and lower MD in the right inferior longitudinal fasciculus (ILF) and left forceps major (≥164μl, p<.01) than age-matched males (n=29). Males did not show any areas of higher FA or lower MD than females, but had higher AD in the right superior longitudinal fasciculus, ILF, and forceps minor (≥ 164μl, p<.01). Pubertal stage did not account for sex disparities. In early adolescence, females' motor tracts may reflect widespread changes, while males may undergo relatively more microstructural change in projection and association fibers. Copyright © 2010 Elsevier B.V. All rights reserved.

White matter structural connectivity and episodic memory in early childhood.

PubMed

Ngo, Chi T; Alm, Kylie H; Metoki, Athanasia; Hampton, William; Riggins, Tracy; Newcombe, Nora S; Olson, Ingrid R

2017-12-01

Episodic memory undergoes dramatic improvement in early childhood; the reason for this is poorly understood. In adults, episodic memory relies on a distributed neural network. Key brain regions that supporting these processes include the hippocampus, portions of the parietal cortex, and portions of prefrontal cortex, each of which shows different developmental profiles. Here we asked whether developmental differences in the axonal pathways connecting these regions may account for the robust gains in episodic memory in young children. Using diffusion weighted imaging, we examined whether white matter connectivity between brain regions implicated in episodic memory differed with age, and were associated with memory performance differences in 4- and 6-year-old children. Results revealed that white matter connecting the hippocampus to the inferior parietal lobule significantly predicted children's performance on episodic memory tasks. In contrast, variation in the white matter connecting the hippocampus to the medial prefrontal cortex did not relate to memory performance. These findings suggest that structural connectivity between the hippocampus and lateral parietal regions is relevant to the development of episodic memory. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Aortic stiffness is associated with white matter integrity in patients with type 1 diabetes.

PubMed

Tjeerdema, Nathanja; Van Schinkel, Linda D; Westenberg, Jos J; Van Elderen, Saskia G; Van Buchem, Mark A; Smit, Johannes W; Van der Grond, Jeroen; De Roos, Albert

2014-09-01

To assess the association between aortic pulse wave velocity (PWV) as a marker of arterial stiffness and diffusion tensor imaging of brain white matter integrity in patients with type 1 diabetes using advanced magnetic resonance imaging (MRI) technology. Forty-one patients with type 1 diabetes (23 men, mean age 44 ± 12 years, mean diabetes duration 24 ± 13 years) were included. Aortic PWV was assessed using through-plane velocity-encoded MRI. Brain diffusion tensor imaging (DTI) measurements were performed on 3-T MRI. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were calculated for white and grey matter integrity. Pearson correlation and multivariable linear regression analyses including cardiovascular risk factors as covariates were assessed. Multivariable linear regression analyses revealed that aortic PWV is independently associated with white matter integrity FA (β = -0.777, p = 0.008) in patients with type 1 diabetes. This effect was independent of age, gender, mean arterial pressure, body mass index, smoking, duration of diabetes and glycated haemoglobin levels. Aortic PWV was not significantly related to grey matter integrity. Our data suggest that aortic stiffness is independently associated with reduced white matter integrity in patients with type 1 diabetes. Aortic stiffness is associated with brain injury. Aortic stiffness exposes small vessels to high pressure fluctuations and flow. Aortic stiffness is associated with microvascular brain injury in diabetes. This suggests a vascular contribution to early subtle microstructural deficits.

Minocycline protects the immature white matter against hyperoxia.

PubMed

Schmitz, Thomas; Krabbe, Grietje; Weikert, Georg; Scheuer, Till; Matheus, Friederike; Wang, Yan; Mueller, Susanne; Kettenmann, Helmut; Matyash, Vitali; Bührer, Christoph; Endesfelder, Stefanie

2014-04-01

Poor neurological outcome in preterm infants is associated with periventricular white matter damage and hypomyelination, often caused by perinatal inflammation, hypoxia-ischemia, and hyperoxia. Minocycline has been demonstrated in animal models to protect the immature brain against inflammation and hypoxia-ischemia by microglial inhibition. Here we studied the effect of minocycline on white matter damage caused by hyperoxia. To mimic the 3- to 4-fold increase of oxygen tension caused by preterm birth, we have used the hyperoxia model in neonatal rats providing 24h exposure to 4-fold increased oxygen concentration (80% instead of 21% O2) from P6 to P7. We analyzed whether minocycline prevents activation of microglia and damage of oligodendroglial precursor cell development, and whether acute treatment of hyperoxia-exposed rats with minocycline improves long term white matter integrity. Minocycline administration during exposure to hyperoxia resulted in decreased apoptotic cell death and in improved proliferation and maturation of oligodendroglial precursor cells (OPC). Minocycline blocked changes in microglial morphology and IL-1β release induced by hyperoxia. In primary microglial cell cultures, minocycline inhibited cytokine release while in mono-cultures of OPCs, it improved survival and proliferation. Long term impairment of white matter diffusivity in MRI/DTI in P30 and P60 animals after neonatal hyperoxia was attenuated by minocycline. Minocycline protects white matter development against oxygen toxicity through direct protection of oligodendroglia and by microglial inhibition. This study moreover demonstrates long term benefits of minocycline on white matter integrity. Copyright © 2014 Elsevier Inc. All rights reserved.

Longitudinal relaxographic imaging of white matter hyperintensities in the elderly

PubMed Central

2014-01-01

Background Incidental white matter hyperintensities (WMHs) are common findings on T2-weighted magnetic resonance images of the aged brain and have been associated with cognitive decline. While a variety of pathogenic mechanisms have been proposed, the origin of WMHs and the extent to which lesions in the deep and periventricular white matter reflect distinct etiologies remains unclear. Our aim was to quantify the fractional blood volume (vb) of small WMHs in vivo using a novel magnetic resonance imaging (MRI) approach and examine the contribution of blood–brain barrier disturbances to WMH formation in the deep and periventricular white matter. Methods Twenty-three elderly volunteers (aged 59–82 years) underwent 7 Tesla relaxographic imaging and fluid-attenuated inversion recovery (FLAIR) MRI. Maps of longitudinal relaxation rate constant (R1) were prepared before contrast reagent (CR) injection and throughout CR washout. Voxelwise estimates of vb were determined by fitting temporal changes in R1 values to a two-site model that incorporates the effects of transendothelial water exchange. Average vb values in deep and periventricular WMHs were determined after semi-automated segmentation of FLAIR images. Ventricular permeability was estimated from the change in CSF R1 values during CR washout. Results In the absence of CR, the total water fraction in both deep and periventricular WMHs was increased compared to normal appearing white matter (NAWM). The vb of deep WMHs was 1.8 ± 0.6 mL/100 g and was significantly reduced compared to NAWM (2.4 ± 0.8 mL/100 g). In contrast, the vb of periventricular WMHs was unchanged compared to NAWM, decreased with ventricular volume and showed a positive association with ventricular permeability. Conclusions Hyperintensities in the deep WM appear to be driven by vascular compromise, while those in the periventricular WM are most likely the result of a compromised ependyma in which the small vessels remain relatively

APOE/TOMM 40 genetic loci, white matter hyperintensities, and cerebral microbleeds

PubMed Central

Lyall, Donald M.; Muñoz Maniega, Susana; Harris, Sarah E.; Bastin, Mark E.; Murray, Catherine; Lutz, Michael W.; Saunders, Ann M.; Roses, Allen D.; Valdés Hernández, Maria del C.; Royle, Natalie A.; Starr, John M.; Porteous, David J.; Deary, Ian J.

2015-01-01

Background Two markers of cerebral small vessel disease are white matter hyperintensities and cerebral microbleeds, which commonly occur in people with Alzheimer's disease. Aim and/or hypothesis To test for independent associations between two Alzheimer's disease‐susceptibility gene loci – APOE ε and the TOMM 40 ‘523’ poly‐T repeat – and white matter hyperintensities/cerebral microbleed burden in community‐dwelling older adults. Methods Participants in the Lothian Birth Cohort 1936 underwent genotyping for APOE ε and TOMM 40 523, and detailed structural brain magnetic resonance imaging at a mean age of 72·70 years (standard deviation = 0·7; range = 71–74). Results No significant effects of APOE ε or TOMM 40 523 genotypes on white matter hyperintensities or cerebral microbleed burden were found amongst 624 participants. Conclusions Lack of association between two Alzheimer's disease susceptibility gene loci and markers of cerebral small vessel disease may reflect the relative health of this population compared with those in other studies in the literature. PMID:26310205

APOE/TOMM40 genetic loci, white matter hyperintensities, and cerebral microbleeds.

PubMed

Lyall, Donald M; Muñoz Maniega, Susana; Harris, Sarah E; Bastin, Mark E; Murray, Catherine; Lutz, Michael W; Saunders, Ann M; Roses, Allen D; Valdés Hernández, Maria del C; Royle, Natalie A; Starr, John M; Porteous, David J; Deary, Ian J; Wardlaw, Joanna M

2015-12-01

Two markers of cerebral small vessel disease are white matter hyperintensities and cerebral microbleeds, which commonly occur in people with Alzheimer's disease. To test for independent associations between two Alzheimer's disease-susceptibility gene loci--APOE ε and the TOMM40 '523' poly-T repeat--and white matter hyperintensities/cerebral microbleed burden in community-dwelling older adults. Participants in the Lothian Birth Cohort 1936 underwent genotyping for APOE ε and TOMM40 523, and detailed structural brain magnetic resonance imaging at a mean age of 72·70 years (standard deviation = 0·7; range = 71-74). No significant effects of APOE ε or TOMM40 523 genotypes on white matter hyperintensities or cerebral microbleed burden were found amongst 624 participants. Lack of association between two Alzheimer's disease susceptibility gene loci and markers of cerebral small vessel disease may reflect the relative health of this population compared with those in other studies in the literature. © 2015 The Authors. International Journal of Stroke published by John Wiley & Sons Ltd on behalf of World Stroke Organization.

White matter damage is related to ataxia severity in SCA3.

PubMed

Kang, J-S; Klein, J C; Baudrexel, S; Deichmann, R; Nolte, D; Hilker, R

2014-02-01

Spinocerebellar ataxia type 3 (SCA3) is the most frequent inherited cerebellar ataxia in Europe, the US and Japan, leading to disability and death through motor complications. Although the affected protein ataxin-3 is found ubiquitously in the brain, grey matter atrophy is predominant in the cerebellum and the brainstem. White matter pathology is generally less severe and thought to occur in the brainstem, spinal cord, and cerebellar white matter. Here, we investigated both grey and white matter pathology in a group of 12 SCA3 patients and matched controls. We used voxel-based morphometry for analysis of tissue loss, and tract-based spatial statistics (TBSS) on diffusion magnetic resonance imaging to investigate microstructural pathology. We analysed correlations between microstructural properties of the brain and ataxia severity, as measured by the Scale for the Assessment and Rating of Ataxia (SARA) score. SCA3 patients exhibited significant loss of both grey and white matter in the cerebellar hemispheres, brainstem including pons and in lateral thalamus. On between-group analysis, TBSS detected widespread microstructural white matter pathology in the cerebellum, brainstem, and bilaterally in thalamus and the cerebral hemispheres. Furthermore, fractional anisotropy in a white matter network comprising frontal, thalamic, brainstem and left cerebellar white matter strongly and negatively correlated with SARA ataxia scores. Tractography identified the thalamic white matter thus implicated as belonging to ventrolateral thalamus. Disruption of white matter integrity in patients suffering from SCA3 is more widespread than previously thought. Moreover, our data provide evidence that microstructural white matter changes in SCA3 are strongly related to the clinical severity of ataxia symptoms.

Angiotensin-converting enzyme insertion/deletion polymorphism is associated with cerebral white matter changes in Alzheimer's disease.

PubMed

Chou, Ping-Song; Wu, Shyh-Jong; Kao, Yi-Hui; Chou, Mei-Chuan; Tai, Shu-Yu; Yang, Yuan-Han

2017-06-01

The presence of cerebral white matter changes (WMC) has been reported as an important predictor of the rapidity of cognitive decline in Alzheimer's disease (AD). The association between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and WMC in AD is yet to be elucidated. The present study aimed to examine the association between the ACE I/D polymorphism and WMC among AD patients in Taiwan. A total of 403 patients clinically diagnosed with AD were recruited in a cross-sectional study carried out in an area hospital in Kaohsiung, Taiwan. The ACE I/D polymorphism was genotyped, and cerebral white matter rating was carried out using the visual rating scale for age-related white matter changes. The I allele was associated with a significantly lower total age-related white matter changes scale score compared with the D allele (4.83 vs 5.93, P = 0.013). The total age-related white matter changes scale score was significantly lower for the I/I genotype than for the I/D (4.37 vs 5.87, P = 0.009) and I/D + D/D genotypes (4.37 vs 5.91, P = 0.006), with no differences observed between the I/I + I/D and the D/D genotypes (5.08 vs 6.09, P = 0.373), after adjustment for age and hypertension. A stratified analysis by sex demonstrated that the I/I genotype was associated with significant lower WMC than other genotypes in women, but not in men. The present study supports the hypothesis that the ACE I/D polymorphism is associated with the severity of WMC in patients with AD. Patients with AD who are homozygous for the I allele might be less likely to develop WMC, especially women. Geriatr Gerontol Int 2017; 17: 945-950. © 2016 Japan Geriatrics Society.

White Matter Lesions: Prevalence and Clinical Phenotype in Asymptomatic Individuals Aged ≥50 Years.

PubMed

David, Jean-Philippe; Ferrat, Emilie; Parisot, Juliette; Naga, Henri; Lakroun, Samia; Menasria, Feriel; Saddedine, Sofiane; Natella, Pierre-André; Paillaud, Elena; Fromentin, Isabelle; Bastuji-Garin, Sylvie

2016-01-01

To assess the prevalence of early confluent/confluent white matter lesions (ec/cWMLs) in asymptomatic individuals aged ≥50 years and to identify associated clinical phenotypes. Cross-sectional analysis of 141 asymptomatic individuals aged ≥50 years assessed at an outpatient department in France. Brain magnetic resonance imaging was rated using the Fazekas scale. Age-adjusted odds ratios (ORs) and 95% confidence intervals were estimated using logistic models to investigate factors associated with ec/cWMLs; independent risk factors were identified by multivariate analysis. Median age was 63 years; 53.9% were women, 32.6% had hypertension, and 76.6% had ≥1 cardiovascular risk factors. The prevalence of ec/cWMLs was 26.2%. Apart from age, independent risk factors were family history of cardiovascular event (OR = 5.55; 1.13-27.32) and hypertension (2.47; 1.05-5.81). Patients with ec/cWMLs had lower cognitive dual-task walking speed (1.15; 0.98-1.40), MMSE (1.41; 1.06-1.89), and FAB scores (5.21; 1.49-19.84). The Scheltens score was independently associated with the WML severity score. ec/cWMLs are common in asymptomatic community-dwelling individuals aged ≥50 years. They are associated with cardiovascular risk factors, impairments in global and executive cognitive function, and Scheltens score elevation. © 2016 S. Karger AG, Basel.

Prenatal exposure to maternal and paternal depressive symptoms and white matter microstructure in children.

PubMed

El Marroun, Hanan; Zou, Runyu; Muetzel, Ryan L; Jaddoe, Vincent W; Verhulst, Frank C; White, Tonya; Tiemeier, Henning

2018-04-01

Prenatal maternal depression has been associated with multiple problems in offspring involving affect, cognition, and neuroendocrine functioning. This suggests that prenatal depression influences neurodevelopment. However, the underlying neurodevelopmental mechanism remains unclear. We prospectively assessed whether maternal depressive symptoms during pregnancy and at the child's age 3 years are related to white matter microstructure in 690 children. The association of paternal depressive symptoms with childhood white matter microstructure was assessed to evaluate genetic or familial confounding. Parental depressive symptoms were measured using the Brief Symptom Inventory. In children aged 6-9 years, we used diffusion tensor imaging to assess white matter microstructure characteristics including fractional anisotropy (FA) and mean diffusivity (MD). Exposure to maternal depressive symptoms during pregnancy was associated with higher MD in the uncinate fasciculus and to lower FA and higher MD in the cingulum bundle. No associations of maternal depressive symptoms at the child's age of 3 years with white matter characteristics were observed. Paternal depressive symptoms also showed a trend toward significance for a lower FA in the cingulum bundle. Prenatal maternal depressive symptoms were associated with higher MD in the uncinate fasciculus and the cingulum bundle. These structures are part of the limbic system, which is involved in motivation, emotion, learning, and memory. As paternal depressive symptoms were also related to lower FA in the cingulum, the observed effect may partly reflect a genetic predisposition and shared environmental family factors and to a lesser extent a specific intrauterine effect. © 2018 Wiley Periodicals, Inc.

White Matter Microstructural Integrity and Neurobehavioral Outcome of HIV-Exposed Uninfected Neonates.

PubMed

Tran, Linh T; Roos, Annerine; Fouche, Jean-Paul; Koen, Nastassja; Woods, Roger P; Zar, Heather J; Narr, Katherine L; Stein, Dan J; Donald, Kirsten A

2016-01-01

The successful implementation of prevention programs for mother-to-child human immunodeficiency virus (HIV) transmission has dramatically reduced the prevalence of infants infected with HIV while increasing that of HIV-exposed uninfected (HEU) children. Neuropsychological assessments indicate that HEU children may exhibit differences in neurodevelopment compared to unexposed children (HUU). Pathological mechanisms leading to such neurodevelopmental delays are not clear. In this observational birth cohort study we explored the integrity of regional white matter microstructure in HEU infants, shortly after birth. Microstructural changes in white matter associated with prenatal HIV exposure were evaluated in HEU infants (n = 15) and matched controls (n = 22) using diffusion tensor imaging and tract-based spatial statistics. Additionally, diffusion values were extracted and compared for white matter tracts of interest, and associations with clinical outcomes from the Dubowitz neonatal neurobehavioral tool were investigated. Higher fractional anisotropy in the middle cerebellar peduncles of HEU compared to HUU neonates was found after correction for age and gender. Scores on the Dubowitz abnormal neurological signs subscale were positively correlated with FA (r = 0.58, P = 0.038) in the left uncinate fasciculus in HEU infants. This is the first study to present data suggesting that prenatal HIV exposure without infection is associated with altered white matter microstructural integrity in the neonatal period. Longitudinal studies of HEU infants as their brains mature are necessary to understand further the significance of prenatal HIV and antiretroviral treatment exposure on white matter integrity and neurodevelopmental outcomes.

White matter integrity in Asperger syndrome: a preliminary diffusion tensor magnetic resonance imaging study in adults.

PubMed

Bloemen, Oswald J N; Deeley, Quinton; Sundram, Fred; Daly, Eileen M; Barker, Gareth J; Jones, Derek K; van Amelsvoort, Therese A M J; Schmitz, Nicole; Robertson, Dene; Murphy, Kieran C; Murphy, Declan G M

2010-10-01

Autistic Spectrum Disorder (ASD), including Asperger syndrome and autism, is a highly genetic neurodevelopmental disorder. There is a consensus that ASD has a biological basis, and it has been proposed that it is a "connectivity" disorder. Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) allows measurement of the microstructural integrity of white matter (a proxy measure of "connectivity"). However, nobody has investigated the microstructural integrity of whole brain white matter in people with Asperger syndrome. We measured the fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD) of white matter, using DT-MRI, in 13 adults with Asperger syndrome and 13 controls. The groups did not differ significantly in overall intelligence and age. FA, MD and RD were assessed using whole brain voxel-based techniques. Adults with Asperger syndrome had a significantly lower FA than controls in 13 clusters. These were largely bilateral and included white matter in the internal capsule, frontal, temporal, parietal and occipital lobes, cingulum and corpus callosum. Adults with Asperger syndrome have widespread significant differences from controls in white matter microstructural integrity.

Clinical associations of white matter damage in cART-treated HIV-positive children in South Africa.

PubMed

Hoare, Jacqueline; Fouche, Jean-Paul; Phillips, Nicole; Joska, John A; Donald, Kirsten A; Thomas, Kevin; Stein, Dan J

2015-04-01

A range of factors contributes to white matter damage in vertically infected HIV-positive children. These may include combination antiretroviral treatment (cART) regimen, sociodemographic factors, nutritional-hematological status, HIV-relevant clinical variables, and cognitive functioning. We explored associations between a number of these factors and diffusion tensor imaging (DTI) measures in 50 cART-treated children aged 6 to 15 years. Fractional anisotropy (FA), mean diffusion (MD), radial diffusion (RD), and axial diffusion (AD) were derived from 48 cerebral white matter regions. Significant associations between a number of the clinical variables and white matter integrity were found. Decreased FA, a measure of neuronal damage, was associated with being on second-line cART, low hemoglobin, and younger age. Children with increased MD, a measure of neuronal damage, were younger, had reduced albumin and hemoglobin, and increased viral load. Decreased AD, a measure of axonal damage, was associated with increased viral load and total protein, decreased albumin and hemoglobin, younger age, poorer fronto-striatal cognition, and being on second-line cART. Increased RD, a measure of myelin loss, was associated with younger age, low current CD4 count, low albumin and hemoglobin, and higher viral load and total protein. The current findings underline the possible association of first-line treatment failure with white matter brain dysfunction in pediatric neuroHIV and the importance of examining the effects of HIV disease in the context of treatable clinical variables such as anemia and nutritional status.

White Matter Maturation Supports the Development of Reasoning Ability Through its Influence on Processing Speed

PubMed Central

Ferrer, E.; Whitaker, K.J.; Steele, J.; Green, C.T.; Wendelken, C.; Bunge, S.A.

2013-01-01

The structure of the human brain changes in several ways throughout childhood and adolescence. Perhaps the most salient of these changes is the strengthening of white matter tracts that enable distal brain regions to communicate with one another more quickly and efficiently. Here, we sought to understand whether and how white matter changes contribute to improved reasoning ability over development. In particular, we sought to understand whether previously reported relationships between white matter microstructure and reasoning are mediated by processing speed. To this end, we analyzed diffusion tensor imaging data as well as data from standard psychometric tests of cognitive abilities from 103 individuals between the ages of 6 and 18. We used structural equation modeling to investigate the network of relationships between brain and behavior variables. Our analyses provide support for the hypothesis that white matter maturation (as indexed either by microstructural organization or volume) supports improved processing speed, which, in turn, supports improved reasoning ability. PMID:24118718

White matter maturation is associated with the emergence of Theory of Mind in early childhood

PubMed Central

Grosse Wiesmann, Charlotte; Schreiber, Jan; Singer, Tania; Steinbeis, Nikolaus; Friederici, Angela D.

2017-01-01

The ability to attribute mental states to other individuals is crucial for human cognition. A milestone of this ability is reached around the age of 4, when children start understanding that others can have false beliefs about the world. The neural basis supporting this critical step is currently unknown. Here, we relate this behavioural change to the maturation of white matter structure in 3- and 4-year-old children. Tract-based spatial statistics and probabilistic tractography show that the developmental breakthrough in false belief understanding is associated with age-related changes in local white matter structure in temporoparietal regions, the precuneus and medial prefrontal cortex, and with increased dorsal white matter connectivity between temporoparietal and inferior frontal regions. These effects are independent of co-developing cognitive abilities. Our findings show that the emergence of mental state representation is related to the maturation of core belief processing regions and their connection to the prefrontal cortex. PMID:28322222

White matter maturation is associated with the emergence of Theory of Mind in early childhood.

PubMed

Grosse Wiesmann, Charlotte; Schreiber, Jan; Singer, Tania; Steinbeis, Nikolaus; Friederici, Angela D

2017-03-21

The ability to attribute mental states to other individuals is crucial for human cognition. A milestone of this ability is reached around the age of 4, when children start understanding that others can have false beliefs about the world. The neural basis supporting this critical step is currently unknown. Here, we relate this behavioural change to the maturation of white matter structure in 3- and 4-year-old children. Tract-based spatial statistics and probabilistic tractography show that the developmental breakthrough in false belief understanding is associated with age-related changes in local white matter structure in temporoparietal regions, the precuneus and medial prefrontal cortex, and with increased dorsal white matter connectivity between temporoparietal and inferior frontal regions. These effects are independent of co-developing cognitive abilities. Our findings show that the emergence of mental state representation is related to the maturation of core belief processing regions and their connection to the prefrontal cortex.

Altered white matter microstructure in adolescent substance users.

PubMed

Bava, Sunita; Frank, Lawrence R; McQueeny, Tim; Schweinsburg, Brian C; Schweinsburg, Alecia D; Tapert, Susan F

2009-09-30

Chronic marijuana use during adolescence is frequently comorbid with heavy alcohol consumption and associated with CNS alterations, yet the influence of early cannabis and alcohol use on microstructural white matter integrity is unclear. Building on evidence that cannabinoid receptors are present in myelin precursors and affect glial cell processing, and that excessive ethanol exposure is associated with persistently impaired myelination, we used diffusion tensor imaging (DTI) to characterize white matter integrity in heavy substance using and non-using adolescents. We evaluated 36 marijuana and alcohol-using (MJ+ALC) adolescents (ages 16-19) and 36 demographically similar non-using controls with DTI. The diffusion parameters fractional anisotropy (FA) and mean diffusivity (MD) were subjected to whole-brain voxelwise group comparisons using tract-based spatial statistics (Smith, S.M., Jenkinson, M., Johansen-Berg, H., Rueckert, D., Nichols, T.E., Mackay, C.E., Watkins, K.E., Ciccarelli, O., Cader, M.Z., Matthews, P.M., Behrens, T.E., 2006. Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 31, 1487-1505). MJ+ALC teens had significantly lower FA than controls in 10 regions, including left superior longitudinal fasciculus (SLF), left postcentral gyrus, bilateral crus cerebri, and inferior frontal and temporal white matter tracts. These diminutions occurred in the context of increased FA in right occipital, internal capsule, and SLF regions. Changes in MD were less distributed, but increased MD was evident in the right occipital lobe, whereas the left inferior longitudinal fasciculus showed lower MD in MJ+ALC users. Findings suggest that fronto-parietal circuitry may be particularly impacted in adolescent users of the most prevalent intoxicants: marijuana and alcohol. Disruptions to white matter in this young group could indicate aberrant axonal and myelin maturation with resultant compromise of fiber integrity. Findings of

White Matter Disruptions in Schizophrenia Are Spatially Widespread and Topologically Converge on Brain Network Hubs.

PubMed

Klauser, Paul; Baker, Simon T; Cropley, Vanessa L; Bousman, Chad; Fornito, Alex; Cocchi, Luca; Fullerton, Janice M; Rasser, Paul; Schall, Ulrich; Henskens, Frans; Michie, Patricia T; Loughland, Carmel; Catts, Stanley V; Mowry, Bryan; Weickert, Thomas W; Shannon Weickert, Cynthia; Carr, Vaughan; Lenroot, Rhoshel; Pantelis, Christos; Zalesky, Andrew

2017-03-01

White matter abnormalities associated with schizophrenia have been widely reported, although the consistency of findings across studies is moderate. In this study, neuroimaging was used to investigate white matter pathology and its impact on whole-brain white matter connectivity in one of the largest samples of patients with schizophrenia. Fractional anisotropy (FA) and mean diffusivity (MD) were compared between patients with schizophrenia or schizoaffective disorder (n = 326) and age-matched healthy controls (n = 197). Between-group differences in FA and MD were assessed using voxel-based analysis and permutation testing. Automated whole-brain white matter fiber tracking and the network-based statistic were used to characterize the impact of white matter pathology on the connectome and its rich club. Significant reductions in FA associated with schizophrenia were widespread, encompassing more than 40% (234ml) of cerebral white matter by volume and involving all cerebral lobes. Significant increases in MD were also widespread and distributed similarly. The corpus callosum, cingulum, and thalamic radiations exhibited the most extensive pathology according to effect size. More than 50% of cortico-cortical and cortico-subcortical white matter fiber bundles comprising the connectome were disrupted in schizophrenia. Connections between hub regions comprising the rich club were disproportionately affected. Pathology did not differ between patients with schizophrenia and schizoaffective disorder and was not mediated by medication. In conclusion, although connectivity between cerebral hubs is most extensively disturbed in schizophrenia, white matter pathology is widespread, affecting all cerebral lobes and the cerebellum, leading to disruptions in the majority of the brain's fiber bundles. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Development of Tract-Specific White Matter Pathways During Early Reading Development in At-Risk Children and Typical Controls.

PubMed

Wang, Yingying; Mauer, Meaghan V; Raney, Talia; Peysakhovich, Barbara; Becker, Bryce L C; Sliva, Danielle D; Gaab, Nadine

2017-04-01

Developmental dyslexia is a neurodevelopmental disorder with a strong genetic basis. Previous studies observed white matter alterations in the left posterior brain regions in adults and school-age children with dyslexia. However, no study yet has examined the development of tract-specific white matter pathways from the pre-reading to the fluent reading stage in children at familial risk for dyslexia (FHD+) versus controls (FHD-). This study examined white matter integrity at pre-reading, beginning, and fluent reading stages cross-sectionally ( n = 78) and longitudinally (n = 45) using an automated fiber-tract quantification method. Our findings depict white matter alterations and atypical lateralization of the arcuate fasciculus at the pre-reading stage in FHD+ versus FHD- children. Moreover, we demonstrate faster white matter development in subsequent good versus poor readers and a positive association between white matter maturation and reading development using a longitudinal design. Additionally, the combination of white matter maturation, familial risk, and psychometric measures best predicted later reading abilities. Furthermore, within FHD+ children, subsequent good readers exhibited faster white matter development in the right superior longitudinal fasciculus compared with subsequent poor readers, suggesting a compensatory mechanism. Overall, our findings highlight the importance of white matter pathway maturation in the development of typical and atypical reading skills. Published by Oxford University Press 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Medial frontal white and gray matter contributions to general intelligence.

PubMed

Ohtani, Toshiyuki; Nestor, Paul G; Bouix, Sylvain; Saito, Yukiko; Hosokawa, Taiga; Kubicki, Marek

2014-01-01

The medial orbitofrontal cortex (mOFC) and rostral anterior cingulate cortex (rACC) are part of a wider neural network that plays an important role in general intelligence and executive function. We used structural brain imaging to quantify magnetic resonance gray matter volume and diffusion tensor white matter integrity of the mOFC-rACC network in 26 healthy participants who also completed neuropsychological tests of intellectual abilities and executive function. Stochastic tractography, the most effective Diffusion Tensor Imaging method for examining white matter connections between adjacent gray matter regions, was employed to assess the integrity of mOFC-rACC pathways. Fractional anisotropy (FA), which reflects the integrity of white matter connections, was calculated. Results indicated that higher intelligence correlated with greater gray matter volumes for both mOFC and rACC, as well as with increased FA for left posterior mOFC-rACC connectivity. Hierarchical regression analyses revealed that DTI-derived FA of left posterior mOFC-rACC uniquely accounted for 29%-34% of the variance in IQ, in comparison to 11%-16% uniquely explained by gray matter volume of the left rACC. Together, left rACC gray matter volume and white matter connectivity between left posterior mOFC and rACC accounted for up to 50% of the variance in general intelligence. This study is to our knowledge the first to examine white matter connectivity between OFC and ACC, two gray matter regions of interests that are very close in physical proximity, and underscores the important independent contributions of variations in rACC gray matter volume and mOFC-rACC white matter connectivity to individual differences in general intelligence.

White matter connectivity and aerobic fitness in male adolescents.

PubMed

Herting, Megan M; Colby, John B; Sowell, Elizabeth R; Nagel, Bonnie J

2014-01-01

Exercise has been shown to have positive effects on the brain and behavior throughout various stages of the lifespan. However, little is known about the impact of exercise on neurodevelopment during the adolescent years, particularly with regard to white matter microstructure, as assessed by diffusion tensor imaging (DTI). Both tract-based spatial statistics (TBSS) and tractography-based along-tract statistics were utilized to examine the relationship between white matter microstructure and aerobic exercise in adolescent males, ages 15-18. Furthermore, we examined the data by both (1) grouping individuals based on aerobic fitness self-reports (high fit (HF) vs. low fit (LF)), and (2) using VO2 peak as a continuous variable across the entire sample. Results showed that HF youth had an overall higher number of streamline counts compared to LF peers, which was driven by group differences in corticospinal tract (CST) and anterior corpus callosum (Fminor). In addition, VO2 peak was negatively related to FA in the left CST. Together, these results suggest that aerobic fitness relates to white matter connectivity and microstructure in tracts carrying frontal and motor fibers during adolescence. Furthermore, the current study highlights the importance of considering the environmental factor of aerobic exercise when examining adolescent brain development. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Diffusion tensor imaging with tract-based spatial statistics reveals local white matter abnormalities in preterm infants.

PubMed

Anjari, Mustafa; Srinivasan, Latha; Allsop, Joanna M; Hajnal, Joseph V; Rutherford, Mary A; Edwards, A David; Counsell, Serena J

2007-04-15

Infants born preterm have a high incidence of neurodevelopmental impairment in later childhood, often associated with poorly defined cerebral white matter abnormalities. Diffusion tensor imaging quantifies the diffusion of water within tissues and can assess microstructural abnormalities in the developing preterm brain. Tract-based spatial statistics (TBSS) is an automated observer-independent method of aligning fractional anisotropy (FA) images from multiple subjects to allow groupwise comparisons of diffusion tensor imaging data. We applied TBSS to test the hypothesis that preterm infants have reduced fractional anisotropy in specific regions of white matter compared to term-born controls. We studied 26 preterm infants with no evidence of focal lesions on conventional magnetic resonance imaging (MRI) at term equivalent age and 6 healthy term-born control infants. We found that the centrum semiovale, frontal white matter and the genu of the corpus callosum showed significantly lower FA in the preterm group. Infants born at less than or equal to 28 weeks gestational age (n=11) displayed additional reductions in FA in the external capsule, the posterior aspect of the posterior limb of the internal capsule and the isthmus and middle portion of the body of the corpus callosum. This study demonstrates that TBSS provides an observer-independent method of identifying white matter abnormalities in the preterm brain at term equivalent age in the absence of focal lesions.

Cortical Gray and Adjacent White Matter Demonstrate Synchronous Maturation in Very Preterm Infants.

PubMed

Smyser, Tara A; Smyser, Christopher D; Rogers, Cynthia E; Gillespie, Sarah K; Inder, Terrie E; Neil, Jeffrey J

2016-08-01

Spatial and functional gradients of development have been described for the maturation of cerebral gray and white matter using histological and radiological approaches. We evaluated these patterns in very preterm (VPT) infants using diffusion tensor imaging. Data were obtained from 3 groups: 1) 22 VPT infants without white matter injury (WMI), of whom all had serial MRI studies during the neonatal period, 2) 19 VPT infants with WMI, of whom 3 had serial MRI studies and 3) 12 healthy, term-born infants. Regions of interest were placed in the cortical gray and adjacent white matter in primary motor, primary visual, visual association, and prefrontal regions. From the MRI data at term-equivalent postmenstrual age, differences in mean diffusivity were found in all areas between VPT infants with WMI and the other 2 groups. In contrast, minimal differences in fractional anisotropy were found between the 3 groups. These findings suggest that cortical maturation is delayed in VPT infants with WMI when compared with term control infants and VPT infants without WMI. From the serial MRI data from VPT infants, synchronous development between gray and white matter was evident in all areas and all groups, with maturation in primary motor and sensory regions preceding that of association areas. This finding highlights the regionally varying but locally synchronous nature of the development of cortical gray matter and its adjacent white matter. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Mapping of ApoE4 related white matter damage using diffusion MRI

NASA Astrophysics Data System (ADS)

Tsao, Sinchai; Gajawelli, Niharika; Hwang, Darryl H.; Kriger, Stephen; Law, Meng; Chui, Helena; Weiner, Michael; Lepore, Natasha

2014-04-01

ApoliopoproteinE Ɛ4 (ApoE-Ɛ4) polymorphism is the most well known genetic risk factor for developing Alzheimers Disease. The exact mechanism through which ApoE 4 increases AD risk is not fully known, but may be related to decreased clearance and increased oligomerization of Aβ. By making measurements of white matter integrity via diffusion MR and correlating the metrics in a voxel-based statistical analysis with ApoE-Ɛ4 genotype (whilst controlling for vascular risk factor, gender, cognitive status and age) we are able to identify changes in white matter associated with carrying an ApoE Ɛ4 allele. We found potentially significant regions (Puncorrected < 0:05) near the hippocampus and the posterior cingulum that were independent of voxels that correlated with age or clinical dementia rating (CDR) status suggesting that ApoE may affect cognitive decline via a pathway in dependent of normal aging and acute insults that can be measured by CDR and Framingham Coronary Risk Score (FCRS).

Inflammation in White Matter: Clinical and Pathophysiological Aspects

ERIC Educational Resources Information Center

Pleasure, David; Soulika, Athena; Singh, Sunit K.; Gallo, Vittorio; Bannerman, Peter

2006-01-01

While the central nervous system (CNS) is generally thought of as an immunopriviledged site, immune-mediated CNS white matter damage can occur in both the perinatal period and in adults, and can result in severe and persistent neurological deficits. Periventricular leukomalacia (PVL) is an inflammatory white matter disease of premature infants…

Does white matter structure or hippocampal volume mediate associations between cortisol and cognitive ageing?

PubMed Central

Cox, Simon R.; MacPherson, Sarah E.; Ferguson, Karen J.; Royle, Natalie A.; Maniega, Susana Muñoz; Hernández, Maria del C. Valdés; Bastin, Mark E.; MacLullich, Alasdair M.J.; Wardlaw, Joanna M.; Deary, Ian J.

2015-01-01

Elevated glucocorticoid (GC) levels putatively damage specific brain regions, which in turn may accelerate cognitive ageing. However, many studies are cross-sectional or have relatively short follow-up periods, making it difficult to relate GCs directly to changes in cognitive ability with increasing age. Moreover, studies combining endocrine, MRI and cognitive variables are scarce, measurement methods vary considerably, and formal tests of the underlying causal hypothesis (cortisol → brain → cognition) are absent. In this study, 90 men, aged 73 years, provided measures of fluid intelligence, processing speed and memory, diurnal and reactive salivary cortisol and two measures of white matter (WM) structure (WM hyperintensity volume from structural MRI and mean diffusivity averaged across 12 major tracts from diffusion tensor MRI), hippocampal volume, and also cognitive ability at age 11. We tested whether negative relationships between cognitive ageing differences (over more than 60 years) and salivary cortisol were significantly mediated by WM and hippocampal volume. Significant associations between reactive cortisol at 73 and cognitive ageing differences between 11 and 73 (r = −.28 to −.36, p < .05) were partially mediated by both WM structural measures, but not hippocampal volume. Cortisol-WM relationships were modest, as was the degree to which WM structure attenuated cortisol–cognition associations (<15%). These data support the hypothesis that GCs contribute to cognitive ageing differences from childhood to the early 70s, partly via brain WM structure. PMID:26298692

Maternal Dietary Choline Status Influences Brain Gray and White Matter Development in Young Pigs

PubMed Central

Mudd, Austin T; Getty, Caitlyn M; Dilger, Ryan N

2018-01-01

Abstract Background Choline is an essential nutrient that is pivotal to proper brain development. Research in animal models suggests that perinatal choline deficiency influences neuron development in the hippocampus and cortex, yet these observations require invasive techniques. Objective This study aimed to characterize the effects of perinatal choline deficiency on gray and white matter development with the use of noninvasive neuroimaging techniques in young pigs. Methods During the last 64 d of the 114-d gestation period Yorkshire sows were provided with a choline-sufficient (CS) or choline-deficient (CD) diet, analyzed to contain 1214 mg or 483 mg total choline/kg diet, respectively. Upon farrowing, pigs (Sus scrofa domesticus) were allowed colostrum consumption for ≤48 h, were further stratified into postnatal treatment groups, and were provided either CS or CD milk replacers, analyzed to contain 1591 or 518 mg total choline/kg diet, respectively, for 28 d. At 30 d of age, pigs were subjected to MRI procedures to assess brain development. Gray and white matter development was assessed through voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) to assess the effects of prenatal and postnatal dietary choline status. Results VBM analysis indicated that prenatally CS pigs exhibited increased (P < 0.01) gray matter in the left and right cortex compared with prenatally CD pigs. Analysis of white matter indicated that prenatally CS pigs exhibited increased (P < 0.01) white matter in the internal capsule, putamen–globus pallidus, and right cortex compared with prenatally CD pigs. No postnatal effects (P > 0.05) of choline status were noted for VBM analyses of gray and white matter. TBSS also showed no significant effects (P > 0.05) of prenatal or postnatal choline status for diffusion values along white matter tracts. Conclusions Observations from this study suggest that prenatal choline deficiency results in altered cortical gray

Effects of Aerobic Capacity on Thrombin-Induced Hydrocephalus and White Matter Injury.

PubMed

Ni, Wei; Gao, Feng; Zheng, Mingzhe; Koch, Lauren G; Britton, Steven L; Keep, Richard F; Xi, Guohua; Hua, Ya

2016-01-01

We have previously shown that intracerebral hemorrhage-induced brain injury is less in rats bred for high aerobic capacity (high capacity runners; HCR) compared with those bred for low aerobic capacity (low capacity runners; LCRs). Thrombin, an essential component in the coagulation cascade, is produced after cerebral hemorrhage. Intraventricular injection of thrombin causes significant hydrocephalus and white matter damage. In the present study, we examined the effect of exercise capacity on thrombin-induced hydrocephalus and white matter damage. Mid-aged (13-month-old) female LCRs (n = 13) and HCRs (n = 12) rats were used in this study. Rats received an intraventricular injection of thrombin (3 U, 50 μl). All rats underwent magnetic resonance imaging (MRI) at 24 h and were then euthanized for brain histology and Western blot. The mortalities were 20 % in LCRs and 33 % in HCRs after thrombin injection (p > 0.05). No rats died after saline injection. Intraventricular thrombin injection resulted in hydrocephalus and periventricular white matter damage as determined on MRI. In LCR rats, thrombin induced significant ventricle enlargement (23.0 ± 2.3 vs12.8 ± 1.9 mm(3) in LCR saline group; p < 0.01) and white matter lesion (9.3 ± 7.6 vs 0.6 ± 0.5 mm(3) in LCR saline group, p < 0.05). In comparison, in HCR rats thrombin induced less ventricular enlargement (17.3 ± 3.9 vs 23.0 ± 2.3 mm(3) in LCRs, p < 0.01) and smaller white matter lesions (2.6 ± 1.2 mm(3) vs 9.3 ± 7.6 mm(3) in LCRs, p < 0.05). In LCR rats, there was also upregulation of heat shock protein-32, a stress marker, and microglial activation in the periventricular white matter. These changes were significantly reduced in HCR rats. Intraventricular injection of thrombin caused more white matter damage and hydrocephalus in rats with low aerobic capacity. A differential effect of thrombin may contribute to differences in the effects of cerebral

Effects of low-level sarin and cyclosarin exposure on white matter integrity in Gulf War Veterans.

PubMed

Chao, Linda L; Zhang, Yu; Buckley, Shannon

2015-05-01

We previously found evidence of reduced gray and white matter volume in Gulf War (GW) veterans with predicted low-level exposure to sarin (GB) and cyclosarin (GF). Because loss of white matter tissue integrity has been linked to both gray and white matter atrophy, the current study sought to test the hypothesis that GW veterans with predicted GB/GF exposure have evidence of disrupted white matter microstructural integrity. Measures of fractional anisotropy and directional (i.e., axial and radial) diffusivity were assessed from the 4T diffusion tensor images (DTI) of 59 GW veterans with predicted GB/GF exposure and 59 "matched" unexposed GW veterans (mean age: 48 ± 7 years). The DTI data were analyzed using regions of interest (ROI) analyses that accounted for age, sex, total brain gray and white matter volume, trauma exposure, posttraumatic stress disorder, current major depression, and chronic multisymptom illness status. There were no significant group differences in fractional anisotropy or radial diffusivity. However, there was increased axial diffusivity in GW veterans with predicted GB/GF exposure compared to matched, unexposed veterans throughout the brain, including the temporal stem, corona radiata, superior and inferior (hippocampal) cingulum, inferior and superior fronto-occipital fasciculus, internal and external capsule, and superficial cortical white matter blades. Post hoc analysis revealed significant correlations between higher fractional anisotropy and lower radial diffusivity with better neurobehavioral performance in unexposed GW veterans. In contrast, only increased axial diffusivity in posterior limb of the internal capsule was associated with better psychomotor function in GW veterans with predicted GB/GF exposure. The finding that increased axial diffusivity in a region of the brain that contains descending corticospinal fibers was associated with better psychomotor function and the lack of significant neurobehavioral deficits in veterans

Influence of cerebral white matter lesions on the activities of daily living of older patients with mild stroke.

PubMed

Yamashita, Yutaka; Wada, Ikuo; Horiba, Mitsuya; Sahashi, Kento

2016-08-01

Neurological symptom severity is a prognostic factor for post-stroke activities of daily living (ADL). Recently, it has been reported that white matter lesions indicate poor functional prognosis in patients with stroke. The present study investigated the influence of white matter lesions on the ADL of older patients with stroke who have mild neurological symptoms. We investigated ADL at discharge in 44 patients with stroke (men, n = 27; women, n = 17; mean age 78 years [range 71-85 years]) aged ≥65 years with National Institutes of Health Stroke Scale scores of ≤5 (cerebral infarction, n = 37; cerebral hemorrhage, n = 7). We used single correlation analysis and multiple regression analysis to investigate factors that correlated with ADL at discharge. ADL at discharge was also evaluated on the basis of white matter lesion severity (Fazekas classification, grades 0-3). Single correlation analysis showed that age (r = -0.36, P = 0.016), male sex (r = 0.362, P = 0.016), neurological symptom severity (r = -0.361, P = 0.016), ADL on starting rehabilitation (r = 0.685, P < 0.001) and white matter lesion severity (r = -0.361, P = 0.016) significantly correlated with ADL at discharge. Multiple regression analysis showed that ADL on starting rehabilitation (β = 0.519, t = 4.723, P < 0.001) and white matter lesion severity (β = -0.309, t = -3.057, P < 0.01) were statistically significant prognostic factors for ADL at discharge. ADL at discharge score was significantly lower in the group with high white matter lesion severity (Fazekas, grade 2) than in the other two groups (Fazekas, grade 0, P < 0.01; Fazekas, grade 1, P < 0.05). Severe white matter lesions are a prognostic factor for poor ADL at discharge in older patients with stroke who have mild neurological symptoms. Geriatr Gerontol Int 2016; 16: 942-947. © 2015 Japan Geriatrics Society.

Sensitive period for white-matter connectivity of superior temporal cortex in deaf people.

PubMed

Li, Yanyan; Ding, Guosheng; Booth, James R; Huang, Ruiwang; Lv, Yating; Zang, Yufeng; He, Yong; Peng, Danling

2012-02-01

Previous studies have shown that white matter in the deaf brain changes due to hearing loss. However, how white-matter development is influenced by early hearing experience of deaf people is still unknown. Using diffusion tensor imaging and tract-based spatial statistics, we compared white-matter structures among three groups of subjects including 60 congenitally deaf individuals, 36 acquired deaf (AD) individuals, and 38 sex- and age-matched hearing controls (HC). The result showed that the deaf individuals had significantly reduced fractional anisotropy (FA) values in bilateral superior temporal cortex and the splenium of corpus callosum compared to HC. The reduction of FA values in acquired deafness correlated with onset age of deafness, but not the duration of deafness. To explore the underlying mechanism of FA changes in the deaf groups, we further analyzed radial and axial diffusivities and found that (1) the reduced FA values in deaf individuals compared to HC is primarily driven by higher radial diffusivity values and (2) in the AD, higher radial diffusivity was correlated with earlier onset age of deafness, but not the duration of deafness. These findings imply that early sensory experience is critical for the growth of fiber myelination, and anatomical reorganization following auditory deprivation is sensitive to early plasticity in the brain. Copyright © 2010 Wiley Periodicals, Inc.

Quantitative T2 mapping of white matter: applications for ageing and cognitive decline

NASA Astrophysics Data System (ADS)

Knight, Michael J.; McCann, Bryony; Tsivos, Demitra; Dillon, Serena; Coulthard, Elizabeth; Kauppinen, Risto A.

2016-08-01

In MRI, the coherence lifetime T2 is sensitive to the magnetic environment imposed by tissue microstructure and biochemistry in vivo. Here we explore the possibility that the use of T2 relaxometry may provide information complementary to that provided by diffusion tensor imaging (DTI) in ageing of healthy controls (HC), Alzheimer’s disease (AD) and mild cognitive impairment (MCI). T2 and diffusion MRI metrics were quantified in HC and patients with MCI and mild AD using multi-echo MRI and DTI. We used tract-based spatial statistics (TBSS) to evaluate quantitative MRI parameters in white matter (WM). A prolonged T2 in WM was associated with AD, and able to distinguish AD from MCI, and AD from HC. Shorter WM T2 was associated with better cognition and younger age in general. In no case was a reduction in T2 associated with poorer cognition. We also applied principal component analysis, showing that WM volume changes independently of  T2, MRI diffusion indices and cognitive performance indices. Our data add to the evidence that age-related and AD-related decline in cognition is in part attributable to WM tissue state, and much less to WM quantity. These observations suggest that WM is involved in AD pathology, and that T2 relaxometry is a potential imaging modality for detecting and characterising WM in cognitive decline and dementia.

Characterization of White Matter Injury in a Rat Model of Chronic Cerebral Hypoperfusion.

PubMed

Choi, Bo-Ryoung; Kim, Dong-Hee; Back, Dong Bin; Kang, Chung Hwan; Moon, Won-Jin; Han, Jung-Soo; Choi, Dong-Hee; Kwon, Kyoung Ja; Shin, Chan Young; Kim, Bo-Ram; Lee, Jongmin; Han, Seol-Heui; Kim, Hahn Young

2016-02-01

Chronic cerebral hypoperfusion can lead to ischemic white matter injury resulting in vascular dementia. To characterize white matter injury in vascular dementia, we investigated disintegration of diverse white matter components using a rat model of chronic cerebral hypoperfusion. Chronic cerebral hypoperfusion was modeled in Wistar rats by permanent occlusion of the bilateral common carotid arteries. We performed cognitive behavioral tests, including the water maze task, odor discrimination task, and novel object test; histological investigation of neuroinflammation, oligodendrocytes, myelin basic protein, and nodal or paranodal proteins at the nodes of Ranvier; and serial diffusion tensor imaging. Cilostazol was administered to protect against white matter injury. Diverse cognitive impairments were induced by chronic cerebral hypoperfusion. Disintegration of white matter was characterized by neuroinflammation, loss of oligodendrocytes, attenuation of myelin density, structural derangement at the nodes of Ranvier, and disintegration of white matter tracts. Cilostazol protected against cognitive impairments and white matter disintegration. White matter injury induced by chronic cerebral hypoperfusion can be characterized by disintegration of diverse white matter components. Cilostazol might be a therapeutic strategy against white matter disintegration in patients with vascular dementia. © 2015 American Heart Association, Inc.

White matter correlates of sensory processing in autism spectrum disorders

PubMed Central

Pryweller, Jennifer R.; Schauder, Kimberly B.; Anderson, Adam W.; Heacock, Jessica L.; Foss-Feig, Jennifer H.; Newsom, Cassandra R.; Loring, Whitney A.; Cascio, Carissa J.

2014-01-01

Autism spectrum disorder (ASD) has been characterized by atypical socio-communicative behavior, sensorimotor impairment and abnormal neurodevelopmental trajectories. DTI has been used to determine the presence and nature of abnormality in white matter integrity that may contribute to the behavioral phenomena that characterize ASD. Although atypical patterns of sensory responding in ASD are well documented in the behavioral literature, much less is known about the neural networks associated with aberrant sensory processing. To address the roles of basic sensory, sensory association and early attentional processes in sensory responsiveness in ASD, our investigation focused on five white matter fiber tracts known to be involved in these various stages of sensory processing: superior corona radiata, centrum semiovale, inferior longitudinal fasciculus, posterior limb of the internal capsule, and splenium. We acquired high angular resolution diffusion images from 32 children with ASD and 26 typically developing children between the ages of 5 and 8. We also administered sensory assessments to examine brain-behavior relationships between white matter integrity and sensory variables. Our findings suggest a modulatory role of the inferior longitudinal fasciculus and splenium in atypical sensorimotor and early attention processes in ASD. Increased tactile defensiveness was found to be related to reduced fractional anisotropy in the inferior longitudinal fasciculus, which may reflect an aberrant connection between limbic structures in the temporal lobe and the inferior parietal cortex. Our findings also corroborate the modulatory role of the splenium in attentional orienting, but suggest the possibility of a more diffuse or separable network for social orienting in ASD. Future investigation should consider the use of whole brain analyses for a more robust assessment of white matter microstructure. PMID:25379451

The brain in myotonic dystrophy 1 and 2: evidence for a predominant white matter disease

PubMed Central

Weber, Bernd; Schoene-Bake, Jan-Christoph; Roeske, Sandra; Mirbach, Sandra; Anspach, Christian; Schneider-Gold, Christiane; Betz, Regina C.; Helmstaedter, Christoph; Tittgemeyer, Marc; Klockgether, Thomas; Kornblum, Cornelia

2011-01-01

more prominent in patients with myotonic dystrophy type 1 with less white matter affection (early disease stages), contrary to patients with myotonic dystrophy type 2. Thus, depression in myotonic dystrophies might be a reactive adjustment disorder rather than a direct consequence of structural brain damage. Associations of white matter affection with age/disease duration as well as patterns of cerebral water diffusion parameters pointed towards an ongoing process of myelin destruction and/or axonal loss in our cross-sectional study design. Our data suggest that both myotonic dystrophy types 1 and 2 are serious white matter diseases with prominent callosal body and limbic system affection. White matter changes dominated the extent of grey matter changes, which might argue against Wallerian degeneration as the major cause of white matter affection in myotonic dystrophies. PMID:22131273

Creatine, Glutamine plus Glutamate, and Macromolecules Are Decreased in the Central White Matter of Premature Neonates around Term

PubMed Central

Le Fur, Yann; Viout, Patrick; Ratiney, Hélène; Confort-Gouny, Sylviane; Cozzone, Patrick J.; Girard, Nadine

2016-01-01

Preterm birth represents a high risk of neurodevelopmental disabilities when associated with white-matter damage. Recent studies have reported cognitive deficits in children born preterm without brain injury on MRI at term-equivalent age. Understanding the microstructural and metabolic underpinnings of these deficits is essential for their early detection. Here, we used diffusion-weighted imaging and single-voxel 1H magnetic resonance spectroscopy (MRS) to compare brain maturation at term-equivalent age in premature neonates with no evidence of white matter injury on conventional MRI except diffuse excessive high-signal intensity, and normal term neonates. Thirty-two infants, 16 term neonates (mean post-conceptional age at scan: 39.8±1 weeks) and 16 premature neonates (mean gestational age at birth: 29.1±2 weeks, mean post-conceptional age at scan: 39.2±1 weeks) were investigated. The MRI/MRS protocol performed at 1.5T involved diffusion-weighted MRI and localized 1H-MRS with the Point RESolved Spectroscopy (PRESS) sequence. Preterm neonates showed significantly higher ADC values in the temporal white matter (P<0.05), the occipital white matter (P<0.005) and the thalamus (P<0.05). The proton spectrum of the centrum semiovale was characterized by significantly lower taurine/H2O and macromolecules/H2O ratios (P<0.05) at a TE of 30 ms, and reduced (creatine+phosphocreatine)/H2O and (glutamine+glutamate)/H2O ratios (P<0.05) at a TE of 135 ms in the preterm neonates than in full-term neonates. Our findings indicate that premature neonates with normal conventional MRI present a delay in brain maturation affecting the white matter and the thalamus. Their brain metabolic profile is characterized by lower levels of creatine, glutamine plus glutamate, and macromolecules in the centrum semiovale, a finding suggesting altered energy metabolism and protein synthesis. PMID:27547969

Vanishing White Matter Disease: A Review with Focus on Its Genetics

ERIC Educational Resources Information Center

Pronk, Jan C.; van Kollenburg, Barbara; Scheper, Gert C.; van der Knaap, Marjo S.

2006-01-01

Leukoencephalopathy with vanishing white matter (VWM) is an autosomal recessive brain disorder, most often with a childhood onset. Magnetic resonance imaging and spectroscopy indicate that, with time, increasing amounts of cerebral white matter vanish and are replaced by fluid. Autopsy confirms white matter rarefaction and cystic degeneration. The…

Thalamic diffusion differences related to cognitive function in white matter lesions.

PubMed

Fernández-Andújar, Marina; Soriano-Raya, Juan José; Miralbell, Júlia; López-Cancio, Elena; Cáceres, Cynthia; Bargalló, Núria; Barrios, Maite; Arenillas, Juan Francisco; Toran, Pere; Alzamora, Maite; Clemente, Imma; Dávalos, Antoni; Mataró, Maria

2014-05-01

Cerebral white matter lesions (WMLs) are related to cognitive deficits, probably due to a disruption of frontal-subcortical circuits. We explored thalamic diffusion differences related to white matter lesions (WMLs) and their association with cognitive function in middle-aged individuals. Ninety-six participants from the Barcelona-AsIA Neuropsychology Study were included. Participants were classified into groups based on low grade and high grade of periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs). Tract-Based Spatial Statistics was used to study thalamic diffusion differences between groups. Mean fractional anisotropy (FA) values in significant areas were calculated for each subject and correlated with cognitive performance. Participants with high-grade PVHs and DWMHs showed lower FA thalamic values compared to those with low-grade PVHs and DWMHs, respectively. Decreased FA thalamic values in high-grade DWMHs, but not high-grade PVH, were related to lower levels of performance in psychomotor speed, verbal fluency, and visuospatial skills. Thalamic diffusion differences are related to lower cognitive function only in participants with high-grade DWMHs. These results support the hypothesis that fronto-subcortical disruption is associated with cognitive function only in DWMHs. Copyright © 2014 Elsevier Inc. All rights reserved.

White Matter Injury and General Movements in High-Risk Preterm Infants.

PubMed

Peyton, C; Yang, E; Msall, M E; Adde, L; Støen, R; Fjørtoft, T; Bos, A F; Einspieler, C; Zhou, Y; Schreiber, M D; Marks, J D; Drobyshevsky, A

2017-01-01

Very preterm infants (birth weight, <1500 g) are at increased risk of cognitive and motor impairment, including cerebral palsy. These adverse neurodevelopmental outcomes are associated with white matter abnormalities on MR imaging at term-equivalent age. Cerebral palsy has been predicted by analysis of spontaneous movements in the infant termed "General Movement Assessment." The goal of this study was to determine the utility of General Movement Assessment in predicting adverse cognitive, language, and motor outcomes in very preterm infants and to identify brain imaging markers associated with both adverse outcomes and aberrant general movements. In this prospective study of 47 preterm infants of 24-30 weeks' gestation, brain MR imaging was performed at term-equivalent age. Infants underwent T1- and T2-weighted imaging for volumetric analysis and DTI. General movements were assessed at 10-15 weeks' postterm age, and neurodevelopmental outcomes were evaluated at 2 years by using the Bayley Scales of Infant and Toddler Development III. Nine infants had aberrant general movements and were more likely to have adverse neurodevelopmental outcomes, compared with infants with normal movements. In infants with aberrant movements, Tract-Based Spatial Statistics analysis identified significantly lower fractional anisotropy in widespread white matter tracts, including the corpus callosum, inferior longitudinal and fronto-occipital fasciculi, internal capsule, and optic radiation. The subset of infants having both aberrant movements and abnormal neurodevelopmental outcomes in cognitive, language, and motor skills had significantly lower fractional anisotropy in specific brain regions. Aberrant general movements at 10-15 weeks' postterm are associated with adverse neurodevelopmental outcomes and specific white matter microstructure abnormalities for cognitive, language, and motor delays. © 2017 by American Journal of Neuroradiology.

Brain-peripheral cell crosstalk in white matter damage and repair.

PubMed

Hayakawa, Kazuhide; Lo, Eng H

2016-05-01

White matter damage is an important part of cerebrovascular disease and may be a significant contributing factor in vascular mechanisms of cognitive dysfunction and dementia. It is well accepted that white matter homeostasis involves multifactorial interactions between all cells in the axon-glia-vascular unit. But more recently, it has been proposed that beyond cell-cell signaling within the brain per se, dynamic crosstalk between brain and systemic responses such as circulating immune cells and stem/progenitor cells may also be important. In this review, we explore the hypothesis that peripheral cells contribute to damage and repair after white matter damage. Depending on timing, phenotype and context, monocyte/macrophage can possess both detrimental and beneficial effects on oligodendrogenesis and white matter remodeling. Endothelial progenitor cells (EPCs) can be activated after CNS injury and the response may also influence white matter repair process. These emerging findings support the hypothesis that peripheral-derived cells can be both detrimental or beneficial in white matter pathology in cerebrovascular disease. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. Copyright © 2015 Elsevier B.V. All rights reserved.

White dwarf stars: cosmic chronometers and dark matter probes

NASA Astrophysics Data System (ADS)

Salaris, Maurizio; Cassisi, Santi

2018-04-01

White dwarfs (WD) are the endpoint of the evolution of the large majority of stars formed in our galaxy. In the last two decades observations and theory have improved to a level that makes it possible to employ WD for determining ages of the stellar populations in the disk of the Milky Way and in the nearest star clusters, and constrain the existence and properties of dark matter (DM) candidates. This review is centred on WD models, age-dating, and DM identification methods, recent results and future developments of the field.

Microstructural white matter tract alteration in Prader-Willi syndrome: A diffusion tensor imaging study.

PubMed

Rice, Lauren J; Lagopoulos, Jim; Brammer, Michael; Einfeld, Stewart L

2017-09-01

Prader-Willi Syndrome (PWS) is a genetic disorder characterized by infantile hypotonia, hyperphagia, hypogonadism, growth hormone deficiency, intellectual disability, and severe emotional and behavioral problems. The brain mechanisms that underpin these disturbances are unknown. Diffusion tensor imaging (DTI) enables in vivo investigation of the microstructural integrity of white matter pathways. To date, only one study has used DTI to examine white matter alterations in PWS. However, that study used selected regions of interest, rather than a whole brain analysis. In the present study, we used diffusion tensor and magnetic resonance (T 1-weighted) imaging to examine microstructural white matter changes in 15 individuals with PWS (17-30 years) and 15 age-and-gender-matched controls. Whole-brain voxel-wise statistical analysis of FA was carried out using tract-based spatial statistics (TBSS). Significantly decreased fractional anisotropy was found localized to the left hemisphere in individuals with PWS within the splenium of the corpus callosum, the internal capsule including the posterior thalamic radiation and the inferior frontal occipital fasciculus (IFOF). Reduced integrity of these white matter pathways in individuals with PWS may relate to orientating attention, emotion recognition, semantic processing, and sensorimotor dysfunction. © 2017 Wiley Periodicals, Inc.

Testing the hypothesis of accelerated cerebral white matter aging in schizophrenia and major depression.

PubMed

Kochunov, Peter; Glahn, David C; Rowland, Laura M; Olvera, Rene L; Winkler, Anderson; Yang, Yi-Hong; Sampath, Hemalatha; Carpenter, Will T; Duggirala, Ravindranath; Curran, Joanne; Blangero, John; Hong, L Elliot

2013-03-01

Elevated rate of aging-related biological and functional decline, termed "accelerated aging," is reported in patients with schizophrenia (SCZ) and major depressive disorder (MDD). We used diffusion tensor imaging derived fractional anisotropy (FA) as a biomarker of aging-related decline in white matter (WM) integrity to test the hypotheses of accelerated aging in SCZ and MDD. The SCZ cohort comprised 58 SCZ patients and 60 controls (aged 20-60 years). The MDD cohort comprised 136 MDD patients and 351 controls (aged 20-79 years). The main outcome measures were the diagnosis-by-age interaction on whole-brain-averaged WM FA values and FA values from 12 major WM tracts. Diagnosis-by-age interaction for the whole-brain average FA was significant for the SCZ (p = .04) but not the MDD (p = .80) cohort. Diagnosis-by-age interaction was nominally significant (p<.05) for five WM tracts for SCZ and for none of the tracts in the MDD cohort. Tract-specific heterochronicity of the onset of age-related decline in SCZ demonstrated strong negative correlations with the age-of-peak myelination and the rates of age-related decline obtained from normative sample (r =-.61 and-.80, p<.05, respectively). No such trends existed for MDD cohort. Cerebral WM showed accelerated aging in SCZ but not in MDD, suggesting some difference in the pathophysiology underlying their WM aging changes. Tract-specific heterochronicity of WM development modulated presentation of accelerated aging in SCZ: WM tracts that matured later in life appeared more sensitive to the pathophysiology of SCZ and demonstrated more susceptibility to disorder-related accelerated decline in FA values with age. This trend was not observed in MDD cohort. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Mechanical properties of gray and white matter brain tissue by indentation

PubMed Central

Budday, Silvia; Nay, Richard; de Rooij, Rijk; Steinmann, Paul; Wyrobek, Thomas; Ovaert, Timothy C.; Kuhl, Ellen

2015-01-01

The mammalian brain is composed of an outer layer of gray matter, consisting of cell bodies, dendrites, and unmyelinated axons, and an inner core of white matter, consisting primarily of myelinated axons. Recent evidence suggests that microstructural differences between gray and white matter play an important role during neurodevelopment. While brain tissue as a whole is rheologically well characterized, the individual features of gray and white matter remain poorly understood. Here we quantify the mechanical properties of gray and white matter using a robust, reliable, and repeatable method, flat-punch indentation. To systematically characterize gray and white matter moduli for varying indenter diameters, loading rates, holding times, post-mortem times, and locations we performed a series of n=192 indentation tests. We found that indenting thick, intact coronal slices eliminates the common challenges associated with small specimens: it naturally minimizes boundary effects, dehydration, swelling, and structural degradation. When kept intact and hydrated, brain slices maintained their mechanical characteristics with standard deviations as low as 5% throughout the entire testing period of five days post mortem. White matter, with an average modulus of 1.895kPa±0.592kPa, was on average 39% stiffer than gray matter, p<0.01, with an average modulus of 1.389kPa±0.289kPa, and displayed larger regional variations. It was also more viscous than gray matter and responded less rapidly to mechanical loading. Understanding the rheological differences between gray and white matter may have direct implications on diagnosing and understanding the mechanical environment in neurodevelopment and neurological disorders. PMID:25819199

Increased White Matter Gyral Depth in Dyslexia: Implications for Corticocortical Connectivity

ERIC Educational Resources Information Center

Casanova, Manuel F.; El-Baz, Ayman S.; Giedd, Jay; Rumsey, Judith M.; Switala, Andrew E.

2010-01-01

Recent studies provide credence to the minicolumnar origin of several developmental conditions, including dyslexia. Characteristics of minicolumnopathies include abnormalities in how the cortex expands and folds. This study examines the depth of the gyral white matter measured in an MRI series of 15 dyslexic adult men and eleven age-matched…

White matter microstructure in boys with persistent depressive disorder.

PubMed

Vilgis, Veronika; Vance, Alasdair; Cunnington, Ross; Silk, Timothy J

2017-10-15

Persistent depressive symptoms in children and adolescents are considered a risk factor for the development of major depressive disorder (MDD) later in life. Previous research has shown alterations in white matter microstructure in pediatric MDD but discrepancies exist as to the specific tracts affected. The current study aimed to improve upon previous methodology and address the question whether previous findings of lower fractional anisotropy (FA) replicate in a sample of children with persistent depressive disorder characterized by mild but more chronic symptoms of depression. White matter microstructure was examined in 25 boys with persistent depressive disorder and 25 typically developing children. Tract specific analysis implemented with the Diffusion Tensor Imaging - ToolKit (DTI-TK) was used to probe fractional anisotropy (FA) in eleven major white matter tracts. Clusters within the left uncinate, inferior fronto-occipital and cerebrospinal tracts showed lower FA in the clinical group. FA in the left uncinate showed a negative association with self-reported symptoms of depression. The results demonstrate lower FA in several white matter tracts in children with persistent depressive disorder. These findings support the contention that early onset depression is associated with altered white matter microstructure, which may contribute to the maintenance and recurrence of symptoms. Copyright © 2017. Published by Elsevier B.V.

White matter tractography using diffusion tensor deflection.

PubMed

Lazar, Mariana; Weinstein, David M; Tsuruda, Jay S; Hasan, Khader M; Arfanakis, Konstantinos; Meyerand, M Elizabeth; Badie, Benham; Rowley, Howard A; Haughton, Victor; Field, Aaron; Alexander, Andrew L

2003-04-01

Diffusion tensor MRI provides unique directional diffusion information that can be used to estimate the patterns of white matter connectivity in the human brain. In this study, the behavior of an algorithm for white matter tractography is examined. The algorithm, called TEND, uses the entire diffusion tensor to deflect the estimated fiber trajectory. Simulations and imaging experiments on in vivo human brains were performed to investigate the behavior of the tractography algorithm. The simulations show that the deflection term is less sensitive than the major eigenvector to image noise. In the human brain imaging experiments, estimated tracts were generated in corpus callosum, corticospinal tract, internal capsule, corona radiata, superior longitudinal fasciculus, inferior longitudinal fasciculus, fronto-occipital fasciculus, and uncinate fasciculus. This approach is promising for mapping the organizational patterns of white matter in the human brain as well as mapping the relationship between major fiber trajectories and the location and extent of brain lesions. Copyright 2003 Wiley-Liss, Inc.

Sex-related difference in human white matter volumes studied: Inspection of the corpus callosum and other white matter by VBM

NASA Astrophysics Data System (ADS)

Shiino, Akihiko; Chen, Yen-Wei; Tanigaki, Kenji; Yamada, Atsushi; Vigers, Piers; Watanabe, Toshiyuki; Tooyama, Ikuo; Akiguchi, Ichiro

2017-01-01

It has been contended that any observed difference of the corpus callosum (CC) size between men and women is not sex-related but brain-size-related. A recent report, however, showed that the midsagittal CC area was significantly larger in women in 37 brain-size-matched pairs of normal young adults. Since this constituted strong evidence of sexual dimorphism and was obtained from publicly available data in OASIS, we examined volume differences within the CC and in other white matter using voxel-based morphometry (VBM). We created a three-dimensional region of interest of the CC and measured its volume. The VBM statistics were analyzed by permutation test and threshold-free cluster enhancement (TFCE) with the significance levels at FWER < 0.05. The CC volume was significantly larger in women in the same 37 brain-size-matched pairs. We found that the CC genu was the subregion showing the most significant sex-related difference. We also found that white matter in the bilateral anterior frontal regions and the left lateral white matter near to Broca’s area were larger in women, whereas there were no significant larger regions in men. Since we used brain-size-matched subjects, our results gave strong volumetric evidence of localized sexual dimorphism of white matter.

Low-Fat Diet With Caloric Restriction Reduces White Matter Microglia Activation During Aging.

PubMed

Yin, Zhuoran; Raj, Divya D; Schaafsma, Wandert; van der Heijden, Roel A; Kooistra, Susanne M; Reijne, Aaffien C; Zhang, Xiaoming; Moser, Jill; Brouwer, Nieske; Heeringa, Peter; Yi, Chun-Xia; van Dijk, Gertjan; Laman, Jon D; Boddeke, Erik W G M; Eggen, Bart J L

2018-01-01

Rodent models of both aging and obesity are characterized by inflammation in specific brain regions, notably the corpus callosum, fornix, and hypothalamus. Microglia, the resident macrophages of the central nervous system, are important for brain development, neural support, and homeostasis. However, the effects of diet and lifestyle on microglia during aging are only partly understood. Here, we report alterations in microglia phenotype and functions in different brain regions of mice on a high-fat diet (HFD) or low-fat diet (LFD) during aging and in response to voluntary running wheel exercise. We compared the expression levels of genes involved in immune response, phagocytosis, and metabolism in the hypothalamus of 6-month-old HFD and LFD mice. We also compared the immune response of microglia from HFD or LFD mice to peripheral inflammation induced by intraperitoneal injection of lipopolysaccharide (LPS). Finally, we investigated the effect of diet, physical exercise, and caloric restriction (40% reduction compared to ad libitum intake) on microglia in 24-month-old HFD and LFD mice. Changes in diet caused morphological changes in microglia, but did not change the microglia response to LPS-induced systemic inflammation. Expression of phagocytic markers (i.e., Mac-2/Lgals3, Dectin-1/Clec7a, and CD16/CD32) in the white matter microglia of 24-month-old brain was markedly decreased in calorically restricted LFD mice. In conclusion, LFD resulted in reduced activation of microglia, which might be an underlying mechanism for the protective role of caloric restriction during aging-associated decline.

Disrupted white matter structural connectivity in heroin abusers.

PubMed

Sun, Yan; Wang, Gui-Bin; Lin, Qi-Xiang; Lu, Lin; Shu, Ni; Meng, Shi-Qiu; Wang, Jun; Han, Hong-Bin; He, Yong; Shi, Jie

2017-01-01

Neurocognitive impairment is one of the factors that put heroin abusers at greater risk for relapse, and deficits in related functional brain connections have been found. However, the alterations in structural brain connections that may underlie these functional and neurocognitive impairments remain largely unknown. In the present study, we investigated topological organization alterations in the structural network of white matter in heroin abusers and examined the relationships between the network changes and clinical measures. We acquired diffusion tensor imaging datasets from 76 heroin abusers and 78 healthy controls. Network-based statistic was applied to identify alterations in interregional white matter connectivity, and graph theory methods were used to analyze the properties of global networks. The participants also completed a battery of neurocognitive measures. One increased subnetwork characterizing widespread abnormalities in structural connectivity was present in heroin users, which mainly composed of default-mode, attentional and visual systems. The connection strength was positively correlated with increases in fractional anisotropy in heroin abusers. Intriguingly, the changes in within-frontal and within-temporal connections in heroin abusers were significantly correlated with daily heroin dosage and impulsivity scores, respectively. These findings suggest that heroin abusers have extensive abnormal white matter connectivity, which may mediate the relationship between heroin dependence and clinical measures. The increase in white matter connectivity may be attributable to the inefficient microstructure integrity of white matter. The present findings extend our understanding of cerebral structural disruptions that underlie neurocognitive and functional deficits in heroin addiction and provide circuit-level markers for this chronic disorder. © 2015 Society for the Study of Addiction.

Evaluation of Atlas-Based White Matter Segmentation with Eve.

PubMed

Plassard, Andrew J; Hinton, Kendra E; Venkatraman, Vijay; Gonzalez, Christopher; Resnick, Susan M; Landman, Bennett A

2015-03-20

Multi-atlas labeling has come in wide spread use for whole brain labeling on magnetic resonance imaging. Recent challenges have shown that leading techniques are near (or at) human expert reproducibility for cortical gray matter labels. However, these approaches tend to treat white matter as essentially homogeneous (as white matter exhibits isointense signal on structural MRI). The state-of-the-art for white matter atlas is the single-subject Johns Hopkins Eve atlas. Numerous approaches have attempted to use tractography and/or orientation information to identify homologous white matter structures across subjects. Despite success with large tracts, these approaches have been plagued by difficulties in with subtle differences in course, low signal to noise, and complex structural relationships for smaller tracts. Here, we investigate use of atlas-based labeling to propagate the Eve atlas to unlabeled datasets. We evaluate single atlas labeling and multi-atlas labeling using synthetic atlases derived from the single manually labeled atlas. On 5 representative tracts for 10 subjects, we demonstrate that (1) single atlas labeling generally provides segmentations within 2mm mean surface distance, (2) morphologically constraining DTI labels within structural MRI white matter reduces variability, and (3) multi-atlas labeling did not improve accuracy. These efforts present a preliminary indication that single atlas labels with correction is reasonable, but caution should be applied. To purse multi-atlas labeling and more fully characterize overall performance, more labeled datasets would be necessary.

Lower Orbital Frontal White Matter Integrity in Adolescents with Bipolar I Disorder

ERIC Educational Resources Information Center

Kafantaris, Vivian; Kingsley, Peter; Ardekani, Babak; Saito, Ema; Lencz, Todd; Lim, Kelvin; Szeszko, Philip

2009-01-01

Patients with bipolar I disorder demonstrated white matter abnormalities in white matter regions as seen through the use of diffusion tensor imaging. The findings suggest that white matter abnormalities in pediatric bipolar disorder may be useful in constructing neurobiological models of the disorder.

Disrupted White Matter Network and Cognitive Decline in Type 2 Diabetes Patients.

PubMed

Zhang, Junying; Liu, Zhen; Li, Zixiao; Wang, Yunxia; Chen, Yaojing; Li, Xin; Chen, Kewei; Shu, Ni; Zhang, Zhanjun

2016-05-06

Type 2 diabetes mellitus is accompanied by cognitive impairment and is associated with an increased risk of dementia. Damage to brain structures such as white matter network disruption may underlie this cognitive disturbance. In the present study, 886 non-diabetic and 163 type 2 diabetic participants completed a battery of neuropsychological tests. Among them, 38 diabetic patients and 34 non-diabetic participants that matched the patients for age/sex/education received a magnetic resonance imaging-based diffusion tensor imaging. Then we calculated the topological properties of the white matter network using a graph theoretical method to investigate network efficiency differences between groups. We found that type 2 diabetic patients had inferior performances compared to the non-diabetic controls, in several cognitive domains involving executive function, spatial processing, memory, and attention. We also found that diabetic patients exhibited a disrupted topological organization of the white matter network (including the global network properties, i.e., network strength, global efficiency, local efficiency and shortest path length, and the nodal efficiency of the right rolandic operculum) in the brain. Moreover, those global network properties and the nodal efficiency of the right rolandic operculum both had positive correlations with executive function in the patient group. The results suggest that type 2 diabetes mellitus leads to an alteration in the topological organization of the cortical white matter network and this alteration may account for the observed cognitive decline.

White matter integrity deficits in prefrontal-amygdala pathways in Williams syndrome.

PubMed

Avery, Suzanne N; Thornton-Wells, Tricia A; Anderson, Adam W; Blackford, Jennifer Urbano

2012-01-16

Williams syndrome is a neurodevelopmental disorder associated with significant non-social fears. Consistent with this elevated non-social fear, individuals with Williams syndrome have an abnormally elevated amygdala response when viewing threatening non-social stimuli. In typically-developing individuals, amygdala activity is inhibited through dense, reciprocal white matter connections with the prefrontal cortex. Neuroimaging studies suggest a functional uncoupling of normal prefrontal-amygdala inhibition in individuals with Williams syndrome, which might underlie both the extreme amygdala activity and non-social fears. This functional uncoupling might be caused by structural deficits in underlying white matter pathways; however, prefrontal-amygdala white matter deficits have yet to be explored in Williams syndrome. We used diffusion tensor imaging to investigate prefrontal-amygdala white matter integrity differences in individuals with Williams syndrome and typically-developing controls with high levels of non-social fear. White matter pathways between the amygdala and several prefrontal regions were isolated using probabilistic tractography. Within each pathway, we tested for between-group differences in three measures of white matter integrity: fractional anisotropy (FA), radial diffusivity (RD), and parallel diffusivity (λ(1)). Individuals with Williams syndrome had lower FA, compared to controls, in several of the prefrontal-amygdala pathways investigated, indicating a reduction in white matter integrity. Lower FA in Williams syndrome was explained by significantly higher RD, with no differences in λ(1), suggestive of lower fiber density or axon myelination in prefrontal-amygdala pathways. These results suggest that deficits in the structural integrity of prefrontal-amygdala white matter pathways might underlie the increased amygdala activity and extreme non-social fears observed in Williams syndrome. Copyright © 2011 Elsevier Inc. All rights reserved.

Racial Differences in Gray Matter Integrity by Diffusion Tensor in Black and White Octogenarians.

PubMed

Liu, Ge; Allen, Ben; Lopez, Oscar; Aizenstein, Howard; Boudreau, Robert; Newman, Anne; Yaffe, Kristine; Kritchevsky, Stephen; Launer, Lenore; Satterfield, Suzanne; Simonsick, Eleanor; Rosano, Caterina

2015-01-01

To quantify racial differences in brain structural characteristics in white and black octogenarians, and to examine whether these characteristics contribute to cognition. Cross-sectional study of 283 adults 79-89 years old (59.4% white;42.0% women) with data on gray matter integrity via diffusion tensor imaging (mean diffusivity), gray matter atrophy (GMA), white matter hyperintensities (WMH), literacy, smoking, drinking, income, hypertension and diabetes. Participants were recruited from an ongoing epidemiological study of older adults living in the community with a range of chronic conditions, physical and cognitive function. Standardized betas (sβ) of neuroimaging markers predicting Digit Symbol Substitution Test (DSST) and Modified Mini-Mental State Examination (3MS) scores were computed in multivariable regression models stratified by race. Compared to whites, blacks had lower DSST (p=0.001) and lower 3MS (p=0.006), but also lower mean diffusivity (i.e. higher gray matter microstructural integrity, p=0.032), independent of gender, income, literacy, body mass index, diabetes and drinking habits. Racial differences were not significant for WMH (p=0.062) or GMA (p=0.4). Among blacks, mean diffusivity and WMH were associated with DSST (sβ=-.209, p=0.037 and -.211, p=.038, respectively) independent of each other and other covariates; among whites, mean diffusivity, but not WMH, was significantly associated with DSST and 3MS (sβ =-.277, p=.002 and -.250, p=0.029, respectively). In this cohort of octogenarians living in the community, blacks appeared to have higher microstructural integrity of gray matter as compared to whites. This neuroimaging marker was related to higher cognition even in the presence of WMH and other cardiovascular conditions. If confirmed, these findings suggest microstructural gray matter integrity may be a target to improve cognition, especially among blacks who survive to very old age with a range of chronic cardiovascular conditions.

Serum S100B Protein is Specifically Related to White Matter Changes in Schizophrenia

PubMed Central

Milleit, Berko; Smesny, Stefan; Rothermundt, Matthias; Preul, Christoph; Schroeter, Matthias L.; von Eiff, Christof; Ponath, Gerald; Milleit, Christine; Sauer, Heinrich; Gaser, Christian

2016-01-01

Background: Schizophrenia can be conceptualized as a form of dysconnectivity between brain regions.To investigate the neurobiological foundation of dysconnectivity, one approach is to analyze white matter structures, such as the pathology of fiber tracks. S100B is considered a marker protein for glial cells, in particular oligodendrocytes and astroglia, that passes the blood brain barrier and is detectable in peripheral blood. Earlier Studies have consistently reported increased S100B levels in schizophrenia. In this study, we aim to investigate associations between S100B and structural white matter abnormalities. Methods: We analyzed data of 17 unmedicated schizophrenic patients (first and recurrent episode) and 22 controls. We used voxel based morphometry (VBM) to detect group differences of white matter structures as obtained from T1-weighted MR-images and considered S100B serum levels as a regressor in an age-corrected interaction analysis. Results: S100B was increased in both patient subgroups. Using VBM, we found clusters indicating significant differences of the association between S100B concentration and white matter. Involved anatomical structures are the posterior cingulate bundle and temporal white matter structures assigned to the superior longitudinal fasciculus. Conclusions: S100B-associated alterations of white matter are shown to be existent already at time of first manifestation of psychosis and are distinct from findings in recurrent episode patients. This suggests involvement of S100B in an ongoing and dynamic process associated with structural brain changes in schizophrenia. However, it remains elusive whether increased S100B serum concentrations in psychotic patients represent a protective response to a continuous pathogenic process or if elevated S100B levels are actively involved in promoting structural brain damage. PMID:27013967

Axonal abnormalities in vanishing white matter.

PubMed

Klok, Melanie D; Bugiani, Marianna; de Vries, Sharon I; Gerritsen, Wouter; Breur, Marjolein; van der Sluis, Sophie; Heine, Vivi M; Kole, Maarten H P; Baron, Wia; van der Knaap, Marjo S

2018-04-01

We aimed to study the occurrence and development of axonal pathology and the influence of astrocytes in vanishing white matter. Axons and myelin were analyzed using electron microscopy and immunohistochemistry on Eif2b4 and Eif2b5 single- and double-mutant mice and patient brain tissue. In addition, astrocyte-forebrain co-culture studies were performed. In the corpus callosum of Eif2b5- mutant mice, myelin sheath thickness, axonal diameter, and G-ratio developed normally up to 4 months. At 7 months, however, axons had become thinner, while in control mice axonal diameters had increased further. Myelin sheath thickness remained close to normal, resulting in an abnormally low G-ratio in Eif2b5- mutant mice. In more severely affected Eif2b4-Eif2b5 double-mutants, similar abnormalities were already present at 4 months, while in milder affected Eif2b4 mutants, few abnormalities were observed at 7 months. Additionally, from 2 months onward an increased percentage of thin, unmyelinated axons and increased axonal density were present in Eif2b5 -mutant mice. Co-cultures showed that Eif2b5 mutant astrocytes induced increased axonal density, also in control forebrain tissue, and that control astrocytes induced normal axonal density, also in mutant forebrain tissue. In vanishing white matter patient brains, axons and myelin sheaths were thinner than normal in moderately and severely affected white matter. In mutant mice and patients, signs of axonal transport defects and cytoskeletal abnormalities were minimal. In vanishing white matter, axons are initially normal and atrophy later. Astrocytes are central in this process. If therapy becomes available, axonal pathology may be prevented with early intervention.

Higher education is an age-independent predictor of white matter integrity and cognitive control in late adolescence.

PubMed

Noble, Kimberly G; Korgaonkar, Mayuresh S; Grieve, Stuart M; Brickman, Adam M

2013-09-01

Socioeconomic status is an important predictor of cognitive development and academic achievement. Late adolescence provides a unique opportunity to study how the attainment of socioeconomic status (in the form of years of education) relates to cognitive and neural development, during a time when age-related cognitive and neural development is ongoing. During late adolescence it is possible to disambiguate age- and education-related effects on the development of these processes. Here we assessed the degree to which higher educational attainment was related to performance on a cognitive control task, controlling for age. We then used diffusion tensor imaging (DTI) to assess the degree to which white matter microstructure might mediate this relationship. When covarying age, significant associations were found between educational attainment and fractional anisotropy (FA) in the superior longitudinal fasciculus (SLF) and cingulum bundle (CB). Further, when covarying age, FA in these regions was associated with cognitive control. Finally, mediation analyses revealed that the age-independent association between educational attainment and cognitive control was completely accounted for by FA in these regions. The uncinate fasciculus, a late-myelinated control region not implicated in cognitive control, did not mediate this effect. © 2013 John Wiley & Sons Ltd.

Abnormal brain white matter microstructure is associated with both pre-hypertension and hypertension

PubMed Central

Gao, He; Bai, Wenjia; Evangelou, Evangelos; Glocker, Ben; O’Regan, Declan P.; Elliott, Paul; Matthews, Paul M.

2017-01-01

Objectives To characterize effects of chronically elevated blood pressure on the brain, we tested for brain white matter microstructural differences associated with normotension, pre-hypertension and hypertension in recently available brain magnetic resonance imaging data from 4659 participants without known neurological or psychiatric disease (62.3±7.4 yrs, 47.0% male) in UK Biobank. Methods For assessment of white matter microstructure, we used measures derived from neurite orientation dispersion and density imaging (NODDI) including the intracellular volume fraction (an estimate of neurite density) and isotropic volume fraction (an index of the relative extra-cellular water diffusion). To estimate differences associated specifically with blood pressure, we applied propensity score matching based on age, sex, educational level, body mass index, and history of smoking, diabetes mellitus and cardiovascular disease to perform separate contrasts of non-hypertensive (normotensive or pre-hypertensive, N = 2332) and hypertensive (N = 2337) individuals and of normotensive (N = 741) and pre-hypertensive (N = 1581) individuals (p<0.05 after Bonferroni correction). Results The brain white matter intracellular volume fraction was significantly lower, and isotropic volume fraction was higher in hypertensive relative to non-hypertensive individuals (N = 1559, each). The white matter isotropic volume fraction also was higher in pre-hypertensive than in normotensive individuals (N = 694, each) in the right superior longitudinal fasciculus and the right superior thalamic radiation, where the lower intracellular volume fraction was observed in the hypertensives relative to the non-hypertensive group. Significance Pathological processes associated with chronically elevated blood pressure are associated with imaging differences suggesting chronic alterations of white matter axonal structure that may affect cognitive functions even with pre-hypertension. PMID:29145428

Investigating the Microstructural Correlation of White Matter in Autism Spectrum Disorder.

PubMed

Dean, Douglas C; Travers, Brittany G; Adluru, Nagesh; Tromp, Do P M; Destiche, Daniel J; Samsin, Danica; Prigge, Molly B; Zielinski, Brandon A; Fletcher, P Thomas; Anderson, Jeffrey S; Froehlich, Alyson L; Bigler, Erin D; Lange, Nicholas; Lainhart, Janet E; Alexander, Andrew L

2016-06-01

White matter microstructure forms a complex and dynamical system that is critical for efficient and synchronized brain function. Neuroimaging findings in children with autism spectrum disorder (ASD) suggest this condition is associated with altered white matter microstructure, which may lead to atypical macroscale brain connectivity. In this study, we used diffusion tensor imaging measures to examine the extent that white matter tracts are interrelated within ASD and typical development. We assessed the strength of inter-regional white matter correlations between typically developing and ASD diagnosed individuals. Using hierarchical clustering analysis, clustering patterns of the pairwise white matter correlations were constructed and revealed to be different between the two groups. Additionally, we explored the use of graph theory analysis to examine the characteristics of the patterns formed by inter-regional white matter correlations and compared these properties between ASD and typical development. We demonstrate that the ASD sample has significantly less coherence in white matter microstructure across the brain compared to that in the typical development sample. The ASD group also presented altered topological characteristics, which may implicate less efficient brain networking in ASD. These findings highlight the potential of graph theory based network characteristics to describe the underlying networks as measured by diffusion magnetic resonance imaging and furthermore indicates that ASD may be associated with altered brain network characteristics. Our findings are consistent with those of a growing number of studies and hypotheses that have suggested disrupted brain connectivity in ASD.

Investigating the Microstructural Correlation of White Matter in Autism Spectrum Disorder

PubMed Central

Travers, Brittany G.; Adluru, Nagesh; Tromp, Do P.M.; Destiche, Daniel J.; Samsin, Danica; Prigge, Molly B.; Zielinski, Brandon A.; Fletcher, P. Thomas; Anderson, Jeffrey S.; Froehlich, Alyson L.; Bigler, Erin D.; Lange, Nicholas; Lainhart, Janet E.; Alexander, Andrew L.

2016-01-01

Abstract White matter microstructure forms a complex and dynamical system that is critical for efficient and synchronized brain function. Neuroimaging findings in children with autism spectrum disorder (ASD) suggest this condition is associated with altered white matter microstructure, which may lead to atypical macroscale brain connectivity. In this study, we used diffusion tensor imaging measures to examine the extent that white matter tracts are interrelated within ASD and typical development. We assessed the strength of inter-regional white matter correlations between typically developing and ASD diagnosed individuals. Using hierarchical clustering analysis, clustering patterns of the pairwise white matter correlations were constructed and revealed to be different between the two groups. Additionally, we explored the use of graph theory analysis to examine the characteristics of the patterns formed by inter-regional white matter correlations and compared these properties between ASD and typical development. We demonstrate that the ASD sample has significantly less coherence in white matter microstructure across the brain compared to that in the typical development sample. The ASD group also presented altered topological characteristics, which may implicate less efficient brain networking in ASD. These findings highlight the potential of graph theory based network characteristics to describe the underlying networks as measured by diffusion magnetic resonance imaging and furthermore indicates that ASD may be associated with altered brain network characteristics. Our findings are consistent with those of a growing number of studies and hypotheses that have suggested disrupted brain connectivity in ASD. PMID:27021440

White Matter Development in Adolescence: The Influence of Puberty and Implications for Affective Disorders

PubMed Central

Ladouceur, Cecile D.; Peper, Jiska S.; Crone, Eveline A.; Dahl, Ronald E.

2011-01-01

There have been rapid advances in understanding a broad range of changes in brain structure and function during adolescence, and a growing interest in identifying which of these neurodevelopmental changes are directly linked with pubertal maturation—at least in part because of their potential to provide insights into the numerous emotional and behavioral health problems that emerge during this developmental period. This review focuses on what is known about the influence of puberty on white matter development in adolescence. We focus on white matter because of its role in providing the structural architectural organization of the brain and as a structural correlate of communication within complex neural systems. We begin with a review of studies that report sex differences or sex by age interactions in white matter development as these findings can provide, although indirectly, information relevant to puberty-related changes. Studies are also critically reviewed based on methodological procedures used to assess pubertal maturation and relations with white matter changes. Findings are discussed in light of their implications for the development of neural systems underlying the regulation of emotion and behavior and how alterations in the development of these systems may mediate risk for affective disorders in vulnerable adolescents. PMID:22247751

In vivo characterization of cortical and white matter neuroaxonal pathology in early multiple sclerosis.

PubMed

Granberg, Tobias; Fan, Qiuyun; Treaba, Constantina Andrada; Ouellette, Russell; Herranz, Elena; Mangeat, Gabriel; Louapre, Céline; Cohen-Adad, Julien; Klawiter, Eric C; Sloane, Jacob A; Mainero, Caterina

2017-11-01

Neuroaxonal pathology is a main determinant of disease progression in multiple sclerosis; however, its underlying pathophysiological mechanisms, including its link to inflammatory demyelination and temporal occurrence in the disease course are still unknown. We used ultra-high field (7 T), ultra-high gradient strength diffusion and T1/T2-weighted myelin-sensitive magnetic resonance imaging to characterize microstructural changes in myelin and neuroaxonal integrity in the cortex and white matter in early stage multiple sclerosis, their distribution in lesional and normal-appearing tissue, and their correlations with neurological disability. Twenty-six early stage multiple sclerosis subjects (disease duration ≤5 years) and 24 age-matched healthy controls underwent 7 T T2*-weighted imaging for cortical lesion segmentation and 3 T T1/T2-weighted myelin-sensitive imaging and neurite orientation dispersion and density imaging for assessing microstructural myelin, axonal and dendrite integrity in lesional and normal-appearing tissue of the cortex and the white matter. Conventional mean diffusivity and fractional anisotropy metrics were also assessed for comparison. Cortical lesions were identified in 92% of early multiple sclerosis subjects and they were characterized by lower intracellular volume fraction (P = 0.015 by paired t-test), lower myelin-sensitive contrast (P = 0.030 by related-samples Wilcoxon signed-rank test) and higher mean diffusivity (P = 0.022 by related-samples Wilcoxon signed-rank test) relative to the contralateral normal-appearing cortex. Similar findings were observed in white matter lesions relative to normal-appearing white matter (all P < 0.001), accompanied by an increased orientation dispersion (P < 0.001 by paired t-test) and lower fractional anisotropy (P < 0.001 by related-samples Wilcoxon signed-rank test) suggestive of less coherent underlying fibre orientation. Additionally, the normal-appearing white matter in multiple sclerosis

Abnormalities in white matter microstructure associated with chronic ketamine use.

PubMed

Edward Roberts, R; Curran, H Valerie; Friston, Karl J; Morgan, Celia J A

2014-01-01

Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that has been found to induce schizophrenia-type symptoms in humans and is a potent and fast-acting antidepressant. It is also a relatively widespread drug of abuse, particularly in China and the UK. Acute administration has been well characterized, but the effect of extended periods of ketamine use-on brain structure in humans-remains poorly understood. We measured indices of white matter microstructural integrity and connectivity in the brain of 16 ketamine users and 16 poly-drug-using controls, and we used probabilistic tractography to quantify changes in corticosubcortical connectivity associated with ketamine use. We found a reduction in the axial diffusivity profile of white matter in a right hemisphere network of white matter regions in ketamine users compared with controls. Within the ketamine-user group, we found a significant positive association between the connectivity profile between the caudate nucleus and the lateral prefrontal cortex and dissociative experiences. These findings suggest that chronic ketamine use may be associated with widespread disruption of white matter integrity, and white matter pathways between subcortical and prefrontal cortical areas may in part predict individual differences in dissociative experiences due to ketamine use.

Effects of insulin resistance on white matter microstructure in middle-aged and older adults

PubMed Central

Coutu, Jean-Philippe; Rosas, H. Diana; Salat, David H.

2014-01-01

Objective: To investigate the potential relationship between insulin resistance (IR) and white matter (WM) microstructure using diffusion tensor imaging in cognitively healthy middle-aged and older adults. Methods: Diffusion tensor imaging was acquired from 127 individuals (age range 41–86 years). IR was evaluated by the homeostasis model assessment of IR (HOMA-IR). Participants were divided into 2 groups based on HOMA-IR values: “high HOMA-IR” (≥2.5, n = 27) and “low HOMA-IR” (<2.5, n = 100). Cross-sectional voxel-based comparisons were performed using Tract-Based Spatial Statistics and anatomically defined regions of interest analysis. Results: The high HOMA-IR group demonstrated decreased axial diffusivity broadly throughout the cerebral WM in areas such as the corpus callosum, corona radiata, cerebral peduncle, posterior thalamic radiation, and right superior longitudinal fasciculus, and WM underlying the frontal, parietal, and temporal lobes, as well as decreased fractional anisotropy in the body and genu of corpus callosum and parts of the superior and anterior corona radiata, compared with the low HOMA-IR group, independent of age, WM signal abnormality volume, and antihypertensive medication status. These regions additionally demonstrated linear associations between diffusion measures and HOMA-IR across all subjects, with higher HOMA-IR values being correlated with lower axial diffusivity. Conclusions: In generally healthy adults, greater IR is associated with alterations in WM tissue integrity. These cross-sectional findings suggest that IR contributes to WM microstructural alterations in middle-aged and older adults. PMID:24771537

Heterochronicity of white matter development and aging explains regional patient control differences in schizophrenia.

PubMed

Kochunov, Peter; Ganjgahi, Habib; Winkler, Anderson; Kelly, Sinead; Shukla, Dinesh K; Du, Xiaoming; Jahanshad, Neda; Rowland, Laura; Sampath, Hemalatha; Patel, Binish; O'Donnell, Patricio; Xie, Zhiyong; Paciga, Sara A; Schubert, Christian R; Chen, Jian; Zhang, Guohao; Thompson, Paul M; Nichols, Thomas E; Hong, L Elliot

2016-12-01

Altered brain connectivity is implicated in the development and clinical burden of schizophrenia. Relative to matched controls, schizophrenia patients show (1) a global and regional reduction in the integrity of the brain's white matter (WM), assessed using diffusion tensor imaging (DTI) fractional anisotropy (FA), and (2) accelerated age-related decline in FA values. In the largest mega-analysis to date, we tested if differences in the trajectories of WM tract development influenced patient-control differences in FA. We also assessed if specific tracts showed exacerbated decline with aging. Three cohorts of schizophrenia patients (total n = 177) and controls (total n = 249; age = 18-61 years) were ascertained with three 3T Siemens MRI scanners. Whole-brain and regional FA values were extracted using ENIGMA-DTI protocols. Statistics were evaluated using mega- and meta-analyses to detect effects of diagnosis and age-by-diagnosis interactions. In mega-analysis of whole-brain averaged FA, schizophrenia patients had lower FA (P = 10 -11 ) and faster age-related decline in FA (P = 0.02) compared with controls. Tract-specific heterochronicity measures, that is, abnormal rates of adolescent maturation and aging explained approximately 50% of the regional variance effects of diagnosis and age-by-diagnosis interaction in patients. Interactive, three-dimensional visualization of the results is available at www.enigma-viewer.org. WM tracts that mature later in life appeared more sensitive to the pathophysiology of schizophrenia and were more susceptible to faster age-related decline in FA values. Hum Brain Mapp 37:4673-4688, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.