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.

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

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

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

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

Myotonic dystrophy types 1 and 2 are progressive multisystemic disorders with potential brain involvement. We compared 22 myotonic dystrophy type 1 and 22 myotonic dystrophy type 2 clinically and neuropsychologically well-characterized patients and a corresponding healthy control group using structural brain magnetic resonance imaging at 3 T (T1/T2/diffusion-weighted). Voxel-based morphometry and diffusion tensor imaging with tract-based spatial statistics were applied for voxel-wise analysis of cerebral grey and white matter affection (Pcorrected < 0.05). We further examined the association of structural brain changes with clinical and neuropsychological data. White matter lesions rated visually were more prevalent and severe in myotonic dystrophy type 1 compared with controls, with frontal white matter most prominently affected in both disorders, and temporal lesions restricted to myotonic dystrophy type 1. Voxel-based morphometry analyses demonstrated extensive white matter involvement in all cerebral lobes, brainstem and corpus callosum in myotonic dystrophy types 1 and 2, while grey matter decrease (cortical areas, thalamus, putamen) was restricted to myotonic dystrophy type 1. Accordingly, we found more prominent white matter affection in myotonic dystrophy type 1 than myotonic dystrophy type 2 by diffusion tensor imaging. Association fibres throughout the whole brain, limbic system fibre tracts, the callosal body and projection fibres (e.g. internal/external capsules) were affected in myotonic dystrophy types 1 and 2. Central motor pathways were exclusively impaired in myotonic dystrophy type 1. We found mild executive and attentional deficits in our patients when neuropsychological tests were corrected for manual motor dysfunctioning. Regression analyses revealed associations of white matter affection with several clinical parameters in both disease entities, but not with neuropsychological performance. We showed that depressed mood and fatigue were 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

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

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

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.

Separation of β-amyloid binding and white matter uptake of 18F-flutemetamol using spectral analysis

PubMed Central

Heurling, Kerstin; Buckley, Christopher; Vandenberghe, Rik; Laere, Koen Van; Lubberink, Mark

2015-01-01

The kinetic components of the β-amyloid ligand 18F-flutemetamol binding in grey and white matter were investigated through spectral analysis, and a method developed for creation of parametric images separating grey and white matter uptake. Tracer uptake in grey and white matter and cerebellar cortex was analyzed through spectral analysis in six subjects, with (n=4) or without (n=2) apparent β-amyloid deposition, having undergone dynamic 18F-flutemetamol scanning with arterial blood sampling. The spectra were divided into three components: slow, intermediate and fast basis function rates. The contribution of each of the components to total volume of distribution (VT) was assessed for different tissue types. The slow component dominated in white matter (average 90%), had a higher contribution to grey matter VT in subjects with β-amyloid deposition (average 44%) than without (average 6%) and was absent in cerebellar cortex, attributing the slow component of 18F-flutemetamol uptake in grey matter to β-amyloid binding. Parametric images of voxel-based spectral analysis were created for VT, the slow component and images segmented based on the slow component contribution; confirming that grey matter and white matter uptake can be discriminated on voxel-level using a threshold for the contribution from the slow component to VT. PMID:26550542

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

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.

Early Gray-Matter and White-Matter Concentration in Infancy Predict Later Language Skills: A Whole Brain Voxel-Based Morphometry Study

ERIC Educational Resources Information Center

Can, Dilara Deniz; Richards, Todd; Kuhl, Patricia K.

2013-01-01

Magnetic Resonance Imaging (MRI) brain scans were obtained from 19 infants at 7 months. Expressive and receptive language performance was assessed at 12 months. Voxel-based morphometry (VBM) identified brain regions where gray-matter and white-matter concentrations at 7 months correlated significantly with children's language scores at 12 months.…

Fiber tracking of brain white matter based on graph theory.

PubMed

Lu, Meng

2015-01-01

Brain white matter tractography is reconstructed via diffusion-weighted magnetic resonance images. Due to the complex structure of brain white matter fiber bundles, fiber crossing and fiber branching are abundant in human brain. And regular methods with diffusion tensor imaging (DTI) can't accurately handle this problem. the biggest problems of the brain tractography. Therefore, this paper presented a novel brain white matter tractography method based on graph theory, so the fiber tracking between two voxels is transformed into locating the shortest path in a graph. Besides, the presented method uses Q-ball imaging (QBI) as the source data instead of DTI, because QBI can provide accurate information about multiple fiber crossing and branching in one voxel using orientation distribution function (ODF). Experiments showed that the presented method can accurately handle the problem of brain white matter fiber crossing and branching, and reconstruct brain tractograhpy both in phantom data and real brain data.

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.

A multivariate pattern analysis study of the HIV-related white matter anatomical structural connections alterations

NASA Astrophysics Data System (ADS)

Tang, Zhenchao; Liu, Zhenyu; Li, Ruili; Cui, Xinwei; Li, Hongjun; Dong, Enqing; Tian, Jie

2017-03-01

It's widely known that HIV infection would cause white matter integrity impairments. Nevertheless, it is still unclear that how the white matter anatomical structural connections are affected by HIV infection. In the current study, we employed a multivariate pattern analysis to explore the HIV-related white matter connections alterations. Forty antiretroviraltherapy- naïve HIV patients and thirty healthy controls were enrolled. Firstly, an Automatic Anatomical Label (AAL) atlas based white matter structural network, a 90 × 90 FA-weighted matrix, was constructed for each subject. Then, the white matter connections deprived from the structural network were entered into a lasso-logistic regression model to perform HIV-control group classification. Using leave one out cross validation, a classification accuracy (ACC) of 90% (P=0.002) and areas under the receiver operating characteristic curve (AUC) of 0.96 was obtained by the classification model. This result indicated that the white matter anatomical structural connections contributed greatly to HIV-control group classification, providing solid evidence that the white matter connections were affected by HIV infection. Specially, 11 white matter connections were selected in the classification model, mainly crossing the regions of frontal lobe, Cingulum, Hippocampus, and Thalamus, which were reported to be damaged in previous HIV studies. This might suggest that the white matter connections adjacent to the HIV-related impaired regions were prone to be damaged.

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.

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.

Fiberprint: A subject fingerprint based on sparse code pooling for white matter fiber analysis.

PubMed

Kumar, Kuldeep; Desrosiers, Christian; Siddiqi, Kaleem; Colliot, Olivier; Toews, Matthew

2017-09-01

White matter characterization studies use the information provided by diffusion magnetic resonance imaging (dMRI) to draw cross-population inferences. However, the structure, function, and white matter geometry vary across individuals. Here, we propose a subject fingerprint, called Fiberprint, to quantify the individual uniqueness in white matter geometry using fiber trajectories. We learn a sparse coding representation for fiber trajectories by mapping them to a common space defined by a dictionary. A subject fingerprint is then generated by applying a pooling function for each bundle, thus providing a vector of bundle-wise features describing a particular subject's white matter geometry. These features encode unique properties of fiber trajectories, such as their density along prominent bundles. An analysis of data from 861 Human Connectome Project subjects reveals that a fingerprint based on approximately 3000 fiber trajectories can uniquely identify exemplars from the same individual. We also use fingerprints for twin/sibling identification, our observations consistent with the twin data studies of white matter integrity. Our results demonstrate that the proposed Fiberprint can effectively capture the variability in white matter fiber geometry across individuals, using a compact feature vector (dimension of 50), making this framework particularly attractive for handling large datasets. Copyright © 2017 Elsevier Inc. All rights reserved.

'Whose atlas I use, his song I sing?' - The impact of anatomical atlases on fiber tract contributions to cognitive deficits after stroke.

PubMed

de Haan, Bianca; Karnath, Hans-Otto

2017-12-01

Nowadays, different anatomical atlases exist for the anatomical interpretation of the results from neuroimaging and lesion analysis studies that investigate the contribution of white matter fiber tract integrity to cognitive (dys)function. A major problem with the use of different atlases in different studies, however, is that the anatomical interpretation of neuroimaging and lesion analysis results might vary as a function of the atlas used. This issue might be particularly prominent in studies that investigate the contribution of white matter fiber tract integrity to cognitive (dys)function. We used a single large-sample dataset of right brain damaged stroke patients with and without cognitive deficit (here: spatial neglect) to systematically compare the influence of three different, widely-used white matter fiber tract atlases (1 histology-based atlas and 2 DTI tractography-based atlases) on conclusions concerning the involvement of white matter fiber tracts in the pathogenesis of cognitive dysfunction. We both calculated the overlap between the statistical lesion analysis results and each long association fiber tract (topological analyses) and performed logistic regressions on the extent of fiber tract damage in each individual for each long association white matter fiber tract (hodological analyses). For the topological analyses, our results suggest that studies that use tractography-based atlases are more likely to conclude that white matter integrity is critical for a cognitive (dys)function than studies that use a histology-based atlas. The DTI tractography-based atlases classified approximately 10 times as many voxels of the statistical map as being located in a long association white matter fiber tract than the histology-based atlas. For hodological analyses on the other hand, we observed that the conclusions concerning the overall importance of long association fiber tract integrity to cognitive function do not necessarily depend on the white matter atlas used, but conclusions may vary as a function of atlas used at the level of individual fiber tracts. Moreover, these analyses revealed that hodological studies that express the individual extent of injury to each fiber tract as a binomial variable are more likely to conclude that white matter integrity is critical for a cognitive function than studies that express the individual extent of injury to each fiber tract as a continuous variable. Copyright © 2017 Elsevier Inc. All rights reserved.

Early gray-matter and white-matter concentration in infancy predict later language skills: a whole brain voxel-based morphometry study.

PubMed

Deniz Can, Dilara; Richards, Todd; Kuhl, Patricia K

2013-01-01

Magnetic resonance imaging (MRI) brain scans were obtained from 19 infants at 7 months. Expressive and receptive language performance was assessed at 12 months. Voxel-based morphometry (VBM) identified brain regions where gray-matter and white-matter concentrations at 7 months correlated significantly with children's language scores at 12 months. Early gray-matter concentration in the right cerebellum, early white-matter concentration in the right cerebellum, and early white-matter concentration in the left posterior limb of the internal capsule (PLIC)/cerebral peduncle were positively and strongly associated with infants' receptive language ability at 12 months. Early gray-matter concentration in the right hippocampus was positively and strongly correlated with infants' expressive language ability at 12 months. Our results suggest that the cerebellum, PLIC/cerebral peduncle, and the hippocampus may be associated with early language development. Potential links between these structural predictors and infants' linguistic functions are discussed. Copyright © 2012 Elsevier Inc. 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.

Rat brain digital stereotaxic white matter atlas with fine tract delineation in Paxinos space and its automated applications in DTI data analysis.

PubMed

Liang, Shengxiang; Wu, Shang; Huang, Qi; Duan, Shaofeng; Liu, Hua; Li, Yuxiao; Zhao, Shujun; Nie, Binbin; Shan, Baoci

2017-11-01

To automatically analyze diffusion tensor images of the rat brain via both voxel-based and ROI-based approaches, we constructed a new white matter atlas of the rat brain with fine tracts delineation in the Paxinos and Watson space. Unlike in previous studies, we constructed a digital atlas image from the latest edition of the Paxinos and Watson. This atlas contains 111 carefully delineated white matter fibers. A white matter network of rat brain based on anatomy was constructed by locating the intersection of all these tracts and recording the nuclei on the pathway of each white matter tract. Moreover, a compatible rat brain template from DTI images was created and standardized into the atlas space. To evaluate the automated application of the atlas in DTI data analysis, a group of rats with right-side middle cerebral artery occlusion (MCAO) and those without were enrolled in this study. The voxel-based analysis result shows that the brain region showing significant declines in signal in the MCAO rats was consistent with the occlusion position. We constructed a stereotaxic white matter atlas of the rat brain with fine tract delineation and a compatible template for the data analysis of DTI images of the rat brain. Copyright © 2017 Elsevier Inc. All rights reserved.

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 the onset or slow the disease progression.

Correlating Cognitive Decline with White Matter Lesion and Brain Atrophy MRI Measurements in Alzheimer’s Disease

PubMed Central

Bilello, Michel; Doshi, Jimit; Nabavizadeh, S. Ali; Toledo, Jon B.; Erus, Guray; Xie, Sharon X.; Trojanowski, John Q.; Han, Xiaoyan; Davatzikos, Christos

2015-01-01

Background Vascular risk factors are increasingly recognized as risks factors for Alzheimer’s disease (AD) and early conversion from mild cognitive impairment (MCI) to dementia. While neuroimaging research in AD has focused on brain atrophy, metabolic function or amyloid deposition, little attention has been paid to the effect of cerebrovascular disease to cognitive decline. Objective To investigate the correlation of brain atrophy and white matter lesions with cognitive decline in AD, MCI, and control subjects. Methods Patients with AD and MCI, and healthy subjects were included in this study. Subjects had a baseline MRI scan, and baseline and follow-up neuropsychological battery (CERAD). Regional volumes were measured, and white matter lesion segmentation was performed. Correlations between rate of CERAD score decline and white matter lesion load and brain structure volume were evaluated. In addition, voxel-based correlations between baseline CERAD scores and atrophy and white matter lesion measures were computed. Results CERAD rate of decline was most significantly associated with lesion loads located in the fornices. Several temporal lobe ROI volumes were significantly associated with CERAD decline. Voxel-based analysis demonstrated strong correlation between baseline CERAD scores and atrophy measures in the anterior temporal lobes. Correlation of baseline CERAD scores with white matter lesion volumes achieved significance in multilobar subcortical white matter. Conclusion Both baseline and declines in CERAD scores correlate with white matter lesion load and gray matter atrophy. Results of this study highlight the dominant effect of volume loss, and underscore the importance of small vessel disease as a contributor to cognitive decline in the elderly. PMID:26402108

Correlating Cognitive Decline with White Matter Lesion and Brain Atrophy Magnetic Resonance Imaging Measurements in Alzheimer's Disease.

PubMed

Bilello, Michel; Doshi, Jimit; Nabavizadeh, S Ali; Toledo, Jon B; Erus, Guray; Xie, Sharon X; Trojanowski, John Q; Han, Xiaoyan; Davatzikos, Christos

2015-01-01

Vascular risk factors are increasingly recognized as risks factors for Alzheimer's disease (AD) and early conversion from mild cognitive impairment (MCI) to dementia. While neuroimaging research in AD has focused on brain atrophy, metabolic function, or amyloid deposition, little attention has been paid to the effect of cerebrovascular disease to cognitive decline. To investigate the correlation of brain atrophy and white matter lesions with cognitive decline in AD, MCI, and control subjects. Patients with AD and MCI, and healthy subjects were included in this study. Subjects had a baseline MRI scan, and baseline and follow-up neuropsychological battery (CERAD). Regional volumes were measured, and white matter lesion segmentation was performed. Correlations between rate of CERAD score decline and white matter lesion load and brain structure volume were evaluated. In addition, voxel-based correlations between baseline CERAD scores and atrophy and white matter lesion measures were computed. CERAD rate of decline was most significantly associated with lesion loads located in the fornices. Several temporal lobe ROI volumes were significantly associated with CERAD decline. Voxel-based analysis demonstrated strong correlation between baseline CERAD scores and atrophy measures in the anterior temporal lobes. Correlation of baseline CERAD scores with white matter lesion volumes achieved significance in multilobar subcortical white matter. Both baseline and declines in CERAD scores correlate with white matter lesion load and gray matter atrophy. Results of this study highlight the dominant effect of volume loss, and underscore the importance of small vessel disease as a contributor to cognitive decline in the elderly.

Partial volume correction and image segmentation for accurate measurement of standardized uptake value of grey matter in the brain.

PubMed

Bural, Gonca; Torigian, Drew; Basu, Sandip; Houseni, Mohamed; Zhuge, Ying; Rubello, Domenico; Udupa, Jayaram; Alavi, Abass

2015-12-01

Our aim was to explore a novel quantitative method [based upon an MRI-based image segmentation that allows actual calculation of grey matter, white matter and cerebrospinal fluid (CSF) volumes] for overcoming the difficulties associated with conventional techniques for measuring actual metabolic activity of the grey matter. We included four patients with normal brain MRI and fluorine-18 fluorodeoxyglucose (F-FDG)-PET scans (two women and two men; mean age 46±14 years) in this analysis. The time interval between the two scans was 0-180 days. We calculated the volumes of grey matter, white matter and CSF by using a novel segmentation technique applied to the MRI images. We measured the mean standardized uptake value (SUV) representing the whole metabolic activity of the brain from the F-FDG-PET images. We also calculated the white matter SUV from the upper transaxial slices (centrum semiovale) of the F-FDG-PET images. The whole brain volume was calculated by summing up the volumes of the white matter, grey matter and CSF. The global cerebral metabolic activity was calculated by multiplying the mean SUV with total brain volume. The whole brain white matter metabolic activity was calculated by multiplying the mean SUV for the white matter by the white matter volume. The global cerebral metabolic activity only reflects those of the grey matter and the white matter, whereas that of the CSF is zero. We subtracted the global white matter metabolic activity from that of the whole brain, resulting in the global grey matter metabolism alone. We then divided the grey matter global metabolic activity by grey matter volume to accurately calculate the SUV for the grey matter alone. The brain volumes ranged between 1546 and 1924 ml. The mean SUV for total brain was 4.8-7. Total metabolic burden of the brain ranged from 5565 to 9617. The mean SUV for white matter was 2.8-4.1. On the basis of these measurements we generated the grey matter SUV, which ranged from 8.1 to 11.3. The accurate metabolic activity of the grey matter can be calculated using the novel segmentation technique that we applied to MRI. By combining these quantitative data with those generated from F-FDG-PET images we were able to calculate the accurate metabolic activity of the grey matter. These types of measurements will be of great value in accurate analysis of the data from patients with neuropsychiatric disorders.

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.

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

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

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 brain. However, most fMRI studies ignored a major part of the brain, the white-matter, discarding signals from it as arising from noise. Here we use resting-state fMRI data from 176 subjects to show that signals from the human white-matter contain meaningful information. We identify 12 functional networks composed of interacting long-distance white-matter tracts. Moreover, we show that these networks are highly correlated to resting-state gray-matter networks, highlighting their functional role. Our findings enable reinterpretation of many existing fMRI datasets, and suggest a new way to explore the white-matter role in cognition and its disturbances in neuropsychiatric disorders. Copyright © 2017 the authors 0270-6474/17/376394-14$15.00/0.

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. Copyright © 2015 Elsevier Inc. All rights reserved.

Migraine with aura and risk of silent brain infarcts and white matter hyperintensities: an MRI study

PubMed Central

Garde, Ellen; Blaabjerg, Morten; Nielsen, Helle H.; Krøigård, Thomas; Østergaard, Kamilla; Møller, Harald S.; Hjelmborg, Jacob; Madsen, Camilla G.; Iversen, Pernille; Kyvik, Kirsten O.; Siebner, Hartwig R.; Ashina, Messoud

2016-01-01

Abstract A small number of population-based studies reported an association between migraine with aura and risk of silent brain infarcts and white matter hyperintensities in females. We investigated these relations in a population-based sample of female twins. We contacted female twins ages 30–60 years identified through the population-based Danish Twin Registry. Based on questionnaire responses, twins were invited to participate in a telephone-based interview conducted by physicians. Headache diagnoses were established according to the International Headache Society criteria. Cases with migraine with aura, their co-twins, and unrelated migraine-free twins (controls) were invited to a brain magnetic resonance imaging scan performed at a single centre. Brain scans were assessed for the presence of infarcts, and white matter hyperintensities (visual rating scales and volumetric analyses) blinded to headache diagnoses. Comparisons were based on 172 cases, 34 co-twins, and 139 control subjects. Compared with control subjects, cases did not differ with regard to frequency of silent brain infarcts (four cases versus one control), periventricular white matter hyperintensity scores [adjusted mean difference (95% confidence interval): −0.1 (−0.5 to 0.2)] or deep white matter hyperintensity scores [adjusted mean difference (95% confidence interval): 0.1 (−0.8 to 1.1)] assessed by Scheltens’ scale. Cases had a slightly higher total white matter hyperintensity volume compared with controls [adjusted mean difference (95% confidence interval): 0.17 (−0.08 to 0.41) cm 3 ] and a similar difference was present in analyses restricted to twin pairs discordant for migraine with aura [adjusted mean difference 0.21 (−0.20 to 0.63)], but these differences did not reach statistical significance. We found no evidence of an association between silent brain infarcts, white matter hyperintensities, and migraine with aura. PMID:27190013

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.

Whole brain white matter connectivity analysis using machine learning: An application to autism.

PubMed

Zhang, Fan; Savadjiev, Peter; Cai, Weidong; Song, Yang; Rathi, Yogesh; Tunç, Birkan; Parker, Drew; Kapur, Tina; Schultz, Robert T; Makris, Nikos; Verma, Ragini; O'Donnell, Lauren J

2018-05-15

In this paper, we propose an automated white matter connectivity analysis method for machine learning classification and characterization of white matter abnormality via identification of discriminative fiber tracts. The proposed method uses diffusion MRI tractography and a data-driven approach to find fiber clusters corresponding to subdivisions of the white matter anatomy. Features extracted from each fiber cluster describe its diffusion properties and are used for machine learning. The method is demonstrated by application to a pediatric neuroimaging dataset from 149 individuals, including 70 children with autism spectrum disorder (ASD) and 79 typically developing controls (TDC). A classification accuracy of 78.33% is achieved in this cross-validation study. We investigate the discriminative diffusion features based on a two-tensor fiber tracking model. We observe that the mean fractional anisotropy from the second tensor (associated with crossing fibers) is most affected in ASD. We also find that local along-tract (central cores and endpoint regions) differences between ASD and TDC are helpful in differentiating the two groups. These altered diffusion properties in ASD are associated with multiple robustly discriminative fiber clusters, which belong to several major white matter tracts including the corpus callosum, arcuate fasciculus, uncinate fasciculus and aslant tract; and the white matter structures related to the cerebellum, brain stem, and ventral diencephalon. These discriminative fiber clusters, a small part of the whole brain tractography, represent the white matter connections that could be most affected in ASD. Our results indicate the potential of a machine learning pipeline based on white matter fiber clustering. Copyright © 2017 Elsevier Inc. All rights reserved.

Spatial patterns of whole brain grey and white matter injury in patients with occult spastic diplegic cerebral palsy.

PubMed

Mu, Xuetao; Nie, Binbin; Wang, Hong; Duan, Shaofeng; Zhang, Zan; Dai, Guanghui; Ma, Qiaozhi; Shan, Baoci; Ma, Lin

2014-01-01

Spastic diplegic cerebral palsy (SDCP) is a common type of cerebral palsy (CP), which presents as a group of motor-impairment syndromes. Previous conventional MRI studies have reported abnormal structural changes in SDCP, such as periventricular leucomalacia. However, there are roughly 27.8% SDCP patients presenting normal appearance in conventional MRI, which were considered as occult SDCP. In this study, sixteen patients with occult SDCP and 16 age- and sex-matched healthy control subjects were collected and the data were acquired on a 3T MR system. We applied voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) analysis to investigate whole brain grey and white matter injury in occult SDCP. By using VBM method, the grey matter volume reduction was revealed in the bilateral basal ganglia regions, thalamus, insula, and left cerebral peduncle, whereas the white matter atrophy was found to be located in the posterior part of corpus callosum and right posterior corona radiata in the occult SDCP patients. By using TBSS, reduced fractional anisotropy (FA) values were detected in multiple white matter regions, including bilateral white matter tracts in prefrontal lobe, temporal lobe, internal and external capsule, corpus callosum, cingulum, thalamus, brainstem and cerebellum. Additionally, several regions of white matter tracts injury were found to be significantly correlated with motor dysfunction. These results collectively revealed the spatial patterns of whole brain grey and white matter injury in occult SDCP.

Differences in regional brain volume related to the extraversion-introversion dimension--a voxel based morphometry study.

PubMed

Forsman, Lea J; de Manzano, Orjan; Karabanov, Anke; Madison, Guy; Ullén, Fredrik

2012-01-01

Extraverted individuals are sociable, behaviorally active, and happy. We report data from a voxel based morphometry study investigating, for the first time, if regional volume in gray and white matter brain regions is related to extraversion. For both gray and white matter, all correlations between extraversion and regional brain volume were negative, i.e. the regions were larger in introverts. Gray matter correlations were found in regions that included the right prefrontal cortex and the cortex around the right temporo-parietal junction--regions that are known to be involved in behavioral inhibition, introspection, and social-emotional processing, e.g. evaluation of social stimuli and reasoning about the mental states of others. White matter correlations extended from the brainstem to widespread cortical regions, and were largely due to global effects, i.e. a larger total white matter volume in introverts. We speculate that these white matter findings may reflect differences in ascending modulatory projections affecting cortical regions involved in behavioral regulation. Copyright © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

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 improved C-statistics: the recalibrated CHA2DS2VASc score 0.62 (95% CI 0.54-0.70; p = 0.024) and the recalibrated Essen Stroke Risk Score 0.63 (95% CI 0.56-0.71; p = 0.031). C-statistics of the white matter hyperintensities score were 0.62 (95% CI 0.52-0.68) to 0.65 (95% CI 0.58-0.73). An increasing burden of white matter hyperintensities was independently associated with recurrent ischemic stroke in a cohort of non-AF ischemic stroke patients. Recalibration of the CHA2DS2VASc score and the Essen Stroke Risk Score with one point for the presence of moderate to severe white matter hyperintensities led to improved discriminatory performance in ischemic stroke recurrence prediction. Risk scores based on white matter hyperintensities alone were at least as accurate as the established clinical risk scores in the prediction of ischemic stroke recurrence. © 2016 S. Karger AG, Basel.

Combining Segmented Grey and White Matter Images Improves Voxel-based Morphometry for the Case of Dilated Lateral Ventricles.

PubMed

Goto, Masami; Abe, Osamu; Aoki, Shigeki; Kamagata, Koji; Hori, Masaaki; Miyati, Tosiaki; Gomi, Tsutomu; Takeda, Tohoru

2018-01-18

To evaluate the error in segmented tissue images and to show the usefulness of the brain image in voxel-based morphometry (VBM) using Statistical Parametric Mapping (SPM) 12 software and 3D T 1 -weighted magnetic resonance images (3D-T 1 WIs) processed to simulate idiopathic normal pressure hydrocephalus (iNPH). VBM analysis was performed on sagittal 3D-T 1 WIs obtained in 22 healthy volunteers using a 1.5T MR scanner. Regions of interest for the lateral ventricles of all subjects were carefully outlined on the original 3D-T 1 WIs, and two types of simulated 3D-T 1 WI were also prepared (non-dilated 3D-T 1 WI as normal control and dilated 3D-T 1 WI to simulate iNPH). All simulated 3D-T 1 WIs were segmented into gray matter, white matter, and cerebrospinal fluid images, and normalized to standard space. A brain image was made by adding the gray and white matter images. After smoothing with a 6-mm isotropic Gaussian kernel, group comparisons (dilated vs non-dilated) were made for gray and white matter, cerebrospinal fluid, and brain images using a paired t-test. In evaluation of tissue volume, estimation error was larger using gray or white matter images than using the brain image, and estimation errors in gray and white matter volume change were found for the brain surface. To our knowledge, this is the first VBM study to show the possibility that VBM of gray and white matter volume on the brain surface may be more affected by individual differences in the level of dilation of the lateral ventricles than by individual differences in gray and white matter volumes. We recommend that VBM evaluation in patients with iNPH should be performed using the brain image rather than the gray and white matter images.

Longitudinal patterns of leukoaraiosis and brain atrophy in symptomatic small vessel disease

PubMed Central

Benjamin, Philip; Zeestraten, Eva; Lawrence, Andrew J.; Barrick, Thomas R.; Markus, Hugh S.

2016-01-01

Abstract Cerebral small vessel disease is a common condition associated with lacunar stroke, cognitive impairment and significant functional morbidity. White matter hyperintensities and brain atrophy, seen on magnetic resonance imaging, are correlated with increasing disease severity. However, how the two are related remains an open question. To better define the relationship between white matter hyperintensity growth and brain atrophy, we applied a semi-automated magnetic resonance imaging segmentation analysis pipeline to a 3-year longitudinal cohort of 99 subjects with symptomatic small vessel disease, who were followed-up for ≥1 years. Using a novel two-stage warping pipeline with tissue repair step, voxel-by-voxel rate of change maps were calculated for each tissue class (grey matter, white matter, white matter hyperintensities and lacunes) for each individual. These maps capture both the distribution of disease and spatial information showing local rates of growth and atrophy. These were analysed to answer three primary questions: first, is there a relationship between whole brain atrophy and magnetic resonance imaging markers of small vessel disease (white matter hyperintensities or lacune volume)? Second, is there regional variation within the cerebral white matter in the rate of white matter hyperintensity progression? Finally, are there regionally specific relationships between the rates of white matter hyperintensity progression and cortical grey matter atrophy? We demonstrate that the rates of white matter hyperintensity expansion and grey matter atrophy are strongly correlated (Pearson’s R = −0.69, P < 1 × 10 −7 ), and significant grey matter loss and whole brain atrophy occurs annually ( P < 0.05). Additionally, the rate of white matter hyperintensity growth was heterogeneous, occurring more rapidly within long association fasciculi. Using voxel-based quantification (family-wise error corrected P < 0.05), we show the rate of white matter hyperintensity progression is associated with increases in cortical grey matter atrophy rates, in the medial-frontal, orbito-frontal, parietal and occipital regions. Conversely, increased rates of global grey matter atrophy are significantly associated with faster white matter hyperintensity growth in the frontal and parietal regions. Together, these results link the progression of white matter hyperintensities with increasing rates of regional grey matter atrophy, and demonstrate that grey matter atrophy is the major contributor to whole brain atrophy in symptomatic cerebral small vessel disease. These measures provide novel insights into the longitudinal pathogenesis of small vessel disease, and imply that therapies aimed at reducing progression of white matter hyperintensities via end-arteriole damage may protect against secondary brain atrophy and consequent functional morbidity. PMID:26936939

Longitudinal patterns of leukoaraiosis and brain atrophy in symptomatic small vessel disease.

PubMed

Lambert, Christian; Benjamin, Philip; Zeestraten, Eva; Lawrence, Andrew J; Barrick, Thomas R; Markus, Hugh S

2016-04-01

Cerebral small vessel disease is a common condition associated with lacunar stroke, cognitive impairment and significant functional morbidity. White matter hyperintensities and brain atrophy, seen on magnetic resonance imaging, are correlated with increasing disease severity. However, how the two are related remains an open question. To better define the relationship between white matter hyperintensity growth and brain atrophy, we applied a semi-automated magnetic resonance imaging segmentation analysis pipeline to a 3-year longitudinal cohort of 99 subjects with symptomatic small vessel disease, who were followed-up for ≥1 years. Using a novel two-stage warping pipeline with tissue repair step, voxel-by-voxel rate of change maps were calculated for each tissue class (grey matter, white matter, white matter hyperintensities and lacunes) for each individual. These maps capture both the distribution of disease and spatial information showing local rates of growth and atrophy. These were analysed to answer three primary questions: first, is there a relationship between whole brain atrophy and magnetic resonance imaging markers of small vessel disease (white matter hyperintensities or lacune volume)? Second, is there regional variation within the cerebral white matter in the rate of white matter hyperintensity progression? Finally, are there regionally specific relationships between the rates of white matter hyperintensity progression and cortical grey matter atrophy? We demonstrate that the rates of white matter hyperintensity expansion and grey matter atrophy are strongly correlated (Pearson's R = -0.69, P < 1 × 10(-7)), and significant grey matter loss and whole brain atrophy occurs annually (P < 0.05). Additionally, the rate of white matter hyperintensity growth was heterogeneous, occurring more rapidly within long association fasciculi. Using voxel-based quantification (family-wise error corrected P < 0.05), we show the rate of white matter hyperintensity progression is associated with increases in cortical grey matter atrophy rates, in the medial-frontal, orbito-frontal, parietal and occipital regions. Conversely, increased rates of global grey matter atrophy are significantly associated with faster white matter hyperintensity growth in the frontal and parietal regions. Together, these results link the progression of white matter hyperintensities with increasing rates of regional grey matter atrophy, and demonstrate that grey matter atrophy is the major contributor to whole brain atrophy in symptomatic cerebral small vessel disease. These measures provide novel insights into the longitudinal pathogenesis of small vessel disease, and imply that therapies aimed at reducing progression of white matter hyperintensities via end-arteriole damage may protect against secondary brain atrophy and consequent functional morbidity. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

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.

Dyslexia and Voxel-Based Morphometry: Correlations between Five Behavioural Measures of Dyslexia and Gray and White Matter Volumes

ERIC Educational Resources Information Center

Tamboer, Peter; Scholte, H. Steven; Vorst, Harrie C. M.

2015-01-01

In voxel-based morphometry studies of dyslexia, the relation between causal theories of dyslexia and gray matter (GM) and white matter (WM) volume alterations is still under debate. Some alterations are consistently reported, but others failed to reach significance. We investigated GM alterations in a large sample of Dutch students (37 dyslexics…

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.

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

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.

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.

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.

Independent component analysis of DTI data reveals white matter covariances in Alzheimer's disease

NASA Astrophysics Data System (ADS)

Ouyang, Xin; Sun, Xiaoyu; Guo, Ting; Sun, Qiaoyue; Chen, Kewei; Yao, Li; Wu, Xia; Guo, Xiaojuan

2014-03-01

Alzheimer's disease (AD) is a progressive neurodegenerative disease with the clinical symptom of the continuous deterioration of cognitive and memory functions. Multiple diffusion tensor imaging (DTI) indices such as fractional anisotropy (FA) and mean diffusivity (MD) can successfully explain the white matter damages in AD patients. However, most studies focused on the univariate measures (voxel-based analysis) to examine the differences between AD patients and normal controls (NCs). In this investigation, we applied a multivariate independent component analysis (ICA) to investigate the white matter covariances based on FA measurement from DTI data in 35 AD patients and 45 NCs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We found that six independent components (ICs) showed significant FA reductions in white matter covariances in AD compared with NC, including the genu and splenium of corpus callosum (IC-1 and IC-2), middle temporal gyral of temporal lobe (IC-3), sub-gyral of frontal lobe (IC-4 and IC-5) and sub-gyral of parietal lobe (IC-6). Our findings revealed covariant white matter loss in AD patients and suggest that the unsupervised data-driven ICA method is effective to explore the changes of FA in AD. This study assists us in understanding the mechanism of white matter covariant reductions in the development of AD.

Quantitative validation of a nonlinear histology-MRI coregistration method using Generalized Q-sampling Imaging in complex human cortical white matter

PubMed Central

Gangolli, Mihika; Holleran, Laurena; Kim, Joong Hee; Stein, Thor D.; Alvarez, Victor; McKee, Ann C.; Brody, David L.

2017-01-01

Advanced diffusion MRI methods have recently been proposed for detection of pathologies such as traumatic axonal injury and chronic traumatic encephalopathy which commonly affect complex cortical brain regions. However, radiological-pathological correlations in human brain tissue that detail the relationship between the multi-component diffusion signal and underlying pathology are lacking. We present a nonlinear voxel based two dimensional coregistration method that is useful for matching diffusion signals to quantitative metrics of high resolution histological images. When validated in ex vivo human cortical tissue at a 250 × 250 × 500 micron spatial resolution, the method proved robust in correlations between generalized q-sampling imaging and histologically based white matter fiber orientations, with r = 0.94 for the primary fiber direction and r = 0.88 for secondary fiber direction in each voxel. Importantly, however, the correlation was substantially worse with reduced spatial resolution or with fiber orientations derived using a diffusion tensor model. Furthermore, we have detailed a quantitative histological metric of white matter fiber integrity termed power coherence capable of distinguishing between architecturally complex but intact white matter from disrupted white matter regions. These methods may allow for more sensitive and specific radiological-pathological correlations of neurodegenerative diseases affecting complex gray and white matter. PMID:28365421

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.

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 matter and reduced white matter in the internal capsule and putamen of young pigs. With the use of noninvasive neuroimaging techniques, results from our study indicate that prenatal choline deficiency greatly alters gray and white matter development in pigs, thereby providing a translational assessment that may be used in clinical populations.

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.

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 differences in autism: The case of white matter microstructure.

PubMed

Koolschijn, P Cédric M P; Caan, Matthan W A; Teeuw, Jalmar; Olabarriaga, Sílvia D; Geurts, Hilde M

2017-01-01

Autism spectrum disorder (ASD) is typified as a brain connectivity disorder in which white matter abnormalities are already present early on in life. However, it is unknown if and to which extent these abnormalities are hard-wired in (older) adults with ASD and how this interacts with age-related white matter changes as observed in typical aging. The aim of this first cross-sectional study in mid- and late-aged adults with ASD was to characterize white matter microstructure and its relationship with age. We utilized diffusion tensor imaging with head motion control in 48 adults with ASD and 48 age-matched controls (30-74 years), who also completed a Flanker task. Intra-individual variability of reaction times (IIVRT) measures based on performance on the Flanker interference task were used to assess IIVRT-white matter microstructure associations. We observed primarily higher mean and radial diffusivity in white matter microstructure in ASD, particularly in long-range fibers, which persisted after taking head motion into account. Importantly, group-by-age interactions revealed higher age-related mean and radial diffusivity in ASD, in projection and association fiber tracts. Subtle dissociations were observed in IIVRT-white matter microstructure relations between groups, with the IIVRT-white matter association pattern in ASD resembling observations in cognitive aging. The observed white matter microstructure differences are lending support to the structural underconnectivity hypothesis in ASD. These reductions seem to have behavioral percussions given the atypical relationship with IIVRT. Taken together, the current results may indicate different age-related patterns of white matter microstructure in adults with ASD. Hum Brain Mapp 38:82-96, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Fully-integrated framework for the segmentation and registration of the spinal cord white and gray matter.

PubMed

Dupont, Sara M; De Leener, Benjamin; Taso, Manuel; Le Troter, Arnaud; Nadeau, Sylvie; Stikov, Nikola; Callot, Virginie; Cohen-Adad, Julien

2017-04-15

The spinal cord white and gray matter can be affected by various pathologies such as multiple sclerosis, amyotrophic lateral sclerosis or trauma. Being able to precisely segment the white and gray matter could help with MR image analysis and hence be useful in further understanding these pathologies, and helping with diagnosis/prognosis and drug development. Up to date, white/gray matter segmentation has mostly been done manually, which is time consuming, induces a bias related to the rater and prevents large-scale multi-center studies. Recently, few methods have been proposed to automatically segment the spinal cord white and gray matter. However, no single method exists that combines the following criteria: (i) fully automatic, (ii) works on various MRI contrasts, (iii) robust towards pathology and (iv) freely available and open source. In this study we propose a multi-atlas based method for the segmentation of the spinal cord white and gray matter that addresses the previous limitations. Moreover, to study the spinal cord morphology, atlas-based approaches are increasingly used. These approaches rely on the registration of a spinal cord template to an MR image, however the registration usually doesn't take into account the spinal cord internal structure and thus lacks accuracy. In this study, we propose a new template registration framework that integrates the white and gray matter segmentation to account for the specific gray matter shape of each individual subject. Validation of segmentation was performed in 24 healthy subjects using T 2 * -weighted images, in 8 healthy subjects using diffusion weighted images (exhibiting inverted white-to-gray matter contrast compared to T 2 *-weighted), and in 5 patients with spinal cord injury. The template registration was validated in 24 subjects using T 2 *-weighted data. Results of automatic segmentation on T 2 *-weighted images was in close correspondence with the manual segmentation (Dice coefficient in the white/gray matter of 0.91/0.71 respectively). Similarly, good results were obtained in data with inverted contrast (diffusion-weighted image) and in patients. When compared to the classical template registration framework, the proposed framework that accounts for gray matter shape significantly improved the quality of the registration (comparing Dice coefficient in gray matter: p=9.5×10 -6 ). While further validation is needed to show the benefits of the new registration framework in large cohorts and in a variety of patients, this study provides a fully-integrated tool for quantitative assessment of white/gray matter morphometry and template-based analysis. All the proposed methods are implemented in the Spinal Cord Toolbox (SCT), an open-source software for processing spinal cord multi-parametric MRI data. Copyright © 2017 Elsevier Inc. 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 mediates small vessel disease-related brain damage.

Structural white matter asymmetries in relation to functional asymmetries during speech perception and production.

PubMed

Ocklenburg, Sebastian; Hugdahl, Kenneth; Westerhausen, René

2013-12-01

Functional hemispheric asymmetries of speech production and perception are a key feature of the human language system, but their neurophysiological basis is still poorly understood. Using a combined fMRI and tract-based spatial statistics approach, we investigated the relation of microstructural asymmetries in language-relevant white matter pathways and functional activation asymmetries during silent verb generation and passive listening to spoken words. Tract-based spatial statistics revealed several leftward asymmetric clusters in the arcuate fasciculus and uncinate fasciculus that were differentially related to activation asymmetries in the two functional tasks. Frontal and temporal activation asymmetries during silent verb generation were positively related to the strength of specific microstructural white matter asymmetries in the arcuate fasciculus. In contrast, microstructural uncinate fasciculus asymmetries were related to temporal activation asymmetries during passive listening. These findings suggest that white matter asymmetries may indeed be one of the factors underlying functional hemispheric asymmetries. Moreover, they also show that specific localized white matter asymmetries might be of greater relevance for functional activation asymmetries than microstructural features of whole pathways. © 2013.

Combining tract- and atlas-based analysis reveals microstructural abnormalities in early Tourette syndrome children.

PubMed

Wen, Hongwei; Liu, Yue; Wang, Jieqiong; Rekik, Islem; Zhang, Jishui; Zhang, Yue; Tian, Hongwei; Peng, Yun; He, Huiguang

2016-05-01

Tourette syndrome (TS) is a neurological disorder that causes uncontrolled repetitive motor and vocal tics in children. Examining the neural basis of TS churned out different research studies that advanced our understanding of the brain pathways involved in its development. Particularly, growing evidence points to abnormalities within the fronto-striato-thalamic pathways. In this study, we combined Tract-Based Spatial Statistics (TBSS) and Atlas-based regions of interest (ROI) analysis approach, to investigate the microstructural diffusion changes in both deep and superficial white matter (SWM) in TS children. We then characterized the altered microstructure of white matter in 27 TS children in comparison with 27 age- and gender-matched healthy controls. We found that fractional anisotropy (FA) decreases and radial diffusivity (RD) increases in deep white matter (DWM) tracts in cortico-striato-thalamo-cortical (CSTC) circuit as well as SWM. Furthermore, we found that lower FA values and higher RD values in white matter regions are correlated with more severe tics, but not tics duration. Besides, we also found both axial diffusivity and mean diffusivity increase using Atlas-based ROI analysis. Our work may suggest that microstructural diffusion changes in white matter is not only restricted to the gray matter of CSTC circuit but also affects SWM within the primary motor and somatosensory cortex, commissural and association fibers. Hum Brain Mapp 37:1903-1919, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

White matter hyperintensities and imaging patterns of brain ageing in the general population.

PubMed

Habes, Mohamad; Erus, Guray; Toledo, Jon B; Zhang, Tianhao; Bryan, Nick; Launer, Lenore J; Rosseel, Yves; Janowitz, Deborah; Doshi, Jimit; Van der Auwera, Sandra; von Sarnowski, Bettina; Hegenscheid, Katrin; Hosten, Norbert; Homuth, Georg; Völzke, Henry; Schminke, Ulf; Hoffmann, Wolfgang; Grabe, Hans J; Davatzikos, Christos

2016-04-01

White matter hyperintensities are associated with increased risk of dementia and cognitive decline. The current study investigates the relationship between white matter hyperintensities burden and patterns of brain atrophy associated with brain ageing and Alzheimer's disease in a large populatison-based sample (n = 2367) encompassing a wide age range (20-90 years), from the Study of Health in Pomerania. We quantified white matter hyperintensities using automated segmentation and summarized atrophy patterns using machine learning methods resulting in two indices: the SPARE-BA index (capturing age-related brain atrophy), and the SPARE-AD index (previously developed to capture patterns of atrophy found in patients with Alzheimer's disease). A characteristic pattern of age-related accumulation of white matter hyperintensities in both periventricular and deep white matter areas was found. Individuals with high white matter hyperintensities burden showed significantly (P < 0.0001) lower SPARE-BA and higher SPARE-AD values compared to those with low white matter hyperintensities burden, indicating that the former had more patterns of atrophy in brain regions typically affected by ageing and Alzheimer's disease dementia. To investigate a possibly causal role of white matter hyperintensities, structural equation modelling was used to quantify the effect of Framingham cardiovascular disease risk score and white matter hyperintensities burden on SPARE-BA, revealing a statistically significant (P < 0.0001) causal relationship between them. Structural equation modelling showed that the age effect on SPARE-BA was mediated by white matter hyperintensities and cardiovascular risk score each explaining 10.4% and 21.6% of the variance, respectively. The direct age effect explained 70.2% of the SPARE-BA variance. Only white matter hyperintensities significantly mediated the age effect on SPARE-AD explaining 32.8% of the variance. The direct age effect explained 66.0% of the SPARE-AD variance. Multivariable regression showed significant relationship between white matter hyperintensities volume and hypertension (P = 0.001), diabetes mellitus (P = 0.023), smoking (P = 0.002) and education level (P = 0.003). The only significant association with cognitive tests was with the immediate recall of the California verbal and learning memory test. No significant association was present with the APOE genotype. These results support the hypothesis that white matter hyperintensities contribute to patterns of brain atrophy found in beyond-normal brain ageing in the general population. White matter hyperintensities also contribute to brain atrophy patterns in regions related to Alzheimer's disease dementia, in agreement with their known additive role to the likelihood of dementia. Preventive strategies reducing the odds to develop cardiovascular disease and white matter hyperintensities could decrease the incidence or delay the onset of dementia. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

White matter hyperintensities and imaging patterns of brain ageing in the general population

PubMed Central

Erus, Guray; Toledo, Jon B.; Zhang, Tianhao; Bryan, Nick; Launer, Lenore J.; Rosseel, Yves; Janowitz, Deborah; Doshi, Jimit; Van der Auwera, Sandra; von Sarnowski, Bettina; Hegenscheid, Katrin; Hosten, Norbert; Homuth, Georg; Völzke, Henry; Schminke, Ulf; Hoffmann, Wolfgang; Grabe, Hans J.; Davatzikos, Christos

2016-01-01

Abstract White matter hyperintensities are associated with increased risk of dementia and cognitive decline. The current study investigates the relationship between white matter hyperintensities burden and patterns of brain atrophy associated with brain ageing and Alzheimer’s disease in a large populatison-based sample ( n = 2367) encompassing a wide age range (20–90 years), from the Study of Health in Pomerania. We quantified white matter hyperintensities using automated segmentation and summarized atrophy patterns using machine learning methods resulting in two indices: the SPARE-BA index (capturing age-related brain atrophy), and the SPARE-AD index (previously developed to capture patterns of atrophy found in patients with Alzheimer’s disease). A characteristic pattern of age-related accumulation of white matter hyperintensities in both periventricular and deep white matter areas was found. Individuals with high white matter hyperintensities burden showed significantly ( P < 0.0001) lower SPARE-BA and higher SPARE-AD values compared to those with low white matter hyperintensities burden, indicating that the former had more patterns of atrophy in brain regions typically affected by ageing and Alzheimer’s disease dementia. To investigate a possibly causal role of white matter hyperintensities, structural equation modelling was used to quantify the effect of Framingham cardiovascular disease risk score and white matter hyperintensities burden on SPARE-BA, revealing a statistically significant ( P < 0.0001) causal relationship between them. Structural equation modelling showed that the age effect on SPARE-BA was mediated by white matter hyperintensities and cardiovascular risk score each explaining 10.4% and 21.6% of the variance, respectively. The direct age effect explained 70.2% of the SPARE-BA variance. Only white matter hyperintensities significantly mediated the age effect on SPARE-AD explaining 32.8% of the variance. The direct age effect explained 66.0% of the SPARE-AD variance. Multivariable regression showed significant relationship between white matter hyperintensities volume and hypertension ( P = 0.001), diabetes mellitus ( P = 0.023), smoking ( P = 0.002) and education level ( P = 0.003). The only significant association with cognitive tests was with the immediate recall of the California verbal and learning memory test. No significant association was present with the APOE genotype. These results support the hypothesis that white matter hyperintensities contribute to patterns of brain atrophy found in beyond-normal brain ageing in the general population. White matter hyperintensities also contribute to brain atrophy patterns in regions related to Alzheimer’s disease dementia, in agreement with their known additive role to the likelihood of dementia. Preventive strategies reducing the odds to develop cardiovascular disease and white matter hyperintensities could decrease the incidence or delay the onset of dementia. PMID:26912649

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.

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.

Neuroanatomical Correlates of Theory of Mind Deficit in Parkinson’s Disease: A Multimodal Imaging Study

PubMed Central

Díez-Cirarda, María; Ojeda, Natalia; Peña, Javier; Cabrera-Zubizarreta, Alberto; Gómez-Beldarrain, María Ángeles; Gómez-Esteban, Juan Carlos; Ibarretxe-Bilbao, Naroa

2015-01-01

Background Parkinson’s disease (PD) patients show theory of mind (ToM) deficit since the early stages of the disease, and this deficit has been associated with working memory, executive functions and quality of life impairment. To date, neuroanatomical correlates of ToM have not been assessed with magnetic resonance imaging in PD. The main objective of this study was to assess cerebral correlates of ToM deficit in PD. The second objective was to explore the relationships between ToM, working memory and executive functions, and to analyse the neural correlates of ToM, controlling for both working memory and executive functions. Methods Thirty-seven PD patients (Hoehn and Yahr median = 2.0) and 15 healthy controls underwent a neuropsychological assessment and magnetic resonance images in a 3T-scanner were acquired. T1-weighted images were analysed with voxel-based morphometry, and white matter integrity and diffusivity measures were obtained from diffusion weighted images and analysed using tract-based spatial statistics. Results PD patients showed impairments in ToM, working memory and executive functions; grey matter loss and white matter reduction compared to healthy controls. Grey matter volume decrease in the precentral and postcentral gyrus, middle and inferior frontal gyrus correlated with ToM deficit in PD. White matter in the superior longitudinal fasciculus (adjacent to the parietal lobe) and white matter adjacent to the frontal lobe correlated with ToM impairment in PD. After controlling for executive functions, the relationship between ToM deficit and white matter remained significant for white matter areas adjacent to the precuneus and the parietal lobe. Conclusions Findings reinforce the existence of ToM impairment from the early Hoehn and Yahr stages in PD, and the findings suggest associations with white matter and grey matter volume decrease. This study contributes to better understand ToM deficit and its neural correlates in PD, which is a basic skill for development of healthy social relationships. PMID:26559669

Neuroanatomical Correlates of Theory of Mind Deficit in Parkinson's Disease: A Multimodal Imaging Study.

PubMed

Díez-Cirarda, María; Ojeda, Natalia; Peña, Javier; Cabrera-Zubizarreta, Alberto; Gómez-Beldarrain, María Ángeles; Gómez-Esteban, Juan Carlos; Ibarretxe-Bilbao, Naroa

2015-01-01

Parkinson's disease (PD) patients show theory of mind (ToM) deficit since the early stages of the disease, and this deficit has been associated with working memory, executive functions and quality of life impairment. To date, neuroanatomical correlates of ToM have not been assessed with magnetic resonance imaging in PD. The main objective of this study was to assess cerebral correlates of ToM deficit in PD. The second objective was to explore the relationships between ToM, working memory and executive functions, and to analyse the neural correlates of ToM, controlling for both working memory and executive functions. Thirty-seven PD patients (Hoehn and Yahr median = 2.0) and 15 healthy controls underwent a neuropsychological assessment and magnetic resonance images in a 3T-scanner were acquired. T1-weighted images were analysed with voxel-based morphometry, and white matter integrity and diffusivity measures were obtained from diffusion weighted images and analysed using tract-based spatial statistics. PD patients showed impairments in ToM, working memory and executive functions; grey matter loss and white matter reduction compared to healthy controls. Grey matter volume decrease in the precentral and postcentral gyrus, middle and inferior frontal gyrus correlated with ToM deficit in PD. White matter in the superior longitudinal fasciculus (adjacent to the parietal lobe) and white matter adjacent to the frontal lobe correlated with ToM impairment in PD. After controlling for executive functions, the relationship between ToM deficit and white matter remained significant for white matter areas adjacent to the precuneus and the parietal lobe. Findings reinforce the existence of ToM impairment from the early Hoehn and Yahr stages in PD, and the findings suggest associations with white matter and grey matter volume decrease. This study contributes to better understand ToM deficit and its neural correlates in PD, which is a basic skill for development of healthy social relationships.

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 hyperintensity volume highlights the growing importance of kidney disease as a possible determinant of cerebrovascular disease and/or as a marker of microangiopathy. PMID:17962588

White matter lesion extension to automatic brain tissue segmentation on MRI.

PubMed

de Boer, Renske; Vrooman, Henri A; van der Lijn, Fedde; Vernooij, Meike W; Ikram, M Arfan; van der Lugt, Aad; Breteler, Monique M B; Niessen, Wiro J

2009-05-01

A fully automated brain tissue segmentation method is optimized and extended with white matter lesion segmentation. Cerebrospinal fluid (CSF), gray matter (GM) and white matter (WM) are segmented by an atlas-based k-nearest neighbor classifier on multi-modal magnetic resonance imaging data. This classifier is trained by registering brain atlases to the subject. The resulting GM segmentation is used to automatically find a white matter lesion (WML) threshold in a fluid-attenuated inversion recovery scan. False positive lesions are removed by ensuring that the lesions are within the white matter. The method was visually validated on a set of 209 subjects. No segmentation errors were found in 98% of the brain tissue segmentations and 97% of the WML segmentations. A quantitative evaluation using manual segmentations was performed on a subset of 6 subjects for CSF, GM and WM segmentation and an additional 14 for the WML segmentations. The results indicated that the automatic segmentation accuracy is close to the interobserver variability of manual segmentations.

NeuN+ Neuronal Nuclei in Non-Human Primate Prefrontal Cortex and Subcortical White Matter After Clozapine Exposure

PubMed Central

Halene, Tobias B.; Kozlenkov, Alexey; Jiang, Yan; Mitchell, Amanda; Javidfar, Behnam; Dincer, Aslihan; Park, Royce; Wiseman, Jennifer; Croxson, Paula; Giannaris, Eustathia Lela; Hof, Patrick R.; Roussos, Panos; Dracheva, Stella; Hemby, Scott E.; Akbarian, Schahram

2016-01-01

Increased neuronal densities in subcortical white matter have been reported for some cases with schizophrenia. The underlying cellular and molecular mechanisms remain unresolved. We exposed 26 young adult macaque monkeys for 6 months to either clozapine, haloperidol or placebo and measured by structural MRI frontal gray and white matter volumes before and after treatment, followed by observer-independent, flow-cytometry-based quantification of neuronal and non-neuronal nuclei and molecular fingerprinting of cell-type specific transcripts. After clozapine exposure, the proportion of nuclei expressing the neuronal marker NeuN increased by approximately 50% in subcortical white matter, in conjunction with a more subtle and non-significant increase in overlying gray matter. Numbers and proportions of nuclei expressing the oligodendrocyte lineage marker, OLIG2, and cell-type specific RNA expression patterns, were maintained after antipsychotic drug exposure. Frontal lobe gray and white matter volumes remained indistinguishable between antipsychotic-drug-exposed and control groups. Chronic clozapine exposure increases the proportion of NeuN+ nuclei in frontal subcortical white matter, without alterations in frontal lobe volumes or cell type-specific gene expression. Further exploration of neurochemical plasticity in non-human primate brain exposed to antipsychotic drugs is warranted. PMID:26776227

Family-based association study of matrix metalloproteinase-3 and -9 haplotypes with susceptibility to ischemic white matter injury.

PubMed

Fornage, Myriam; Mosley, Thomas H; Jack, Clifford R; de Andrade, Mariza; Kardia, Sharon L R; Boerwinkle, Eric; Turner, Stephen T

2007-01-01

Susceptibility to ischemic damage to the subcortical white matter of the brain has a strong genetic basis. Dysregulation of matrix metalloproteinases (MMPs) contributes to loss of cerebrovascular integrity and white matter injury. We investigated whether sequence variation in the genes encoding MMP3 and MMP9 is associated with variation in leukoaraiosis volume, determined by magnetic resonance imaging, in non-Hispanic whites and African-Americans using family-based association tests. Seven hundred and fifty-six white and 671 African-American individuals from sibships ascertained through two or more siblings with hypertension were genotyped for 7 and 8 haplotype-tagging polymorphisms in the MMP3 and MMP9 genes, respectively. MMP3 sequence variation was significantly associated with variation in leukoaraiosis volume in Whites. Two common haplotypes with opposing relationships to leukoaraiosis volume were identified. MMP9 sequence variation was also significantly associated with variation in leukoaraiosis volume in both African-Americans and Whites. Different haplotypes contributed to these associations in the two racial groups. These findings add to the growing body of evidence from animal models and human clinical studies suggesting a role of MMPs in ischemic white matter injury. They provide the basis for further investigation of the role of these genes in susceptibility and/or progression to clinical disease.

[Analysis of mechanism of transition zones among β, δ and γ dispersions in brain white matter and grey matter].

PubMed

Tian, Rui; Lu, Mai

2017-08-01

In order to explore the application of the dielectric properties of white matter and grey matter in β, δ and γ dispersion transition zones used in clinical medicine and microwave imaging technology, we calculated the dielectric constant and its increment by using Cole-Cole equation. Based on the mutation of the increment of dielectric constant, the frequency range of three dispersions were evaluated. The dominate dispersion and the corresponding polarization mechanism were analyzed by using Cole-Cole circle. The results showed that there are 3 transition zones in brain white matter, which occur between β and δ dispersion, δ and γ dispersion and β and γ dispersion respectively. In grey matter, there are only 2 transition zones, which are between β and δ dispersion and δ and γ dispersion respectively. By comparing the frequency range of white matter and grey matter, the frequency range in white matter is broader than that in grey matter for the transition zone of β and δ dispersion with the β dispersion occupying dominate position in both tissues, and the corresponding polarization mechanism is interfacial polarization. For the transition zone of δ and γ dispersion, the frequency range in white matter is also broader than that in grey matter with the δ dispersion occupying dominate position in both tissues, and the corresponding polarization mechanism is orientation polarization. This study can provide basic theory and reference for diagnosis of brain diseases and microwave imaging technology.

BDNF Val66Met polymorphism modulates the effect of loneliness on white matter microstructure in young adults.

PubMed

Meng, Jie; Hao, Lei; Wei, Dongtao; Sun, Jiangzhou; Li, Yu; Qiu, Jiang

2017-12-01

Loneliness is a common experience. Susceptibility to loneliness is a stable trait and is heritable. Previous studies have suggested that loneliness may impact regional gray matter density and brain activation to social stimuli, but its relation to white matter structure and how it may interact with genetic factors remains unclear. In this study, we investigated whether and how a common polymorphism (Val66Met) in the brain-derived neurotrophic factor gene modulated the association between loneliness and white matter microstructure in 162 young adults. The tract-based spatial statistics analyses revealed that the relationships between loneliness and white matter microstructures were significantly different between Val/Met heterozygotes and Val/Val homozygotes. Specifically, loneliness was significantly correlated with reduced fractional anisotropy and increased radial diffusivity in widespread white matter fibers within Val/Met heterozygotes. It was also significantly correlated with increased radial diffusivity in Met/Met genotypes but showed no significant association with white matter measures in Val/Val genotypes. Furthermore, the associations between loneliness and fractional anisotropy (or radial diffusivity) in Val/Met heterozygotes turned out to be global effects. These results provide evidence that loneliness may interact with the BDNF Val66Met polymorphism to shape the microstructures of white matter, and the Val/Met heterozygotes may be more susceptible to social environment. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

[The effection of white matter abnormality to auditory and speech rehabilitation after cochlear implantation in prelingual deafness children].

PubMed

Zhang, X Y; Liang, M J; Liu, J H; Li, X H; Zhen, Y Q; Weng, Y L

2017-04-20

Objective: To investigatethe effection of white matter abnormality to auditory and speech rehabilitation after cochlear implantation in prelingual deafness children. Method: Thirty-five children with white matter abnormality were included in this study. The degree of leukoaraiosis was evaluated by Scheltens scale based on MRI.The hearing and speechrecovery level was rated by auditory behavior grading standards(CAP) and speech intelligibility grading standards(SIR) at 6 months, 12 months, and 24 months post operation. Result: The CAP scores and SIR scores of the children with white matter abnormality were lower than those of the control group at 6 months after operation ( P <0.05).The SIR scores of the children with white matter abnormality at 12 months and 24 months post operation were significantly lower than those of the control group.There was no statistically significant difference between the CAP scores of the two groups at 12 and 24 months after operation( P >0.05).Schelten classification had a greater impact on SIR scores than on CAP scores. Conclusion: The effect of white matter abnormality on auditory and speech rehabilitation after cochlear implantation was related to the degree of leukoencephalopathy. When the lesion of white matter abnormality was larger, the level of hearing and verbal rehabilitation was lower, and the speech rehabilitation was more significantly impacted by white matter lesions degree. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

Characterizing white matter tissue in large strain via asymmetric indentation and inverse finite element modeling.

PubMed

Feng, Yuan; Lee, Chung-Hao; Sun, Lining; Ji, Songbai; Zhao, Xuefeng

2017-01-01

Characterizing the mechanical properties of white matter is important to understand and model brain development and injury. With embedded aligned axonal fibers, white matter is typically modeled as a transversely isotropic material. However, most studies characterize the white matter tissue using models with a single anisotropic invariant or in a small-strain regime. In this study, we combined a single experimental procedure - asymmetric indentation - with inverse finite element (FE) modeling to estimate the nearly incompressible transversely isotropic material parameters of white matter. A minimal form comprising three parameters was employed to simulate indentation responses in the large-strain regime. The parameters were estimated using a global optimization procedure based on a genetic algorithm (GA). Experimental data from two indentation configurations of porcine white matter, parallel and perpendicular to the axonal fiber direction, were utilized to estimate model parameters. Results in this study confirmed a strong mechanical anisotropy of white matter in large strain. Further, our results suggested that both indentation configurations are needed to estimate the parameters with sufficient accuracy, and that the indenter-sample friction is important. Finally, we also showed that the estimated parameters were consistent with those previously obtained via a trial-and-error forward FE method in the small-strain regime. These findings are useful in modeling and parameterization of white matter, especially under large deformation, and demonstrate the potential of the proposed asymmetric indentation technique to characterize other soft biological tissues with transversely isotropic properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

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 Hyperintensity Associations with Cerebral Blood Flow in Elderly Subjects Stratified by Cerebrovascular Risk.

PubMed

Bahrani, Ahmed A; Powell, David K; Yu, Guoquiang; Johnson, Eleanor S; Jicha, Gregory A; Smith, Charles D

2017-04-01

This study aims to add clarity to the relationship between deep and periventricular brain white matter hyperintensities (WMHs), cerebral blood flow (CBF), and cerebrovascular risk in older persons. Deep white matter hyperintensity (dWMH) and periventricular white matter hyperintensity (pWMH) and regional gray matter (GM) and white matter (WM) blood flow from arterial spin labeling were quantified from magnetic resonance imaging scans of 26 cognitively normal elderly subjects stratified by cerebrovascular disease (CVD) risk. Fluid-attenuated inversion recovery images were acquired using a high-resolution 3-dimensional (3-D) sequence that reduced partial volume effects seen with slice-based techniques. dWMHs but not pWMHs were increased in patients at high risk of CVD; pWMHs but not dWMHs were associated with decreased regional cortical (GM) blood flow. We also found that blood flow in WM is decreased in regions of both pWMH and dWMH, with a greater degree of decrease in pWMH areas. WMHs are usefully divided into dWMH and pWMH regions because they demonstrate differential effects. 3-D regional WMH volume is a potentially valuable marker for CVD based on associations with cortical CBF and WM CBF. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Multiple White Matter Volume Reductions in Patients with Panic Disorder: Relationships between Orbitofrontal Gyrus Volume and Symptom Severity and Social Dysfunction

PubMed Central

Konishi, Jun; Asami, Takeshi; Hayano, Fumi; Yoshimi, Asuka; Hayasaka, Shunsuke; Fukushima, Hiroshi; Whitford, Thomas J.; Inoue, Tomio; Hirayasu, Yoshio

2014-01-01

Numerous brain regions are believed to be involved in the neuropathology of panic disorder (PD) including fronto-limbic regions, thalamus, brain stem, and cerebellum. However, while several previous studies have demonstrated volumetric gray matter reductions in these brain regions, there have been no studies evaluating volumetric white matter changes in the fiber bundles connecting these regions. In addition, although patients with PD typically exhibit social, interpersonal and occupational dysfunction, the neuropathologies underlying these dysfunctions remain unclear. A voxel-based morphometry study was conducted to evaluate differences in regional white matter volume between 40 patients with PD and 40 healthy control subjects (HC). Correlation analyses were performed between the regional white matter volumes and patients' scores on the Panic Disorder Severity Scale (PDSS) and the Global Assessment of Functioning (GAF). Patients with PD demonstrated significant volumetric reductions in widespread white matter regions including fronto-limbic, thalamo-cortical and cerebellar pathways (p<0.05, FDR corrected). Furthermore, there was a significant negative relationship between right orbitofrontal gyrus (OFG) white matter volume and the severity of patients' clinical symptoms, as assessed with the PDSS. A significant positive relationship was also observed between patients' right OFG volumes and their scores on the GAF. Our results suggest that volumetric reductions in widespread white matter regions may play an important role in the pathology of PD. In particular, our results suggest that structural white matter abnormalities in the right OFG may contribute to the social, personal and occupational dysfunction typically experienced by patients with PD. PMID:24663245

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 neuroanatomical bases of early childhood stuttering, and possible white matter developmental changes that may lead to recovery versus persistent stuttering. The white matter changes point to possible structural connectivity deficits in children who stutter, in interrelated neural circuits that enable skilled movement control through efficient sensorimotor integration and timing of movements. PMID:25619509

White matter integrity between left basal ganglia and left prefrontal cortex is compromised in gambling disorder.

PubMed

van Timmeren, Tim; Jansen, Jochem M; Caan, Matthan W A; Goudriaan, Anna E; van Holst, Ruth J

2017-11-01

Pathological gambling (PG) is a behavioral addiction characterized by an inability to stop gambling despite the negative consequences, which may be mediated by cognitive flexibility deficits. Indeed, impaired cognitive flexibility has previously been linked to PG and also to reduced integrity of white matter connections between the basal ganglia and the prefrontal cortex. It remains unclear, however, how white matter integrity problems relate to cognitive inflexibility seen in PG. We used a cognitive switch paradigm during functional magnetic resonance imaging in pathological gamblers (PGs; n = 26) and healthy controls (HCs; n = 26). Cognitive flexibility performance was measured behaviorally by accuracy and reaction time on the switch task, while brain activity was measured in terms of blood oxygen level-dependent responses. We also used diffusion tensor imaging on a subset of data (PGs = 21; HCs = 21) in combination with tract-based spatial statistics and probabilistic fiber tracking to assess white matter integrity between the basal ganglia and the dorsolateral prefrontal cortex. Although there were no significant group differences in either task performance, related neural activity or tract-based spatial statistics, PGs did show decreased white matter integrity between the left basal ganglia and prefrontal cortex. Our results complement and expand similar findings from a previous study in alcohol-dependent patients. Although we found no association between white matter integrity and task performance here, decreased white matter connections may contribute to a diminished ability to recruit prefrontal networks needed for regulating behavior in PG. Hence, our findings could resonate an underlying risk factor for PG, and we speculate that these findings may extend to addiction in general. © 2016 Society for the Study of Addiction.

Microstructural abnormalities in white and gray matter in obese adolescents with and without type 2 diabetes.

PubMed

Nouwen, Arie; Chambers, Alison; Chechlacz, Magdalena; Higgs, Suzanne; Blissett, Jacqueline; Barrett, Timothy G; Allen, Harriet A

2017-01-01

In adults, type 2 diabetes and obesity have been associated with structural brain changes, even in the absence of dementia. Some evidence suggested similar changes in adolescents with type 2 diabetes but comparisons with a non-obese control group have been lacking. The aim of the current study was to examine differences in microstructure of gray and white matter between adolescents with type 2 diabetes, obese adolescents and healthy weight adolescents. Magnetic resonance imaging data were collected from 15 adolescents with type 2 diabetes, 21 obese adolescents and 22 healthy weight controls. Volumetric differences in the gray matter between the three groups were examined using voxel based morphology, while tract based spatial statistics was used to examine differences in the microstructure of the white matter. Adolescents with type 2 diabetes and obese adolescents had reduced gray matter volume in the right hippocampus, left putamen and caudate, bilateral amygdala and left thalamus compared to healthy weight controls. Type 2 diabetes was also associated with significant regional changes in fractional anisotropy within the corpus callosum, fornix, left inferior fronto-occipital fasciculus, left uncinate, left internal and external capsule. Fractional anisotropy reductions within these tracts were explained by increased radial diffusivity, which may suggest demyelination of white matter tracts. Mean diffusivity and axial diffusivity did not differ between the groups. Our data shows that adolescent obesity alone results in reduced gray matter volume and that adolescent type 2 diabetes is associated with both white and gray matter abnormalities.

Reduced structural connectivity within a prefrontal-motor-subcortical network in amyotrophic lateral sclerosis.

PubMed

Buchanan, Colin R; Pettit, Lewis D; Storkey, Amos J; Abrahams, Sharon; Bastin, Mark E

2015-05-01

To investigate white matter structural connectivity changes associated with amyotrophic lateral sclerosis (ALS) using network analysis and compare the results with those obtained using standard voxel-based methods, specifically Tract-based Spatial Statistics (TBSS). MRI data were acquired from 30 patients with ALS and 30 age-matched healthy controls. For each subject, 85 grey matter regions (network nodes) were identified from high resolution structural MRI, and network connections formed from the white matter tracts generated by diffusion MRI and probabilistic tractography. Whole-brain networks were constructed using strong constraints on anatomical plausibility and a weighting reflecting tract-averaged fractional anisotropy (FA). Analysis using Network-based Statistics (NBS), without a priori selected regions, identified an impaired motor-frontal-subcortical subnetwork (10 nodes and 12 bidirectional connections), consistent with upper motor neuron pathology, in the ALS group compared with the controls (P = 0.020). Reduced FA in three of the impaired network connections, which involved fibers of the corticospinal tract, correlated with rate of disease progression (P ≤ 0.024). A novel network-tract comparison revealed that the connections involved in the affected network had a strong correspondence (mean overlap of 86.2%) with white matter tracts identified as having reduced FA compared with the control group using TBSS. These findings suggest that white matter degeneration in ALS is strongly linked to the motor cortex, and that impaired structural networks identified using NBS have a strong correspondence to affected white matter tracts identified using more conventional voxel-based methods. © 2014 Wiley Periodicals, Inc.

Alterations in white matter volume and its correlation with neuropsychological scales in patients with Alzheimer's disease: a DARTEL-based voxel-based morphometry study.

PubMed

Moon, Chung-Man; Shin, Il-Seon; Jeong, Gwang-Woo

2017-02-01

Background Non-invasive imaging markers can be used to diagnose Alzheimer's disease (AD) in its early stages, but an optimized quantification analysis to measure the brain integrity has been less studied. Purpose To evaluate white matter volume change and its correlation with neuropsychological scales in patients with AD using a diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL)-based voxel-based morphometry (VBM). Material and Methods The 21 participants comprised 11 patients with AD and 10 age-matched healthy controls. High-resolution magnetic resonance imaging (MRI) data were processed by VBM analysis based on DARTEL algorithm. Results The patients showed significant white matter volume reductions in the posterior limb of the internal capsule, cerebral peduncle of the midbrain, and parahippocampal gyrus compared to healthy controls. In correlation analysis, the parahippocampal volume was positively correlated with the Korean-mini mental state examination score in AD. Conclusion This study provides an evidence for localized white matter volume deficits in conjunction with cognitive dysfunction in AD. These findings would be helpful to understand the neuroanatomical mechanisms in AD and to robust the diagnostic accuracy for AD.

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

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 and FA values at term equivalent age were associated with subsequent neurodevelopmental performance. This study suggests multiple perinatal risk factors have an independent association with diffuse white matter injury at term equivalent age and exposure to multiple perinatal risk factors exacerbates dMRI defined, clinically significant white matter injury. Our findings support the multiple hit hypothesis for preterm white matter injury.

A comparison of three fiber tract delineation methods and their impact on white matter analysis.

PubMed

Sydnor, Valerie J; Rivas-Grajales, Ana María; Lyall, Amanda E; Zhang, Fan; Bouix, Sylvain; Karmacharya, Sarina; Shenton, Martha E; Westin, Carl-Fredrik; Makris, Nikos; Wassermann, Demian; O'Donnell, Lauren J; Kubicki, Marek

2018-05-19

Diffusion magnetic resonance imaging (dMRI) is an important method for studying white matter connectivity in the brain in vivo in both healthy and clinical populations. Improvements in dMRI tractography algorithms, which reconstruct macroscopic three-dimensional white matter fiber pathways, have allowed for methodological advances in the study of white matter; however, insufficient attention has been paid to comparing post-tractography methods that extract white matter fiber tracts of interest from whole-brain tractography. Here we conduct a comparison of three representative and conceptually distinct approaches to fiber tract delineation: 1) a manual multiple region of interest-based approach, 2) an atlas-based approach, and 3) a groupwise fiber clustering approach, by employing methods that exemplify these approaches to delineate the arcuate fasciculus, the middle longitudinal fasciculus, and the uncinate fasciculus in 10 healthy male subjects. We enable qualitative comparisons across methods, conduct quantitative evaluations of tract volume, tract length, mean fractional anisotropy, and true positive and true negative rates, and report measures of intra-method and inter-method agreement. We discuss methodological similarities and differences between the three approaches and the major advantages and drawbacks of each, and review research and clinical contexts for which each method may be most apposite. Emphasis is given to the means by which different white matter fiber tract delineation approaches may systematically produce variable results, despite utilizing the same input tractography and reliance on similar anatomical knowledge. Copyright © 2018. Published by Elsevier Inc.

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

Plasticity of left perisylvian white-matter tracts is associated with individual differences in math learning.

PubMed

Jolles, Dietsje; Wassermann, Demian; Chokhani, Ritika; Richardson, Jennifer; Tenison, Caitlin; Bammer, Roland; Fuchs, Lynn; Supekar, Kaustubh; Menon, Vinod

2016-04-01

Plasticity of white matter tracts is thought to be essential for cognitive development and academic skill acquisition in children. However, a dearth of high-quality diffusion tensor imaging (DTI) data measuring longitudinal changes with learning, as well as methodological difficulties in multi-time point tract identification have limited our ability to investigate plasticity of specific white matter tracts. Here, we examine learning-related changes of white matter tracts innervating inferior parietal, prefrontal and temporal regions following an intense 2-month math tutoring program. DTI data were acquired from 18 third grade children, both before and after tutoring. A novel fiber tracking algorithm based on a White Matter Query Language (WMQL) was used to identify three sections of the superior longitudinal fasciculus (SLF) linking frontal and parietal (SLF-FP), parietal and temporal (SLF-PT) and frontal and temporal (SLF-FT) cortices, from which we created child-specific probabilistic maps. The SLF-FP, SLF-FT, and SLF-PT tracts identified with the WMQL method were highly reliable across the two time points and showed close correspondence to tracts previously described in adults. Notably, individual differences in behavioral gains after 2 months of tutoring were specifically correlated with plasticity in the left SLF-FT tract. Our results extend previous findings of individual differences in white matter integrity, and provide important new insights into white matter plasticity related to math learning in childhood. More generally, our quantitative approach will be useful for future studies examining longitudinal changes in white matter integrity associated with cognitive skill development.

White matter changes and word finding failures with increasing age.

PubMed

Stamatakis, Emmanuel A; Shafto, Meredith A; Williams, Guy; Tam, Phyllis; Tyler, Lorraine K

2011-01-07

Increasing life expectancy necessitates the better understanding of the neurophysiological underpinnings of age-related cognitive changes. The majority of research examining structural-cognitive relationships in aging focuses on the role of age-related changes to grey matter integrity. In the current study, we examined the relationship between age-related changes in white matter and language production. More specifically, we concentrated on word-finding failures, which increase with age. We used Diffusion tensor MRI (a technique used to image, in vivo, the diffusion of water molecules in brain tissue) to relate white matter integrity to measures of successful and unsuccessful picture naming. Diffusion tensor images were used to calculate Fractional Anisotropy (FA) images. FA is considered to be a measure of white matter organization/integrity. FA images were related to measures of successful picture naming and to word finding failures using voxel-based linear regression analyses. Successful naming rates correlated positively with white matter integrity across a broad range of regions implicated in language production. However, word finding failure rates correlated negatively with a more restricted region in the posterior aspect of superior longitudinal fasciculus. The use of DTI-MRI provides evidence for the relationship between age-related white matter changes in specific language regions and word finding failures in old age.

Longitudinal Changes in White Matter Fractional Anisotropy in Adult-Onset Niemann-Pick Disease Type C Patients Treated with Miglustat.

PubMed

Bowman, Elizabeth A; Velakoulis, Dennis; Desmond, Patricia; Walterfang, Mark

2018-01-01

Niemann-Pick disease type C (NPC) is a rare neurometabolic disorder resulting in impaired intracellular lipid trafficking. The only disease-modifying treatment currently available is miglustat, an iminosugar that inhibits the accumulation of lipid metabolites in neurons and other cells. This longitudinal diffusion tensor imaging (DTI) study examined how the rate of white matter change differed between treated and non-treated adult-onset NPC patient groups. Nine adult-onset NPC patients (seven undergoing treatment with miglustat, two not treated) underwent DTI neuroimaging. Rates of change in white matter structure as indexed by Tract-Based Spatial Statistics (TBSS) of fractional anisotropy were compared between treated and untreated patients. Treated patients were found to have a significantly slower rate of white matter change in the corticospinal tracts, the thalamic radiation and the inferior longitudinal fasciculus. This is further evidence that miglustat treatment may have a protective effect on white matter structure in the adult-onset form of the disease.

Vertex- and atlas-based comparisons in measures of cortical thickness, gyrification and white matter volume between humans and chimpanzees.

PubMed

Hopkins, William D; Li, Xiang; Crow, Tim; Roberts, Neil

2017-01-01

What changes in cortical organisation characterise global and localised variation between humans and chimpanzees remains a topic of considerable interest in evolutionary neuroscience. Here, we examined regional variation in cortical thickness, gyrification and white matter in samples of human and chimpanzee brains. Both species were MRI scanned on the same platform using identical procedures. The images were processed and segmented by FSL and FreeSurfer and the relative changes in cortical thickness, gyrification and white matter across the entire cortex were compared between species. In general, relative to chimpanzees, humans had significantly greater gyrification and significantly thinner cortex, particularly in the frontal lobe. Human brains also had disproportionately higher white matter volumes in the frontal lobe, particularly in prefrontal regions. Collectively, the findings suggest that after the split from the common ancestor, white matter expansion and subsequently increasing gyrification occurred in the frontal lobe possibly due to increased selection for human cognitive and motor specialisations.

Longitudinal changes in microstructural white matter metrics in Alzheimer's disease.

PubMed

Mayo, Chantel D; Mazerolle, Erin L; Ritchie, Lesley; Fisk, John D; Gawryluk, Jodie R

2017-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Current avenues of AD research focus on pre-symptomatic biomarkers that will assist with early diagnosis of AD. The majority of magnetic resonance imaging (MRI) based biomarker research to date has focused on neuronal loss in grey matter and there is a paucity of research on white matter. Longitudinal DTI data from the Alzheimer's Disease Neuroimaging Initiative 2 database were used to examine 1) the within-group microstructural white matter changes in individuals with AD and healthy controls at baseline and year one; and 2) the between-group microstructural differences in individuals with AD and healthy controls at both time points. 1) Within-group: longitudinal Tract-Based Spatial Statistics revealed that individuals with AD and healthy controls both had widespread reduced fractional anisotropy (FA) and increased mean diffusivity (MD) with changes in the hippocampal cingulum exclusive to the AD group. 2) Between-group: relative to healthy controls, individuals with AD had lower FA and higher MD in the hippocampal cingulum, as well as the corpus callosum, internal and external capsule; corona radiata; posterior thalamic radiation; superior and inferior longitudinal fasciculus; fronto-occipital fasciculus; cingulate gyri; fornix; uncinate fasciculus; and tapetum. The current results indicate that sensitivity to white matter microstructure is a promising avenue for AD biomarker research. Additional longitudinal studies on both white and grey matter are warranted to further evaluate potential clinical utility.

Diffusion Tensor Imaging of Pedophilia.

PubMed

Cantor, James M; Lafaille, Sophie; Soh, Debra W; Moayedi, Massieh; Mikulis, David J; Girard, Todd A

2015-11-01

Pedophilia is a principal motivator of child molestation, incurring great emotional and financial burdens on victims and society. Even among pedophiles who never commit any offense,the condition requires lifelong suppression and control. Previous comparison using voxel-based morphometry (VBM)of MR images from a large sample of pedophiles and controls revealed group differences in white matter. The present study therefore sought to verify and characterize white matter involvement using diffusion tensor imaging (DTI), which better captures the microstructure of white matter than does VBM. Pedophilics ex offenders (n=24) were compared with healthy, age-matched controls with no criminal record and no indication of pedophilia (n=32). White matter microstructure was analyzed with Tract-Based Spatial Statistics, and the trajectories of implicated fiber bundles were identified by probabilistic tractography. Groups showed significant, highly focused differences in DTI parameters which related to participants’ genital responses to sexual depictions of children, but not to measures of psychopathy or to childhood histories of physical abuse, sexual abuse, or neglect. Some previously reported gray matter differences were suggested under highly liberal statistical conditions (p(uncorrected)<.005), but did not survive ordinary statistical correction (whole brain per voxel false discovery rate of 5%). These results confirm that pedophilia is characterized by neuroanatomical differences in white matter microstructure, over and above any neural characteristics attributable to psychopathy and childhood adversity, which show neuroanatomic footprints of their own. Although some gray matter structures were implicated previously, only few have emerged reliably.

Alterations in White Matter Integrity in Young Adults with Smartphone Dependence

PubMed Central

Hu, Yuanming; Long, Xiaojing; Lyu, Hanqing; Zhou, Yangyang; Chen, Jianxiang

2017-01-01

Smartphone dependence (SPD) is increasingly regarded as a psychological problem, however, the underlying neural substrates of SPD is still not clear. High resolution magnetic resonance imaging provides a useful tool to help understand and manage the disorder. In this study, a tract-based spatial statistics (TBSS) analysis on diffusion tensor imaging (DTI) was used to measure white matter integrity in young adults with SPD. A total of 49 subjects were recruited and categorized into SPD and control group based on their clinical behavioral tests. To localize regions with abnormal white matter integrity in SPD, the voxel-wise analysis of fractional anisotropy (FA) and mean diffusivity (MD) on the whole brain was performed by TBSS. The correlation between the quantitative variables of brain structures and the behavior measures were performed. Our result demonstrated that SPD had significantly lower white matter integrity than controls in superior longitudinal fasciculus (SLF), superior corona radiata (SCR), internal capsule, external capsule, sagittal stratum, fornix/stria terminalis and midbrain structures. Correlation analysis showed that the observed abnormalities in internal capsule and stria terminalis were correlated with the severity of dependence and behavioral assessments. Our finding facilitated a primary understanding of white matter characteristics in SPD and indicated that the structural deficits might link to behavioral impairments. PMID:29163108

Visual System Involvement in Patients with Newly Diagnosed Parkinson Disease.

PubMed

Arrigo, Alessandro; Calamuneri, Alessandro; Milardi, Demetrio; Mormina, Enricomaria; Rania, Laura; Postorino, Elisa; Marino, Silvia; Di Lorenzo, Giuseppe; Anastasi, Giuseppe Pio; Ghilardi, Maria Felice; Aragona, Pasquale; Quartarone, Angelo; Gaeta, Michele

2017-12-01

Purpose To assess intracranial visual system changes of newly diagnosed Parkinson disease in drug-naïve patients. Materials and Methods Twenty patients with newly diagnosed Parkinson disease and 20 age-matched control subjects were recruited. Magnetic resonance (MR) imaging (T1-weighted and diffusion-weighted imaging) was performed with a 3-T MR imager. White matter changes were assessed by exploring a white matter diffusion profile by means of diffusion-tensor imaging-based parameters and constrained spherical deconvolution-based connectivity analysis and by means of white matter voxel-based morphometry (VBM). Alterations in occipital gray matter were investigated by means of gray matter VBM. Morphologic analysis of the optic chiasm was based on manual measurement of regions of interest. Statistical testing included analysis of variance, t tests, and permutation tests. Results In the patients with Parkinson disease, significant alterations were found in optic radiation connectivity distribution, with decreased lateral geniculate nucleus V2 density (F, -8.28; P < .05), a significant increase in optic radiation mean diffusivity (F, 7.5; P = .014), and a significant reduction in white matter concentration. VBM analysis also showed a significant reduction in visual cortical volumes (P < .05). Moreover, the chiasmatic area and volume were significantly reduced (P < .05). Conclusion The findings show that visual system alterations can be detected in early stages of Parkinson disease and that the entire intracranial visual system can be involved. © RSNA, 2017 Online supplemental material is available for this article.

Automatic Segmentation of the Cortical Grey and White Matter in MRI Using a Region-Growing Approach Based on Anatomical Knowledge

NASA Astrophysics Data System (ADS)

Wasserthal, Christian; Engel, Karin; Rink, Karsten; Brechmann, Andr'e.

We propose an automatic procedure for the correct segmentation of grey and white matter in MR data sets of the human brain. Our method exploits general anatomical knowledge for the initial segmentation and for the subsequent refinement of the estimation of the cortical grey matter. Our results are comparable to manual segmentations.

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.

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.

Genetic Study of White Matter Integrity in UK Biobank (N=8448) and the Overlap With Stroke, Depression, and Dementia.

PubMed

Rutten-Jacobs, Loes C A; Tozer, Daniel J; Duering, Marco; Malik, Rainer; Dichgans, Martin; Markus, Hugh S; Traylor, Matthew

2018-06-01

Structural integrity of the white matter is a marker of cerebral small vessel disease, which is the major cause of vascular dementia and a quarter of all strokes. Genetic studies provide a way to obtain novel insights in the disease mechanism underlying cerebral small vessel disease. The aim was to identify common variants associated with microstructural integrity of the white matter and to elucidate the relationships of white matter structural integrity with stroke, major depressive disorder, and Alzheimer disease. This genome-wide association analysis included 8448 individuals from UK Biobank-a population-based cohort study that recruited individuals from across the United Kingdom between 2006 and 2010, aged 40 to 69 years. Microstructural integrity was measured as fractional anisotropy- (FA) and mean diffusivity (MD)-derived parameters on diffusion tensor images. White matter hyperintensity volumes (WMHV) were assessed on T2-weighted fluid-attenuated inversion recovery images. We identified 1 novel locus at genome-wide significance ( VCAN [versican]: rs13164785; P =3.7×10 -18 for MD and rs67827860; P =1.3×10 -14 for FA). LD score regression showed a significant genome-wide correlation between FA, MD, and WMHV (FA-WMHV rG 0.39 [SE, 0.15]; MD-WMHV rG 0.56 [SE, 0.19]). In polygenic risk score analysis, FA, MD, and WMHV were significantly associated with lacunar stroke, MD with major depressive disorder, and WMHV with Alzheimer disease. Genetic variants within the VCAN gene may play a role in the mechanisms underlying microstructural integrity of the white matter in the brain measured as FA and MD. Mechanisms underlying white matter alterations are shared with cerebrovascular disease, and inherited differences in white matter microstructure impact on Alzheimer disease and major depressive disorder. © 2018 The Authors.

Disruption of White Matter Integrity in Adult Survivors of Childhood Brain Tumors: Correlates with Long-Term Intellectual Outcomes.

PubMed

King, Tricia Z; Wang, Liya; Mao, Hui

2015-01-01

Although chemotherapy and radiation treatment have contributed to increased survivorship, treatment-induced brain injury has been a concern when examining long-term intellectual outcomes of survivors. Specifically, disruption of brain white matter integrity and its relationship to intellectual outcomes in adult survivors of childhood brain tumors needs to be better understood. Fifty-four participants underwent diffusion tensor imaging in addition to structural MRI and an intelligence test (IQ). Voxel-wise group comparisons of fractional anisotropy calculated from DTI data were performed using Tract Based Spatial Statistics (TBSS) on 27 survivors (14 treated with radiation with and without chemotherapy and 13 treated without radiation treatment on average over 13 years since diagnosis) and 27 healthy comparison participants. Whole brain white matter fractional anisotropy (FA) differences were explored between each group. The relationships between IQ and FA in the regions where statistically lower FA values were found in survivors were examined, as well as the role of cumulative neurological factors. The group of survivors treated with radiation with and without chemotherapy had lower IQ relative to the group of survivors without radiation treatment and the healthy comparison group. TBSS identified white matter regions with significantly different mean fractional anisotropy between the three different groups. A lower level of white matter integrity was found in the radiation with or without chemotherapy treated group compared to the group without radiation treatment and also the healthy control group. The group without radiation treatment had a lower mean FA relative to healthy controls. The white matter disruption of the radiation with or without chemotherapy treated survivors was positively correlated with IQ and cumulative neurological factors. Lower long-term intellectual outcomes of childhood brain tumor survivors are associated with lower white matter integrity. Radiation and adjunct chemotherapy treatment may play a role in greater white matter disruption. The relationships between white matter integrity and IQ, as well as cumulative neurological risk factors exist in young adult survivors of childhood brain tumors.

Multimodal neuroimaging of frontal white matter microstructure in early phase schizophrenia: the impact of early adolescent cannabis use

PubMed Central

2013-01-01

Background A disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, could be responsible for the clinical symptoms and cognitive dysfunctions observed in schizophrenia. White matter, which comprises axons and their myelin sheaths, provides the physical foundation for functional connectivity in the brain. Myelin sheaths are located around the axons and provide insulation through the lipid membranes of oligodendrocytes. Empirical data suggests oligodendroglial dysfunction in schizophrenia, based on findings of abnormal myelin maintenance and repair in regions of deep white matter. The aim of this in vivo neuroimaging project is to assess the impact of early adolescent onset of regular cannabis use on brain white matter tissue integrity, and to differentiate this impact from the white matter abnormalities associated with schizophrenia. The ultimate goal is to determine the liability of early adolescent use of cannabis on brain white matter, in a vulnerable brain. Methods/Design Young adults with schizophrenia at the early stage of the illness (less than 5 years since diagnosis) will be the focus of this project. Four magnetic resonance imaging measurements will be used to assess different cellular aspects of white matter: a) diffusion tensor imaging, b) localized proton magnetic resonance spectroscopy with a focus on the neurochemical N-acetylaspartate, c) the transverse relaxation time constants of regional tissue water, d) and of N-acetylaspartate. These four neuroimaging indices will be assessed within the same brain region of interest, that is, a large white matter fibre bundle located in the frontal region, the left superior longitudinal fasciculus. Discussion We will expand our knowledge regarding current theoretical models of schizophrenia with a more comprehensive multimodal neuroimaging approach to studying the underlying cellular abnormalities of white matter, while taking into consideration the important confounding variable of early adolescent onset of regular cannabis use. PMID:24131511

Multimodal neuroimaging of frontal white matter microstructure in early phase schizophrenia: the impact of early adolescent cannabis use.

PubMed

Bernier, Denise; Cookey, Jacob; McAllindon, David; Bartha, Robert; Hanstock, Christopher C; Newman, Aaron J; Stewart, Sherry H; Tibbo, Philip G

2013-10-17

A disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, could be responsible for the clinical symptoms and cognitive dysfunctions observed in schizophrenia. White matter, which comprises axons and their myelin sheaths, provides the physical foundation for functional connectivity in the brain. Myelin sheaths are located around the axons and provide insulation through the lipid membranes of oligodendrocytes. Empirical data suggests oligodendroglial dysfunction in schizophrenia, based on findings of abnormal myelin maintenance and repair in regions of deep white matter. The aim of this in vivo neuroimaging project is to assess the impact of early adolescent onset of regular cannabis use on brain white matter tissue integrity, and to differentiate this impact from the white matter abnormalities associated with schizophrenia. The ultimate goal is to determine the liability of early adolescent use of cannabis on brain white matter, in a vulnerable brain. Young adults with schizophrenia at the early stage of the illness (less than 5 years since diagnosis) will be the focus of this project. Four magnetic resonance imaging measurements will be used to assess different cellular aspects of white matter: a) diffusion tensor imaging, b) localized proton magnetic resonance spectroscopy with a focus on the neurochemical N-acetylaspartate, c) the transverse relaxation time constants of regional tissue water, d) and of N-acetylaspartate. These four neuroimaging indices will be assessed within the same brain region of interest, that is, a large white matter fibre bundle located in the frontal region, the left superior longitudinal fasciculus. We will expand our knowledge regarding current theoretical models of schizophrenia with a more comprehensive multimodal neuroimaging approach to studying the underlying cellular abnormalities of white matter, while taking into consideration the important confounding variable of early adolescent onset of regular cannabis use.

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 were found in the VPT group. Global efficiency was reduced in the children born VPT with a history of WMI and GMH/IVH. These findings are evidence for under-developed and less connected white matter in children born VPT, contributing to our understanding of white matter development within this population.

Regional white matter abnormalities in drug-naive, first-episode schizophrenia patients and their healthy unaffected siblings.

PubMed

Lyu, Hailong; Hu, Maorong; Eyler, Lisa T; Jin, Hua; Wang, Juan; Ou, Jianjun; Guo, Xiaofeng; He, Zhong; Liu, Fang; Zhao, Jingping; Guo, Wenbin

2015-03-01

Shared neuropathological features between schizophrenia patients and their siblings may represent intermediate phenotypes of schizophrenia and can be used to investigate genetic susceptibility to the illness. This study aimed to discover regional white matter abnormalities in first-episode schizophrenia (FES) patients and their unaffected siblings compared to healthy subjects in the Chinese Han population using optimized Voxel-Based Morphometry (VBM). A total of 51 drug-naive, FES patients, 45 of their unaffected siblings and 59 healthy comparisons were studied with magnetic resonance imaging (MRI). FES patients exhibited significant regional white matter deficits in the left inferior frontal gyrus and left joint of external capsule and internal capsule compared with healthy subjects (corrected FDR, p<0.005). The sibling group also showed significant white matter deficits in these two regions compared with the healthy comparison group (uncorrected, p<0.001). White matter deficits with a less stringent threshold for significance in the left cerebellum anterior lobe, left middle frontal gyrus, left hippocampus, right anterior cingulate and right internal capsule were observed in patients compared to their siblings. Our findings extend those from previous VBM analyses showing that FES patients and their unaffected siblings may share white matter deficits in the left inferior frontal gyrus and the left joint of external capsule and internal capsule. These regional white matter deficits may be related to genetic factors related to schizophrenia susceptibility. © The Royal Australian and New Zealand College of Psychiatrists 2014.

Links between white matter microstructure and cortisol reactivity to stress in early childhood: evidence for moderation by parenting.

PubMed

Sheikh, Haroon I; Joanisse, Marc F; Mackrell, Sarah M; Kryski, Katie R; Smith, Heather J; Singh, Shiva M; Hayden, Elizabeth P

2014-01-01

Activity of the hypothalamic-pituitary-adrenal axis (measured via cortisol reactivity) may be a biological marker of risk for depression and anxiety, possibly even early in development. However, the structural neural correlates of early cortisol reactivity are not well known, although these would potentially inform broader models of mechanisms of risk, especially if the early environment further shapes these relationships. Therefore, we examined links between white matter architecture and young girls' cortisol reactivity and whether early caregiving moderated these links. We recruited 45 6-year-old girls based on whether they had previously shown high or low cortisol reactivity to a stress task at age 3. White matter integrity was assessed by calculating fractional anisotropy (FA) of diffusion-weighted magnetic resonance imaging scans. Parenting styles were measured via a standardized parent-child interaction task. Significant associations were found between FA in white matter regions adjacent to the left thalamus, the right anterior cingulate cortex, and the right superior frontal gyrus (all ps < .001). Further, positive early caregiving moderated the effect of high cortisol reactivity on white matter FA (all ps ≤ .05), with high stress reactive girls who received greater parent positive affect showing white matter structure more similar to that of low stress reactive girls. Results show associations between white matter integrity of various limbic regions of the brain and early cortisol reactivity to stress and provide preliminary support for the notion that parenting may moderate associations.

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.

White matter integrity as a predictor of response to treatment in first episode psychosis.

PubMed

Reis Marques, Tiago; Taylor, Heather; Chaddock, Chris; Dell'acqua, Flavio; Handley, Rowena; Reinders, A A T Simone; Mondelli, Valeria; Bonaccorso, Stefania; Diforti, Marta; Simmons, Andrew; David, Anthony S; Murray, Robin M; Pariante, Carmine M; Kapur, Shitij; Dazzan, Paola

2014-01-01

The integrity of brain white matter connections is central to a patient's ability to respond to pharmacological interventions. This study tested this hypothesis using a specific measure of white matter integrity, and examining its relationship to treatment response using a prospective design in patients within their first episode of psychosis. Diffusion tensor imaging data were acquired in 63 patients with first episode psychosis and 52 healthy control subjects (baseline). Response was assessed after 12 weeks and patients were classified as responders or non-responders according to treatment outcome. At this second time-point, they also underwent a second diffusion tensor imaging scan. Tract-based spatial statistics were used to assess fractional anisotropy as a marker of white matter integrity. At baseline, non-responders showed lower fractional anisotropy than both responders and healthy control subjects (P < 0.05; family-wise error-corrected), mainly in the uncinate, cingulum and corpus callosum, whereas responders were indistinguishable from healthy control subjects. After 12 weeks, there was an increase in fractional anisotropy in both responders and non-responders, positively correlated with antipsychotic exposure. This represents one of the largest, controlled investigations of white matter integrity and response to antipsychotic treatment early in psychosis. These data, together with earlier findings on cortical grey matter, suggest that grey and white matter integrity at the start of treatment is an important moderator of response to antipsychotics. These findings can inform patient stratification to anticipate care needs, and raise the possibility that antipsychotics may restore white matter integrity as part of the therapeutic response.

Information processing speed mediates the relationship between white matter and general intelligence in schizophrenia.

PubMed

Alloza, Clara; Cox, Simon R; Duff, Barbara; Semple, Scott I; Bastin, Mark E; Whalley, Heather C; Lawrie, Stephen M

2016-08-30

Several authors have proposed that schizophrenia is the result of impaired connectivity between specific brain regions rather than differences in local brain activity. White matter abnormalities have been suggested as the anatomical substrate for this dysconnectivity hypothesis. Information processing speed may act as a key cognitive resource facilitating higher order cognition by allowing multiple cognitive processes to be simultaneously available. However, there is a lack of established associations between these variables in schizophrenia. We hypothesised that the relationship between white matter and general intelligence would be mediated by processing speed. White matter water diffusion parameters were studied using Tract-based Spatial Statistics and computed within 46 regions-of-interest (ROI). Principal component analysis was conducted on these white matter ROI for fractional anisotropy (FA) and mean diffusivity, and on neurocognitive subtests to extract general factors of white mater structure (gFA, gMD), general intelligence (g) and processing speed (gspeed). There was a positive correlation between g and gFA (r= 0.67, p =0.001) that was partially and significantly mediated by gspeed (56.22% CI: 0.10-0.62). These findings suggest a plausible model of structure-function relations in schizophrenia, whereby white matter structure may provide a neuroanatomical substrate for general intelligence, which is partly supported by speed of information processing. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

White matter microstructure damage in tremor-dominant Parkinson's disease patients.

PubMed

Luo, ChunYan; Song, Wei; Chen, Qin; Yang, Jing; Gong, QiYong; Shang, Hui-Fang

2017-07-01

Resting tremor is one of the cardinal motor features of Parkinson's disease (PD). Several lines of evidence suggest resting tremor may have different underlying pathophysiological processes from those of bradykinesia and rigidity. The current study aims to identify white matter microstructural abnormalities associated with resting tremor in PD. We recruited 60 patients with PD (30 with tremor-dominant PD and 30 with nontremor-dominant PD) and 26 normal controls. All participants underwent clinical assessment and diffusion tensor MRI. We used tract-based spatial statistics to investigate white matter integrity across the entire white matter tract skeleton. Compared with both healthy controls and the nontremor-dominant PD patients, the tremor-dominant PD patients were characterized by increased mean diffusivity (MD) and axial diffusivity (AD) along multiple white matter tracts, mainly involving the cerebello-thalamo-cortical (CTC) pathway. The mean AD value in clusters with significant difference was correlated with resting tremor score in the tremor-dominant PD patients. There was no significant difference between the nontremor-dominant PD patients and controls. Our results support the notion that resting tremor in PD is a distinct condition in which significant microstructural white matter changes exist and provide evidence for the involvement of the CTC in tremor genesis of PD.

Characterization of neurons in the cortical white matter in human temporal lobe epilepsy.

PubMed

Richter, Zsófia; Janszky, József; Sétáló, György; Horváth, Réka; Horváth, Zsolt; Dóczi, Tamás; Seress, László; Ábrahám, Hajnalka

2016-10-01

The aim of the present work was to characterize neurons in the archi- and neocortical white matter, and to investigate their distribution in mesial temporal sclerosis. Immunohistochemistry and quantification of neurons were performed on surgically resected tissue sections of patients with therapy-resistant temporal lobe epilepsy. Temporal lobe tissues of patients with tumor but without epilepsy and that from autopsy were used as controls. Neurons were identified with immunohistochemistry using antibodies against NeuN, calcium-binding proteins, transcription factor Tbr1 and neurofilaments. We found significantly higher density of neurons in the archi- and neocortical white matter of patients with temporal lobe epilepsy than in that of controls. Based on their morphology and neurochemical content, both excitatory and inhibitory cells were present among these neurons. A subset of neurons in the white matter was Tbr-1-immunoreactive and these neurons coexpressed NeuN and neurofilament marker SMI311R. No colocalization of Tbr1 was observed with the inhibitory neuronal markers, calcium-binding proteins. We suggest that a large population of white matter neurons comprises remnants of the subplate. Furthermore, we propose that a subset of white matter neurons was arrested during migration, highlighting the role of cortical maldevelopment in epilepsy associated with mesial temporal sclerosis. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

White matter injuries induced by MK-801 in a mouse model of schizophrenia based on NMDA antagonism.

PubMed

Xiu, Yun; Kong, Xiang-Ru; Zhang, Lei; Qiu, Xuan; Chao, Feng-Lei; Peng, Chao; Gao, Yuan; Huang, Chun-Xia; Wang, San-Rong; Tang, Yong

2014-08-01

The etiology of schizophrenia (SZ) is complex and largely unknown. Neuroimaging and postmortem studies have suggested white matter disturbances in SZ. In the present study, we tested the white matter deficits hypothesis of SZ using a mouse model of SZ induced by NMDA receptor antagonist MK-801. We found that mice with repeated chronic MK-801 administration showed increased locomotor activity in the open field test, less exploration of a novel environment in the hole-board test, and increased anxiety in the elevated plus maze but no impairments were observed in coordination or motor function on accelerating rota-rod. The total white matter volume and corpus callosum volume in mice treated with MK-801 were significantly decreased compared to control mice treated with saline. Myelin basic protein and 2', 3'-cyclic nucleotide 3'-phosphodiesterase were also significantly decreased in the mouse model of SZ. Furthermore, we observed degenerative changes of myelin sheaths in the mouse model of SZ. These results provide further evidence of white matter deficits in SZ and indicate that the animal model of SZ induced by MK-801 is a useful model to investigate mechanisms underlying white matter abnormalities in SZ. Copyright © 2014 Wiley Periodicals, Inc.

Gray Matter Atrophy Is Primarily Related to Demyelination of Lesions in Multiple Sclerosis: A Diffusion Tensor Imaging MRI Study.

PubMed

Tóth, Eszter; Szabó, Nikoletta; Csete, Gergõ; Király, András; Faragó, Péter; Spisák, Tamás; Bencsik, Krisztina; Vécsei, László; Kincses, Zsigmond T

2017-01-01

Objective: Cortical pathology, periventricular demyelination, and lesion formation in multiple sclerosis (MS) are related (Hypothesis 1). Factors in the cerebrospinal fluid close to these compartments could possibly drive the parallel processes. Alternatively, the cortical atrophy could be caused by remote axonal transection (Hypothesis 2). Since MRI can differentiate between demyelination and axon loss, we used this imaging modality to investigate the correlation between the pattern of diffusion parameter changes in the periventricular- and deep white matter and the gray matter atrophy. Methods: High-resolution T1-weighted, FLAIR, and diffusion MRI images were acquired in 52 RRMS patients and 50 healthy, age-matched controls. We used EDSS to estimate the clinical disability. We used Tract Based Spatial Statistics to compare diffusion parameters (fractional anisotropy, mean, axial, and radial diffusivity) between groups. We evaluated global brain, white, and gray matter atrophy with SIENAX. Averaged, standard diffusion parameters were calculated in four compartment: periventricular lesioned and normal appearing white matter, non-periventricular lesioned and normal appearing white matter. PLS regression was used to identify which diffusion parameter and in which compartment best predicts the brain atrophy and clinical disability. Results: In our diffusion tensor imaging study compared to controls we found extensive alterations of fractional anisotropy, mean and radial diffusivity and smaller changes of axial diffusivity (maximal p > 0.0002) in patients that suggested demyelination in the lesioned and in the normal appearing white matter. We found significant reduction in total brain, total white, and gray matter (patients: 718.764 ± 14.968, 323.237 ± 7.246, 395.527 ± 8.050 cm 3 , controls: 791.772 ± 22.692, 355.350 ± 10.929, 436.422 ± 12.011 cm 3 ; mean ± SE), ( p < 0.015; p < 0.0001; p < 0.009; respectively) of patients compared to controls. The PLS analysis revealed a combination of demyelination-like diffusion parameters (higher mean and radial diffusivity in patients) in the lesions and in the non-lesioned periventricular white matter, which best predicted the gray matter atrophy ( p < 0.001). Similarly, EDSS was best predicted by the radial diffusivity of the lesions and the non-lesioned periventricular white matter, but axial diffusivity of the periventricular lesions also contributed significantly ( p < 0.0001). Interpretation: Our investigation showed that gray matter atrophy and white matter demyelination are related in MS but white matter axonal loss does not significantly contribute to the gray matter pathology.

White matter pathology in ALS and lower motor neuron ALS variants: a diffusion tensor imaging study using tract-based spatial statistics.

PubMed

Prudlo, Johannes; Bißbort, Charlotte; Glass, Aenne; Grossmann, Annette; Hauenstein, Karlheinz; Benecke, Reiner; Teipel, Stefan J

2012-09-01

The aim of this work was to investigate white-matter microstructural changes within and outside the corticospinal tract in classical amyotrophic lateral sclerosis (ALS) and in lower motor neuron (LMN) ALS variants by means of diffusion tensor imaging (DTI). We investigated 22 ALS patients and 21 age-matched controls utilizing a whole-brain approach with a 1.5-T scanner for DTI. The patient group was comprised of 15 classical ALS- and seven LMN ALS-variant patients (progressive muscular atrophy, flail arm and flail leg syndrome). Disease severity was measured by the revised version of the functional rating scale. White matter fractional anisotropy (FA) was assessed using tract-based spatial statistics (TBSS) and a region of interest (ROI) approach. We found significant FA reductions in motor and extra-motor cerebral fiber tracts in classical ALS and in the LMN ALS-variant patients compared to controls. The voxel-based TBSS results were confirmed by the ROI findings. The white matter damage correlated with the disease severity in the patient group and was found in a similar distribution, but to a lesser extent, among the LMN ALS-variant subgroup. ALS and LMN ALS variants are multisystem degenerations. DTI shows the potential to determine an earlier diagnosis, particularly in LMN ALS variants. The statistically identical findings of white matter lesions in classical ALS and LMN variants as ascertained by DTI further underline that these variants should be regarded as part of the ALS spectrum.

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.

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.

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.

Optimization of white matter tractography for pre-surgical planning and image-guided surgery.

PubMed

Arfanakis, Konstantinos; Gui, Minzhi; Lazar, Mariana

2006-01-01

Accurate localization of white matter fiber tracts in relation to brain tumors is a goal of critical importance to the neurosurgical community. White matter fiber tractography by means of diffusion tensor magnetic resonance imaging (DTI) is the only non-invasive method that can provide estimates of brain connectivity. However, conventional tractography methods are based on data acquisition techniques that suffer from image distortions and artifacts. Thus, a large percentage of white matter fiber bundles are distorted, and/or terminated early, while others are completely undetected. This severely limits the potential of fiber tractography in pre-surgical planning and image-guided surgery. In contrast, Turboprop-DTI is a technique that provides images with significantly fewer distortions and artifacts than conventional DTI data acquisition methods. The purpose of this study was to evaluate fiber tracking results obtained from Turboprop-DTI data. It was demonstrated that Turboprop may be a more appropriate DTI data acquisition technique for tracing white matter fibers than conventional DTI methods, especially in applications such as pre-surgical planning and image-guided surgery.

Exploratory analysis of diffusion tensor imaging in children with attention deficit hyperactivity disorder: evidence of abnormal white matter structure.

PubMed

Pastura, Giuseppe; Doering, Thomas; Gasparetto, Emerson Leandro; Mattos, Paulo; Araújo, Alexandra Prüfer

2016-06-01

Abnormalities in the white matter microstructure of the attentional system have been implicated in the aetiology of attention deficit hyperactivity disorder (ADHD). Diffusion tensor imaging (DTI) is a promising magnetic resonance imaging (MRI) technology that has increasingly been used in studies of white matter microstructure in the brain. The main objective of this work was to perform an exploratory analysis of white matter tracts in a sample of children with ADHD versus typically developing children (TDC). For this purpose, 13 drug-naive children with ADHD of both genders underwent MRI using DTI acquisition methodology and tract-based spatial statistics. The results were compared to those of a sample of 14 age- and gender-matched TDC. Lower fractional anisotropy was observed in the splenium of the corpus callosum, right superior longitudinal fasciculus, bilateral retrolenticular part of the internal capsule, bilateral inferior fronto-occipital fasciculus, left external capsule and posterior thalamic radiation (including right optic radiation). We conclude that white matter tracts in attentional and motor control systems exhibited signs of abnormal microstructure in this sample of drug-naive children with ADHD.

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.

Structural Changes after Videogame Practice Related to a Brain Network Associated with Intelligence

ERIC Educational Resources Information Center

Colom, Roberto; Quiroga, Ma. Angeles; Solana, Ana Beatriz; Burgaleta, Miguel; Roman, Francisco J.; Privado, Jesus; Escorial, Sergio; Martinez, Kenia; Alvarez-Linera, Juan; Alfayate, Eva; Garcia, Felipe; Lepage, Claude; Hernandez-Tamames, Juan Antonio; Karama, Sherif

2012-01-01

Here gray and white matter changes after four weeks of videogame practice were analyzed using optimized voxel-based morphometry (VBM), cortical surface and cortical thickness indices, and white matter integrity computed from several projection, commissural, and association tracts relevant to cognition. Beginning with a sample of one hundred young…

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.

Probabilistic diffusion tractography reveals improvement of structural network in musicians.

PubMed

Li, Jianfu; Luo, Cheng; Peng, Yueheng; Xie, Qiankun; Gong, Jinnan; Dong, Li; Lai, Yongxiu; Li, Hong; Yao, Dezhong

2014-01-01

Musicians experience a large amount of information transfer and integration of complex sensory, motor, and auditory processes when training and playing musical instruments. Therefore, musicians are a useful model in which to investigate neural adaptations in the brain. Here, based on diffusion-weighted imaging, probabilistic tractography was used to determine the architecture of white matter anatomical networks in musicians and non-musicians. Furthermore, the features of the white matter networks were analyzed using graph theory. Small-world properties of the white matter network were observed in both groups. Compared with non-musicians, the musicians exhibited significantly increased connectivity strength in the left and right supplementary motor areas, the left calcarine fissure and surrounding cortex and the right caudate nucleus, as well as a significantly larger weighted clustering coefficient in the right olfactory cortex, the left medial superior frontal gyrus, the right gyrus rectus, the left lingual gyrus, the left supramarginal gyrus, and the right pallidum. Furthermore, there were differences in the node betweenness centrality in several regions. However, no significant differences in topological properties were observed at a global level. We illustrated preliminary findings to extend the network level understanding of white matter plasticity in musicians who have had long-term musical training. These structural, network-based findings may indicate that musicians have enhanced information transmission efficiencies in local white matter networks that are related to musical training.

Time-to-Surgery and Pre-operative Cerebral Hemodynamics Predict Post-operative White Matter Injury in Neonates with Hypoplastic Left Heart Syndrome

PubMed Central

Lynch, Jennifer M.; Buckley, Erin M.; Schwab, Peter J.; McCarthy, Ann L.; Winters, Madeline E.; Busch, David R.; Xiao, Rui; Goff, Donna A.; Nicolson, Susan C.; Montenegro, Lisa M.; Fuller, Stephanie; Gaynor, J. William; Spray, Thomas L.; Yodh, Arjun G.; Naim, Maryam Y.; Licht, Daniel J.

2014-01-01

Objective Hypoxic-ischemic white mater brain injury commonly occurs in neonates with hypoplastic left heart syndrome (HLHS). Approximately half of the HLHS survivors exhibit neurobehavioral symptoms believed to be associated with this injury, though the exact timing of the injury is not known. Methods Neonates with HLHS were recruited for pre- and post-operative monitoring of cerebral oxygen saturation (ScO2), cerebral oxygen extraction fraction (OEF), and cerebral blood flow (CBF) using two non-invasive optical-based techniques, namely diffuse optical spectroscopy and diffuse correlation spectroscopy. Anatomical magnetic resonance imaging (MRI) scans were performed prior to and approximately one week after surgery in order to quantify the extent and timing of the acquired white matter injury. Risk factors for developing new or worsened white matter injury were assessed using uni- and multi-variate logistic regression. Results Thirty-seven neonates with HLHS were studied. In a univariate analysis, neonates who developed a large volume of new, or worsened, postoperative white matter injury had a significantly longer time-to-surgery (p=0.0003). In a multivariate model, longer time between birth and surgery (i.e., time-to-surgery), delayed sternal closure, and higher pre-operative CBF were predictors of post-operative white matter injury. Additionally, longer time-to-surgery and higher pre-operative CBF on morning of surgery were correlated with lower ScO2 (p=0.03 and p=0.05) and higher OEF (p=0.05 and p=0.05). Conclusions Longer time-to-surgery is associated with new post-operative white matter injury in otherwise healthy neonates with HLHS. The results suggest that earlier Norwood palliation may decrease the likelihood of acquiring postoperative white matter injury. PMID:25109755

Impact of Apolipoprotein E4 Polymorphism on the Gray Matter Volume and the White Matter Integrity in Subjective Memory Impairment without White Matter Hyperintensities: Voxel-Based Morphometry and Tract-Based Spatial Statistics Study under 3-Tesla MRI.

PubMed

Lee, Young-Min; Ha, Ji-Kyung; Park, Je-Min; Lee, Byung-Dae; Moon, EunSoo; Chung, Young-In; Kim, Ji-Hoon; Kim, Hak-Jin; Mun, Chi-Woong; Kim, Tae-Hyung; Kim, Young-Hoon

2016-01-01

The aim of this study is to compare gray matter (GM) volume and white matter (WM) integrity in Apolipoprotein E4 (ApoE ε4) carriers with that of ApoE ε4 noncarriers using the voxel-based morphometry and diffusion tensor imaging (DTI) to investigate the effect of the ApoE ε4 on brain structures in subjective memory impairment (SMI) without white matter hyperintensities (WMH). Altogether, 26 participants with SMI without WMH were finally recruited from the Memory impairment clinics of Pusan National University Hospital in Korea. All participants were ApoE genotyped (ApoE ε4 carriers: n = 13, matched ApoE ε4 noncarriers: n = 13) and underwent 3-tesla magnetic resonance imaging (MRI) including 3-dimensional volumetric images for GM volume and DTI for WM integrity. ApoE ε4 carriers compared with noncarriers in SMI without WMH showed the atrophy of GM in inferior temporal gyrus, inferior parietal lobule, anterior cingulum, middle frontal gyrus, and precentral gyrus and significantly lower fractional anisotropy WM values in the splenium of corpus callosum and anterior corona radiate. Our findings suggest that the ApoE ε4 is associated with both atrophy of GM volume and disruption of WM integrity in SMI without WMH. Copyright © 2015 by the American Society of Neuroimaging.

White matter microstructure and impulsivity in methamphetamine dependence with and without a history of psychosis.

PubMed

Uhlmann, Anne; Fouche, Jean-Paul; Lederer, Katharina; Meintjes, Ernesta M; Wilson, Don; Stein, Dan J

2016-06-01

Methamphetamine (MA) use may lead to white matter injury and to a range of behavioral problems and psychiatric disorders, including psychosis. The present study sought to assess white matter microstructural impairment as well as impulsive behavior in MA dependence and MA-associated psychosis (MAP). Thirty patients with a history of MAP, 39 participants with MA dependence and 40 healthy controls underwent diffusion tensor imaging (DTI). Participants also completed the UPPS-P impulsive behavior questionnaire. We applied tract-based spatial statistics (TBSS) to investigate group differences in mean diffusivity (MD), fractional anisotropy (FA), axial (λ‖ ) and radial diffusivity (λ⊥ ), and their association with impulsivity scores and psychotic symptoms. The MAP group displayed widespread higher MD, λ‖ and λ⊥ levels compared to both controls and the MA group, and lower FA in extensive white matter areas relative to controls. MD levels correlated positively with negative psychotic symptoms in MAP. No significant DTI group differences were found between the MA group and controls. Both clinical groups showed high levels of impulsivity, and this dysfunction was associated with DTI measures in frontal white matter tracts. MAP patients show distinct patterns of impaired white matter integrity of global nature relative to controls and the MA group. Future work to investigate the precise nature and timing of alterations in MAP is needed. The results are further suggestive of frontal white matter pathology playing a role in impulsivity in MA dependence and MAP. Hum Brain Mapp 37:2055-2067, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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.

Association of increased genotypes risk for bipolar disorder with brain white matter integrity investigated with tract-based spatial statistics: Special Section on "Translational and Neuroscience Studies in Affective Disorders". Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders. The main aim is to briefly summarise relevant research findings in clinical neuroscience with particular regards to specific innovative topics in mood and anxiety disorders.

PubMed

Squarcina, L; Houenou, J; Altamura, A C; Soares, J; Brambilla, P

2017-10-15

Diffusion tensor imaging (DTI) studies, which allow the in-vivo investigation of brain tissue integrity, have shown that bipolar disorder (BD) patients present signs of white matter dysconnectivity. In parallel, genome-wide association studies (GWAS) identified several risk genetic variants for BD. In this mini-review, we summarized DTI studies coupling tract-based spatial statistics (TBSS), a reliable technique exploring white matter axon bundles, and genetics in BD. We performed a bibliographic search on PUBMED, using the search terms "TBSS", "genetics", "genome", "genes", "polymorphism", "bipolar disorder". Ten studies met these inclusion criteria. ANK3 and ZNF804A polymorphisms have shown the most consistent results, with the risk alleles showing abnormal white matter integrity in patients with BD. Current studies are limited by the investigation of single SNPs in small and chronically treated samples. Most considered TBSS-DTI studies found associations between decreased white matter integrity and genetic risk variants. These results suggest an involvement of dysmyelination in the pathogenesis of BD. The combination of TBSS with genotyping can be powerful to unveil the role of white matter in BD, in conjunction with risk genes. Future DTI studies should combine TBSS and GWAS in large populations of drug-free or minimally treated patients with BD at the onset of the disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Activations in gray and white matter are modulated by uni-manual responses during within and inter-hemispheric transfer: effects of response hand and right-handedness.

PubMed

Diwadkar, Vaibhav A; Bellani, Marcella; Chowdury, Asadur; Savazzi, Silvia; Perlini, Cinzia; Marinelli, Veronica; Zoccatelli, Giada; Alessandrini, Franco; Ciceri, Elisa; Rambaldelli, Gianluca; Ruggieri, Mirella; Carlo Altamura, A; Marzi, Carlo A; Brambilla, Paolo

2017-08-14

Because the visual cortices are contra-laterally organized, inter-hemispheric transfer tasks have been used to behaviorally probe how information briefly presented to one hemisphere of the visual cortex is integrated with responses resulting from the ipsi- or contra-lateral motor cortex. By forcing rapid information exchange across diverse regions, these tasks robustly activate not only gray matter regions, but also white matter tracts. It is likely that the response hand itself (dominant or non-dominant) modulates gray and white matter activations during within and inter-hemispheric transfer. Yet the role of uni-manual responses and/or right hand dominance in modulating brain activations during such basic tasks is unclear. Here we investigated how uni-manual responses with either hand modulated activations during a basic visuo-motor task (the established Poffenberger paradigm) alternating between inter- and within-hemispheric transfer conditions. In a large sample of strongly right-handed adults (n = 49), we used a factorial combination of transfer condition [Inter vs. Within] and response hand [Dominant(Right) vs. Non-Dominant (Left)] to discover fMRI-based activations in gray matter, and in narrowly defined white matter tracts. These tracts were identified using a priori probabilistic white matter atlases. Uni-manual responses with the right hand strongly modulated activations in gray matter, and notably in white matter. Furthermore, when responding with the left hand, activations during inter-hemispheric transfer were strongly predicted by the degree of right-hand dominance, with increased right-handedness predicting decreased fMRI activation. Finally, increasing age within the middle-aged sample was associated with a decrease in activations. These results provide novel evidence of complex relationships between uni-manual responses in right-handed subjects, and activations during within- and inter-hemispheric transfer suggest that the organization of the motor system exerts sophisticated functional effects. Moreover, our evidence of activation in white matter tracts is consistent with prior studies, confirming fMRI-detectable white matter activations which are systematically modulated by experimental condition.

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.

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.

White matter microstructure on diffusion tensor imaging is associated with conventional magnetic resonance imaging findings and cognitive function in adolescents born preterm

PubMed Central

FELDMAN, HEIDI M; LEE, ELIANA S; LOE, IRENE M; YEOM, KRISTEN W; GRILL-SPECTOR, KALANIT; LUNA, BEATRIZ

2013-01-01

AIM Diffusion tensor imaging (DTI) was used to evaluate white matter architecture after preterm birth. The goals were (1) to compare white matter microstructure in two cohorts of preterm- and term-born children; and (2) within preterm groups, to determine if sex, gestational age, birthweight, white matter injury score from conventional magnetic resonance imaging (MRI), or IQ was associated with DTI measures. METHOD Participants (n=121; 66 females, 55 males) were aged 9 to 16 years. They comprised 58 preterm children (site 1, n=25; and site 2, n=33) born at less than 36 weeks’ gestation (mean 29.4wks; birthweight 1289g) and 63 term children (site 1, n=40; site 2, n=23) born at more than 37 weeks’ gestation. DTI was analyzed using tract-based spatial statistics. Diffusion measures were fractional anisotropy, axial, radial, and mean diffusivity. RESULTS In no region of the white matter skeleton was fractional anisotropy lower in the preterm group at either site. Within the preterm groups, fractional anisotropy was significantly associated with white matter injury score, but not sex, gestational age, or birthweight. At site 1, fractional anisotropy was associated with IQ. INTERPRETATION DTI contributes to understanding individual differences after preterm birth but may not differentiate a relatively high-functioning group of preterm children from a matched group of term-born children. PMID:22803787

Running exercise protects the capillaries in white matter in a rat model of depression.

PubMed

Chen, Lin-Mu; Zhang, Ai-Pin; Wang, Fei-Fei; Tan, Chuan-Xue; Gao, Yuan; Huang, Chun-Xia; Zhang, Yi; Jiang, Lin; Zhou, Chun-Ni; Chao, Feng-Lei; Zhang, Lei; Tang, Yong

2016-12-01

Running has been shown to improve depressive symptoms when used as an adjunct to medication. However, the mechanisms underlying the antidepressant effects of running are not fully understood. Changes of capillaries in white matter have been discovered in clinical patients and depression model rats. Considering the important part of white matter in depression, running may cause capillary structural changes in white matter. Chronic unpredictable stress (CUS) rats were provided with a 4-week running exercise (from the fifth week to the eighth week) for 20 minutes each day for 5 consecutive days each week. Anhedonia was measured by a behavior test. Furthermore, capillary changes were investigated in the control group, the CUS/Standard group, and the CUS/Running group using stereological methods. The 4-week running increased sucrose consumption significantly in the CUS/Running group and had significant effects on the total volume, total length, and total surface area of the capillaries in the white matter of depression rats. These results demonstrated that exercise-induced protection of the capillaries in white matter might be one of the structural bases for the exercise-induced treatment of depression. It might provide important parameters for further study of the vascular mechanisms of depression and a new research direction for the development of clinical antidepressant means. J. Comp. Neurol. 524:3577-3586, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

White matter tract signatures of impaired social cognition in frontotemporal lobar degeneration

PubMed Central

Downey, Laura E.; Mahoney, Colin J.; Buckley, Aisling H.; Golden, Hannah L.; Henley, Susie M.; Schmitz, Nicole; Schott, Jonathan M.; Simpson, Ivor J.; Ourselin, Sebastien; Fox, Nick C.; Crutch, Sebastian J.; Warren, Jason D.

2015-01-01

Impairments of social cognition are often leading features in frontotemporal lobar degeneration (FTLD) and likely to reflect large-scale brain network disintegration. However, the neuroanatomical basis of impaired social cognition in FTLD and the role of white matter connections have not been defined. Here we assessed social cognition in a cohort of patients representing two core syndromes of FTLD, behavioural variant frontotemporal dementia (bvFTD; n = 29) and semantic variant primary progressive aphasia (svPPA; n = 15), relative to healthy older individuals (n = 37) using two components of the Awareness of Social Inference Test, canonical emotion identification and sarcasm identification. Diffusion tensor imaging (DTI) was used to derive white matter tract correlates of social cognition performance and compared with the distribution of grey matter atrophy on voxel-based morphometry. The bvFTD and svPPA groups showed comparably severe deficits for identification of canonical emotions and sarcasm, and these deficits were correlated with distributed and overlapping white matter tract alterations particularly affecting frontotemporal connections in the right cerebral hemisphere. The most robust DTI associations were identified in white matter tracts linking cognitive and evaluative processing with emotional responses: anterior thalamic radiation, fornix (emotion identification) and uncinate fasciculus (sarcasm identification). DTI associations of impaired social cognition were more consistent than corresponding grey matter associations. These findings delineate a brain network substrate for the social impairment that characterises FTLD syndromes. The findings further suggest that DTI can generate sensitive and functionally relevant indexes of white matter damage in FTLD, with potential to transcend conventional syndrome boundaries. PMID:26236629

Distinct white matter abnormalities in different idiopathic generalized epilepsy syndromes.

PubMed

Liu, Min; Concha, Luis; Beaulieu, Christian; Gross, Donald W

2011-12-01

By definition idiopathic generalized epilepsy (IGE) is not associated with structural abnormalities on conventional magnetic resonance imaging (MRI). However, recent quantitative studies suggest white and gray matter alterations in IGE. The purpose of this study was to investigate whether there are white and/or gray matter structural differences between controls and two subsets of IGE, namely juvenile myoclonic epilepsy (JME) and IGE with generalized tonic-clonic seizures only (IGE-GTC). We assessed white matter integrity and gray matter volume using diffusion tensor tractography-based analysis of fractional anisotropy and voxel-based morphometry, respectively, in 25 patients with IGE, all of whom had experienced generalized tonic-clonic convulsions. Specifically, 15 patients with JME and 10 patients with IGE-GTC were compared to two groups of similarly matched controls separately. Correlations between total lifetime generalized tonic-clonic seizures and fractional anisotropy were investigated for both groups. Tractography revealed lower fractional anisotropy in specific tracts including the crus of the fornix, body of corpus callosum, uncinate fasciculi, superior longitudinal fasciculi, anterior limb of internal capsule, and corticospinal tracts in JME with respect to controls, whereas there were no fractional anisotropy differences in IGE-GTC. No correlation was found between fractional anisotropy and total lifetime generalized tonic-clonic seizures for either JME or IGE-GTC. Although false discovery rate-corrected voxel-based morphometry (VBM) showed no gray matter volume differences between patient and control groups, spatial extent cluster-corrected VBM analysis suggested a trend of gray matter volume reduction in frontal and central regions in both patient groups, more lateral in JME and more medial in IGE-GTC. The findings support the idea that the clinical syndromes of JME and IGE-GTC have unique anatomic substrates. The fact that the primary clinical difference between JME and IGE-GTC is the occurrence of myoclonus in the former raises the possibility that disruption of white matter integrity may be the underlying mechanism responsible for myoclonus in JME. The cross-sectional study design and relatively small number of subjects limits the conclusions that can be drawn here; however, the absence of a correlation between fractional anisotropy and lifetime seizures is suggestive that the white matter abnormalities observed in JME may not be secondary to seizures. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

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

Evaluation of cortical local field potential diffusion in stereotactic electro-encephalography recordings: A glimpse on white matter signal.

PubMed

Mercier, Manuel R; Bickel, Stephan; Megevand, Pierre; Groppe, David M; Schroeder, Charles E; Mehta, Ashesh D; Lado, Fred A

2017-02-15

While there is a strong interest in meso-scale field potential recording using intracranial electroencephalography with penetrating depth electrodes (i.e. stereotactic EEG or S-EEG) in humans, the signal recorded in the white matter remains ignored. White matter is generally considered electrically neutral and often included in the reference montage. Moreover, re-referencing electrophysiological data is a critical preprocessing choice that could drastically impact signal content and consequently the results of any given analysis. In the present stereotactic electroencephalography study, we first illustrate empirically the consequences of commonly used references (subdermal, white matter, global average, local montage) on inter-electrode signal correlation. Since most of these reference montages incorporate white matter signal, we next consider the difference between signals recorded in cortical gray matter and white matter. Our results reveal that electrode contacts located in the white matter record a mixture of activity, with part arising from the volume conduction (zero time delay) of activity from nearby gray matter. Furthermore, our analysis shows that white matter signal may be correlated with distant gray matter signal. While residual passive electrical spread from nearby matter may account for this relationship, our results suggest the possibility that this long distance correlation arises from the white matter fiber tracts themselves (i.e. activity from distant gray matter traveling along axonal fibers with time lag larger than zero); yet definitive conclusions about the origin of the white matter signal would require further experimental substantiation. By characterizing the properties of signals recorded in white matter and in gray matter, this study illustrates the importance of including anatomical prior knowledge when analyzing S-EEG data. Copyright © 2017 Elsevier Inc. All rights reserved.

Tract-Specific Analyses of Diffusion Tensor Imaging Show Widespread White Matter Compromise in Autism Spectrum Disorder

ERIC Educational Resources Information Center

Shukla, Dinesh K.; Keehn, Brandon; Muller, Ralph-Axel

2011-01-01

Background: Previous diffusion tensor imaging (DTI) studies have shown white matter compromise in children and adults with autism spectrum disorder (ASD), which may relate to reduced connectivity and impaired function of distributed networks. However, tract-specific evidence remains limited in ASD. We applied tract-based spatial statistics (TBSS)…

White Matter Microstructure of the Human Mirror Neuron System Is Related to Symptom Severity in Adults with Autism

ERIC Educational Resources Information Center

Fründt, Odette; Schulz, Robert; Schöttle, Daniel; Cheng, Bastian; Thomalla, Götz; Braaß, Hanna; Ganos, Christos; David, Nicole; Peiker, Ina; Engel, Andreas K.; Bäumer, Tobias; Münchau, Alexander

2018-01-01

Mirror neuron system (MNS) dysfunctions might underlie deficits in autism spectrum disorders (ASD). Diffusion tensor imaging based probabilistic tractography was conducted in 15 adult ASD patients and 13 matched, healthy controls. Fractional anisotropy (FA) was quantified to assess group differences in tract-related white matter microstructure of…

Correlation between Gray/White Matter Volume and Cognition in Healthy Elderly People

ERIC Educational Resources Information Center

Taki, Yasuyuki; Kinomura, Shigeo; Sato, Kazunori; Goto, Ryoi; Wu, Kai; Kawashima, Ryuta; Fukuda, Hiroshi

2011-01-01

This study applied volumetric analysis and voxel-based morphometry (VBM) of brain magnetic resonance (MR) images to assess whether correlations exist between global and regional gray/white matter volume and the cognitive functions of semantic memory and short-term memory, which are relatively well preserved with aging, using MR image data from 109…

Gray and white matter changes and their relation to illness trajectory in first episode psychosis.

PubMed

Keymer-Gausset, Alejandro; Alonso-Solís, Anna; Corripio, Iluminada; Sauras-Quetcuti, Rosa B; Pomarol-Clotet, Edith; Canales-Rodriguez, Erick J; Grasa-Bello, Eva; Álvarez, Enric; Portella, Maria J

2018-03-01

Previous works have studied structural brain characteristics in first-episode psychosis (FEP), but few have focused on the relation between brain differences and illness trajectories. The aim of this study is to analyze gray and white matter changes in FEP patients and their relation with one-year clinical outcomes. A sample of 41 FEP patients and 41 healthy controls (HC), matched by age and educational level was scanned with a 3T MRI during the first month of illness onset. One year later, patients were assigned to two illness trajectories (schizophrenia and non-schizophrenia). Voxel-based morphometry (VBM) was used for gray matter and Tract-based spatial statistics (TBSS) was used for white matter data analysis. VBM revealed significant and widespread bilateral gray matter density differences between FEP and HC groups in areas that included the right insular Cortex, the inferior frontal gyrus and orbito-frontal cortices, and segments of the occipital cortex. TBSS showed a significant lower fractional anisotropy (FA) in 8 clusters that included segments of the anterior thalamic radiation, the left body and forceps minor of corpus callosum, the right anterior segment of the inferior fronto-occipital fasciculus and the anterior segments of the cingulum. The sub-groups comparison revealed significant lower FA in the schizophrenia sub-group in two clusters: the anterior thalamic radiation and the anterior segment of left cingulum. These findings are coherent with previous morphology studies. The results suggest that gray and white matter abnormalities are present at early stages of the disease, and white matter differences may distinguish different illness prognosis. Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.

Longitudinal regression analysis of spatial-temporal growth patterns of geometrical diffusion measures in early postnatal brain development with diffusion tensor imaging

PubMed Central

Chen, Yasheng; An, Hongyu; Zhu, Hongtu; Jewells, Valerie; Armao, Diane; Shen, Dinggang; Gilmore, John H.; Lin, Weili

2011-01-01

Although diffusion tensor imaging (DTI) has provided substantial insights into early brain development, most DTI studies based on fractional anisotropy (FA) and mean diffusivity (MD) may not capitalize on the information derived from the three principal diffusivities (e.g. eigenvalues). In this study, we explored the spatial and temporal evolution of white matter structures during early brain development using two geometrical diffusion measures, namely, linear (Cl) and planar (Cp) diffusion anisotropies, from 71 longitudinal datasets acquired from 29 healthy, full-term pediatric subjects. The growth trajectories were estimated with generalized estimating equations (GEE) using linear fitting with logarithm of age (days). The presence of the white matter structures in Cl and Cp was observed in neonates, suggesting that both the cylindrical and fanning or crossing structures in various white matter regions may already have been formed at birth. Moreover, we found that both Cl and Cp evolved in a temporally nonlinear and spatially inhomogeneous manner. The growth velocities of Cl in central white matter were significantly higher when compared to peripheral, or more laterally located, white matter: central growth velocity Cl = 0.0465±0.0273/log(days), versus peripheral growth velocity Cl=0.0198±0.0127/log(days), p<10−6. In contrast, the growth velocities of Cp in central white matter were significantly lower than that in peripheral white matter: central growth velocity Cp= 0.0014±0.0058/log(days), versus peripheral growth velocity Cp = 0.0289±0.0101/log(days), p<10−6. Depending on the underlying white matter site which is analyzed, our findings suggest that ongoing physiologic and microstructural changes in the developing brain may exert different effects on the temporal evolution of these two geometrical diffusion measures. Thus, future studies utilizing DTI with correlative histological analysis in the study of early brain development are warranted. PMID:21784163

Brain structural differences associated with the behavioural phenotype in children with Williams syndrome.

PubMed

Campbell, Linda E; Daly, Eileen; Toal, Fiona; Stevens, Angela; Azuma, Rayna; Karmiloff-Smith, Annette; Murphy, Declan G M; Murphy, Kieran C

2009-03-03

We investigated structural brain morphology of intellectually disabled children with Williams (WS) syndrome and its relationship to the behavioural phenotype. We compared the neuroanatomy of 15 children (mean age:13+/-2) with WS and 15 age/gender-matched healthy children using a manual region-of-interest analysis to measure bulk (white+grey) tissue volumes and unbiased fully-automated voxel-based morphometry to assess differences in grey/white matter throughout the brain. Ratings of abnormal behaviours were correlated with brain structure. Compared to controls, the brains of children with WS had a decreased volume of the right parieto-occipital regions and basal ganglia. We identified reductions of grey matter of the parieto-occipital regions, left putamen/globus pallidus and thalamus; and in white matter of the basal ganglia and right posterior cingulate gyrus. In contrast, significant increases of grey matter were identified in the frontal lobes, anterior cingulate gyrus, left temporal lobe, and of white matter bilaterally in the anterior cingulate. Inattention in WS was correlated with volumetric differences in the frontal lobes, caudate nucleus and cerebellum, and hyperactivity was related to differences in the left temporal and parietal lobes and cerebellum. Finally, ratings of peer problems were related to differences in the temporal lobes, right basal ganglia and frontal lobe. In one of the first studies of brain structure in intellectually disabled children with WS using voxel-based morphometry, our findings suggest that this group has specific differences in grey/white matter morphology. In addition, it was found that structural differences were correlated to ratings of inattention, hyperactivity and peer problems in children with WS.

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

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.

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.

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.

Accelerated White Matter Aging in Schizophrenia: Role of White Matter Blood Perfusion

PubMed Central

Chiappelli, Joshua; McMahon, Robert; Muellerklein, Florian; Wijtenburg, S. Andrea; White, Michael G.; Rowland, Laura M.; Hong, L. Elliot

2014-01-01

Elevated rate of age-related decline in white matter integrity, indexed by fractional anisotropy (FA) from diffusion tensor imaging, was reported in patients with schizophrenia. Its etiology is unknown. We hypothesized that a decline of blood perfusion to the white matter may underlie the accelerated age-related reduction in FA in schizophrenia. Resting white matter perfusion and FA were collected using pseudo-continuous arterial spin labeling and high-angular-resolution diffusion tensor imaging, respectively, in 50 schizophrenia patients and 70 controls (age=18-63 years). Main outcome measures were the diagnosis-by-age interaction on whole-brain white matter perfusion, and FA. Significant age-related decline in brain white matter perfusion and FA were present in both groups. Age-by-diagnosis interaction was significant for FA (p<0.001) but not white matter perfusion. Age-by-diagnosis interaction for FA values remained significant even after accounting for age-related decline in perfusion. Therefore, we replicated the finding of an increased rate of age-related white matter FA decline in schizophrenia, and observed a significant age-related decline in white matter blood perfusion, although the latter did not contribute to the accelerated age-related decline in FA. The results suggest that factors other than reduced perfusion account for the accelerated age-related decline in white matter integrity in schizophrenia. PMID:24680326

Intra-individual variability in information processing speed reflects white matter microstructure in multiple sclerosis.

PubMed

Mazerolle, Erin L; Wojtowicz, Magdalena A; Omisade, Antonina; Fisk, John D

2013-01-01

Slowed information processing speed is commonly reported in persons with multiple sclerosis (MS), and is typically investigated using clinical neuropsychological tests, which provide sensitive indices of mean-level information processing speed. However, recent studies have demonstrated that within-person variability or intra-individual variability (IIV) in information processing speed may be a more sensitive indicator of neurologic status than mean-level performance on clinical tests. We evaluated the neural basis of increased IIV in mildly affected relapsing-remitting MS patients by characterizing the relation between IIV (controlling for mean-level performance) and white matter integrity using diffusion tensor imaging (DTI). Twenty women with relapsing-remitting MS and 20 matched control participants completed the Computerized Test of Information Processing (CTIP), from which both mean response time and IIV were calculated. Other clinical measures of information processing speed were also collected. Relations between IIV on the CTIP and DTI metrics of white matter microstructure were evaluated using tract-based spatial statistics. We observed slower and more variable responses on the CTIP in MS patients relative to controls. Significant relations between white matter microstructure and IIV were observed for MS patients. Increased IIV was associated with reduced integrity in more white matter tracts than was slowed information processing speed as measured by either mean CTIP response time or other neuropsychological test scores. Thus, despite the common use of mean-level performance as an index of cognitive dysfunction in MS, IIV may be more sensitive to the overall burden of white matter disease at the microstructural level. Furthermore, our study highlights the potential value of considering within-person fluctuations, in addition to mean-level performance, for uncovering brain-behavior relationships in neurologic disorders with widespread white matter pathology.

Design and validation of diffusion MRI models of white matter

NASA Astrophysics Data System (ADS)

Jelescu, Ileana O.; Budde, Matthew D.

2017-11-01

Diffusion MRI is arguably the method of choice for characterizing white matter microstructure in vivo. Over the typical duration of diffusion encoding, the displacement of water molecules is conveniently on a length scale similar to that of the underlying cellular structures. Moreover, water molecules in white matter are largely compartmentalized which enables biologically-inspired compartmental diffusion models to characterize and quantify the true biological microstructure. A plethora of white matter models have been proposed. However, overparameterization and mathematical fitting complications encourage the introduction of simplifying assumptions that vary between different approaches. These choices impact the quantitative estimation of model parameters with potential detriments to their biological accuracy and promised specificity. First, we review biophysical white matter models in use and recapitulate their underlying assumptions and realms of applicability. Second, we present up-to-date efforts to validate parameters estimated from biophysical models. Simulations and dedicated phantoms are useful in assessing the performance of models when the ground truth is known. However, the biggest challenge remains the validation of the “biological accuracy” of estimated parameters. Complementary techniques such as microscopy of fixed tissue specimens have facilitated direct comparisons of estimates of white matter fiber orientation and densities. However, validation of compartmental diffusivities remains challenging, and complementary MRI-based techniques such as alternative diffusion encodings, compartment-specific contrast agents and metabolites have been used to validate diffusion models. Finally, white matter injury and disease pose additional challenges to modeling, which are also discussed. This review aims to provide an overview of the current state of models and their validation and to stimulate further research in the field to solve the remaining open questions and converge towards consensus.

Design and validation of diffusion MRI models of white matter

PubMed Central

Jelescu, Ileana O.; Budde, Matthew D.

2018-01-01

Diffusion MRI is arguably the method of choice for characterizing white matter microstructure in vivo. Over the typical duration of diffusion encoding, the displacement of water molecules is conveniently on a length scale similar to that of the underlying cellular structures. Moreover, water molecules in white matter are largely compartmentalized which enables biologically-inspired compartmental diffusion models to characterize and quantify the true biological microstructure. A plethora of white matter models have been proposed. However, overparameterization and mathematical fitting complications encourage the introduction of simplifying assumptions that vary between different approaches. These choices impact the quantitative estimation of model parameters with potential detriments to their biological accuracy and promised specificity. First, we review biophysical white matter models in use and recapitulate their underlying assumptions and realms of applicability. Second, we present up-to-date efforts to validate parameters estimated from biophysical models. Simulations and dedicated phantoms are useful in assessing the performance of models when the ground truth is known. However, the biggest challenge remains the validation of the “biological accuracy” of estimated parameters. Complementary techniques such as microscopy of fixed tissue specimens have facilitated direct comparisons of estimates of white matter fiber orientation and densities. However, validation of compartmental diffusivities remains challenging, and complementary MRI-based techniques such as alternative diffusion encodings, compartment-specific contrast agents and metabolites have been used to validate diffusion models. Finally, white matter injury and disease pose additional challenges to modeling, which are also discussed. This review aims to provide an overview of the current state of models and their validation and to stimulate further research in the field to solve the remaining open questions and converge towards consensus. PMID:29755979

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.

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

AxTract: Toward microstructure informed tractography.

PubMed

Girard, Gabriel; Daducci, Alessandro; Petit, Laurent; Thiran, Jean-Philippe; Whittingstall, Kevin; Deriche, Rachid; Wassermann, Demian; Descoteaux, Maxime

2017-11-01

Diffusion-weighted (DW) magnetic resonance imaging (MRI) tractography has become the tool of choice to probe the human brain's white matter in vivo. However, tractography algorithms produce a large number of erroneous streamlines (false positives), largely due to complex ambiguous tissue configurations. Moreover, the relationship between the resulting streamlines and the underlying white matter microstructure characteristics remains poorly understood. In this work, we introduce a new approach to simultaneously reconstruct white matter fascicles and characterize the apparent distribution of axon diameters within fascicles. To achieve this, our method, AxTract, takes full advantage of the recent development DW-MRI microstructure acquisition, modeling, and reconstruction techniques. This enables AxTract to separate parallel fascicles with different microstructure characteristics, hence reducing ambiguities in areas of complex tissue configuration. We report a decrease in the incidence of erroneous streamlines compared to the conventional deterministic tractography algorithms on simulated data. We also report an average increase in streamline density over 15 known fascicles of the 34 healthy subjects. Our results suggest that microstructure information improves tractography in crossing areas of the white matter. Moreover, AxTract provides additional microstructure information along the fascicle that can be studied alongside other streamline-based indices. Overall, AxTract provides the means to distinguish and follow white matter fascicles using their microstructure characteristics, bringing new insights into the white matter organization. This is a step forward in microstructure informed tractography, paving the way to a new generation of algorithms able to deal with intricate configurations of white matter fibers and providing quantitative brain connectivity analysis. Hum Brain Mapp 38:5485-5500, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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 psychosis. Copyright © 2017 Society of Biological Psychiatry. All rights reserved.

Minimally invasive trans-portal resection of deep intracranial lesions.

PubMed

Raza, S M; Recinos, P F; Avendano, J; Adams, H; Jallo, G I; Quinones-Hinojosa, A

2011-02-01

The surgical management of deep intra-axial lesions still requires microsurgical approaches that utilize retraction of deep white matter to obtain adequate visualization. We report our experience with a new tubular retractor system, designed specifically for intracranial applications, linked with frameless neuronavigation for a cohort of intraventricular and deep intra-axial tumors. The ViewSite Brain Access System (Vycor, Inc) was used in a series of 9 adult and pediatric patients with a variety of pathologies. Histological diagnoses either resected or biopsied with the system included: colloid cyst, DNET, papillary pineal tumor, anaplastic astrocytoma, toxoplasmosis and lymphoma. The locations of the lesions approached include: lateral ventricle, basal ganglia, pulvinar/posterior thalamus and insular cortex. Post-operative imaging was assessed to determine extent of resection and extent of white matter damage along the surgical trajectory (based on T (2)/FLAIR and diffusion restriction/ADC signal). Satisfactory resection or biopsy was obtained in all patients. Radiographic analysis demonstrated evidence of white matter damage along the surgical trajectory in one patient. None of the patients experienced neurological deficits as a result of white matter retraction/manipulation. Based on a retrospective review of our experience, we feel that this access system, when used in conjunction with frameless neuronavigational systems, provides adequate visualization for tumor resection while permitting the use of standard microsurgical techniques through minimally invasive craniotomies. Our initial data indicate that this system may minimize white matter injury, but further studies are necessary. © Georg Thieme Verlag KG Stuttgart · New York.

Limbic and corpus callosum aberrations in adolescents with bipolar disorder: a tract-based spatial statistics analysis.

PubMed

Barnea-Goraly, Naama; Chang, Kiki D; Karchemskiy, Asya; Howe, Meghan E; Reiss, Allan L

2009-08-01

Bipolar disorder (BD) is a common and debilitating condition, often beginning in adolescence. Converging evidence from genetic and neuroimaging studies indicates that white matter abnormalities may be involved in BD. In this study, we investigated white matter structure in adolescents with familial bipolar disorder using diffusion tensor imaging (DTI) and a whole brain analysis. We analyzed DTI images using tract-based spatial statistics (TBSS), a whole-brain voxel-by-voxel analysis, to investigate white matter structure in 21 adolescents with BD, who also were offspring of at least one parent with BD, and 18 age- and IQ-matched control subjects. Fractional anisotropy (FA; a measure of diffusion anisotropy), trace values (average diffusivity), and apparent diffusion coefficient (ADC; a measure of overall diffusivity) were used as variables in this analysis. In a post hoc analysis, we correlated between FA values, behavioral measures, and medication exposure. Adolescents with BD had lower FA values than control subjects in the fornix, the left mid-posterior cingulate gyrus, throughout the corpus callosum, in fibers extending from the fornix to the thalamus, and in parietal and occipital corona radiata bilaterally. There were no significant between-group differences in trace or ADC values and no significant correlation between behavioral measures, medication exposure, and FA values. Significant white matter tract alterations in adolescents with BD were observed in regions involved in emotional, behavioral, and cognitive regulation. These results suggest that alterations in white matter are present early in the course of disease in familial BD.

Gray matter and white matter abnormalities in online game addiction.

PubMed

Weng, Chuan-Bo; Qian, Ruo-Bing; Fu, Xian-Ming; Lin, Bin; Han, Xiao-Peng; Niu, Chao-Shi; Wang, Ye-Han

2013-08-01

Online game addiction (OGA) has attracted greater attention as a serious public mental health issue. However, there are only a few brain magnetic resonance imaging studies on brain structure about OGA. In the current study, we used voxel-based morphometry (VBM) analysis and tract-based spatial statistics (TBSS) to investigate the microstructural changes in OGA and assessed the relationship between these morphology changes and the Young's Internet Addiction Scale (YIAS) scores within the OGA group. Compared with healthy subjects, OGA individuals showed significant gray matter atrophy in the right orbitofrontal cortex, bilateral insula, and right supplementary motor area. According to TBSS analysis, OGA subjects had significantly reduced FA in the right genu of corpus callosum, bilateral frontal lobe white matter, and right external capsule. Gray matter volumes (GMV) of the right orbitofrontal cortex, bilateral insula and FA values of the right external capsule were significantly positively correlated with the YIAS scores in the OGA subjects. Our findings suggested that microstructure abnormalities of gray and white matter were present in OGA subjects. This finding may provide more insights into the understanding of the underlying neural mechanisms of OGA. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

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.

Strategic Role of Frontal White Matter Tracts in Vascular Cognitive Impairment: A Voxel-Based Lesion-Symptom Mapping Study in CADASIL

ERIC Educational Resources Information Center

Duering, Marco; Zieren, Nikola; Herve, Dominique; Jouvent, Eric; Reyes, Sonia; Peters, Nils; Pachai, Chahin; Opherk, Christian; Chabriat, Hugues; Dichgans, Martin

2011-01-01

Cerebral small vessel disease is the most common cause of vascular cognitive impairment. It typically manifests with lacunar infarcts and ischaemic white matter lesions. However, little is known about how these lesions relate to the cognitive symptoms. Previous studies have found a poor correlation between the burden of ischaemic lesions and…

Altered Development of White Matter in Youth at High Familial Risk for Bipolar Disorder: A Diffusion Tensor Imaging Study

ERIC Educational Resources Information Center

Versace, Amelia; Ladouceur, Cecile D.; Romero, Soledad; Birmaher, Boris; Axelson, David A.; Kupfer, David J.; Phillips, Mary L.

2010-01-01

Objective: To study white matter (WM) development in youth at high familial risk for bipolar disorder (BD). WM alterations are reported in youth and adults with BD. WM undergoes important maturational changes in adolescence. Age-related changes in WM microstructure using diffusion tensor imaging with tract-based spatial statistics in healthy…

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.

Association of Retinopathy and Retinal Microvascular Abnormalities With Stroke and Cerebrovascular Disease.

PubMed

Hughes, Alun D; Falaschetti, Emanuela; Witt, Nicholas; Wijetunge, Sumangali; Thom, Simon A McG; Tillin, Therese; Aldington, Steve J; Chaturvedi, Nish

2016-11-01

Abnormalities of the retinal circulation may be associated with cerebrovascular disease. We investigated associations between retinal microvascular abnormalities and (1) strokes and subclinical cerebral infarcts and (2) cerebral white matter lesions in a UK-based triethnic population-based cohort. A total of 1185 participants (age, 68.8±6.1 years; 77% men) underwent retinal imaging and cerebral magnetic resonance imaging. Cerebral infarcts and white matter hyperintensities were identified on magnetic resonance imaging, retinopathy was graded, and retinal vessels were measured. Higher retinopathy grade (odds ratio [OR], 1.40 [95% confidence interval (95% CI), 1.16-1.70]), narrower arteriolar diameter (OR, 0.98 [95% CI, 0.97-0.99]), fewer symmetrical arteriolar bifurcations (OR, 0.84 [95% CI, 0.75-0.95]), higher arteriolar optimality deviation (OR, 1.16 [95% CI, 1.00-1.34]), and more tortuous venules (OR, 1.20 [95% CI, 1.09-1.32]) were associated with strokes/infarcts and white matter hyperintensities. Associations with quantitative retinal microvascular measures were independent of retinopathy. Abnormalities of the retinal microvasculature are independently associated with stroke, cerebral infarcts, and white matter lesions. © 2016 American Heart Association, 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.

Age exacerbates HIV-associated white matter abnormalities.

PubMed

Seider, Talia R; Gongvatana, Assawin; Woods, Adam J; Chen, Huaihou; Porges, Eric C; Cummings, Tiffany; Correia, Stephen; Tashima, Karen; Cohen, Ronald A

2016-04-01

Both HIV disease and advanced age have been associated with alterations to cerebral white matter, as measured with white matter hyperintensities (WMH) on fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI), and more recently with diffusion tensor imaging (DTI). This study investigates the combined effects of age and HIV serostatus on WMH and DTI measures, as well as the relationships between these white matter measures, in 88 HIV seropositive (HIV+) and 49 seronegative (HIV-) individuals aged 23-79 years. A whole-brain volumetric measure of WMH was quantified from FLAIR images using a semi-automated process, while fractional anisotropy (FA) was calculated for 15 regions of a whole-brain white matter skeleton generated using tract-based spatial statistics (TBSS). An age by HIV interaction was found indicating a significant association between WMH and older age in HIV+ participants only. Similarly, significant age by HIV interactions were found indicating stronger associations between older age and decreased FA in the posterior limbs of the internal capsules, cerebral peduncles, and anterior corona radiata in HIV+ vs. HIV- participants. The interactive effects of HIV and age were stronger with respect to whole-brain WMH than for any of the FA measures. Among HIV+ participants, greater WMH and lower anterior corona radiata FA were associated with active hepatitis C virus infection, a history of AIDS, and higher current CD4 cell count. Results indicate that age exacerbates HIV-associated abnormalities of whole-brain WMH and fronto-subcortical white matter integrity.

Tract-based analysis of white matter integrity in psychotic and nonpsychotic bipolar disorder.

PubMed

Ji, Andrew; Godwin, Douglass; Rutlin, Jerrel; Kandala, Sridhar; Shimony, Joshua S; Mamah, Daniel

2017-02-01

At least 50% of individuals with bipolar disorder (BD) present with psychosis during their lifetime. Psychotic symptoms have sometimes been linked to specific genetic and phenotypic markers. This study aims to explore potential differences between bipolar disorder subtypes by measuring white matter integrity of the brain and relationships with clinical measures. Diffusion tensor imaging and clinical measures were acquired from 102 participants, grouped as psychotic bipolar disorder (PBD) (n=48), non-psychotic bipolar disorder (NBD) (n=24), and healthy controls (n=30). We utilized a powerful, automated tool (TRACULA: Tracts Constrained by Underlying Anatomy) to analyze the fractional anisotropy (FA) and mean diffusivity (MD) of 18 white matter tracts. Decreased FA in numerous tracts was observed in bipolar disorder groups compared to healthy controls: bilateral cingulum-cingulate gyrus bundles, corticospinal tracts, and superior longitudinal fasciculi as well as the right hemisphere cingulum-angular bundle. Only left uncinate fasciculus FA differed between PBD and NPBD groups. We found no group differences in MD. Positive symptoms correlated with FA in the superior (inversely) and inferior (directly) longitudinal fasciculi. Negative symptoms directly correlated with mean FA of the corticospinal tract and cingulum-angular bundle. Neurotropic, mood-stabilizing medication prescribed for individuals with BD may interact with measures of white matter integrity in our BD participants. Our results indicate decreased white matter coherence in BD. Minimal differences in white matter FA between PBD and NPBD participants suggest related underlying neurobiology. Copyright © 2016 Elsevier B.V. All rights reserved.

Retained executive abilities in mild cognitive impairment are associated with increased white matter network connectivity.

PubMed

Farrar, Danielle C; Mian, Asim Z; Budson, Andrew E; Moss, Mark B; Koo, Bang Bon; Killiany, Ronald J

2018-01-01

To describe structural network differences in individuals with mild cognitive impairment (MCI) with high versus low executive abilities, as reflected by measures of white matter connectivity using diffusion tensor imaging (DTI). This was a retrospective, cross-sectional study. Of the 128 participants from the Alzheimer's Disease Neuroimaging Initiative database who had both a DTI scan as well as a diagnosis of MCI, we used an executive function score to classify the top 15 scoring patients as high executive ability, and the bottom-scoring 16 patients as low executive ability. Using a regions-of-interest-based analysis, we constructed networks and calculated graph theory measures on the constructed networks. We used automated tractography in order to compare differences in major white matter tracts. The high executive ability group yielded greater network size, density and clustering coefficient. The high executive ability group reflected greater fractional anisotropy bilaterally in the inferior and superior longitudinal fasciculi. The network measures of the high executive ability group demonstrated greater white matter integrity. This suggests that white matter reserve may confer greater protection of executive abilities. Loss of this reserve may lead to greater impairment in the progression to Alzheimer's disease dementia. • The MCI high executive ability group yielded a larger network. • The MCI high executive ability group had greater FA in numerous tracts. • White matter reserve may confer greater protection of executive abilities. • Loss of executive reserve may lead to greater impairment in AD dementia.

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.

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 subjects had diffusely lower intracellular volume fractions than the white matter in controls (P = 0.029 by unpaired t-test). Cortical thickness did not differ significantly between multiple sclerosis subjects and controls. Higher orientation dispersion in the left primary motor-somatosensory cortex was associated with increased Expanded Disability Status Scale scores in surface-based general linear modelling (P < 0.05). Microstructural pathology was frequent in early multiple sclerosis, and present mainly focally in cortical lesions, whereas more diffusely in white matter. These results suggest early demyelination with loss of cells and/or cell volumes in cortical and white matter lesions, with additional axonal dispersion in white matter lesions. In the cortex, focal lesion changes might precede diffuse atrophy with cortical thinning. Findings in the normal-appearing white matter reveal early axonal pathology outside inflammatory demyelinating lesions. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Regional reliability of quantitative signal targeting with alternating radiofrequency (STAR) labeling of arterial regions (QUASAR).

PubMed

Tatewaki, Yasuko; Higano, Shuichi; Taki, Yasuyuki; Thyreau, Benjamin; Murata, Takaki; Mugikura, Shunji; Ito, Daisuke; Takase, Kei; Takahashi, Shoki

2014-01-01

Quantitative signal targeting with alternating radiofrequency labeling of arterial regions (QUASAR) is a recent spin labeling technique that could improve the reliability of brain perfusion measurements. Although it is considered reliable for measuring gray matter as a whole, it has never been evaluated regionally. Here we assessed this regional reliability. Using a 3-Tesla Philips Achieva whole-body system, we scanned four times 10 healthy volunteers, in two sessions 2 weeks apart, to obtain QUASAR images. We computed perfusion images and ran a voxel-based analysis within all brain structures. We also calculated mean regional cerebral blood flow (rCBF) within regions of interest configured for each arterial territory distribution. The mean CBF over whole gray matter was 37.74 with intraclass correlation coefficient (ICC) of .70. In white matter, it was 13.94 with an ICC of .30. Voxel-wise ICC and coefficient-of-variation maps showed relatively lower reliability in watershed areas and white matter especially in deeper white matter. The absolute mean rCBF values were consistent with the ones reported from PET, as was the relatively low variability in different feeding arteries. Thus, QUASAR reliability for regional perfusion is high within gray matter, but uncertain within white matter. © 2014 The Authors. Journal of Neuroimaging published by the American Society of Neuroimaging.

Regional Reliability of Quantitative Signal Targeting with Alternating Radiofrequency (STAR) Labeling of Arterial Regions (QUASAR)

PubMed Central

Tatewaki, Yasuko; Higano, Shuichi; Taki, Yasuyuki; Thyreau, Benjamin; Murata, Takaki; Mugikura, Shunji; Ito, Daisuke; Takase, Kei; Takahashi, Shoki

2014-01-01

BACKGROUND AND PURPOSE Quantitative signal targeting with alternating radiofrequency labeling of arterial regions (QUASAR) is a recent spin labeling technique that could improve the reliability of brain perfusion measurements. Although it is considered reliable for measuring gray matter as a whole, it has never been evaluated regionally. Here we assessed this regional reliability. METHODS Using a 3-Tesla Philips Achieva whole-body system, we scanned four times 10 healthy volunteers, in two sessions 2 weeks apart, to obtain QUASAR images. We computed perfusion images and ran a voxel-based analysis within all brain structures. We also calculated mean regional cerebral blood flow (rCBF) within regions of interest configured for each arterial territory distribution. RESULTS The mean CBF over whole gray matter was 37.74 with intraclass correlation coefficient (ICC) of .70. In white matter, it was 13.94 with an ICC of .30. Voxel-wise ICC and coefficient-of-variation maps showed relatively lower reliability in watershed areas and white matter especially in deeper white matter. The absolute mean rCBF values were consistent with the ones reported from PET, as was the relatively low variability in different feeding arteries. CONCLUSIONS Thus, QUASAR reliability for regional perfusion is high within gray matter, but uncertain within white matter. PMID:25370338

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

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.

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.

Multimodal MR-imaging reveals large-scale structural and functional connectivity changes in profound early blindness

PubMed Central

Bauer, Corinna M.; Hirsch, Gabriella V.; Zajac, Lauren; Koo, Bang-Bon; Collignon, Olivier

2017-01-01

In the setting of profound ocular blindness, numerous lines of evidence demonstrate the existence of dramatic anatomical and functional changes within the brain. However, previous studies based on a variety of distinct measures have often provided inconsistent findings. To help reconcile this issue, we used a multimodal magnetic resonance (MR)-based imaging approach to provide complementary structural and functional information regarding this neuroplastic reorganization. This included gray matter structural morphometry, high angular resolution diffusion imaging (HARDI) of white matter connectivity and integrity, and resting state functional connectivity MRI (rsfcMRI) analysis. When comparing the brains of early blind individuals to sighted controls, we found evidence of co-occurring decreases in cortical volume and cortical thickness within visual processing areas of the occipital and temporal cortices respectively. Increases in cortical volume in the early blind were evident within regions of parietal cortex. Investigating white matter connections using HARDI revealed patterns of increased and decreased connectivity when comparing both groups. In the blind, increased white matter connectivity (indexed by increased fiber number) was predominantly left-lateralized, including between frontal and temporal areas implicated with language processing. Decreases in structural connectivity were evident involving frontal and somatosensory regions as well as between occipital and cingulate cortices. Differences in white matter integrity (as indexed by quantitative anisotropy, or QA) were also in general agreement with observed pattern changes in the number of white matter fibers. Analysis of resting state sequences showed evidence of both increased and decreased functional connectivity in the blind compared to sighted controls. Specifically, increased connectivity was evident between temporal and inferior frontal areas. Decreases in functional connectivity were observed between occipital and frontal and somatosensory-motor areas and between temporal (mainly fusiform and parahippocampus) and parietal, frontal, and other temporal areas. Correlations in white matter connectivity and functional connectivity observed between early blind and sighted controls showed an overall high degree of association. However, comparing the relative changes in white matter and functional connectivity between early blind and sighted controls did not show a significant correlation. In summary, these findings provide complimentary evidence, as well as highlight potential contradictions, regarding the nature of regional and large scale neuroplastic reorganization resulting from early onset blindness. PMID:28328939

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.

Differing patterns of brain structural abnormalities between black and white patients with their first episode of psychosis.

PubMed

Morgan, K D; Dazzan, P; Morgan, C; Lappin, J; Hutchinson, G; Chitnis, X; Suckling, J; Fearon, P; Jones, P B; Leff, J; Murray, R M

2010-07-01

African-Caribbean and black African people living in the UK are reported to have a higher incidence of diagnosed psychosis compared with white British people. It has been argued that this may be a consequence of misdiagnosis. If this is true they might be less likely to show the patterns of structural brain abnormalities reported in white British patients. The aim of this study therefore was to investigate whether there are differences in the prevalence of structural brain abnormalities in white and black first-episode psychosis patients. We obtained dual-echo (proton density/T2-weighted) images from a sample of 75 first-episode psychosis patients and 68 healthy controls. We used high resolution magnetic resonance imaging and voxel-based methods of image analysis. Two separate analyses were conducted: (1) 34 white British patients were compared with 33 white British controls; (2) 41 African-Caribbean and black African patients were compared with 35 African-Caribbean and black African controls. White British patients and African-Caribbean/black African patients had ventricular enlargement and increased lenticular nucleus volume compared with their respective ethnic controls. The African-Caribbean/black African patients also showed reduced global grey matter and increased lingual gyrus grey-matter volume. The white British patients had no regional or global grey-matter loss compared with their normal ethnic counterparts but showed increased grey matter in the left superior temporal lobe and right parahippocampal gyrus. We found no evidence in support of our hypothesis. Indeed, the finding of reduced global grey-matter volume in the African-Caribbean/black African patients but not in the white British patients was contrary to our prediction.

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

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.

An unusual neuroimaging finding and response to immunotherapy in a child with genetically confirmed vanishing white matter disease.

PubMed

Singh, Rahul Raman; Livingston, John; Lim, Ming; Berry, Ian R; Siddiqui, Ata

2017-03-01

We present an unusual neuroimaging finding in a young girl with genetically confirmed vanishing white matter disease and a possible response to immunotherapy. 2.5 yr old girl, presented with acute onset unsteadiness and encephalopathy following a viral illness. MRI showed global symmetric white matter abnormality, with symmetric enhancement of cranial nerves (III and V) and of cervical and lumbar roots. She received immunotherapy for her encephalopathic illness with white matter changes. Follow up neuroimaging showed resolution of white matter edema and resolution of the change in the brainstem. Genetic testing confirmed a diagnosis of vanishing white matter disease (VWMD). Craniospinal nerve enhancement and possible response to immunotherapy has not been described in vanishing white matter disease. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Modulation on brain gray matter activity and white matter integrity by APOE ε4 risk gene in cognitively intact elderly: A multimodal neuroimaging study.

PubMed

Cai, Suping; Jiang, Yuanyuan; Wang, Yubo; Wu, Xiaoming; Ren, Junchan; Lee, Min Seob; Lee, Sunghoon; Huang, Liyu

2017-03-30

Apolipoprotein E (APOE) ε4 allele is the genetic risk factor with the most established evidence for sporadic Alzheimer's disease. Previous neuroimaging studies have demonstrated insufficiently consistent functional and structural changes among healthy APOE ε4 carriers when compared to non-carriers. Here, in a cognitively intact elderly group (a total of 110: 45 APOE ε4 carriers, 65 non-carriers), we aimed to investigate the potential role of APOE ε4 in the modulation of grey matter activity, white matter integrity, and brain morphology before the development of clinically significant symptoms and signs, by methods of: amplitude of low frequency fluctuations and regional homogeneity analysis based on resting state fMRI, and fiber tractography approach based on diffusion tensor imaging. Our results revealed that compared to non-carriers, APOE ε4 carriers showed: (1) an inconsistent pattern of activity change in the default mode network, including increased gray matter activity in anterior cingulate cortex and medial prefrontal cortex and decreased activity in precuneus; (2) lower mean diffusivity (MD) in fibers of corona radiata and corpus callosum, and lower axial diffusivity in genu of corpus callosum; and (3) significant positive correlation between the MD value of the right superior corona radiate and gross white matter volume; significant negative correlation between the MD value of the right superior corona radiate and Mini-Mental State Examination (MMSE) score. Our results suggested that APOE ε4 gene can modulate gray matter activity and white matter integrity in cognitive and memory related regions, even before any clinical or neuropsychic symtoms or signs of imminent disease. Copyright © 2017 Elsevier B.V. All rights reserved.

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…

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.

Neurofilament light protein in blood predicts regional atrophy in Huntington disease

PubMed Central

Johnson, Eileanoir B.; Byrne, Lauren M.; Gregory, Sarah; Rodrigues, Filipe B.; Blennow, Kaj; Durr, Alexandra; Leavitt, Blair R.; Roos, Raymund A.; Zetterberg, Henrik; Tabrizi, Sarah J.; Scahill, Rachael I.

2018-01-01

Objective Neurofilament light (NfL) protein in blood plasma has been proposed as a prognostic biomarker of neurodegeneration in a number of conditions, including Huntington disease (HD). This study investigates the regional distribution of NfL-associated neural pathology in HD gene expansion carriers. Methods We examined associations between NfL measured in plasma and regionally specific atrophy in cross-sectional (n = 198) and longitudinal (n = 177) data in HD gene expansion carriers from the international multisite TRACK-HD study. Using voxel-based morphometry, we measured associations between baseline NfL levels and both baseline gray matter and white matter volume; and longitudinal change in gray matter and white matter over the subsequent 3 years in HD gene expansion carriers. Results After controlling for demographics, associations between increased NfL levels and reduced brain volume were seen in cortical and subcortical gray matter and within the white matter. After also controlling for known predictors of disease progression (age and CAG repeat length), associations were limited to the caudate and putamen. Longitudinally, NfL predicted subsequent occipital gray matter atrophy and widespread white matter reduction, both before and after correction for other predictors of disease progression. Conclusions These findings highlight the value of NfL as a dynamic marker of brain atrophy and, more generally, provide further evidence of the strong association between plasma NfL level, a candidate blood biomarker, and pathologic neuronal change. PMID:29367444

White matter integrity in highly traumatized adults with and without post-traumatic stress disorder.

PubMed

Fani, Negar; King, Tricia Z; Jovanovic, Tanja; Glover, Ebony M; Bradley, Bekh; Choi, Kisueng; Ely, Timothy; Gutman, David A; Ressler, Kerry J

2012-11-01

Prior structural imaging studies of post-traumatic stress disorder (PTSD) have observed smaller volumes of the hippocampus and cingulate cortex, yet little is known about the integrity of white matter connections between these structures in PTSD samples. The few published studies using diffusion tensor imaging (DTI) to measure white matter integrity in PTSD have described individuals with focal trauma rather than chronically stressed individuals, which limits generalization of findings to this population; in addition, these studies have lacked traumatized comparison groups without PTSD. The present DTI study examined microstructural integrity of white matter tracts in a sample of highly traumatized African-American women with (n=25) and without (n=26) PTSD using a tract-based spatial statistical approach, with threshold-free cluster enhancement. Our findings indicated that, relative to comparably traumatized controls, decreased integrity (measured by fractional anisotropy) of the posterior cingulum was observed in participants with PTSD (p<0.05). These findings indicate that reduced microarchitectural integrity of the cingulum, a white matter fiber that connects the entorhinal and cingulate cortices, appears to be associated with PTSD symptomatology. The role of this pathway in problems that characterize PTSD, such as inadequate extinction of learned fear, as well as attention and explicit memory functions, are discussed.

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

Alterations of White Matter Integrity Related to the Season of Birth in Schizophrenia: A DTI Study

PubMed Central

Giezendanner, Stéphanie; Walther, Sebastian; Razavi, Nadja; Van Swam, Claudia; Fisler, Melanie Sarah; Soravia, Leila Maria; Andreotti, Jennifer; Schwab, Simon; Jann, Kay; Wiest, Roland; Horn, Helge; Müller, Thomas Jörg; Dierks, Thomas; Federspiel, Andrea

2013-01-01

In schizophrenia there is a consistent epidemiological finding of a birth excess in winter and spring. Season of birth is thought to act as a proxy indicator for harmful environmental factors during foetal maturation. There is evidence that prenatal exposure to harmful environmental factors may trigger pathologic processes in the neurodevelopment, which subsequently increase the risk of schizophrenia. Since brain white matter alterations have repeatedly been found in schizophrenia, the objective of this study was to investigate whether white matter integrity was related to the season of birth in patients with schizophrenia. Thirty-four patients with schizophrenia and 33 healthy controls underwent diffusion tensor imaging. Differences in the fractional anisotropy maps of schizophrenia patients and healthy controls born in different seasons were analysed with tract-based spatial statistics. A significant main effect of season of birth and an interaction of group and season of birth showed that patients born in summer had significantly lower fractional anisotropy in widespread white matter regions than those born in the remainder of the year. Additionally, later age of schizophrenia onset was found in patients born in winter months. The current findings indicate a relationship of season of birth and white matter alterations in schizophrenia and consequently support the neurodevelopmental hypothesis of early pathological mechanisms in schizophrenia. PMID:24086548

Structural white matter differences underlying heterogeneous learning abilities after TBI.

PubMed

Chiou, Kathy S; Genova, Helen M; Chiaravalloti, Nancy D

2016-12-01

The existence of learning deficits after traumatic brain injury (TBI) is generally accepted; however, our understanding of the structural brain mechanisms underlying learning impairment after TBI is limited. Furthermore, our understanding of learning after TBI is often at risk for overgeneralization, as research often overlooks within sample heterogeneity in learning abilities. The present study examined differences in white matter integrity in a sample of adults with moderate to severe TBI who differed in learning abilities. Adults with moderate to severe TBI were grouped into learners and non-learners based upon achievement of the learning criterion of the open-trial Selective Reminding Test (SRT). Diffusion tensor imaging (DTI) was used to identify white matter differences between the learners and non-learners. Adults with TBI who were able to meet the learning criterion had greater white matter integrity (as indicated by higher fractional anisotropy [FA] values) in the right anterior thalamic radiation, forceps minor, inferior fronto-occipital fasciculus, and forceps minor than non-learners. The results of the study suggest that differences in white matter integrity may explain the observed heterogeneity in learning ability after moderate to severe TBI. This also supports emerging evidence for the involvement of the thalamus in higher order cognition, and the role of thalamo-cortical tracts in connecting functional networks associated with learning.

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.

Early treatment of minocycline alleviates white matter and cognitive impairments after chronic cerebral hypoperfusion

PubMed Central

Ma, Jing; Zhang, Jing; Hou, Wei Wei; Wu, Xiao Hua; Liao, Ru Jia; Chen, Ying; Wang, Zhe; Zhang, Xiang Nan; Zhang, Li San; Zhou, Yu Dong; Chen, Zhong; Hu, Wei Wei

2015-01-01

Subcortical ischemic vascular dementia (SIVD) caused by chronic cerebral hypoperfusion develops with progressive white matter and cognitive impairments, yet no effective therapy is available. We investigated the temporal effects of minocycline on an experimental SIVD exerted by right unilateral common carotid arteries occlusion (rUCCAO). Minocycline treated at the early stage (day 0–3), but not the late stage after rUCCAO (day 4–32) alleviated the white matter and cognitive impairments, and promoted remyelination. The actions of minocycline may not involve the inhibition of microglia activation, based on the effects after the application of a microglial activation inhibitor, macrophage migration inhibitory factor, and co-treatment with lipopolysaccharides. Furthermore, minocycline treatment at the early stage promoted the proliferation of oligodendrocyte progenitor cells (OPCs) in subventricular zone, increased OPC number and alleviated apoptosis of mature oligodendrocytes in white matter. In vitro, minocycline promoted OPC proliferation and increased the percentage of OPCs in S and G2/M phases. We provided direct evidence that early treatment is critical for minocycline to alleviate white matter and cognitive impairments after chronic cerebral hypoperfusion, which may be due to its robust effects on OPC proliferation and mature oligodendrocyte loss. So, early therapeutic time window may be crucial for its application in SIVD. PMID:26174710

Defining the nature of the cerebral abnormalities in the premature infant: a qualitative magnetic resonance imaging study.

PubMed

Inder, Terrie E; Wells, Scott J; Mogridge, Nina B; Spencer, Carole; Volpe, Joseph J

2003-08-01

The aim of this study was to define qualitatively the nature and extent of white and gray matter abnormalities in a longitudinal population-based study of infants with very low birth weight. Perinatal factors were then related to the presence and severity of magnetic resonance imaging (MRI) abnormalities. From November 1998 to December 2000, 100 consecutive premature infants admitted to the neonatal intensive care unit at Christchurch Women's Hospital were recruited (98% eligible) after informed parental consent to undergo an MRI scan at term equivalent. The scans were analyzed by a single neuroradiologist experienced in pediatric MRI, with a second independent scoring of the MRI using a combination of criteria for white matter (cysts, signal abnormality, loss of volume, ventriculomegaly, corpus callosal thinning, myelination) and gray matter (gray matter signal abnormality, gyration, subarachnoid space). Results were analyzed against individual item scores as well as the presence of moderate-severe white matter score, total gray matter score, and total brain score. The mean gestational age was 27.9+/-2.4 weeks (range, 23-32 weeks), and mean birth weight was 1063+/-292 g. The greatest univariate predictors for moderate-severe white matter abnormality were lower gestational age (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.1-1.7; P<.01), maternal fever (OR, 2.2; 95% CI, 1.1-4.6; P<.04), proven sepsis in the infant at delivery (OR, 1.8; 95% CI, 1.1-3.6; P=0.03), inotropic support (OR, 2.7; 95% CI, 1.5-4.5; P<.001), patent ductus arteriosus (OR, 2.2; 95% CI, 1.2-3.8; P=.01), grade III/IV intraventricular hemorrhage (P=.015), and the occurrence of a pneumothorax (P=.05). There was a significant protective effect of intrauterine growth restriction (OR, 0.51; 95% CI, 0.23-0.99; P=.04). Gray matter abnormality was highly related to the presence and severity of white matter abnormality. A unique pattern of cerebral abnormality consisting of significant diffuse white matter atrophy, ventriculomegaly, immature gyral development, and enlarged subarachnoid space was found in 10 of 11 infants with birth gestation <26 weeks. Given the later outcome of these infants, this pattern may have very high risk for later global neurodevelopmental disability. This MRI study confirms a high incidence of cerebral white matter abnormality at term in an unselected population of premature infants, which is predominantly a result of noncystic injury in the extremely immature infant. We confirm that the major perinatal risk factors for white matter abnormality are related to perinatal infection, particularly maternal fever and infant sepsis, and hypotension with inotrope use. We have defined a distinct pattern of diffuse white and gray matter abnormality in the extremely immature infant.

White Matter Hyperintensities and Changes in White Matter Integrity in Patients with Alzheimer’s Disease

PubMed Central

Wang, Liya; Goldstein, Felicia C.; Levey, Allan I.; Lah, James J.; Meltzer, Carolyn C.; Holder, Chad A.; Mao, Hui

2012-01-01

Purpose White matter hyperintensities (WMHs) are a risk factor for Alzheimer’s disease (AD). This study investigated the relationship between WMHs and white matter changes in AD using diffusion tensor imaging (DTI) and the sensitivity of each DTI index in distinguishing AD with WMHs. Subjects and Methods Forty-four subjects with WMHs were included. Subjects were classified into three groups based on the Scheltens rating scale: 15 AD patients with mild WMHs, 12 AD patients with severe WMHs, and 17 controls with mild WMHs. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (DR) and axial diffusivity (DA) were analyzed using the region of interest and Tract-Based Spatial Statistics methods. Sensitivity and specificity of DTI indices in distinguishing AD groups from the controls were evaluated. Results AD patients with mild WMHs exhibited differences from control subjects in most DTI indices in the medial temporal and frontal areas; however, differences in DTI indices from AD patients with mild WMHs and AD patients with severe WMHs were found in the parietal and occipital areas. FA and DR were more sensitive measurements than MD and DA in differentiating AD patients from controls, while MD was a more sensitive measurement in distinguishing AD patients with severe WMHs from those with mild WMHs. Conclusions WMHs may contribute to the white matter changes in AD brains, specifically in temporal and frontal areas. Changes in parietal and occipital lobes may be related to the severity of WMHs. DR may serve as an imaging marker of myelin deficits associated with AD. PMID:21152911

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.

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-motor cerebral and cognitive change in this disorder.

Pediatric Patients Demonstrate Progressive T1-Weighted Hyperintensity in the Dentate Nucleus following Multiple Doses of Gadolinium-Based Contrast Agent.

PubMed

Roberts, D R; Chatterjee, A R; Yazdani, M; Marebwa, B; Brown, T; Collins, H; Bolles, G; Jenrette, J M; Nietert, P J; Zhu, X

2016-12-01

While there have been recent reports of brain retention of gadolinium following gadolinium-based contrast agent administration in adults, a retrospective series of pediatric patients has not previously been reported, to our knowledge. We investigated the relationship between the number of prior gadolinium-based contrast agent doses and increasing T1 signal in the dentate nucleus on unenhanced T1-weighted MR imaging. We hypothesized that despite differences in pediatric physiology and the smaller gadolinium-based contrast agent doses that pediatric patients are typically administered based on weighted-adjusted dosing, the pediatric brain would also demonstrate dose-dependent increasing T1 signal in the dentate nucleus. We included children with multiple gadolinium-based contrast agent administrations at our institution. A blinded reader placed ROIs within the dentate nucleus and adjacent cerebellar white matter. To eliminate reader bias, we also performed automated ROI delineation of the dentate nucleus, cerebellar white matter, and pons. Dentate-to-cerebellar white matter and dentate-to pons ratios were compared with the number of gadolinium-based contrast agent administrations. During 20 years at our institution, 280 patients received at least 5 gadolinium-based contrast agent doses, with 1 patient receiving 38 doses. Sixteen patients met the inclusion/exclusion criteria for ROI analysis. Blinded reader dentate-to-cerebellar white matter ratios were significantly associated with gadolinium-based contrast agent doses (r s = 0.77, P = .001). The dentate-to-pons ratio and dentate-to-cerebellar white matter ratios based on automated ROI placement were also significantly correlated with gadolinium-based contrast agent doses (t = 4.98, P < .0001 and t = 2.73, P < .02, respectively). In pediatric patients, the number of prior gadolinium-based contrast agent doses is significantly correlated with progressive T1-weighted dentate hyperintensity. Definitive confirmation of gadolinium deposition requires tissue analysis. Any potential clinical sequelae of gadolinium retention in the developing brain are unknown. Given this uncertainty, we suggest taking a cautious stance, including the use, in pediatric patients, of higher stability, macrocyclic agents, which in both human and animal studies have been shown to be associated with lower levels of gadolinium deposition, and detailed documentation of dosing. Most important, a patient should not be deprived of a well-indicated contrasted MR examination. © 2016 by American Journal of Neuroradiology.

[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.

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

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 Integrity Dissociates Verbal Memory and Auditory Attention Span in Emerging Adults with Congenital Heart Disease.

PubMed

Brewster, Ryan C; King, Tricia Z; Burns, Thomas G; Drossner, David M; Mahle, William T

2015-01-01

White matter disruptions have been identified in individuals with congenital heart disease (CHD). However, no specific theory-driven relationships between microstructural white matter disruptions and cognition have been established in CHD. We conducted a two-part study. First, we identified significant differences in fractional anisotropy (FA) of emerging adults with CHD using Tract-Based Spatial Statistics (TBSS). TBSS analyses between 22 participants with CHD and 18 demographically similar controls identified five regions of normal appearing white matter with significantly lower FA in CHD, and two higher. Next, two regions of lower FA in CHD were selected to examine theory-driven differential relationships with cognition: voxels along the left uncinate fasciculus (UF; a tract theorized to contribute to verbal memory) and voxels along the right middle cerebellar peduncle (MCP; a tract previously linked to attention). In CHD, a significant positive correlation between UF FA and memory was found, r(20)=.42, p=.049 (uncorrected). There was no correlation between UF and auditory attention span. A positive correlation between MCP FA and auditory attention span was found, r(20)=.47, p=.027 (uncorrected). There was no correlation between MCP and memory. In controls, no significant relationships were identified. These results are consistent with previous literature demonstrating lower FA in younger CHD samples, and provide novel evidence for disrupted white matter integrity in emerging adults with CHD. Furthermore, a correlational double dissociation established distinct white matter circuitry (UF and MCP) and differential cognitive correlates (memory and attention span, respectively) in young adults with CHD.

Vanishing white matter disease presenting as opsoclonus myoclonus syndrome in childhood--a case report and review of the literature.

PubMed

Klingelhoefer, Lisa; Misbahuddin, Anjum; Jawad, Tania; Mellers, John; Jarosz, Jozef; Weeks, Robert; Ray Chaudhuri, Kallol

2014-07-01

Vanishing white matter disease is caused by mutations of the eukaryotic translation initiation factor 2B (EIF2B) and is a prevalent cause of inherited childhood leukoencephalopathy. Infantile and early childhood onset forms are associated with chronic progressive neurological signs, with episodes of rapid, neurological, and poor prognosis, with death in few months or years. In contrast, onset in late childhood and adult onset is rare and is associated with long-term survival because of milder signs and slow progression. We present a patient with a genetically proven vanishing white matter disease, typical brain MRI, presenting with opsoclonus myoclonus in early childhood and a delayed development of adult multifocal dystonia and schizoaffective disorder with continued survival. In addition we have also reviewed the relevant literature based on 42 previous articles summarizing clinical details of 318 individuals with vanishing white matter disease (single case reports to case series). In 283, genetic mutation of EIF2B was confirmed with the onset of vanishing white matter disease reported as antenatal (seven), infantile (eight), early childhood (107), between infantile and early childhood (20), late childhood (25), between early and late childhood (three), adult (68), and between late childhood and adult (21). Various movement disorders have been described with vanishing white matter disease either at presentation (mimicking an opsoclonus myoclonus syndrome) or in adulthood (dystonia and myoclonus) with continuing survival. Relatively preserved cognition is a novel presentation and is reported in this article along with a comprehensive literature review. Copyright © 2014 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.

Individual Differences in Reasoning and Visuospatial Attention are Associated with Prefrontal and Parietal White Matter Tracts in Healthy Older Adults

PubMed Central

Monge, Zachary A.; Greenwood, Pamela M.; Parasuraman, Raja; Strenziok, Maren

2016-01-01

Objective Although reasoning and attention are two cognitive processes necessary for ensuring the efficiency of many everyday activities in older adults, the role of white matter integrity in these processes has been little studied. This is an important question due to the role of white matter integrity as a neural substrate of cognitive aging. Here, we sought to examine the white matter tracts subserving reasoning and visuospatial attention in healthy older adults. Method Sixty-one adults aged 60 and older completed a battery of cognitive tests to assess reasoning and visuospatial attention. In addition, diffusion tensor images were collected to assess Fractional Anisotropy (FA) – a measure of white matter integrity. A principle component analysis of the test scores yielded two components: reasoning and visuospatial attention. Whole-brain correlations between FA and the cognitive components were submitted to probabilistic tractography analyses for visualization of cortical targets of tracts. Results For reasoning, bilateral thalamo-anterior prefrontal, anterior corpus callosum, and corpus callosum body tracts interconnecting the superior frontal cortices and right cingulum bundle were found. For visuospatial attention, a right inferior fronto-parietal tract, and bilateral parietal and temporal connections were found. Conclusions We conclude that in older adults, prefrontal cortex white matter tracts and interhemispheric communication are important in higher order cognitive functioning. On the other hand, right-sided fronto-parietal tracts appear to be critical for supporting control of cognitive processes, such as redirecting attention. Researchers may use our results to develop neuroscience-based interventions for older adults targeting brain mechanisms involved in cognitive plasticity. PMID:26986750

Chronic cigarette smoking and the microstructural integrity of white matter in healthy adults

PubMed Central

Paul, Robert H.; Grieve, Stuart M.; Niaura, Raymond; David, Sean P.; Laidlaw, David H.; Cohen, Ronald; Sweet, Lawrence; Taylor, George; Clark, C. Richard; Pogun, Sakire; Gordon, Evian

2008-01-01

Results from recent studies suggest that chronic cigarette smoking is associated with increased white matter volume in the brain as determined by in vivo neuroimaging. We used diffusion tensor imaging to examine the microstructural integrity of the white matter in 10 chronic smokers and 10 nonsmokers. All individuals were healthy, without histories of medical or psychiatric illness. Fractional anisotropy (FA) and trace were measured in the genu, body, and splenium of the corpus callosum. FA provides a measure of directional versus nondirectional water diffusion, whereas trace provides a measure of nondirectional water diffusion. Lower FA and higher trace values are considered to reflect less brain integrity. Voxel-based morphometry was used to define volumes in each of these regions of the corpus callosum. Chronic smokers exhibited significantly higher FA in the body and whole corpus callosum and a strong trend for higher FA in the splenium compared with nonsmokers. FA did not differ between groups in the genu, and neither trace nor white matter volumes differed between groups in any of the regions of interest. When subdivided by Fagerström score (low vs. high), the low Fagerström group exhibited significantly higher FA in the body of the corpus callosum compared with the high Fagerström group and the nonsmokers. These results suggest that, among healthy adults, lower exposure to cigarette smoking is associated with increased microstructural integrity of the white matter compared with either no exposure or higher exposure. Additional studies are needed to further explore differences in white matter integrity between smokers and nonsmokers. PMID:18188754

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.

Characterization of white matter integrity deficits in cocaine-dependent individuals with substance-induced psychosis compared with non-psychotic cocaine users.

PubMed

Willi, Taylor S; Barr, Alasdair M; Gicas, Kristina; Lang, Donna J; Vila-Rodriguez, Fidel; Su, Wayne; Thornton, Allen E; Leonova, Olga; Giesbrecht, Chantelle J; Procyshyn, Ric M; Rauscher, Alexander; MacEwan, William G; Honer, William G; Panenka, William J

2017-05-01

With sufficient drug exposure, some individuals develop transient psychotic symptoms referred to as 'substance-induced psychosis' (SIP), which closely resemble the symptoms observed in schizophrenia spectrum disorders. The comparability in psychotic presentation between SIP and the schizophrenias suggests that similar underlying neural deficits may contribute to the emergence of psychosis across these disorders. Only a small number of studies have investigated structural alterations in SIP, and all have been limited to volumetric imaging methods, with none controlling for the effects of chronic drug exposure. To investigate white matter abnormalities associated with SIP, diffusion tensor imaging was employed in a group of individuals with cocaine-associated psychosis (CAP; n = 24) and a cocaine-dependent non-psychotic (CDN) group (n = 43). Tract-based spatial statistics was used to investigate group differences in white matter diffusion parameters. The CAP group showed significantly lower fractional anisotropy values than the CDN group (p < 0.05) in voxels within white matter tracts of fronto-temporal, fronto-thalamic and interhemispheric pathways. The greatest differences in white matter integrity were present in the corpus callosum, corona radiata, bilateral superior longitudinal fasciculi and bilateral inferior longitudinal fasciculi. Additionally, the CAP group had voxels of significantly higher radial diffusivity in a subset of the previously mentioned pathways. These results are the first description of white matter integrity abnormalities in a SIP sample and indicate that differences in these pathways may be a shared factor in the expression of different forms of psychosis. © 2016 Society for the Study of Addiction.

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.

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.

Computer-aided diagnosis of HIE based on segmentation of MRI

NASA Astrophysics Data System (ADS)

Sun, Ziguang; Li, Chungui; Wang, Qin

2009-10-01

Computer-aided diagnosis has become one of the major research subjects in medical imaging and diagnostic radiology. Hypoxic-ischemic encephalopathy (HIE), remains a serious condition that causes significant mortality and long-term morbidity to neonates. We adopt self-organizing feature maps to segment the tissues, such as white matter and grey matter in the magnetic resonance images. The borderline between white matter and grey matter can be found and the doubtful regions along with the borderline can be localized, then the feature in doubtful regions can be quantified. The method can assist doctors to easily diagnose whether a neonate is ill with mild HIE.

The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis.

PubMed

Debette, Stéphanie; Markus, H S

2010-07-26

To review the evidence for an association of white matter hyperintensities with risk of stroke, cognitive decline, dementia, and death. Systematic review and meta-analysis. PubMed from 1966 to 23 November 2009. Prospective longitudinal studies that used magnetic resonance imaging and assessed the impact of white matter hyperintensities on risk of incident stroke, cognitive decline, dementia, and death, and, for the meta-analysis, studies that provided risk estimates for a categorical measure of white matter hyperintensities, assessing the impact of these lesions on risk of stroke, dementia, and death. Population studied, duration of follow-up, method used to measure white matter hyperintensities, definition of the outcome, and measure of the association of white matter hyperintensities with the outcome. 46 longitudinal studies evaluated the association of white matter hyperintensities with risk of stroke (n=12), cognitive decline (n=19), dementia (n=17), and death (n=10). 22 studies could be included in a meta-analysis (nine of stroke, nine of dementia, eight of death). White matter hyperintensities were associated with an increased risk of stroke (hazard ratio 3.3, 95% confidence interval 2.6 to 4.4), dementia (1.9, 1.3 to 2.8), and death (2.0, 1.6 to 2.7). An association of white matter hyperintensities with a faster decline in global cognitive performance, executive function, and processing speed was also suggested. White matter hyperintensities predict an increased risk of stroke, dementia, and death. Therefore white matter hyperintensities indicate an increased risk of cerebrovascular events when identified as part of diagnostic investigations, and support their use as an intermediate marker in a research setting. Their discovery should prompt detailed screening for risk factors of stroke and dementia.

Progressive Assessment of Ischemic Injury to White Matter Using Diffusion Tensor Imaging: A Preliminary Study of a Macaque Model of Stroke.

PubMed

Zhang, Xiaodong; Yan, Yumei; Tong, Frank; Li, Chun-Xia; Jones, Benjamin; Wang, Silun; Meng, Yuguang; Muly, E Chris; Kempf, Doty; Howell, Leonard

2018-01-01

Previous Diffusion Tensor Imaging (DTI) studies have demonstrated the temporal evolution of stroke injury in grey matter and white matter can be characterized by DTI indices. However, it still remains not fully understood how the DTI indices of white matter are altered progressively during the hyperacute (first 6 hours) and acute stage of stroke (≤ 1 week). In the present study, DTI was employed to characterize the temporal evolution of infarction and white matter injury after stroke insult using a macaque model with permanent ischemic occlusion. Permanent middle cerebral artery (MCA) occlusion was induced in rhesus monkeys (n=4, 10-21 years old). The brain lesion was examined longitudinally with DTI during the hyperacute phase (2-6 hours, n=4), 48 hours (n=4) and 96 hours (n=3) post-occlusion. Cortical infarction was seen in all animals. The Mean Diffusivity (MD) in lesion regions decreased substantially at the first time point (2 hours post stroke) (35%, p <0.05, compared to the contralateral side) and became pseudo-normalized at 96 hours. In contrast, evident FA reduction was seen at 48 hours (39%, p <0.10) post-stroke. MD reduction in white matter bundles of the lesion area was much less than that in the grey matter during the hyper-acute phase but significant change was observed 4 hours (4.2%, p < 0.05) post stroke . Also, MD pseudonormalisation was seen at 96 hours post stroke. There was a significant correlation between the temporal changes of MD in white matter bundles and those in whole lesion areas during the entire study period. Meanwhile, no obvious fractional anisotropy (FA) changes were seen during the hyper-acute phase in either the entire infarct region or white matter bundles. Significant FA alteration was observed in entire lesion areas and injured white matter bundles 48 and 96 hours post stroke. The stroke lesion in grey matter and white matter was validated by pathological findings. The temporal evolution of ischemic injury to the grey matter and white matter from 2 to 96 hours after stroke onset was characterized using a macaque model and DTI. Progressive MD changes in white matter bundles are seen from hyperacute phase to acute phase after permanent MCA occlusion and temporally correlated with the MD changes in entire infarction regions. MD reduction in white matter bundles is mild in comparison with that in the grey matter but significant and progressive, indicating it may be useful to detect early white matter degeneration after stroke.

Edge Density Imaging: Mapping the Anatomic Embedding of the Structural Connectome Within the White Matter of the Human Brain

PubMed Central

Owen, Julia P.; Chang, Yi-Shin; Mukherjee, Pratik

2015-01-01

The structural connectome has emerged as a powerful tool to characterize the network architecture of the human brain and shows great potential for generating important new biomarkers for neurologic and psychiatric disorders. The edges of the cerebral graph traverse white matter to interconnect cortical and subcortical nodes, although the anatomic embedding of these edges is generally overlooked in the literature. Mapping the paths of the connectome edges could elucidate the relative importance of individual white matter tracts to the overall network topology of the brain and also lead to a better understanding of the effect of regionally-specific white matter pathology on cognition and behavior. In this work, we introduce edge density imaging (EDI), which maps the number of network edges that pass through every white matter voxel. Test-retest analysis shows good to excellent reliability for edge density (ED) measurements, with consistent results using different cortical and subcortical parcellation schemes and different diffusion MR imaging acquisition parameters. We also demonstrate that ED yields complementary information to both traditional and emerging voxel-wise metrics of white matter microstructure and connectivity, including fractional anisotropy, track density, fiber orientation dispersion and neurite density. Our results demonstrate spatially ordered variations of ED throughout the white matter, notably including greater ED in posterior than anterior cerebral white matter. The EDI framework is employed to map the white matter regions that are enriched with pathways connecting rich club nodes and also those with high densities of intra-modular and inter-modular edges. We show that periventricular white matter has particularly high ED and high densities of rich club edges, which is significant for diseases in which these areas are selectively affected, ranging from white matter injury of prematurity in infants to leukoaraiosis in the elderly. Using edge betweenness centrality, we identify specific white matter regions involved in a large number of shortest paths, some containing highly connected rich club edges while others are relatively isolated within individual modules. Overall, these findings reveal an intricate relationship between white matter anatomy and the structural connectome, motivating further exploration of EDI for biomarkers of cognition and behavior. PMID:25592996

Utility of a Multiparametric Quantitative MRI Model That Assesses Myelin and Edema for Evaluating Plaques, Periplaque White Matter, and Normal-Appearing White Matter in Patients with Multiple Sclerosis: A Feasibility Study.

PubMed

Hagiwara, A; Hori, M; Yokoyama, K; Takemura, M Y; Andica, C; Kumamaru, K K; Nakazawa, M; Takano, N; Kawasaki, H; Sato, S; Hamasaki, N; Kunimatsu, A; Aoki, S

2017-02-01

T1 and T2 values and proton density can now be quantified on the basis of a single MR acquisition. The myelin and edema in a voxel can also be estimated from these values. The purpose of this study was to evaluate a multiparametric quantitative MR imaging model that assesses myelin and edema for characterizing plaques, periplaque white matter, and normal-appearing white matter in patients with MS. We examined 3T quantitative MR imaging data from 21 patients with MS. The myelin partial volume, excess parenchymal water partial volume, the inverse of T1 and transverse T2 relaxation times (R1, R2), and proton density were compared among plaques, periplaque white matter, and normal-appearing white matter. All metrics differed significantly across the 3 groups ( P < .001). Those in plaques differed most from those in normal-appearing white matter. The percentage changes of the metrics in plaques and periplaque white matter relative to normal-appearing white matter were significantly more different from zero for myelin partial volume (mean, -61.59 ± 20.28% [plaque relative to normal-appearing white matter], and mean, -10.51 ± 11.41% [periplaque white matter relative to normal-appearing white matter]), and excess parenchymal water partial volume (13.82 × 10 3 ± 49.47 × 10 3 % and 51.33 × 10 2 ± 155.31 × 10 2 %) than for R1 (-35.23 ± 13.93% and -6.08 ± 8.66%), R2 (-21.06 ± 11.39% and -4.79 ± 6.79%), and proton density (23.37 ± 10.30% and 3.37 ± 4.24%). Multiparametric quantitative MR imaging captures white matter damage in MS. Myelin partial volume and excess parenchymal water partial volume are more sensitive to the MS disease process than R1, R2, and proton density. © 2017 by American Journal of Neuroradiology.

Skeleton-based region competition for automated gray matter and white matter segmentation of human brain MR images

NASA Astrophysics Data System (ADS)

Chu, Yong; Chen, Ya-Fang; Su, Min-Ying; Nalcioglu, Orhan

2005-04-01

Image segmentation is an essential process for quantitative analysis. Segmentation of brain tissues in magnetic resonance (MR) images is very important for understanding the structural-functional relationship for various pathological conditions, such as dementia vs. normal brain aging. Different brain regions are responsible for certain functions and may have specific implication for diagnosis. Segmentation may facilitate the analysis of different brain regions to aid in early diagnosis. Region competition has been recently proposed as an effective method for image segmentation by minimizing a generalized Bayes/MDL criterion. However, it is sensitive to initial conditions - the "seeds", therefore an optimal choice of "seeds" is necessary for accurate segmentation. In this paper, we present a new skeleton-based region competition algorithm for automated gray and white matter segmentation. Skeletons can be considered as good "seed regions" since they provide the morphological a priori information, thus guarantee a correct initial condition. Intensity gradient information is also added to the global energy function to achieve a precise boundary localization. This algorithm was applied to perform gray and white matter segmentation using simulated MRI images from a realistic digital brain phantom. Nine different brain regions were manually outlined for evaluation of the performance in these separate regions. The results were compared to the gold-standard measure to calculate the true positive and true negative percentages. In general, this method worked well with a 96% accuracy, although the performance varied in different regions. We conclude that the skeleton-based region competition is an effective method for gray and white matter segmentation.

Hypothalamic tumors impact gray and white matter volumes in fronto-limbic brain areas.

PubMed

Özyurt, Jale; Müller, Hermann L; Warmuth-Metz, Monika; Thiel, Christiane M

2017-04-01

Patients with hypothalamic involvement of a sellar/parasellar tumor often suffer from cognitive and social-emotional deficits that a lesion in the hypothalamus cannot fully explain. It is conceivable that these deficits are partly due to distal changes in hypothalamic networks, evolving secondary to a focal lesion. Focusing on childhood-onset craniopharyngioma patients, we aimed at investigating the impact of hypothalamic lesions on gray and white matter areas densely connected to the hypothalamus, and to relate structural changes to neuropsychological deficits frequently observed in patients. We performed a voxel-based morphometric analysis based on data of 11 childhood-onset craniopharyngioma patients with hypothalamic tumor involvement, and 18 healthy controls (median age: 17.2 and 17.4 yrs.). Whole-brain analyses were used to test for volumetric differences between the groups (T-tests) and subsequent regression analyses were used to correlate neuropsychological performance with gray and white matter volumes within the patient group. Patients compared to controls had significantly reduced gray matter volumes in areas of the anterior and posterior limbic subsystems which are densely connected with the hypothalamus. In addition, a reduction in white matter volumes was observed in tracts connecting the hypothalamus to other limbic areas. Worse long-term memory retrieval was correlated with smaller gray matter volumes in the posterior cingulate cortex. Our data provide the first evidence that hypothalamic tumor involvement impacts gray and white matter volumes in limbic areas, outside the area of tumor growth. Notably, the functional range of the two limbic subsystems affected, strikingly parallels the two major domains of psychological complaints in patients i.e., deficits in episodic memory and in socio-emotional functioning. We suggest that focal hypothalamic lesions may trigger distal changes in connected brain areas, which then contribute to the impairments in cognitive, social and emotional performance often observable in patients, and not explicable by a hypothalamic lesion alone. Copyright © 2017 Elsevier Ltd. All rights reserved.

White Matter Fiber-based Analysis of T1w/T2w Ratio Map.

PubMed

Chen, Haiwei; Budin, Francois; Noel, Jean; Prieto, Juan Carlos; Gilmore, John; Rasmussen, Jerod; Wadhwa, Pathik D; Entringer, Sonja; Buss, Claudia; Styner, Martin

2017-02-01

To develop, test, evaluate and apply a novel tool for the white matter fiber-based analysis of T1w/T2w ratio maps quantifying myelin content. The cerebral white matter in the human brain develops from a mostly non-myelinated state to a nearly fully mature white matter myelination within the first few years of life. High resolution T1w/T2w ratio maps are believed to be effective in quantitatively estimating myelin content on a voxel-wise basis. We propose the use of a fiber-tract-based analysis of such T1w/T2w ratio data, as it allows us to separate fiber bundles that a common regional analysis imprecisely groups together, and to associate effects to specific tracts rather than large, broad regions. We developed an intuitive, open source tool to facilitate such fiber-based studies of T1w/T2w ratio maps. Via its Graphical User Interface (GUI) the tool is accessible to non-technical users. The framework uses calibrated T1w/T2w ratio maps and a prior fiber atlas as an input to generate profiles of T1w/T2w values. The resulting fiber profiles are used in a statistical analysis that performs along-tract functional statistical analysis. We applied this approach to a preliminary study of early brain development in neonates. We developed an open-source tool for the fiber based analysis of T1w/T2w ratio maps and tested it in a study of brain development.

White matter fiber-based analysis of T1w/T2w ratio map

NASA Astrophysics Data System (ADS)

Chen, Haiwei; Budin, Francois; Noel, Jean; Prieto, Juan Carlos; Gilmore, John; Rasmussen, Jerod; Wadhwa, Pathik D.; Entringer, Sonja; Buss, Claudia; Styner, Martin

2017-02-01

Purpose: To develop, test, evaluate and apply a novel tool for the white matter fiber-based analysis of T1w/T2w ratio maps quantifying myelin content. Background: The cerebral white matter in the human brain develops from a mostly non-myelinated state to a nearly fully mature white matter myelination within the first few years of life. High resolution T1w/T2w ratio maps are believed to be effective in quantitatively estimating myelin content on a voxel-wise basis. We propose the use of a fiber-tract-based analysis of such T1w/T2w ratio data, as it allows us to separate fiber bundles that a common regional analysis imprecisely groups together, and to associate effects to specific tracts rather than large, broad regions. Methods: We developed an intuitive, open source tool to facilitate such fiber-based studies of T1w/T2w ratio maps. Via its Graphical User Interface (GUI) the tool is accessible to non-technical users. The framework uses calibrated T1w/T2w ratio maps and a prior fiber atlas as an input to generate profiles of T1w/T2w values. The resulting fiber profiles are used in a statistical analysis that performs along-tract functional statistical analysis. We applied this approach to a preliminary study of early brain development in neonates. Results: We developed an open-source tool for the fiber based analysis of T1w/T2w ratio maps and tested it in a study of brain development.

A Tractography Comparison between Turboprop and Spin-Echo Echo-Planar Diffusion Tensor Imaging

PubMed Central

Gui, Minzhi; Peng, Huiling; Carew, John D.; Lesniak, Maciej S.; Arfanakis, Konstantinos

2008-01-01

The development of accurate, non-invasive methods for mapping white matter fiber-tracts is of critical importance. However, fiber-tracking is typically performed on diffusion tensor imaging (DTI) data obtained with echo-planar-based imaging techniques (EPI), which suffer from susceptibility-related image artifacts, and image warping due to eddy-currents. Thus, a number of white matter fiber-bundles mapped using EPI-based DTI data are distorted and/or terminated early. This severely limits the clinical potential of fiber-tracking. In contrast, Turboprop-MRI provides images with significantly fewer susceptibility and eddy-current-related artifacts than EPI. The purpose of this work was to compare fiber-tracking results obtained from DTI data acquired with Turboprop-DTI and EPI-based DTI. It was shown that, in brain regions near magnetic field inhomogeneities, white matter fiber-bundles obtained with EPI-based DTI were distorted and/or partially detected, when magnetic susceptibility-induced distortions were not corrected. After correction, residual distortions were still present and several fiber-tracts remained partially detected. In contrast, when using Turboprop-DTI data, all traced fiber-tracts were in agreement with known anatomy. The inter-session reproducibility of tractography results was higher for Turboprop than EPI-based DTI data in regions near field inhomogeneities. Thus, Turboprop may be a more appropriate DTI data acquisition technique for tracing white matter fibers near regions with significant magnetic susceptibility differences, as well as in longitudinal studies of such fibers. However, the intra-session reproducibility of tractography results was higher for EPI-based than Turboprop DTI data. Thus, EPI-based DTI may be more advantageous for tracing fibers minimally affected by field inhomogeneities. PMID:18621131

A tractography comparison between turboprop and spin-echo echo-planar diffusion tensor imaging.

PubMed

Gui, Minzhi; Peng, Huiling; Carew, John D; Lesniak, Maciej S; Arfanakis, Konstantinos

2008-10-01

The development of accurate, non-invasive methods for mapping white matter fiber-tracts is of critical importance. However, fiber-tracking is typically performed on diffusion tensor imaging (DTI) data obtained with echo-planar-based imaging techniques (EPI), which suffer from susceptibility-related image artifacts, and image warping due to eddy-currents. Thus, a number of white matter fiber-bundles mapped using EPI-based DTI data are distorted and/or terminated early. This severely limits the clinical potential of fiber-tracking. In contrast, Turboprop-MRI provides images with significantly fewer susceptibility and eddy-current-related artifacts than EPI. The purpose of this work was to compare fiber-tracking results obtained from DTI data acquired with Turboprop-DTI and EPI-based DTI. It was shown that, in brain regions near magnetic field inhomogeneities, white matter fiber-bundles obtained with EPI-based DTI were distorted and/or partially detected, when magnetic susceptibility-induced distortions were not corrected. After correction, residual distortions were still present and several fiber-tracts remained partially detected. In contrast, when using Turboprop-DTI data, all traced fiber-tracts were in agreement with known anatomy. The inter-session reproducibility of tractography results was higher for Turboprop than EPI-based DTI data in regions near field inhomogeneities. Thus, Turboprop may be a more appropriate DTI data acquisition technique for tracing white matter fibers near regions with significant magnetic susceptibility differences, as well as in longitudinal studies of such fibers. However, the intra-session reproducibility of tractography results was higher for EPI-based than Turboprop DTI data. Thus, EPI-based DTI may be more advantageous for tracing fibers minimally affected by field inhomogeneities.

Glutaric aciduria type 1: neuroimaging features with clinical correlation.

PubMed

Mohammad, Shaimaa Abdelsattar; Abdelkhalek, Heba Salah; Ahmed, Khaled A; Zaki, Osama K

2015-10-01

Glutaric aciduria type 1 is a rare neurometabolic disease with high morbidity. To describe the MR imaging abnormalities in glutaric aciduria type 1 and to identify any association between the clinical and imaging features. MRI scans of 29 children (mean age: 16.9 months) with confirmed diagnosis of glutaric aciduria type 1 were retrospectively reviewed. Gray matter and white matter scores were calculated based on a previously published pattern-recognition approach of assessing leukoencephalopathies. Hippocampal formation and opercular topography were assessed in relation to the known embryological basis. MRI scores were correlated with morbidity score. The most consistent MRI abnormality was widened operculum with dilatation of the subarachnoid spaces surrounding underdeveloped frontotemporal lobes. Incomplete hippocampal inversion was also seen. The globus pallidus was the most frequently involved gray matter structure (86%). In addition to the central tegmental tract, white matter abnormalities preferentially involved the central and periventricular regions. The morbidity score correlated with the gray matter abnormality score (P = 0.004). Patients with dystonia had higher gray matter and morbidity scores. Morbidity is significantly correlated with abnormality of gray matter, rather than white matter, whether secondary to acute encephalopathic crisis or insidious onset disease.

Asymmetrical flow field-flow fractionation of white wine chromophoric colloidal matter.

PubMed

Coelho, Christian; Parot, Jérémie; Gonsior, Michael; Nikolantonaki, Maria; Schmitt-Kopplin, Philippe; Parlanti, Edith; Gougeon, Régis D

2017-04-01

Two analytical separation methods-size-exclusion chromatography and asymmetrical flow field-flow fractionation-were implemented to evaluate the integrity of the colloidal composition of Chardonnay white wine and the impact of pressing and fermentations on the final macromolecular composition. Wine chromophoric colloidal matter, representing UV-visible-absorbing wine macromolecules, was evaluated by optical and structural measurements combined with the description of elution profiles obtained by both separative techniques. The objective of this study was to apply these two types of fractionation on a typical Chardonnay white wine produced in Burgundy and to evaluate how each of them impacted the determination of the macromolecular chromophoric content of wine. UV-visible and fluorescence measurements of collected fractions were successfully applied. An additional proteomic study revealed that grape and microorganism proteins largely impacted the composition of chromophoric colloidal matter of Chardonnay wines. Asymmetrical flow field-flow fractionation appeared to be more reliable and less invasive with respect to the native chemical environment of chromophoric wine macromolecules, and hence is recommended as a tool to fractionate chromophoric colloidal matter in white wines. Graphical Abstract An innovative macromolecular separation method based on Asymmetrical Flow Field-Flow Fractionation was developed to better control colloidal dynamics across Chardonnay white winemaking.

Correlations between Stroop task performance and white matter lesion measures in late-onset major depression.

PubMed

Dalby, Rikke B; Frandsen, Jesper; Chakravarty, M Mallar; Ahdidan, Jamila; Sørensen, Leif; Rosenberg, Raben; Østergaard, Leif; Videbech, Poul

2012-05-31

Cerebral white matter lesions (WMLs) are believed to play an important role in a subset of patients with late-onset depression by affecting the white matter connectivity in circuitries essential for mood and cognition. In this study we used diffusion tensor imaging-based (DTI-based) tractography to assess white matter fiber tracts affected by deep WMLs (DWMLs) in patients with late-onset major depression and age- and gender-matched controls. Tractography outcome, illustrated as pathways affected by DWMLs, was analyzed for associations with cognitive performance on the Stroop Test (ST). The patients (n=17) performed significantly worse on the ST than the controls (n=22). Poor performance on the ST correlated with higher lesion load. Regression analysis showed a significant correlation between poor performance on the ST and tracts affected by DWMLs in multiple brain areas in the control group, but very sparse correlation in the patient group. Our results suggest that DWMLs play an important role in the cognitive performance of controls,whereas their influence in depressed patients is overruled by additional, state-dependent factors. Future focus on the tract-specific localization of WMLs using DTI tractography may reveal important associations between neuroconnectivity and clinical measures. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

White matter tractography by means of Turboprop diffusion tensor imaging.

PubMed

Arfanakis, Konstantinos; Gui, Minzhi; Lazar, Mariana

2005-12-01

White matter fiber-tractography by means of diffusion tensor imaging (DTI) is a noninvasive technique that provides estimates of the structural connectivity of the brain. However, conventional fiber-tracking methods using DTI are based on echo-planar image acquisitions (EPI), which suffer from image distortions and artifacts due to magnetic susceptibility variations and eddy currents. Thus, a large percentage of white matter fiber bundles that are mapped using EPI-based DTI data are distorted, and/or terminated early, while others are completely undetected. This severely limits the potential of fiber-tracking techniques. In contrast, Turboprop imaging is a multiple-shot gradient and spin-echo (GRASE) technique that provides images with significantly fewer susceptibility and eddy current-related artifacts than EPI. The purpose of this work was to evaluate the performance of fiber-tractography techniques when using data obtained with Turboprop-DTI. All fiber pathways that were mapped were found to be in agreement with the anatomy. There were no visible distortions in any of the traced fiber bundles, even when these were located in the vicinity of significant magnetic field inhomogeneities. Additionally, the Turboprop-DTI data used in this research were acquired in less than 19 min of scan time. Thus, Turboprop appears to be a promising DTI data acquisition technique for tracing white matter fibers.

Voxel-based morphometry in autopsy proven PSP and CBD.

PubMed

Josephs, Keith A; Whitwell, Jennifer L; Dickson, Dennis W; Boeve, Bradley F; Knopman, David S; Petersen, Ronald C; Parisi, Joseph E; Jack, Clifford R

2008-02-01

The aim of this study was to compare the patterns of grey and white matter atrophy on MRI in autopsy confirmed progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), and to determine whether the patterns vary depending on the clinical syndrome. Voxel-based morphometry was used to compare patterns of atrophy in 13 PSP and 11 CBD subjects and 24 controls. PSP and CBD subjects were also subdivided into those with a dominant dementia or extrapyramidal syndrome. PSP subjects showed brainstem atrophy with involvement of the cortex and underlying white matter. Frontoparietal grey and subcortical grey matter atrophy occurred in CBD. When subdivided, PSP subjects with an extrapyramidal syndrome had more brainstem atrophy and less cortical atrophy than CBD subjects with an extrapyramidal syndrome. PSP subjects with a dementia syndrome had more subcortical white matter atrophy than CBD subjects with a dementia syndrome. These results show regional differences between PSP and CBD that are useful in predicting the underlying pathology, and help to shed light on the in vivo distribution of regional atrophy in PSP and CBD.

Explaining the heterogeneity of functional connectivity findings in multiple sclerosis: An empirically informed modeling study.

PubMed

Tewarie, Prejaas; Steenwijk, Martijn D; Brookes, Matthew J; Uitdehaag, Bernard M J; Geurts, Jeroen J G; Stam, Cornelis J; Schoonheim, Menno M

2018-06-01

To understand the heterogeneity of functional connectivity results reported in the literature, we analyzed the separate effects of grey and white matter damage on functional connectivity and networks in multiple sclerosis. For this, we employed a biophysical thalamo-cortical model consisting of interconnected cortical and thalamic neuronal populations, informed and amended by empirical diffusion MRI tractography data, to simulate functional data that mimic neurophysiological signals. Grey matter degeneration was simulated by decreasing within population connections and white matter degeneration by lowering between population connections, based on lesion predilection sites in multiple sclerosis. For all simulations, functional connectivity and functional network organization are quantified by phase synchronization and network integration, respectively. Modeling results showed that both cortical and thalamic grey matter damage induced a global increase in functional connectivity, whereas white matter damage induced an initially increased connectivity followed by a global decrease. Both white and especially grey matter damage, however, induced a decrease in network integration. These empirically informed simulations show that specific topology and timing of structural damage are nontrivial aspects in explaining functional abnormalities in MS. Insufficient attention to these aspects likely explains contradictory findings in multiple sclerosis functional imaging studies so far. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Correlation between pulmonary function and brain volume in healthy elderly subjects.

PubMed

Taki, Yasuyuki; Kinomura, Shigeo; Ebihara, Satoru; Thyreau, Benjamin; Sato, Kazunori; Goto, Ryoi; Kakizaki, Masako; Tsuji, Ichiro; Kawashima, Ryuta; Fukuda, Hiroshi

2013-06-01

Cigarette smoking decreases brain regional gray matter volume and is related to chronic obstructive lung disease (COPD). COPD leads to decreased pulmonary function, which is represented by forced expiratory volume in one second percentage (FEV1.0 %); however, it is unclear if decreased pulmonary function is directly related to brain gray matter volume decline. Because there is a link between COPD and cognitive decline, revealing a direct relationship between pulmonary function and brain structure is important to better understand how pulmonary function affects brain structure and cognitive function. Therefore, the purpose of this study was to analyze whether there were significant correlations between FEV1.0 % and brain regional gray and white matter volumes using brain magnetic resonance (MR) image data from 109 community-dwelling healthy elderly individuals. Brain MR images were processed with voxel-based morphometry using a custom template by applying diffeomorphic anatomical registration using the exponentiated lie algebra procedure. We found a significant positive correlation between the regional white matter volume of the cerebellum and FEV1.0 % after adjusting for age, sex, and intracranial volume. Our results suggest that elderly individuals who have a lower FEV1.0 % have decreased regional white matter volume in the cerebellum. Therefore, preventing decreased pulmonary function is important for cerebellar white matter volume in the healthy elderly population.

Effects of Surgery and Proton Therapy on Cerebral White Matter of Craniopharyngioma Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uh, Jinsoo, E-mail: jinsoo.uh@stjude.org; Merchant, Thomas E.; Li, Yimei

Purpose: The purpose of this study was to determine radiation dose effect on the structural integrity of cerebral white matter in craniopharyngioma patients receiving surgery and proton therapy. Methods and Materials: Fifty-one patients (2.1-19.3 years of age) with craniopharyngioma underwent surgery and proton therapy in a prospective therapeutic trial. Anatomical magnetic resonance images acquired after surgery but before proton therapy were inspected to identify white matter structures intersected by surgical corridors and catheter tracks. Longitudinal diffusion tensor imaging (DTI) was performed to measure microstructural integrity changes in cerebral white matter. Fractional anisotropy (FA) derived from DTI was statistically analyzed for 51more » atlas-based white matter structures of the brain to determine radiation dose effect. FA in surgery-affected regions in the corpus callosum was compared to that in its intact counterpart to determine whether surgical defects affect radiation dose effect. Results: Surgical defects were seen most frequently in the corpus callosum because of transcallosal resection of tumors and insertion of ventricular or cyst catheters. Longitudinal DTI data indicated reductions in FA 3 months after therapy, which was followed by a recovery in most white matter structures. A greater FA reduction was correlated with a higher radiation dose in 20 white matter structures, indicating a radiation dose effect. The average FA in the surgery-affected regions before proton therapy was smaller (P=.0001) than that in their non–surgery-affected counterparts with more intensified subsequent reduction of FA (P=.0083) after therapy, suggesting that surgery accentuated the radiation dose effect. Conclusions: DTI data suggest that mild radiation dose effects occur in patients with craniopharyngioma receiving surgery and proton therapy. Surgical defects present at the time of proton therapy appear to accentuate the radiation dose effect longitudinally. This study supports consideration of pre-existing surgical defects and their locations in proton therapy planning and studies of treatment effect.« less

Imaging Findings Associated with Cognitive Performance in Primary Lateral Sclerosis and Amyotrophic Lateral Sclerosis

PubMed Central

Meoded, Avner; Kwan, Justin Y.; Peters, Tracy L.; Huey, Edward D.; Danielian, Laura E.; Wiggs, Edythe; Morrissette, Arthur; Wu, Tianxia; Russell, James W.; Bayat, Elham; Grafman, Jordan; Floeter, Mary Kay

2013-01-01

Introduction Executive dysfunction occurs in many patients with amyotrophic lateral sclerosis (ALS), but it has not been well studied in primary lateral sclerosis (PLS). The aims of this study were to (1) compare cognitive function in PLS to that in ALS patients, (2) explore the relationship between performance on specific cognitive tests and diffusion tensor imaging (DTI) metrics of white matter tracts and gray matter volumes, and (3) compare DTI metrics in patients with and without cognitive and behavioral changes. Methods The Delis-Kaplan Executive Function System (D-KEFS), the Mattis Dementia Rating Scale (DRS-2), and other behavior and mood scales were administered to 25 ALS patients and 25 PLS patients. Seventeen of the PLS patients, 13 of the ALS patients, and 17 healthy controls underwent structural magnetic resonance imaging (MRI) and DTI. Atlas-based analysis using MRI Studio software was used to measure fractional anisotropy, and axial and radial diffusivity of selected white matter tracts. Voxel-based morphometry was used to assess gray matter volumes. The relationship between diffusion properties of selected association and commissural white matter and performance on executive function and memory tests was explored using a linear regression model. Results More ALS than PLS patients had abnormal scores on the DRS-2. DRS-2 and D-KEFS scores were related to DTI metrics in several long association tracts and the callosum. Reduced gray matter volumes in motor and perirolandic areas were not associated with cognitive scores. Conclusion The changes in diffusion metrics of white matter long association tracts suggest that the loss of integrity of the networks connecting fronto-temporal areas to parietal and occipital areas contributes to cognitive impairment. PMID:24052798

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.

White matter microstructure within the superior longitudinal fasciculus modulates the degree of response conflict indexed by N2 in healthy adults.

PubMed

Gao, Shudan; Liu, Peng; Guo, Jialu; Zhu, Yuanqiang; Liu, Peng; Sun, Jinbo; Yang, Xuejuan; Qin, Wei

2017-12-01

Response conflict can be induced by priming multiple responses competing for control of action in trials. The N2 is one functionally-related cognitive control index for response conflict. And yet the underlying whiter matter neural substrates of inter-individual difference in conflict N2 remain unclear. So the aim of present study was to address the white matter microstructure of the N2 responsible for conflict by directly relating the amplitude cost of the event-related potential (ERP) N2 component to diffusion tensor imaging (DTI) indices in healthy subjects. Thirty healthy subjects underwent DTI scanning and electrophysiology recording during a modified Flanker task. N2 was a stimulus-locked negative ERP component. Fractional anisotropy (FA) was calculated based on DTI measures and was assumed to reflect the integrity of myelinate fiber bundles. Therefore, we tested the relationship between N2 amplitude and FA in brain white matter. Results showed that FA, an index for white matter characteristics, in the right superior longitudinal fasciculus (SLF) was significantly positively associated with N2 amplitude cost. The N2 amplitude cost also predicted response time (RT) cost in the Flanker task. Higher FA was associated with larger N2 amplitude cost, suggesting that changes in white matter integrity in the SLF may account for changes in efficient transmission of fronto-parietal modulatory conflict signals. Copyright © 2017 Elsevier B.V. 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.

The hidden-Markov brain: comparison and inference of white matter hyperintensities on magnetic resonance imaging (MRI)

NASA Astrophysics Data System (ADS)

Pham, Tuan D.; Salvetti, Federica; Wang, Bing; Diani, Marco; Heindel, Walter; Knecht, Stefan; Wersching, Heike; Baune, Bernhard T.; Berger, Klaus

2011-02-01

Rating and quantification of cerebral white matter hyperintensities on magnetic resonance imaging (MRI) are important tasks in various clinical and scientific settings. As manual evaluation is time consuming and imprecise, much effort has been made to automate the quantification of white matter hyperintensities. There is rarely any report that attempts to study the similarity/dissimilarity of white matter hyperintensity patterns that have different sizes, shapes and spatial localizations on the MRI. This paper proposes an original computational neuroscience framework for such a conceptual study with a standpoint that the prior knowledge about white matter hyperintensities can be accumulated and utilized to enable a reliable inference of the rating of a new white matter hyperintensity observation. This computational approach for rating inference of white matter hyperintensities, which appears to be the first study, can be utilized as a computerized rating-assisting tool and can be very economical for diagnostic evaluation of brain tissue lesions.

Emotion detection deficits and changes in personality traits linked to loss of white matter integrity in primary progressive aphasia.

PubMed

Multani, Namita; Galantucci, Sebastiano; Wilson, Stephen M; Shany-Ur, Tal; Poorzand, Pardis; Growdon, Matthew E; Jang, Jung Yun; Kramer, Joel H; Miller, Bruce L; Rankin, Katherine P; Gorno-Tempini, Maria Luisa; Tartaglia, Maria Carmela

2017-01-01

Non-cognitive features including personality changes are increasingly recognized in the three PPA variants (semantic-svPPA, non fluent-nfvPPA, and logopenic-lvPPA). However, differences in emotion processing among the PPA variants and its association with white matter tracts are unknown. We compared emotion detection across the three PPA variants and healthy controls (HC), and related them to white matter tract integrity and cortical degeneration. Personality traits in the PPA group were also examined in relation to white matter tracts. Thirty-three patients with svPPA, nfvPPA, lvPPA, and 32 HC underwent neuropsychological assessment, emotion evaluation task (EET), and MRI scan. Patients' study partners were interviewed on the Clinical Dementia Rating Scale (CDR) and completed an interpersonal traits assessment, the Interpersonal Adjective Scale (IAS). Diffusion tensor imaging of uncinate fasciculus (UF), superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF), and voxel-based morphometry to derive gray matter volumes for orbitofrontal cortex (OFC), anterior temporal lobe (ATL) regions were performed. In addition, gray matter volumes of white matter tract-associated regions were also calculated: inferior frontal gyrus (IFG), posterior temporal lobe (PTL), inferior parietal lobe (IPL) and occipital lobe (OL). ANCOVA was used to compare EET performance. Partial correlation and multivariate linear regression were conducted to examine association between EET and neuroanatomical regions affected in PPA. All three variants of PPA performed significantly worse than HC on EET, and the svPPA group was least accurate at recognizing emotions. Performance on EET was related to the right UF, SLF, and ILF integrity. Regression analysis revealed EET performance primarily relates to the right UF integrity. The IAS subdomain, cold-hearted, was also associated with right UF integrity. Disease-specific emotion recognition and personality changes occur in the three PPA variants and are likely associated with disease-specific neuroanatomical changes. Loss of white matter integrity contributes as significantly as focal atrophy in behavioral changes in PPA.

Neurofilament light protein in blood predicts regional atrophy in Huntington disease.

PubMed

Johnson, Eileanoir B; Byrne, Lauren M; Gregory, Sarah; Rodrigues, Filipe B; Blennow, Kaj; Durr, Alexandra; Leavitt, Blair R; Roos, Raymund A; Zetterberg, Henrik; Tabrizi, Sarah J; Scahill, Rachael I; Wild, Edward J

2018-02-20

Neurofilament light (NfL) protein in blood plasma has been proposed as a prognostic biomarker of neurodegeneration in a number of conditions, including Huntington disease (HD). This study investigates the regional distribution of NfL-associated neural pathology in HD gene expansion carriers. We examined associations between NfL measured in plasma and regionally specific atrophy in cross-sectional (n = 198) and longitudinal (n = 177) data in HD gene expansion carriers from the international multisite TRACK-HD study. Using voxel-based morphometry, we measured associations between baseline NfL levels and both baseline gray matter and white matter volume; and longitudinal change in gray matter and white matter over the subsequent 3 years in HD gene expansion carriers. After controlling for demographics, associations between increased NfL levels and reduced brain volume were seen in cortical and subcortical gray matter and within the white matter. After also controlling for known predictors of disease progression (age and CAG repeat length), associations were limited to the caudate and putamen. Longitudinally, NfL predicted subsequent occipital gray matter atrophy and widespread white matter reduction, both before and after correction for other predictors of disease progression. These findings highlight the value of NfL as a dynamic marker of brain atrophy and, more generally, provide further evidence of the strong association between plasma NfL level, a candidate blood biomarker, and pathologic neuronal change. © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Longitudinal white matter change in frontotemporal dementia subtypes and sporadic late onset Alzheimer's disease.

PubMed

Elahi, Fanny M; Marx, Gabe; Cobigo, Yann; Staffaroni, Adam M; Kornak, John; Tosun, Duygu; Boxer, Adam L; Kramer, Joel H; Miller, Bruce L; Rosen, Howard J

2017-01-01

Degradation of white matter microstructure has been demonstrated in frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). In preparation for clinical trials, ongoing studies are investigating the utility of longitudinal brain imaging for quantification of disease progression. To date only one study has examined sample size calculations based on longitudinal changes in white matter integrity in FTLD. To quantify longitudinal changes in white matter microstructural integrity in the three canonical subtypes of frontotemporal dementia (FTD) and AD using diffusion tensor imaging (DTI). 60 patients with clinical diagnoses of FTD, including 27 with behavioral variant frontotemporal dementia (bvFTD), 14 with non-fluent variant primary progressive aphasia (nfvPPA), and 19 with semantic variant PPA (svPPA), as well as 19 patients with AD and 69 healthy controls were studied. We used a voxel-wise approach to calculate annual rate of change in fractional anisotropy (FA) and mean diffusivity (MD) in each group using two time points approximately one year apart. Mean rates of change in FA and MD in 48 atlas-based regions-of-interest, as well as global measures of cognitive function were used to calculate sample sizes for clinical trials (80% power, alpha of 5%). All FTD groups showed statistically significant baseline and longitudinal white matter degeneration, with predominant involvement of frontal tracts in the bvFTD group, frontal and temporal tracts in the PPA groups and posterior tracts in the AD group. Longitudinal change in MD yielded a larger number of regions with sample sizes below 100 participants per therapeutic arm in comparison with FA. SvPPA had the smallest sample size based on change in MD in the fornix (n = 41 participants per study arm to detect a 40% effect of drug), and nfvPPA and AD had their smallest sample sizes based on rate of change in MD within the left superior longitudinal fasciculus (n = 49 for nfvPPA, and n = 23 for AD). BvFTD generally showed the largest sample size estimates (minimum n = 140 based on MD in the corpus callosum). The corpus callosum appeared to be the best region for a potential study that would include all FTD subtypes. Change in global measure of functional status (CDR box score) yielded the smallest sample size for bvFTD (n = 71), but clinical measures were inferior to white matter change for the other groups. All three of the canonical subtypes of FTD are associated with significant change in white matter integrity over one year. These changes are consistent enough that drug effects in future clinical trials could be detected with relatively small numbers of participants. While there are some differences in regions of change across groups, the genu of the corpus callosum is a region that could be used to track progression in studies that include all subtypes.

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 daily persistent headache population as a whole and not specific to the presence or absence of brain imaging lesions except for a post-surgery trigger, which was significantly more likely to occur in the white matter positive group. Migraine associated symptoms occurred in 77% of the white matter negative subgroup compared with 46% of the white matter positive subgroup, which was a significant difference. White matter abnormalities and infarct-like lesions do not appear to occur in primary new daily persistent headache patients. Only new daily persistent headache patients with risk factors (cardiovascular/cerebrovascular or migraine) developed white matter abnormalities on brain magnetic resonance imaging. No patient with new daily persistent headache developed infarct-like lesions. New daily persistent headache triggering events (outside of possibly post-surgery) or the presence of migrainous symptoms did not appear to enhance the development of white matter abnormalities. © International Headache Society 2015.

Changes in functional organization and white matter integrity in the connectome in Parkinson's disease.

PubMed

Tinaz, Sule; Lauro, Peter M; Ghosh, Pritha; Lungu, Codrin; Horovitz, Silvina G

2017-01-01

Parkinson's disease (PD) leads to dysfunction in multiple cortico-striatal circuits. The neurodegeneration has also been associated with impaired white matter integrity. This structural and functional "disconnection" in PD needs further characterization. We investigated the structural and functional organization of the PD whole brain connectome consisting of 200 nodes using diffusion tensor imaging and resting-state functional MRI, respectively. Data from 20 non-demented PD patients on dopaminergic medication and 20 matched controls were analyzed using graph theory-based methods. We focused on node strength, clustering coefficient, and local efficiency as measures of local network properties; and network modularity as a measure of information flow. PD patients showed reduced white matter connectivity in frontoparietal-striatal nodes compared to controls, but no change in modular organization of the white matter tracts. PD group also showed reduction in functional local network metrics in many nodes distributed across the connectome. There was also decreased functional modularity in the core cognitive networks including the default mode and dorsal attention networks, and sensorimotor network, as well as a lack of modular distinction in the orbitofrontal and basal ganglia nodes in the PD group compared to controls. Our results suggest that despite subtle white matter connectivity changes, the overall structural organization of the PD connectome remains robust at relatively early disease stages. However, there is a breakdown in the functional modular organization of the PD connectome.

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.

A cross-sectional and follow-up voxel-based morphometric MRI study in adolescent anorexia nervosa.

PubMed

Castro-Fornieles, Josefina; Bargalló, Nuria; Lázaro, Luisa; Andrés, Susana; Falcon, Carles; Plana, Maria Teresa; Junqué, Carme

2009-01-01

The objective was to examine whether cerebral volumes are reduced, and in what regions, in adolescents with anorexia nervosa and to study changes after nutritional recovery. Twelve anorexia nervosa (DSM-IV) patients aged 11-17 consecutively admitted to an Eating Disorders Unit were assessed by means of psychopathological scales, neuropsychological battery and voxel-based morphometric (VBM) magnetic resonance imaging at admission and after 7 months' follow-up. Nine control subjects of similar age, gender and estimated intelligence level were also studied. The two groups showed differences in gray matter (F=22.2; p<0.001) and cerebrospinal fluid (CSF) (F=21.2; p<0.001) but not in white matter volumes. In anorexic patients, gray matter volume correlated negatively with the copy time from the Rey Complex Figure Test. In the regional VBM study several temporal and parietal gray matter regions were reduced. During follow-up there was a greater global increase in gray matter (F=10.7; p=0.004) and decrease in CSF (F=22.1; p=0.001) in anorexic patients. The increase in gray matter correlated with a decrease in cortisol (Spearman correlation=-0.73; p=0.017). At follow-up there were no differences in global gray matter (F=2.1; p=0.165), white matter (F=0.02, p=0.965) or CSF (F=1.8; p=0.113) volumes between both groups. There were still some smaller areas, in the right temporal and both supplementary motor area, showing differences between them in the regional VBM study. In conclusion, in adolescent anorexic patients gray matter is more affected than white matter and mainly involves the posterior regions of the brain. Overall gray matter alterations are reversible after nutritional recovery.

Measurable Supratentorial White Matter Volume Changes in Patients with Diffuse Intrinsic Pontine Glioma Treated with an Anti-Vascular Endothelial Growth Factor Agent, Steroids, and Radiation.

PubMed

Svolos, P; Reddick, W E; Edwards, A; Sykes, A; Li, Y; Glass, J O; Patay, Z

2017-06-01

Assessing the response to treatment in infiltrative brain tumors by using lesion volume-based response criteria is challenging. We hypothesized that in such tumors, volume measurements alone may not accurately capture changes in actual tumor burden during treatment. We longitudinally evaluated volume changes in both normal-appearing supratentorial white matter and the brain stem lesions in patients treated for diffuse intrinsic pontine glioma to determine to what extent adjuvant systemic therapies may skew the accuracy of tumor response assessments based on volumetric analysis. The anatomic MR imaging and diffusion tensor imaging data of 26 patients with diffuse intrinsic pontine glioma were retrospectively analyzed. Treatment included conformal radiation therapy in conjunction with vandetanib and dexamethasone. Volumetric and diffusion data were analyzed with time, and differences between time points were evaluated statistically. Normalized brain stem lesion volume decreased during combined treatment (slope = -0.222, P < .001) and increased shortly after completion of radiation therapy (slope = 0.422, P < .001). Supratentorial white matter volume steadily and significantly decreased with time (slope = -0.057, P < .001). Longitudinal changes in brain stem lesion volume are robust; less pronounced but measurable changes occur in the supratentorial white matter. Volume changes in nonirradiated supratentorial white matter during the disease course reflect the effects of systemic medication on the water homeostasis of normal parenchyma. Our data suggest that adjuvant nontumor-targeted therapies may have a more substantial effect on lesion volume changes than previously thought; hence, an apparent volume decrease in infiltrative tumors receiving combined therapies may lead to overestimation of the actual response and tumor control. © 2017 by American Journal of Neuroradiology.

Visible Virchow-Robin spaces on magnetic resonance imaging of Alzheimer's disease patients and normal elderly from the Sunnybrook Dementia Study.

PubMed

Ramirez, Joel; Berezuk, Courtney; McNeely, Alicia A; Scott, Christopher J M; Gao, Fuqiang; Black, Sandra E

2015-01-01

Visible Virchow-Robin spaces (VRS) are commonly used markers for small vessel disease in aging and dementia. However, as previous reports were based on subjective visual ratings, the goal of this project was to validate and apply an MRI-based quantitative measure of VRS as a potential neuroimaging biomarker. A modified version of Lesion Explorer was applied to MRIs from Alzheimer's disease patients (AD: n = 203) and normal elderly controls (NC: n = 94). Inter-rater reliability, technique validity, group/gender differences, and correlations with other small vessel disease markers were examined (lacunes and white matter hyperintensities, WMH). Inter-rater reliability and spatial congruence was excellent (ICC = 0.99, SI = 0.96), and VRS volumes were highly correlated with established rating scales (CS: ρ = 0.84, p < 0.001; BG: ρ = 0.75, p < 0.001). Compared to NC, AD had significantly greater volumes of WMH (p < 0.01), lacunes (p < 0.001), and VRS in the white matter (p < 0.01), but not in the basal ganglia (n.s.). Compared to women, demented and non-demented men had greater VRS in the white matter (p < 0.001), but not in the basal ganglia (n.s.). Additionally, VRS were correlated with lacunes and WMH, but only in AD (r = 0.3, p < 0.01). Compared to women, men may be more susceptible to greater volumes of VRS, particularly in the white matter. RESULTS support the hypothesis that VRS in the white matter may be more related to AD-related vascular pathology compared to VRS found in the basal ganglia. Future work using this novel VRS segmentation tool will examine its potential utility as an imaging biomarker of vascular rather than parenchymal amyloid.

Abnormal fronto-parietal white matter organisation in the superior longitudinal fasciculus branches in autism spectrum disorders.

PubMed

Fitzgerald, Jacqueline; Leemans, Alexander; Kehoe, Elizabeth; O'Hanlon, Erik; Gallagher, Louise; McGrath, Jane

2018-03-01

Core features of autism spectrum disorder (ASD) may be underpinned by disrupted functional and structural neural connectivity. Abnormal fronto-parietal functional connectivity has been widely reported in the literature; this may be underpinned by disrupted microstructural organisation of white matter. The superior longitudinal fasciculus (SLF) is a major fronto-parietal white matter tract, the structure of which has been little studied in ASD. The fronto-parietal projections of this tract (SLF I, II and III) are thought to play an important role in a number of cognitive functions including attention and visuospatial processing. To date, the isolation of the fronto-parietal branches of the SLF has been hampered by limitations of traditional tractography approaches. Constrained spherical deconvolution (CSD)-based tractography is an advanced approach that allows valid isolation of the fronto-parietal branches of the SLF. Diffusion MRI data were acquired from 45 participants with ASD and 45 age- and IQ-matched controls. The SLF I, II and III branches were isolated using CSD-based tractography in ExploreDTI. Significantly greater fractional anisotropy (FA) was observed in the right SLF II relative to controls. The ASD group also showed greater linear diffusion coefficient in the left SLF I and the right SLF II. In the SLF II, the ASD group had significantly greater right lateralisation of FA in comparison with the control group. The clinical and functional implications of increased FA in white matter are poorly understood; however, it is possible that this increased white matter organisation in the SLF in ASD may contribute to relative processing advantages in the condition. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Verbal working memory performance correlates with regional white matter structures in the frontoparietal regions.

PubMed

Takeuchi, Hikaru; Taki, Yasuyuki; Sassa, Yuko; Hashizume, Hiroshi; Sekiguchi, Atsushi; Fukushima, Ai; Kawashima, Ryuta

2011-10-01

Working memory is the limited capacity storage system involved in the maintenance and manipulation of information over short periods of time. Previous imaging studies have suggested that the frontoparietal regions are activated during working memory tasks; a putative association between the structure of the frontoparietal regions and working memory performance has been suggested based on the analysis of individuals with varying pathologies. This study aimed to identify correlations between white matter and individual differences in verbal working memory performance in normal young subjects. We performed voxel-based morphometry (VBM) analyses using T1-weighted structural images as well as voxel-based analyses of fractional anisotropy (FA) using diffusion tensor imaging. Using the letter span task, we measured verbal working memory performance in normal young adult men and women (mean age, 21.7 years, SD=1.44; 42 men and 13 women). We observed positive correlations between working memory performance and regional white matter volume (rWMV) in the frontoparietal regions. In addition, FA was found to be positively correlated with verbal working memory performance in a white matter region adjacent to the right precuneus. These regions are consistently recruited by working memory. Our findings suggest that, among normal young subjects, verbal working memory performance is associated with various regions that are recruited during working memory tasks, and this association is not limited to specific parts of the working memory network. Copyright © 2011 Elsevier Ltd. All rights reserved.

Recognition of white matter bundles using local and global streamline-based registration and clustering.

PubMed

Garyfallidis, Eleftherios; Côté, Marc-Alexandre; Rheault, Francois; Sidhu, Jasmeen; Hau, Janice; Petit, Laurent; Fortin, David; Cunanne, Stephen; Descoteaux, Maxime

2018-04-15

Virtual dissection of diffusion MRI tractograms is cumbersome and needs extensive knowledge of white matter anatomy. This virtual dissection often requires several inclusion and exclusion regions-of-interest that make it a process that is very hard to reproduce across experts. Having automated tools that can extract white matter bundles for tract-based studies of large numbers of people is of great interest for neuroscience and neurosurgical planning. The purpose of our proposed method, named RecoBundles, is to segment white matter bundles and make virtual dissection easier to perform. This can help explore large tractograms from multiple persons directly in their native space. RecoBundles leverages latest state-of-the-art streamline-based registration and clustering to recognize and extract bundles using prior bundle models. RecoBundles uses bundle models as shape priors for detecting similar streamlines and bundles in tractograms. RecoBundles is 100% streamline-based, is efficient to work with millions of streamlines and, most importantly, is robust and adaptive to incomplete data and bundles with missing components. It is also robust to pathological brains with tumors and deformations. We evaluated our results using multiple bundles and showed that RecoBundles is in good agreement with the neuroanatomical experts and generally produced more dense bundles. Across all the different experiments reported in this paper, RecoBundles was able to identify the core parts of the bundles, independently from tractography type (deterministic or probabilistic) or size. Thus, RecoBundles can be a valuable method for exploring tractograms and facilitating tractometry studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Individual differences in reasoning and visuospatial attention are associated with prefrontal and parietal white matter tracts in healthy older adults.

PubMed

Monge, Zachary A; Greenwood, Pamela M; Parasuraman, Raja; Strenziok, Maren

2016-07-01

Although reasoning and attention are 2 cognitive processes necessary for ensuring the efficiency of many everyday activities in older adults, the role of white matter integrity in these processes has been little studied. This is an important question due to the role of white matter integrity as a neural substrate of cognitive aging. Here, we sought to examine the white matter tracts subserving reasoning and visuospatial attention in healthy older adults. Sixty-one adults ages 60 and older completed a battery of cognitive tests to assess reasoning and visuospatial attention. In addition, diffusion tensor images were collected to assess fractional anisotropy (FA), a measure of white matter integrity. A principle components analysis of the test scores yielded 2 components: reasoning and visuospatial attention. Whole-brain correlations between FA and the cognitive components were submitted to probabilistic tractography analyses for visualization of cortical targets of tracts. For reasoning, bilateral thalamo-anterior prefrontal, anterior corpus callosum, and corpus callosum body tracts interconnecting the superior frontal cortices and right cingulum bundle were found. For visuospatial attention, a right inferior fronto-parietal tract and bilateral parietal and temporal connections were found. We conclude that in older adults, prefrontal cortex white matter tracts and interhemispheric communication are important in higher order cognitive functioning. On the other hand, right-sided fronto-parietal tracts appear to be critical for supporting control of cognitive processes, such as redirecting attention. Researchers may use our results to develop neuroscience-based interventions for older adults targeting brain mechanisms involved in cognitive plasticity. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Assessment of white matter abnormalities in paranoid schizophrenia and bipolar mania patients.

PubMed

Cui, Liqian; Chen, Zhuangfei; Deng, Wei; Huang, Xiaoqi; Li, Mingli; Ma, Xiaohong; Huang, Chaohua; Jiang, Lijun; Wang, Yingcheng; Wang, Qiang; Collier, David A; Gong, Qiyong; Li, Tao

2011-12-30

White matter abnormalities have been repeatedly reported in both schizophrenia and bipolar disorder (BD) in diffusion tensor imaging (DTI) studies, but the empirical evidence about the diagnostic specificity of white matter abnormalities in these disorders is still limited. This study sought to investigate the alterations in fractional anisotropy (FA) in white matter throughout the entire brain of patients from Chengdu, China with paranoid schizophrenia and bipolar mania. For this purpose, DTI was used to assess white matter integrity in patients with paranoid schizophrenia (n=25) and psychotic bipolar mania (n=18) who had been treated with standard pharmacotherapy for fewer than 5 days at the time of study, as well as in normal controls (n=30). The differences in FA were measured by use of voxel-based analysis. The results show that reduced FA was found in the left posterior corona radiata (PCR) in patients with psychotic bipolar mania and paranoid schizophrenia compared to the controls. Patients with psychotic bipolar mania also showed a significant reduction in FA in right posterior corona radiata and in right anterior thalamic radiation (ATR). A direct comparison between the two patient groups found no significant differences in any regions, and none of the findings were associated with illness duration. Correlation analysis indicated that FA values showed a significant negative correlation with positive symptom scores on the Positive and Negative Syndrome Scale in the left frontal-parietal lobe in the paranoid schizophrenia. It was concluded that common abnormalities in the left PCR might imply an overlap in white matter pathology in the two disorders and might be related to shared risk factors for the two disorders. 2011 Elsevier Ireland Ltd. All rights reserved.

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

Acute White-Matter Abnormalities in Sports-Related Concussion: A Diffusion Tensor Imaging Study from the NCAA-DoD CARE Consortium.

PubMed

Mustafi, Sourajit Mitra; Harezlak, Jaroslaw; Koch, Kevin M; Nencka, Andrew S; Meier, Timothy; West, John D; Giza, Christopher C; DiFiori, John; Guskiewicz, Kevin K; Mihalik, Jason; LaConte, Stephen M; Duma, Stefan M; Broglio, Steven P; Saykin, Andrew J; McCrea, Michael; McAllister, Thomas; Wu, Yu-Chien

2017-10-25

Sport-related concussion (SRC) is an important public health issue. While standardized assessment tools are useful in the clinical management of acute concussion, the underlying pathophysiology of SRC and the time course of physiological recovery after injury remain unclear. In this study, we used diffusion tensor imaging (DTI) to detect white-matter alterations in football players within 48 hours after SRC. As part of the NCAA-DoD CARE Consortium study of SRC, 30 American football players diagnosed with acute concussion, and 28 matched controls received clinical assessments and underwent advanced MRI scans. To avoid selection bias and partial voluming effects, whole-brain skeletonized white matter was examined via tract-based spatial statistics (TBSS) to investigate between group differences in DTI metrics and their associations with clinical outcome measures. Mean diffusivity was significantly higher in the brain white matter of the concussed athletes, particularly in frontal and sub-frontal long white-matter tracts. While no DTI metric was associated to any clinical measure in the contact-sport controls, in the concussed group, DTI exhibited correlations with clinical measures. Axial diffusivity demonstrated a significant positive correlation with the Brief Symptom Inventory (BSI) and a trend for a positive correlation with the symptom severity score of the Sports Concussion Assessment Tool (SCAT). In addition, concussed athletes with higher fractional anisotropy performed worse on the cognitive component of the Standardized Assessment of Concussion (SAC). Overall, the results of this study are consistent with the hypothesis that SRC is associated with changes in white-matter tracts shortly after injury, and these differences are correlated clinically with acute symptoms and functional impairments.

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 connections among many diverse different brain regions. PMID:24139595

White matter microstructure in a genetically defined group at increased risk of autism symptoms, and a comparison with idiopathic autism: an exploratory study.

PubMed

Goddard, Marcia N; van Rijn, Sophie; Rombouts, Serge A R B; Swaab, Hanna

2016-12-01

Klinefelter syndrome (47,XXY) is associated with physical, behavioral, and cognitive consequences. Deviations in brain structure and function have been reported, but structural characteristics of white matter have barely been assessed. This exploratory diffusion tensor imaging study assessed white matter microstructure in boys with 47,XXY compared with non-clinical, male controls. Additionally, both similarities and differences between 47,XXY and autism spectrum disorders (ASD) have been reported in cognition, behavior and neural architecture. To further investigate these brain-behavior pathways, white matter microstructure in boys with 47,XXY was compared to that of boys with ASD. Fractional anisotropy (FA), radial diffusivity (Dr), axial diffusivity (Da), and mean diffusivity (MD) were assessed in 47,XXY (n = 9), ASD (n = 18), and controls (n = 14), using tract-based spatial statistics. Compared with controls, boys with 47,XXY have reduced FA, coupled with reduced Da, in the corpus callosum. Boys with 47,XXY also have reduced Dr. in the left anterior corona radiata and sagittal striatum compared with controls. Compared with boys with ASD, boys with 47,XXY show reduced Da in the right inferior fronto-occipital fasciculus. Although this study is preliminary considering the small sample size, reduced white matter integrity in the corpus callosum may be a contributing factor in the cognitive and behavioral problems associated with 47,XXY. In addition, the differences in white matter microstructure between 47,XXY and ASD may be important for our understanding of the mechanisms that are fundamental to behavioral outcome in social dysfunction, and may be targeted through intervention.

Investigating the capability to resolve complex white matter structures with high b-value diffusion magnetic resonance imaging on the MGH-USC Connectom scanner.

PubMed

Fan, Qiuyun; Nummenmaa, Aapo; Witzel, Thomas; Zanzonico, Roberta; Keil, Boris; Cauley, Stephen; Polimeni, Jonathan R; Tisdall, Dylan; Van Dijk, Koene R A; Buckner, Randy L; Wedeen, Van J; Rosen, Bruce R; Wald, Lawrence L

2014-11-01

One of the major goals of the NIH Blueprint Human Connectome Project was to map and quantify the white matter connections in the brain using diffusion tractography. Given the prevalence of complex white matter structures, the capability of resolving local white matter geometries with multiple crossings in the diffusion magnetic resonance imaging (dMRI) data is critical. Increasing b-value has been suggested for delineation of the finer details of the orientation distribution function (ODF). Although increased gradient strength and duration increase sensitivity to highly restricted intra-axonal water, gradient strength limitations require longer echo times (TE) to accommodate the increased diffusion encoding times needed to achieve a higher b-value, exponentially lowering the signal-to-noise ratio of the acquisition. To mitigate this effect, the MGH-USC Connectom scanner was built with 300 mT/m gradients, which can significantly reduce the TE of high b-value diffusion imaging. Here we report comparisons performed across b-values based on q-ball ODF metrics to investigate whether high b-value diffusion imaging on the Connectom scanner can improve resolving complex white matter structures. The q-ball ODF features became sharper as the b-value increased, with increased power fraction in higher order spherical harmonic series of the ODF and increased peak heights relative to the overall size of the ODF. Crossing structures were detected in an increasingly larger fraction of white matter voxels and the spatial distribution of two-way and three-way crossing structures was largely consistent with known anatomy. Results indicate that dMRI with high diffusion encoding on the Connectom system is a promising tool to better characterize, and ultimately understand, the underlying structural organization and motifs in the human brain.

Differential contributions of dorso-ventral and rostro-caudal prefrontal white matter tracts to cognitive control in healthy older adults.

PubMed

Strenziok, Maren; Greenwood, Pamela M; Santa Cruz, Sophia A; Thompson, James C; Parasuraman, Raja

2013-01-01

Prefrontal cortex mediates cognitive control by means of circuitry organized along dorso-ventral and rostro-caudal axes. Along the dorso-ventral axis, ventrolateral PFC controls semantic information, whereas dorsolateral PFC encodes task rules. Along the rostro-caudal axis, anterior prefrontal cortex encodes complex rules and relationships between stimuli, whereas posterior prefrontal cortex encodes simple relationships between stimuli and behavior. Evidence of these gradients of prefrontal cortex organization has been well documented in fMRI studies, but their functional correlates have not been examined with regard to integrity of underlying white matter tracts. We hypothesized that (a) the integrity of specific white matter tracts is related to cognitive functioning in a manner consistent with the dorso-ventral and rostro-caudal organization of the prefrontal cortex, and (b) this would be particularly evident in healthy older adults. We assessed three cognitive processes that recruit the prefrontal cortex and can distinguish white matter tracts along the dorso-ventral and rostro-caudal dimensions -episodic memory, working memory, and reasoning. Correlations between cognition and fractional anisotropy as well as fiber tractography revealed: (a) Episodic memory was related to ventral prefrontal cortex-thalamo-hippocampal fiber integrity; (b) Working memory was related to integrity of corpus callosum body fibers subserving dorsolateral prefrontal cortex; and (c) Reasoning was related to integrity of corpus callosum body fibers subserving rostral and caudal dorsolateral prefrontal cortex. These findings confirm the ventrolateral prefrontal cortex's role in semantic control and the dorsolateral prefrontal cortex's role in rule-based processing, in accordance with the dorso-ventral prefrontal cortex gradient. Reasoning-related rostral and caudal superior frontal white matter may facilitate different levels of task rule complexity. This study is the first to demonstrate dorso-ventral and rostro-caudal prefrontal cortex processing gradients in white matter integrity.

Evaluation of diffusion kurtosis imaging in ex vivo hypomyelinated mouse brains.

PubMed

Kelm, Nathaniel D; West, Kathryn L; Carson, Robert P; Gochberg, Daniel F; Ess, Kevin C; Does, Mark D

2016-01-01

Diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), and DKI-derived white matter tract integrity metrics (WMTI) were experimentally evaluated ex vivo through comparisons to histological measurements and established magnetic resonance imaging (MRI) measures of myelin in two knockout mouse models with varying degrees of hypomyelination. DKI metrics of mean and radial kurtosis were found to be better indicators of myelin content than conventional DTI metrics. The biophysical WMTI model based on the DKI framework reported on axon water fraction with good accuracy in cases with near normal axon density, but did not provide additional specificity to myelination. Overall, DKI provided additional information regarding white matter microstructure compared with DTI, making it an attractive method for future assessments of white matter development and pathology. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Damage to white matter bottlenecks contributes to language impairments after left hemispheric stroke.

PubMed

Griffis, Joseph C; Nenert, Rodolphe; Allendorfer, Jane B; Szaflarski, Jerzy P

2017-01-01

Damage to the white matter underlying the left posterior temporal lobe leads to deficits in multiple language functions. The posterior temporal white matter may correspond to a bottleneck where both dorsal and ventral language pathways are vulnerable to simultaneous damage. Damage to a second putative white matter bottleneck in the left deep prefrontal white matter involving projections associated with ventral language pathways and thalamo-cortical projections has recently been proposed as a source of semantic deficits after stroke. Here, we first used white matter atlases to identify the previously described white matter bottlenecks in the posterior temporal and deep prefrontal white matter. We then assessed the effects of damage to each region on measures of verbal fluency, picture naming, and auditory semantic decision-making in 43 chronic left hemispheric stroke patients. Damage to the posterior temporal bottleneck predicted deficits on all tasks, while damage to the anterior bottleneck only significantly predicted deficits in verbal fluency. Importantly, the effects of damage to the bottleneck regions were not attributable to lesion volume, lesion loads on the tracts traversing the bottlenecks, or damage to nearby cortical language areas. Multivariate lesion-symptom mapping revealed additional lesion predictors of deficits. Post-hoc fiber tracking of the peak white matter lesion predictors using a publicly available tractography atlas revealed evidence consistent with the results of the bottleneck analyses. Together, our results provide support for the proposal that spatially specific white matter damage affecting bottleneck regions, particularly in the posterior temporal lobe, contributes to chronic language deficits after left hemispheric stroke. This may reflect the simultaneous disruption of signaling in dorsal and ventral language processing streams.

Effect of chorioamnionitis on brain development and injury in premature newborns.

PubMed

Chau, Vann; Poskitt, Kenneth J; McFadden, Deborah E; Bowen-Roberts, Tim; Synnes, Anne; Brant, Rollin; Sargent, Michael A; Soulikias, Wendy; Miller, Steven P

2009-08-01

The association of chorioamnionitis and noncystic white matter injury, a common brain injury in premature newborns, remains controversial. Our objectives were to determine the association of chorioamnionitis and postnatal risk factors with white matter injury, and the effects of chorioamnionitis on early brain development, using advanced magnetic resonance imaging. Ninety-two preterm newborns (24-32 weeks gestation) were studied at a median age of 31.9 weeks and again at 40.3 weeks gestation. Histopathological chorioamnionitis and white matter injury were scored using validated systems. Measures of brain metabolism (N-acetylaspartate/choline and lactate/choline) on magnetic resonance spectroscopy, and microstructure (average diffusivity and fractional anisotropy) on diffusion tensor imaging were calculated from predefined brain regions. Thirty-one (34%) newborns were exposed to histopathological chorioamnionitis, and 26 (28%) had white matter injury. Histopathological chorioamnionitis was not associated with an increased risk of white matter injury (relative risk: 1.2; p = 0.6). Newborns with postnatal infections and hypotension requiring therapy were at higher risk of white matter injury (p < 0.03). Adjusting for gestational age at scan and regions of interest, histopathological chorioamnionitis did not significantly affect brain metabolic and microstructural development (p > 0.1). In contrast, white matter injury was associated with lower N-acetylaspartate/choline (-8.9%; p = 0.009) and lower white matter fractional anisotropy (-11.9%; p = 0.01). Histopathological chorioamnionitis does not appear to be associated with an increased risk of white matter injury on magnetic resonance imaging or with abnormalities of brain development. In contrast, postnatal infections and hypotension are associated with an increased risk of white matter injury in the premature newborn.

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.

Monitoring interferon β treatment response with magnetic resonance spectroscopy in relapsing remitting multiple sclerosis.

PubMed

Yetkin, Mehmet Fatih; Mirza, Meral; Dönmez, Halil

2016-09-01

The aim of this study is to compare the white matter of multiple sclerosis (MS) patients with healthy controls and to monitor the response to the treatment with magnetic resonance spectroscopy (MRS).Fifteen healthy controls and 36 recently diagnosed MS patients never treated with interferon β were included in this study. In the patient group, MRS was performed before treatment, at 6th and 12th month after the initiation of treatment and once in control group. Patient group was divided into 3 interferon groups randomly. Physical examination findings were recorded as Expanded Disability Status Scale scores before treatment, at 6th and 12th month of interferon treatment.At the end of 1 year follow up, 26 of 36 patients completed the study. In patients' white matter lesions, N-acetylaspartate/creatine (NAA/Cr) ratios were lower than control group's white matters. NAA/Cr ratios were higher in control group's white matter than patient's normal appearing white matter but this difference was not statistically significant. There was no difference in choline/creatine (Cho/Cr) ratios between 2 groups. In follow-up period, NAA/Cr and Cho/Cr ratios obtained from patients' white matter lesions and normal appearing white matter did not change statistically.This study showed that in MS patients' white matters, especially in white matter lesions, neuron viability is reduced compared with healthy controls' normal white matter; and in the patients treated with interferon β NAA/Cr ratios remained stable. These stable levels of metabolite ratios in the patients who received interferon β therapy can be explained with either the shortness of the follow-up period post-treatment or may reflect a positive effect of the beta interferon therapy on the progress of MS.

White matter hyperintensities in migraine: Clinical significance and central pulsatile hemodynamic correlates.

PubMed

Cheng, Chun-Yu; Cheng, Hao-Min; Chen, Shih-Pin; Chung, Chih-Ping; Lin, Yung-Yang; Hu, Han-Hwa; Chen, Chen-Huan; Wang, Shuu-Jiun

2018-06-01

Background The role of central pulsatile hemodynamics in the pathogenesis of white matter hyperintensities in migraine patients has not been clarified. Methods Sixty patients with migraine (20-50 years old; women, 68%) without overt vascular risk factors and 30 demographically-matched healthy controls were recruited prospectively. Cerebral white matter hyperintensities volume was determined by T1-weighted magnetic resonance imaging with CUBE-fluid-attenuated-inversion-recovery sequences. Central systolic blood pressure, carotid-femoral pulse wave velocity, and carotid augmentation index were measured by applanation tonometry. Carotid pulsatility index was derived from Doppler ultrasound carotid artery flow analysis. Results Compared to the controls, the migraine patients had higher white matter hyperintensities frequency (odds ratio, 2.75; p = 0.04) and greater mean white matter hyperintensities volume (0.174 vs. 0.049, cm 3 , p = 0.04). Multivariable regression analysis showed that white matter hyperintensities volume in migraine patients was positively associated with central systolic blood pressure ( p = 0.04) and carotid-femoral pulse wave velocity ( p < 0.001), but negatively associated with carotid pulsatility index ( p = 0.04) after controlling for potential confounding factors. The interaction effects observed indicated that the influence of carotid-femoral pulse wave velocity ( p = 0.004) and central systolic blood pressure ( p = 0.03) on white matter hyperintensities formation was greater for the lower-carotid pulsatility index subgroup of migraine patients. White matter hyperintensities volume in migraine patients increased with decreasing carotid pulsatility index and with increasing central systolic blood pressure or carotid-femoral pulse wave velocity. Conclusions White matter hyperintensities are more common in patients with migraine than in healthy controls. Increased aortic stiffness or central systolic blood pressure in the presence of low intracranial artery resistance may predispose patients with migraine to white matter hyperintensities formation.

Sleep Duration and White Matter Quality in Middle-Aged Adults

PubMed Central

Yaffe, Kristine; Nasrallah, Ilya; Hoang, Tina D.; Lauderdale, Diane S.; Knutson, Kristen L.; Carnethon, Mercedes R.; Launer, Lenore J.; Lewis, Cora E.; Sidney, Stephen

2016-01-01

Study Objectives: Sleep duration has been associated with risk of dementia and stroke, but few studies have investigated the relationship between sleep duration and brain MRI measures, particularly in middle age. Methods: In a prospective cohort of 613 black and white adults (mean age = 45.4 years) enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study, participants reported typical sleep duration, dichotomized into moderate sleep duration (> 6 to ≤ 8 h) and short sleep duration (≤ 6 h) at baseline (2005–2006). Five years later, we obtained brain MRI markers of white matter including fractional anisotropy, mean diffusivity, and white matter hyperintensities. Results: Compared to moderate sleepers, short sleepers had an elevated ratio of white matter hyperintensities to normal tissue in the parietal region (OR = 2.31, 95% CI: 1.47, 3.61) adjusted for age, race/sex, education, hypertension, stroke/TIA, depression, smoking status, and physical activity. White matter diffusivity was also higher, approximately a 0.2 standard deviation difference, in frontal, parietal, and temporal white matter regions, among those reporting shorter sleep duration in (P < 0.05 for all). Conclusions: Short sleep duration was associated with worse markers of white matter integrity in midlife. These mid-life differences in white matter may underlie the link between poor sleep and risk of dementia and stroke. Citation: Yaffe K, Nasrallah I, Hoang TD, Lauderdale DS, Knutson KL, Carnethon MR, Launer LJ, Lewis CE, Sidney S. Sleep duration and white matter quality in middle-aged adults. SLEEP 2016;39(9):1743–1747. PMID:27397561

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.

Pathways to Seeing Music: Enhanced Structural Connectivity in Colored-Music Synesthesia

PubMed Central

Zamm, Anna; Schlaug, Gottfried; Eagleman, David M.; Loui, Psyche

2013-01-01

Synesthesia, a condition in which a stimulus in one sensory modality consistently and automatically triggers concurrent percepts in another modality, provides a window into the neural correlates of cross-modal associations. While research on grapheme-color synesthesia has provided evidence for both hyperconnectivity/hyperbinding and disinhibited feedback as possible underlying mechanisms, less research has explored the neuroanatomical basis of other forms of synesthesia. In the current study we investigated the white matter correlates of colored-music synesthesia. As these synesthetes report seeing colors upon hearing musical sounds, we hypothesized they might show different patterns of connectivity between visual and auditory association areas. We used diffusion tensor imaging to trace the white matter tracts in temporal and occipital lobe regions in 10 synesthetes and 10 matched non-synesthete controls. Results showed that synesthetes possessed different hemispheric patterns of fractional anisotropy, an index of white matter integrity, in the inferior fronto-occipital fasciculus (IFOF), a major white matter pathway that connects visual and auditory association areas to frontal regions. Specifically, white matter integrity within the right IFOF was significantly greater in synesthetes than controls. Furthermore, white matter integrity in synesthetes was correlated with scores on audiovisual tests of the Synesthesia Battery, especially in white matter underlying the right fusiform gyrus. Our findings provide the first evidence of a white matter substrate of colored-music synesthesia, and suggest that enhanced white matter connectivity is involved in enhanced cross-modal associations. PMID:23454047

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

Utilizing Mutual Information Analysis to Explore the Relationship Between Gray and White Matter Structural Pathologies in Schizophrenia.

PubMed

Lyall, Amanda E; Savadjiev, Peter; Del Re, Elisabetta C; Seitz, Johanna; O'Donnell, Lauren J; Westin, Carl-Fredrik; Mesholam-Gately, Raquelle I; Petryshen, Tracey; Wojcik, Joanne D; Nestor, Paul; Niznikiewicz, Margaret; Goldstein, Jill; Seidman, Larry J; McCarley, Robert W; Shenton, Martha E; Kubicki, Marek

2018-04-03

Schizophrenia has been characterized as a neurodevelopmental disorder, with structural brain abnormalities reported at all stages. However, at present, it remains unclear whether gray and white matter abnormalities represent related or independent pathologies in schizophrenia. In this study, we present findings from an integrative analysis exploring the morphological relationship between gray and white matter in 45 schizophrenia participants and 49 healthy controls. We utilized mutual information (MI), a measure of how much information two variables share, to assess the morphological dependence between gray and white matter in three segments of the corpus callsoum, and the gray matter regions these segments connect: (1) the genu and the left and right rostral middle frontal gyrus (rMFG), (2) the isthmus and the left and right superior temporal gyrus (STG), (3) the splenium and the left and right lateral occipital gyrus (LOG). We report significantly reduced MI between white matter tract dispersion of the right hemispheric callosal connections to the STG and both cortical thickness and area in the right STG in schizophrenia patients, despite a lack of group differences in cortical thickness, surface area, or dispersion. We believe that this reduction in morphological dependence between gray and white matter may reflect a possible decoupling of the developmental processes that shape morphological features of white and gray matter early in life. The present study also demonstrates the importance of studying the relationship between gray and white matter measures, as opposed to restricting analyses to gray and white matter measures independently.

Brain volumes predict neurodevelopment in adolescents after surgery for congenital heart disease.

PubMed

von Rhein, Michael; Buchmann, Andreas; Hagmann, Cornelia; Huber, Reto; Klaver, Peter; Knirsch, Walter; Latal, Beatrice

2014-01-01

Patients with complex congenital heart disease are at risk for neurodevelopmental impairments. Evidence suggests that brain maturation can be delayed and pre- and postoperative brain injury may occur, and there is limited information on the long-term effect of congenital heart disease on brain development and function in adolescent patients. At a mean age of 13.8 years, 39 adolescent survivors of childhood cardiopulmonary bypass surgery with no structural brain lesions evident through conventional cerebral magnetic resonance imaging and 32 healthy control subjects underwent extensive neurodevelopmental assessment and cerebral magnetic resonance imaging. Cerebral scans were analysed quantitatively using surface-based and voxel-based morphometry. Compared with control subjects, patients had lower total brain (P = 0.003), white matter (P = 0.004) and cortical grey matter (P = 0.005) volumes, whereas cerebrospinal fluid volumes were not different. Regional brain volume reduction ranged from 5.3% (cortical grey matter) to 11% (corpus callosum). Adolescents with cyanotic heart disease showed more brain volume loss than those with acyanotic heart disease, particularly in the white matter, thalami, hippocampi and corpus callosum (all P-values < 0.05). Brain volume reduction correlated significantly with cognitive, motor and executive functions (grey matter: P < 0.05, white matter: P < 0.01). Our findings suggest that there are long-lasting cerebral changes in adolescent survivors of cardiopulmonary bypass surgery for congenital heart disease and that these changes are associated with functional outcome.

Similar white matter but opposite grey matter changes in schizophrenia and high-functioning autism.

PubMed

Katz, J; d'Albis, M-A; Boisgontier, J; Poupon, C; Mangin, J-F; Guevara, P; Duclap, D; Hamdani, N; Petit, J; Monnet, D; Le Corvoisier, P; Leboyer, M; Delorme, R; Houenou, J

2016-07-01

High-functioning autism (HFA) and schizophrenia (SZ) are two of the main neurodevelopmental disorders, sharing several clinical dimensions and risk factors. Their exact relationship is poorly understood, and few studies have directly compared both disorders. Our aim was thus to directly compare neuroanatomy of HFA and SZ using a multimodal MRI design. We scanned 79 male adult subjects with 3T MRI (23 with HFA, 24 with SZ and 32 healthy controls, with similar non-verbal IQ). We compared them using both diffusion-based whole-brain tractography and T1 voxel-based morphometry. HFA and SZ groups exhibited similar white matter alterations in the left fronto-occipital inferior fasciculus with a decrease in generalized fractional anisotropy compared with controls. In grey matter, the HFA group demonstrated bilateral prefrontal and anterior cingulate increases in contrast with prefrontal and left temporal reductions in SZ. HFA and SZ may share common white matter deficits in long-range connections involved in social functions, but opposite grey matter abnormalities in frontal regions that subserve complex cognitive functions. Our results are consistent with the fronto-occipital underconnectivity theory of HFA and the altered connectivity hypothesis of SZ and suggest the existence of both associated and diametrical liabilities to these two conditions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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

Toll-like Receptor 2: A Novel Therapeutic Target for Ischemic White Matter Injury and Oligodendrocyte Death

PubMed Central

Choi, Jun Young

2017-01-01

Despite paramount clinical significance of white matter stroke, there is a paucity of researches on the pathomechanism of ischemic white matter damage and accompanying oligodendrocyte (OL) death. Therefore, a large gap exists between clinical needs and laboratory researches in this disease entity. Recent works have started to elucidate cellular and molecular basis of white matter injury under ischemic stress. In this paper, we briefly introduce white matter stroke from a clinical point of view and review pathophysiology of ischemic white matter injury characterized by OL death and demyelination. We present a series of evidence that Toll-like receptor 2 (TLR2), one of the membranous pattern recognition receptors, plays a cell-autonomous protective role in ischemic OL death and ensuing demyelination. Moreover, we also discuss our recent findings that its endogenous ligand, high-mobility group box 1 (HMGB1), is released from dying OLs and exerts autocrine trophic effects on OLs and myelin sheath under ischemic condition. We propose that modulation of TLR2 and its endogenous ligand HMGB1 can be a novel therapeutic target for ischemic white matter disease. PMID:28912641

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.

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.

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

Relationship between white matter integrity and serum cortisol levels in drug-naive patients with major depressive disorder: diffusion tensor imaging study using tract-based spatial statistics.

PubMed

Liu, Xiaodan; Watanabe, Keita; Kakeda, Shingo; Yoshimura, Reiji; Abe, Osamu; Ide, Satoru; Hayashi, Kenji; Katsuki, Asuka; Umene-Nakano, Wakako; Watanabe, Rieko; Ueda, Issei; Nakamura, Jun; Korogi, Yukunori

2016-06-01

Higher daytime cortisol levels because of a hyperactive hypothalamic-pituitary-adrenal axis have been reported in patients with major depressive disorder (MDD). The elevated glucocorticoids inhibit the proliferation of the oligodendrocytes that are responsible for myelinating the axons of white matter fibre tracts. To evaluate the relationship between white matter integrity and serum cortisol levels during a first depressive episode in drug-naive patients with MDD (MDD group) using a tract-based spatial statistics (TBSS) method. The MDD group (n = 29) and a healthy control group (n = 47) underwent diffusion tensor imaging (DTI) scans and an analysis was conducted using TBSS. Morning blood samples were obtained from both groups for cortisol measurement. Compared with the controls, the MDD group had significantly reduced fractional anisotropy values (P<0.05, family-wise error (FWE)-corrected) in the inferior fronto-occipital fasciculus, uncinate fasciculus and anterior thalamic radiation. The fractional anisotropy values of the inferior fronto-occipital fasciculus, uncinate fasciculus and anterior thalamic radiation had significantly negative correlations with the serum cortisol levels in the MDD group (P<0.05, FWE-corrected). Our findings indicate that the elevated cortisol levels in the MDD group may injure the white matter integrity in the frontal-subcortical and frontal-limbic circuits. © The Royal College of Psychiatrists 2016.

Susceptibility Tensor Imaging (STI) of the Brain

PubMed Central

Li, Wei; Liu, Chunlei; Duong, Timothy Q.; van Zijl, Peter C.M.; Li, Xu

2016-01-01

Susceptibility tensor imaging (STI) is a recently developed MRI technique that allows quantitative determination of orientation-independent magnetic susceptibility parameters from the dependence of gradient echo signal phase on the orientation of biological tissues with respect to the main magnetic field. By modeling the magnetic susceptibility of each voxel as a symmetric rank-2 tensor, individual magnetic susceptibility tensor elements as well as the mean magnetic susceptibility (MMS) and magnetic susceptibility anisotropy (MSA) can be determined for brain tissues that would still show orientation dependence after conventional scalar-based quantitative susceptibility mapping (QSM) to remove such dependence. Similar to diffusion tensor imaging (DTI), STI allows mapping of brain white matter fiber orientations and reconstruction of 3D white matter pathways using the principal eigenvectors of the susceptibility tensor. In contrast to diffusion anisotropy, the main determinant factor of susceptibility anisotropy in brain white matter is myelin. Another unique feature of susceptibility anisotropy of white matter is its sensitivity to gadolinium-based contrast agents. Mechanistically, MRI-observed susceptibility anisotropy is mainly attributed to the highly ordered lipid molecules in myelin sheath. STI provides a consistent interpretation of the dependence of phase and susceptibility on orientation at multiple scales. This article reviews the key experimental findings and physical theories that led to the development of STI, its practical implementations, and its applications for brain research. PMID:27120169

The Neuroanatomy of Genetic Subtype Differences in Prader-Willi Syndrome

PubMed Central

Honea, Robyn A.; Holsen, Laura M.; Lepping, Rebecca J.; Perea, Rodrigo; Butler, Merlin G.; Brooks, William M.; Savage, Cary R.

2012-01-01

Objective Despite behavioral differences between genetic subtypes of Prader-Willi syndrome, no studies have been published characterizing brain structure in these subgroups. Our goal was to examine differences in the brain structure phenotype of common subtypes of Prader-Willi syndrome (PWS) [chromosome 15q deletions and maternal uniparental disomy 15 (UPD)]. Methods Fifteen individuals with PWS due to a typical deletion ((DEL) Type I; n=5, Type II; n=10), 8 with PWS due to UPD, and 25 age-matched healthy-weight individuals (HWC) participated in structural magnetic resonance imaging (MRI) scans. A custom voxel-based morphometry processing stream was used to examine regional differences in gray and white matter volume between groups, covarying for age, sex, and body mass index (BMI). Results Overall, compared to HWC, PWS individuals had lower gray matter volumes that encompassed the prefrontal, orbitofrontal and temporal cortices, hippocampus and parahippocampal gyrus, and lower white matter volumes in the brain stem, cerebellum, medial temporal and frontal cortex. Compared to UPD, the DEL subtypes had lower gray matter volume primarily in the prefrontal and temporal cortices, and lower white matter in the parietal cortex. The UPD subtype had more extensive lower gray and white matter volumes in the orbitofrontal and limbic cortices compared to HWC. Conclusions These preliminary findings are the first structural neuroimaging findings to support potentially separate neural mechanisms mediating the behavioral differences seen in these genetic subtypes. PMID:22241551

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.

Fibre-specific white matter reductions in Alzheimer's disease and mild cognitive impairment.

PubMed

Mito, Remika; Raffelt, David; Dhollander, Thijs; Vaughan, David N; Tournier, J-Donald; Salvado, Olivier; Brodtmann, Amy; Rowe, Christopher C; Villemagne, Victor L; Connelly, Alan

2018-01-04

Alzheimer's disease is increasingly considered a large-scale network disconnection syndrome, associated with progressive aggregation of pathological proteins, cortical atrophy, and functional disconnections between brain regions. These pathological changes are posited to arise in a stereotypical spatiotemporal manner, targeting intrinsic networks in the brain, most notably the default mode network. While this network-specific disruption has been thoroughly studied with functional neuroimaging, changes to specific white matter fibre pathways within the brain's structural networks have not been closely investigated, largely due to the challenges of modelling complex white matter structure. Here, we applied a novel technique known as 'fixel-based analysis' to comprehensively investigate fibre tract-specific differences at a within-voxel level (called 'fixels') to assess potential axonal loss in subjects with Alzheimer's disease and mild cognitive impairment. We hypothesized that patients with Alzheimer's disease would exhibit extensive degeneration across key fibre pathways connecting default network nodes, while patients with mild cognitive impairment would exhibit selective degeneration within fibre pathways connecting regions previously identified as functionally implicated early in Alzheimer's disease. Diffusion MRI data from Alzheimer's disease (n = 49), mild cognitive impairment (n = 33), and healthy elderly control subjects (n = 95) were obtained from the Australian Imaging, Biomarkers and Lifestyle study of ageing. We assessed microstructural differences in fibre density, and macrostructural differences in fibre bundle morphology using fixel-based analysis. Whole-brain analysis was performed to compare groups across all white matter fixels. Subsequently, we performed a tract of interest analysis comparing fibre density and cross-section across 11 selected white matter tracts, to investigate potentially subtle degeneration within fibre pathways in mild cognitive impairment, initially by clinical diagnosis alone, and then by including amyloid status (i.e. a positive or negative amyloid PET scan). Our whole-brain analysis revealed significant white matter loss manifesting both microstructurally and macrostructurally in Alzheimer's disease patients, evident in specific fibre pathways associated with default mode network nodes. Reductions in fibre density and cross-section in mild cognitive impairment patients were only exhibited within the posterior cingulum when statistical analyses were limited to tracts of interest. Interestingly, these degenerative changes did not appear to be associated with high amyloid accumulation, given that amyloid-negative, but not positive, mild cognitive impairment subjects exhibited subtle focal left posterior cingulum deficits. The findings of this study demonstrated a stereotypical distribution of white matter degeneration in patients with Alzheimer's disease, which was in line with canonical findings from other imaging modalities, and with a network-based conceptualization of the disease. © The Author(s) (2018). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

White matter alterations and their associations with motor function in young adults born preterm with very low birth weight.

PubMed

Hollund, Ingrid Marie Husby; Olsen, Alexander; Skranes, Jon; Brubakk, Ann-Mari; Håberg, Asta K; Eikenes, Live; Evensen, Kari Anne I

2018-01-01

Very low birth weight (VLBW: ≤ 1500 g) individuals have an increased risk of white matter alterations and neurodevelopmental problems, including fine and gross motor problems. In this hospital-based follow-up study, the main aim was to examine white matter microstructure and its relationship to fine and gross motor function in 31 VLBW young adults without cerebral palsy compared with 31 term-born controls, at mean age 22.6 ± 0.7 years. The participants were examined with tests of fine and gross motor function (Trail Making Test-5: TMT-5, Grooved Pegboard, Triangle from Movement Assessment Battery for Children-2: MABC-2 and High-level Mobility Assessment Tool: HiMAT) and diffusion tensor imaging (DTI). Probabilistic tractography of motor pathways of the corticospinal tract (CST) and corpus callosum (CC) was performed. Fractional anisotropy (FA) was calculated in non-crossing (capsula interna in CST, body of CC) and crossing (centrum semiovale) fibre regions along the tracts and examined for group differences. Associations between motor test scores and FA in the CST and CC were investigated with linear regression. Tract-based spatial statistics (TBSS) was used to examine group differences in DTI metrics in all major white matter tracts. The VLBW group had lower scores on all motor tests compared with controls, however, only statistically significant for TMT-5. Based on tractography, FA in the VLBW group was lower in non-crossing fibre regions and higher in crossing fibre regions of the CST compared with controls. Within the VLBW group, poorer fine motor function was associated with higher FA in crossing fibre regions of the CST, and poorer bimanual coordination was additionally associated with lower FA in crossing fibre regions of the CC. Poorer gross motor function was associated with lower FA in crossing fibre regions of the CST and CC. There were no associations between motor function and FA in non-crossing fibre regions of the CST and CC within the VLBW group. In the TBSS analysis, the VLBW group had lower FA and higher mean diffusivity compared with controls in all major white matter tracts. The findings in this study may indicate that the associations between motor function and FA are caused by other tracts crossing the CST and CC, and/or by alterations in the periventricular white matter in the centrum semiovale. Some of the associations were in the opposite direction than hypothesized, thus higher FA does not always indicate better function. Furthermore, widespread white matter alterations in VLBW individuals persist into young adulthood.

Quantitative MRI assessments of white matter in children treated for acute lymphoblastic leukemia

NASA Astrophysics Data System (ADS)

Reddick, Wilburn E.; Glass, John O.; Helton, Kathleen J.; Li, Chin-Shang; Pui, Ching-Hon

2005-04-01

The purpose of this study was to use objective quantitative MR imaging methods to prospectively assess changes in the physiological structure of white matter during the temporal evolution of leukoencephalopathy (LE) in children treated for acute lymphoblastic leukemia. The longitudinal incidence, extent (proportion of white matter affect), and intensity (elevation of T1 and T2 relaxation rates) of LE was evaluated for 44 children. A combined imaging set consisting of T1, T2, PD, and FLAIR MR images and white matter, gray matter and CSF a priori maps from a spatially normalized atlas were analyzed with a neural network segmentation based on a Kohonen Self-Organizing Map (SOM). Quantitative T1 and T2 relaxation maps were generated using a nonlinear parametric optimization procedure to fit the corresponding multi-exponential models. A Cox proportional regression was performed to estimate the effect of intravenous methotrexate (IV-MTX) exposure on the development of LE followed by a generalized linear model to predict the probability of LE in new patients. Additional T-tests of independent samples were performed to assess differences in quantitative measures of extent and intensity at four different points in therapy. Higher doses and more courses of IV-MTX placed patients at a higher risk of developing LE and were associated with more intense changes affecting more of the white matter volume; many of the changes resolved after completion of therapy. The impact of these changes on neurocognitive functioning and quality of life in survivors remains to be determined.

Characterizing structure connectivity correlation with the default mode network in Alzheimer's patients and normal controls

NASA Astrophysics Data System (ADS)

Guo, Jia; Xu, Peng; Song, Chao; Yao, Li; Zhao, Xiaojie

2012-03-01

Magnetic resonance diffusion tensor imaging (DTI) is a kind of effective measure to do non-invasive investigation on brain fiber structure at present. Studies of fiber tracking based on DTI showed that there was structural connection of white matter fiber among the nodes of resting-state functional network, denoting that the connection of white matter was the basis of gray matter regions in functional network. Nevertheless, relationship between these structure connectivity regions and functional network has not been clearly indicated. Moreover, research of fMRI found that activation of default mode network (DMN) in Alzheimer's disease (AD) was significantly descended, especially in hippocampus and posterior cingulated cortex (PCC). The relationship between this change of DMN activity and structural connection among functional networks needs further research. In this study, fast marching tractography (FMT) algorithm was adopted to quantitative calculate fiber connectivity value between regions, and hippocampus and PCC which were two important regions in DMN related with AD were selected to compute white matter connection region between them in elderly normal control (NC) and AD patient. The fiber connectivity value was extracted to do the correlation analysis with activity intensity of DMN. Results showed that, between PCC and hippocampus of NC, there exited region with significant high connectivity value of white matter fiber whose performance has relatively strong correlation with the activity of DMN, while there was no significant white matter connection region between them for AD patient which might be related with reduced network activation in these two regions of AD.

Hierarchical brain tissue segmentation and its application in multiple sclerosis and Alzheimer's disease

NASA Astrophysics Data System (ADS)

Lei, Tianhu; Udupa, Jayaram K.; Moonis, Gul; Schwartz, Eric; Balcer, Laura

2005-04-01

Based on Fuzzy Connectedness (FC) object delineation principles and algorithms, a hierarchical brain tissue segmentation technique has been developed for MR images. After MR image background intensity inhomogeneity correction and intensity standardization, three FC objects for cerebrospinal fluid (CSF), gray matter (GM), and white matter (WM) are generated via FC object delineation, and an intracranial (IC) mask is created via morphological operations. Then, the IC mask is decomposed into parenchymal (BP) and CSF masks, while the BP mask is separated into WM and GM masks. WM mask is further divided into pure and dirty white matter masks (PWM and DWM). In Multiple Sclerosis studies, a severe white matter lesion (LS) mask is defined from DWM mask. Based on the segmented brain tissue images, a histogram-based method has been developed to find disease-specific, image-based quantitative markers for characterizing the macromolecular manifestation of the two diseases. These same procedures have been applied to 65 MS (46 patients and 19 normal subjects) and 25 AD (15 patients and 10 normal subjects) data sets, each of which consists of FSE PD- and T2-weighted MR images. Histograms representing standardized PD and T2 intensity distributions and their numerical parameters provide an effective means for characterizing the two diseases. The procedures are systematic, nearly automated, robust, and the results are reproducible.

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 were complementary to diffusivity metrics. Kurtosis together with diffusivity can more comprehensively characterize microstructural compositions and age-related changes than diffusivity alone. Combined with proper model, it may also assist in providing neurobiological interpretations of the identified alterations. Copyright © 2014 Elsevier Inc. All rights reserved.

Developmental Patterns of Doublecortin Expression and White Matter Neuron Density in the Postnatal Primate Prefrontal Cortex and Schizophrenia

PubMed Central

Fung, Samantha J.; Joshi, Dipesh; Allen, Katherine M.; Sivagnanasundaram, Sinthuja; Rothmond, Debora A.; Saunders, Richard; Noble, Pamela L.; Webster, Maree J.; Shannon Weickert, Cynthia

2011-01-01

Postnatal neurogenesis occurs in the subventricular zone and dentate gyrus, and evidence suggests that new neurons may be present in additional regions of the mature primate brain, including the prefrontal cortex (PFC). Addition of new neurons to the PFC implies local generation of neurons or migration from areas such as the subventricular zone. We examined the putative contribution of new, migrating neurons to postnatal cortical development by determining the density of neurons in white matter subjacent to the cortex and measuring expression of doublecortin (DCX), a microtubule-associated protein involved in neuronal migration, in humans and rhesus macaques. We found a striking decline in DCX expression (human and macaque) and density of white matter neurons (humans) during infancy, consistent with the arrival of new neurons in the early postnatal cortex. Considering the expansion of the brain during this time, the decline in white matter neuron density does not necessarily indicate reduced total numbers of white matter neurons in early postnatal life. Furthermore, numerous cells in the white matter and deep grey matter were positive for the migration-associated glycoprotein polysialiated-neuronal cell adhesion molecule and GAD65/67, suggesting that immature migrating neurons in the adult may be GABAergic. We also examined DCX mRNA in the PFC of adult schizophrenia patients (n = 37) and matched controls (n = 37) and did not find any difference in DCX mRNA expression. However, we report a negative correlation between DCX mRNA expression and white matter neuron density in adult schizophrenia patients, in contrast to a positive correlation in human development where DCX mRNA and white matter neuron density are higher earlier in life. Accumulation of neurons in the white matter in schizophrenia would be congruent with a negative correlation between DCX mRNA and white matter neuron density and support the hypothesis of a migration deficit in schizophrenia. PMID:21966452

Genetic effect of MTHFR C677T polymorphism on the structural covariance network and white-matter integrity in Alzheimer's disease.

PubMed

Chang, Yu-Tzu; Hsu, Shih-Wei; Tsai, Shih-Jen; Chang, Ya-Ting; Huang, Chi-Wei; Liu, Mu-En; Chen, Nai-Ching; Chang, Wen-Neng; Hsu, Jung-Lung; Lee, Chen-Chang; Chang, Chiung-Chih

2017-06-01

The 677 C to T transition in the MTHFR gene is a genetic determinant for hyperhomocysteinemia. We investigated whether this polymorphism modulates gray matter (GM) structural covariance networks independently of white-matter integrity in patients with Alzheimer's disease (AD). GM structural covariance networks were constructed by 3D T1-magnetic resonance imaging and seed-based analysis. The patients were divided into two genotype groups: C homozygotes (n = 73) and T carriers (n = 62). Using diffusion tensor imaging and white-matter parcellation, 11 fiber bundle integrities were compared between the two genotype groups. Cognitive test scores were the major outcome factors. The T carriers had higher homocysteine levels, lower posterior cingulate cortex GM volume, and more clusters in the dorsal medial lobe subsystem showing stronger covariance strength. Both posterior cingulate cortex seed and interconnected peak cluster volumes predicted cognitive test scores, especially in the T carriers. There were no between-group differences in fiber tract diffusion parameters. The MTHFR 677T polymorphism modulates posterior cingulate cortex-anchored structural covariance strength independently of white matter integrities. Hum Brain Mapp 38:3039-3051, 2017. © 2017 The Authors Human Brain Mapping Published Wiley by Periodicals, Inc. © 2017 The Authors Human Brain Mapping Published Wiley by Periodicals, Inc.

White matter changes in Alzheimer's disease: a focus on myelin and oligodendrocytes.

PubMed

Nasrabady, Sara E; Rizvi, Batool; Goldman, James E; Brickman, Adam M

2018-03-02

Alzheimer's disease (AD) is conceptualized as a progressive consequence of two hallmark pathological changes in grey matter: extracellular amyloid plaques and neurofibrillary tangles. However, over the past several years, neuroimaging studies have implicated micro- and macrostructural abnormalities in white matter in the risk and progression of AD, suggesting that in addition to the neuronal pathology characteristic of the disease, white matter degeneration and demyelination may be also important pathophysiological features. Here we review the evidence for white matter abnormalities in AD with a focus on myelin and oligodendrocytes, the only source of myelination in the central nervous system, and discuss the relationship between white matter changes and the hallmarks of Alzheimer's disease. We review several mechanisms such as ischemia, oxidative stress, excitotoxicity, iron overload, Aβ toxicity and tauopathy, which could affect oligodendrocytes. We conclude that white matter abnormalities, and in particular myelin and oligodendrocytes, could be mechanistically important in AD pathology and could be potential treatment targets.

White versus gray matter: fMRI hemodynamic responses show similar characteristics, but differ in peak amplitude

PubMed Central

2012-01-01

Background There is growing evidence for the idea of fMRI activation in white matter. In the current study, we compared hemodynamic response functions (HRF) in white matter and gray matter using 4 T fMRI. White matter fMRI activation was elicited in the isthmus of the corpus callosum at both the group and individual levels (using an established interhemispheric transfer task). Callosal HRFs were compared to HRFs from cingulate and parietal activation. Results Examination of the raw HRF revealed similar overall response characteristics. Finite impulse response modeling confirmed that the WM HRF characteristics were comparable to those of the GM HRF, but had significantly decreased peak response amplitudes. Conclusions Overall, the results matched a priori expectations of smaller HRF responses in white matter due to the relative drop in cerebral blood flow (CBF) and cerebral blood volume (CBV). Importantly, the findings demonstrate that despite lower CBF and CBV, white matter fMRI activation remained within detectable ranges at 4 T. PMID:22852798

Cerebral White Matter Integrity and Cognitive Aging: Contributions from Diffusion Tensor Imaging

PubMed Central

Madden, David J.; Bennett, Ilana J.; Song, Allen W.

2009-01-01

The integrity of cerebral white matter is critical for efficient cognitive functioning, but little is known regarding the role of white matter integrity in age-related differences in cognition. Diffusion tensor imaging (DTI) measures the directional displacement of molecular water and as a result can characterize the properties of white matter that combine to restrict diffusivity in a spatially coherent manner. This review considers DTI studies of aging and their implications for understanding adult age differences in cognitive performance. Decline in white matter integrity contributes to a disconnection among distributed neural systems, with a consistent effect on perceptual speed and executive functioning. The relation between white matter integrity and cognition varies across brain regions, with some evidence suggesting that age-related effects exhibit an anterior-posterior gradient. With continued improvements in spatial resolution and integration with functional brain imaging, DTI holds considerable promise, both for theories of cognitive aging and for translational application. PMID:19705281

A voxel-based morphometry study of regional gray and white matter correlate of self-disclosure.

PubMed

Wang, ShanShan; Wei, DongTao; Li, WenFu; Li, HaiJiang; Wang, KangCheng; Xue, Song; Zhang, Qinglin; Qiu, Jiang

2014-01-01

Self-disclosure is an important performance in human social communication. Generally, an individual is likely to have a good physical and mental health if he is prone to self-disclosure under stressful life events. However, as for now, little is known about the neural structure associated with self-disclosure. Therefore, in this study, we used voxel-based morphometry to explore regional gray matter volume (rGMV) and white matter volume (rWMV) associated with self-disclosure measured by the Jourard Self-disclosure Questionnaire in a large sample of college students. Results showed that individual self-disclosure was significantly and positively associated with rGMV of the left postcentral gyrus, which might be related to strengthen individual's ability of body feeling; while self-disclosure was significantly and negatively associated with rGMV of the right orbitofrontal cortex (OFC), which might be involved in increased positive emotion experience seeking (intrinsically rewarding). In addition, individual self-disclosure was also associated with smaller rWMV in the right inferior parietal lobule (IPL). These findings suggested a biological basis for individual self-disclosure, distributed across different gray and white matter areas of the brain.

A systematic review and meta-analysis of structural magnetic resonance imaging studies investigating cognitive and social activity levels in older adults.

PubMed

Anatürk, M; Demnitz, N; Ebmeier, K P; Sexton, C E

2018-06-22

Population aging has prompted considerable interest in identifying modifiable factors that may help protect the brain and its functions. Collectively, epidemiological studies show that leisure activities with high mental and social demands are linked with better cognition in old age. The extent to which socio-intellectual activities relate to the brain's structure is, however, not yet fully understood. This systematic review and meta-analysis summarizes magnetic resonance imaging studies that have investigated whether cognitive and social activities correlate with measures of gray and white matter volume, white matter microstructure and white matter lesions. Across eighteen included studies (total n = 8429), activity levels were associated with whole-brain white matter volume, white matter lesions and regional gray matter volume, although effect sizes were small. No associations were found for global gray matter volume and the evidence concerning white matter microstructure was inconclusive. While the causality of the reviewed associations needs to be established, our findings implicate socio-intellectual activity levels as promising targets for interventions aimed at promoting healthy brain aging. Copyright © 2018. Published by Elsevier Ltd.

Implicit and Explicit Racial Attitudes Changed During Black Lives Matter.

PubMed

Sawyer, Jeremy; Gampa, Anup

2018-07-01

Lab-based interventions have been ineffective in changing individuals' implicit racial attitudes for more than brief durations, and exposure to high-status Black exemplars like Obama has proven ineffective in shifting societal-level racial attitudes. Antiracist social movements, however, offer a potential societal-level alternative for reducing racial bias. Racial attitudes were examined before and during Black Lives Matter (BLM) and its high points of struggle with 1,369,204 participants from 2009 to 2016. After controlling for changes in participant demographics, overall implicit attitudes were less pro-White during BLM than pre-BLM, became increasingly less pro-White across BLM, and were less pro-White during most periods of high BLM struggle. Considering changes in implicit attitudes by participant race, Whites became less implicitly pro-White during BLM, whereas Blacks showed little change. Regarding explicit attitudes, Whites became less pro-White and Blacks became less pro-Black during BLM, each moving toward an egalitarian "no preference" position.

Thinner retinal layers are associated with changes in the visual pathway: A population-based study.

PubMed

Mutlu, Unal; Ikram, Mohammad K; Roshchupkin, Gennady V; Bonnemaijer, Pieter W M; Colijn, Johanna M; Vingerling, Johannes R; Niessen, Wiro J; Ikram, Mohammad A; Klaver, Caroline C W; Vernooij, Meike W

2018-06-23

Increasing evidence shows that thinner retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL), assessed on optical coherence tomography (OCT), are reflecting global brain atrophy. Yet, little is known on the relation of these layers with specific brain regions. Using voxel-based analysis, we aimed to unravel specific brain regions associated with these retinal layers. We included 2,235 persons (mean age: 67.3 years, 55% women) from the Rotterdam Study (2007-2012) who had gradable retinal OCT images and brain magnetic resonance imaging (MRI) scans, including diffusion tensor (DT) imaging. Thicknesses of peripapillary RNFL and perimacular GCL were measured using an automated segmentation algorithm. Voxel-based morphometry protocols were applied to process DT-MRI data. We investigated the association between retinal layer thickness with voxel-wise gray matter density and white matter microstructure by performing linear regression models. We found that thinner RNFL and GCL were associated with lower gray matter density in the visual cortex, and with lower fractional anisotropy and higher mean diffusivity in white matter tracts that are part of the optic radiation. Furthermore, thinner GCL was associated with lower gray matter density of the thalamus. Thinner RNFL and GCL are associated with gray and white matter changes in the visual pathway suggesting that retinal thinning on OCT may be specifically associated with changes in the visual pathway rather than with changes in the global brain. These findings may serve as a basis for understanding visual symptoms in elderly patients, patients with Alzheimer's disease, or patients with posterior cortical atrophy. © 2018 Wiley Periodicals, Inc.

What’s special about task in dystonia? A voxel-based morphometry and diffusion weighted imaging study

PubMed Central

Ramdhani, Ritesh A.; Kumar, Veena; Velickovic, Miodrag; Frucht, Steven J.; Tagliati, Michele; Simonyan, Kristina

2014-01-01

Background Numerous brain imaging studies have demonstrated structural changes in the basal ganglia, thalamus, sensorimotor cortex and cerebellum across different forms of primary dystonia. However, our understanding of brain abnormalities contributing to the clinically well-described phenomenon of task-specificity in dystonia remained limited. Methods We used high-resolution MRI with voxel-based morphometry and diffusion tensor imaging with tract-based spatial statistics of fractional anisotropy to examine gray and white matter organization in two task-specific dystonia forms, writer’s cramp and laryngeal dystonia, and two non-task-specific dystonia forms, cervical dystonia and blepharospasm. Results A direct comparison between the both dystonia forms revealed that characteristic gray matter volumetric changes in task-specific dystonia involve the brain regions responsible for sensorimotor control during writing and speaking, such as primary somatosensory cortex, middle frontal gyrus, superior/inferior temporal gyrus, middle/posterior cingulate cortex, occipital cortex as well as the striatum and cerebellum (lobules VI-VIIa). These gray matter changes were accompanied by white matter abnormalities in the premotor cortex, middle/inferior frontal gyrus, genu of the corpus callosum, anterior limb/genu of the internal capsule, and putamen. Conversely, gray matter volumetric changes in non-task-specific group were limited to the left cerebellum (lobule VIIa) only, while white matter alterations were found to underlie the primary sensorimotor cortex, inferior parietal lobule and middle cingulate gyrus. Conclusion Distinct microstructural patterns in task-specific and non-task-specific dystonias may represent neuroimaging markers and provide evidence that these two dystonia subclasses likely follow divergent pathophysiological mechanisms precipitated by different triggers. PMID:24925463

Segregation of the Brain into Gray and White Matter: A Design Minimizing Conduction Delays

PubMed Central

Wen, Quan; Chklovskii, Dmitri B

2005-01-01

A ubiquitous feature of the vertebrate anatomy is the segregation of the brain into white and gray matter. Assuming that evolution maximized brain functionality, what is the reason for such segregation? To answer this question, we posit that brain functionality requires high interconnectivity and short conduction delays. Based on this assumption we searched for the optimal brain architecture by comparing different candidate designs. We found that the optimal design depends on the number of neurons, interneuronal connectivity, and axon diameter. In particular, the requirement to connect neurons with many fast axons drives the segregation of the brain into white and gray matter. These results provide a possible explanation for the structure of various regions of the vertebrate brain, such as the mammalian neocortex and neostriatum, the avian telencephalon, and the spinal cord. PMID:16389299

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.

Microstructural White Matter Changes Underlying Cognitive and Behavioural Impairment in ALS – An In Vivo Study Using DTI

PubMed Central

Kasper, Elisabeth; Schuster, Christina; Machts, Judith; Kaufmann, Joern; Bittner, Daniel; Vielhaber, Stefan; Benecke, Reiner; Teipel, Stefan; Prudlo, Johannes

2014-01-01

Background A relevant fraction of patients with amyotrophic lateral sclerosis (ALS) exhibit a fronto-temporal pattern of cognitive and behavioural disturbances with pronounced deficits in executive functioning and cognitive control of behaviour. Structural imaging shows a decline in fronto-temporal brain areas, but most brain imaging studies did not evaluate cognitive status. We investigated microstructural white matter changes underlying cognitive impairment using diffusion tensor imaging (DTI) in a large cohort of ALS patients. Methods We assessed 72 non-demented ALS patients and 65 matched healthy control subjects using a comprehensive neuropsychological test battery and DTI. We compared DTI measures of fiber tract integrity using tract-based spatial statistics among ALS patients with and without cognitive impairment and healthy controls. Neuropsychological performance and behavioural measures were correlated with DTI measures. Results Patients without cognitive impairment demonstrated white matter changes predominantly in motor tracts, including the corticospinal tract and the body of corpus callosum. Those with impairments (ca. 30%) additionally presented significant white matter alterations in extra-motor regions, particularly the frontal lobe. Executive and memory performance and behavioural measures were correlated with fiber tract integrity in large association tracts. Conclusion In non-demented cognitively impaired ALS patients, white matter changes measured by DTI are related to disturbances of executive and memory functions, including prefrontal and temporal regions. In a group comparison, DTI is able to observe differences between cognitively unimpaired and impaired ALS patients. PMID:25501028

Microglial activation in white matter lesions and nonlesional white matter of ageing brains.

PubMed

Simpson, J E; Ince, P G; Higham, C E; Gelsthorpe, C H; Fernando, M S; Matthews, F; Forster, G; O'Brien, J T; Barber, R; Kalaria, R N; Brayne, C; Shaw, P J; Stoeber, K; Williams, G H; Lewis, C E; Wharton, S B

2007-12-01

White matter lesions (WML), a common feature in brain ageing, are classified as periventricular (PVL) or deep subcortical (DSCL), depending on their anatomical location. Microglial activation is implicated in a number of neurodegenerative diseases, but the microglial response in WML is poorly characterized and its role in pathogenesis unknown. We have characterized the microglial response in WML and control white matter using immunohistochemistry to markers of microglial activation and of proliferation. WML of brains from an unbiased population-based autopsy cohort (Medical Research Council's Cognitive Function and Ageing Study) were identified by post mortem magnetic resonance imaging and sampled for histology. PVL contain significantly more activated microglia, expressing major histocompatibility complex (MHC) class II and the costimulatory molecules B7-2 and CD40, than either control white matter (WM) or DSCL. Furthermore, we show that significantly more microglia express the replication licensing protein minichromosome maintenance protein 2 within PVL, suggesting this is a more proliferation-permissive environment than DSCL. Although microglial activation occurs in both PVL and DSCL, our findings suggest a difference in pathogenesis between these lesion-types: the ramified, activated microglia associated with PVL may reflect immune activation resulting from disruption of the blood brain barrier, while the microglia within DSCL may reflect an innate, amoeboid phagocytic phenotype. We also show that microglia in control WM from lesional cases express significantly more MHC II than control WM from nonlesional ageing brain, suggesting that WML occur in a 'field-effect' of abnormal WM.

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

White Matter Integrity, Creativity, and Psychopathology: Disentangling Constructs with Diffusion Tensor Imaging

PubMed Central

Jung, Rex E.; Grazioplene, Rachael; Caprihan, Arvind; Chavez, Robert S.; Haier, Richard J.

2010-01-01

That creativity and psychopathology are somehow linked remains a popular but controversial idea in neuroscience research. Brain regions implicated in both psychosis-proneness and creative cognition include frontal projection zones and association fibers. In normal subjects, we have previously demonstrated that a composite measure of divergent thinking (DT) ability exhibited significant inverse relationships in frontal lobe areas with both cortical thickness and metabolite concentration of N-acetyl-aspartate (NAA). These findings support the idea that creativity may reside upon a continuum with psychopathology. Here we examine whether white matter integrity, assessed by Fractional Anisotropy (FA), is related to two measures of creativity (Divergent Thinking and Openness to Experience). Based on previous findings, we hypothesize inverse correlations within fronto-striatal circuits. Seventy-two healthy, young adult (18–29 years) subjects were scanned on a 3 Tesla scanner with Diffusion Tensor Imaging. DT measures were scored by four raters (α = .81) using the Consensual Assessment Technique, from which a composite creativity index (CCI) was derived. We found that the CCI was significantly inversely related to FA within the left inferior frontal white matter (t = 5.36, p = .01), and Openness was inversely related to FA within the right inferior frontal white matter (t = 4.61, p = .04). These findings demonstrate an apparent overlap in specific white matter architecture underlying the normal variance of divergent thinking, openness, and psychotic-spectrum traits, consistent with the idea of a continuum. PMID:20339554

Relationship between symptom dimensions and white matter alterations in obsessive-compulsive disorder.

PubMed

Yagi, Michiyo; Hirano, Yoshiyuki; Nakazato, Michiko; Nemoto, Kiyotaka; Ishikawa, Kazuhiro; Sutoh, Chihiro; Miyata, Haruko; Matsumoto, Junko; Matsumoto, Koji; Masuda, Yoshitada; Obata, Takayuki; Iyo, Masaomi; Shimizu, Eiji; Nakagawa, Akiko

2017-06-01

To investigate the relationship between the severities of symptom dimensions in obsessive-compulsive disorder (OCD) and white matter alterations. We applied tract-based spatial statistics for diffusion tensor imaging (DTI) acquired by 3T magnetic resonance imaging. First, we compared fractional anisotropy (FA) between 20 OCD patients and 30 healthy controls (HC). Then, applying whole brain analysis, we searched the brain regions showing correlations between the severities of symptom dimensions assessed by Obsessive-Compulsive Inventory-Revised and FA in all participants. Finally, we calculated the correlations between the six symptom dimensions and multiple DTI measures [FA, axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD)] in a region-of-interest (ROI) analysis and explored the differences between OCD patients and HC. There were no between-group differences in FA or brain region correlations between the severities of symptom dimensions and FA in any of the participants. ROI analysis revealed negative correlations between checking severity and left inferior frontal gyrus white matter and left middle temporal gyrus white matter and a positive correlation between ordering severity and right precuneus in FA in OCD compared with HC. We also found negative correlations between ordering severity and right precuneus in RD, between obsessing severities and right supramarginal gyrus in AD and MD, and between hoarding severity and right insular gyrus in AD. Our study supported the hypothesis that the severities of respective symptom dimensions are associated with different patterns of white matter alterations.

DEWS (DEep White matter hyperintensity Segmentation framework): A fully automated pipeline for detecting small deep white matter hyperintensities in migraineurs.

PubMed

Park, Bo-Yong; Lee, Mi Ji; Lee, Seung-Hak; Cha, Jihoon; Chung, Chin-Sang; Kim, Sung Tae; Park, Hyunjin

2018-01-01

Migraineurs show an increased load of white matter hyperintensities (WMHs) and more rapid deep WMH progression. Previous methods for WMH segmentation have limited efficacy to detect small deep WMHs. We developed a new fully automated detection pipeline, DEWS (DEep White matter hyperintensity Segmentation framework), for small and superficially-located deep WMHs. A total of 148 non-elderly subjects with migraine were included in this study. The pipeline consists of three components: 1) white matter (WM) extraction, 2) WMH detection, and 3) false positive reduction. In WM extraction, we adjusted the WM mask to re-assign misclassified WMHs back to WM using many sequential low-level image processing steps. In WMH detection, the potential WMH clusters were detected using an intensity based threshold and region growing approach. For false positive reduction, the detected WMH clusters were classified into final WMHs and non-WMHs using the random forest (RF) classifier. Size, texture, and multi-scale deep features were used to train the RF classifier. DEWS successfully detected small deep WMHs with a high positive predictive value (PPV) of 0.98 and true positive rate (TPR) of 0.70 in the training and test sets. Similar performance of PPV (0.96) and TPR (0.68) was attained in the validation set. DEWS showed a superior performance in comparison with other methods. Our proposed pipeline is freely available online to help the research community in quantifying deep WMHs in non-elderly adults.

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

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.

Cholinergic Potentiation and Audiovisual Repetition-Imitation Therapy Improve Speech Production and Communication Deficits in a Person with Crossed Aphasia by Inducing Structural Plasticity in White Matter Tracts

PubMed Central

Berthier, Marcelo L.; De-Torres, Irene; Paredes-Pacheco, José; Roé-Vellvé, Núria; Thurnhofer-Hemsi, Karl; Torres-Prioris, María J.; Alfaro, Francisco; Moreno-Torres, Ignacio; López-Barroso, Diana; Dávila, Guadalupe

2017-01-01

Donepezil (DP), a cognitive-enhancing drug targeting the cholinergic system, combined with massed sentence repetition training augmented and speeded up recovery of speech production deficits in patients with chronic conduction aphasia and extensive left hemisphere infarctions (Berthier et al., 2014). Nevertheless, a still unsettled question is whether such improvements correlate with restorative structural changes in gray matter and white matter pathways mediating speech production. In the present study, we used pharmacological magnetic resonance imaging to study treatment-induced brain changes in gray matter and white matter tracts in a right-handed male with chronic conduction aphasia and a right subcortical lesion (crossed aphasia). A single-patient, open-label multiple-baseline design incorporating two different treatments and two post-treatment evaluations was used. The patient received an initial dose of DP (5 mg/day) which was maintained during 4 weeks and then titrated up to 10 mg/day and administered alone (without aphasia therapy) during 8 weeks (Endpoint 1). Thereafter, the drug was combined with an audiovisual repetition-imitation therapy (Look-Listen-Repeat, LLR) during 3 months (Endpoint 2). Language evaluations, diffusion weighted imaging (DWI), and voxel-based morphometry (VBM) were performed at baseline and at both endpoints in JAM and once in 21 healthy control males. Treatment with DP alone and combined with LLR therapy induced marked improvement in aphasia and communication deficits as well as in selected measures of connected speech production, and phrase repetition. The obtained gains in speech production remained well-above baseline scores even 4 months after ending combined therapy. Longitudinal DWI showed structural plasticity in the right frontal aslant tract and direct segment of the arcuate fasciculus with both interventions. VBM revealed no structural changes in other white matter tracts nor in cortical areas linked by these tracts. In conclusion, cholinergic potentiation alone and combined with a model-based aphasia therapy improved language deficits by promoting structural plastic changes in right white matter tracts. PMID:28659776

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

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.

Functional connectivity and activity of white matter in somatosensory pathways under tactile stimulations.

PubMed

Wu, Xi; Yang, Zhipeng; Bailey, Stephen K; Zhou, Jiliu; Cutting, Laurie E; Gore, John C; Ding, Zhaohua

2017-05-15

Functional MRI has proven to be effective in detecting neural activity in brain cortices on the basis of blood oxygenation level dependent (BOLD) contrast, but has relatively poor sensitivity for detecting neural activity in white matter. To demonstrate that BOLD signals in white matter are detectable and contain information on neural activity, we stimulated the somatosensory system and examined distributions of BOLD signals in related white matter pathways. The temporal correlation profiles and frequency contents of BOLD signals were compared between stimulation and resting conditions, and between relevant white matter fibers and background regions, as well as between left and right side stimulations. Quantitative analyses show that, overall, MR signals from white matter fiber bundles in the somatosensory system exhibited significantly greater temporal correlations with the primary sensory cortex and greater signal power during tactile stimulations than in a resting state, and were stronger than corresponding measurements for background white matter both during stimulations and in a resting state. The temporal correlation and signal power under stimulation were found to be twice those observed from the same bundle in a resting state, and bore clear relations with the side of stimuli. These indicate that BOLD signals in white matter fibers encode neural activity related to their functional roles connecting cortical volumes, which are detectable with appropriate methods. Copyright © 2017 Elsevier Inc. All rights reserved.

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

In Vivo Evidence of Reduced Integrity of the Gray-White Matter Boundary in Autism Spectrum Disorder.

PubMed

Andrews, Derek Sayre; Avino, Thomas A; Gudbrandsen, Maria; Daly, Eileen; Marquand, Andre; Murphy, Clodagh M; Lai, Meng-Chuan; Lombardo, Michael V; Ruigrok, Amber N V; Williams, Steven C; Bullmore, Edward T; The Mrc Aims Consortium; Suckling, John; Baron-Cohen, Simon; Craig, Michael C; Murphy, Declan G M; Ecker, Christine

2017-02-01

Atypical cortical organization and reduced integrity of the gray-white matter boundary have been reported by postmortem studies in individuals with autism spectrum disorder (ASD). However, there are no in vivo studies that examine these particular features of cortical organization in ASD. Hence, we used structural magnetic resonance imaging to examine differences in tissue contrast between gray and white matter in 98 adults with ASD and 98 typically developing controls, to test the hypothesis that individuals with ASD have significantly reduced tissue contrast. More specifically, we examined contrast as a percentage between gray and white matter tissue signal intensities (GWPC) sampled at the gray-white matter boundary, and across different cortical layers. We found that individuals with ASD had significantly reduced GWPC in several clusters throughout the cortex (cluster, P < 0.05). As expected, these reductions were greatest when tissue intensities were sampled close to gray-white matter interface, which indicates a less distinct gray-white matter boundary in ASD. Our in vivo findings of reduced GWPC in ASD are therefore consistent with prior postmortem findings of a less well-defined gray-white matter boundary in ASD. Taken together, these results indicate that GWPC might be utilized as an in vivo proxy measure of atypical cortical microstructural organization in future studies. © The Author 2017. Published by Oxford University Press.

Patterns of white matter damage are non-random and associated with cognitive function in secondary progressive multiple sclerosis.

PubMed

Meijer, K A; Cercignani, M; Muhlert, N; Sethi, V; Chard, D; Geurts, J J G; Ciccarelli, O

2016-01-01

In multiple sclerosis (MS), white matter damage is thought to contribute to cognitive dysfunction, which is especially prominent in secondary progressive MS (SPMS). While studies in healthy subjects have revealed patterns of correlated fractional anisotropy (FA) across white matter tracts, little is known about the underlying patterns of white matter damage in MS. In the present study, we aimed to map the SPMS-related covariance patterns of microstructural white matter changes, and investigated whether or not these patterns were associated with cognitive dysfunction. Diffusion MRI was acquired from 30 SPMS patients and 32 healthy controls (HC). A tensor model was fitted and FA maps were processed using tract-based spatial statistics (TBSS) in order to obtain a skeletonised map for each subject. The skeletonised FA maps of patients only were decomposed into 18 spatially independent components (ICs) using independent component analysis. Comprehensive cognitive assessment was conducted to evaluate five cognitive domains. Correlations between cognitive performance and (1) severity of FA abnormalities of the extracted ICs (i.e. z-scores relative to FA values of HC) and (2) IC load (i.e. FA covariance of a particular IC) were examined. SPMS patients showed lower FA values of all examined patterns of correlated FA (i.e. spatially independent components) than HC (p < 0.01). Tracts visually assigned to the supratentorial commissural class were most severely damaged (z = - 3.54; p < 0.001). Reduced FA was significantly correlated with reduced IC load (i.e. FA covariance) (r = 0.441; p < 0.05). Lower mean FA and component load of the supratentorial projection tracts and limbic association tracts classes were associated with worse cognitive function, including executive function, working memory and verbal memory. Despite the presence of white matter damage, it was possible to reveal patterns of FA covariance across SPMS patients. This could indicate that white matter tracts belonging to the same cluster, and thus with similar characteristics, tend to follow similar trends during neurodegeneration. Furthermore, these underlying FA patterns might help to explain cognitive dysfunction in SPMS.

In Vivo Assessment of Brain White Matter Inflammation in Multiple Sclerosis with (18)F-PBR111 PET.

PubMed

Colasanti, Alessandro; Guo, Qi; Muhlert, Nils; Giannetti, Paolo; Onega, Mayca; Newbould, Rexford D; Ciccarelli, Olga; Rison, Stuart; Thomas, Charlotte; Nicholas, Richard; Muraro, Paolo A; Malik, Omar; Owen, David R; Piccini, Paola; Gunn, Roger N; Rabiner, Eugenii A; Matthews, Paul M

2014-07-01

PET radioligand binding to the 18-kD translocator protein (TSPO) in the brains of patients with multiple sclerosis (MS) primarily reflects activated microglia and macrophages. We previously developed genetic stratification for accurate quantitative estimation of TSPO using second-generation PET radioligands. In this study, we used (18)F-PBR111 PET and MR imaging to measure relative binding in the lesional, perilesional, and surrounding normal-appearing white matter of MS patients, as an index of the innate immune response. (18)F-PBR111 binding was quantified in 11 MS patients and 11 age-matched healthy volunteers, stratified according to the rs6971 TSPO gene polymorphism. Fluid-attenuated inversion recovery and magnetization transfer ratio (MTR) MR imaging were used to segment the white matter in MS patients as lesions, perilesional volumes, nonlesional white matter with reduced MTR, and nonlesional white matter with normal MTR. (18)F-PBR111 binding was higher in the white matter lesions and perilesional volumes of MS patients than in white matter of healthy controls (P < 0.05). Although there was substantial heterogeneity in binding between different lesions, a within-subject analysis showed higher (18)F-PBR111 binding in MS lesions (P < 0.05) and in perilesional (P < 0.05) and nonlesional white matter with reduced MTR (P < 0.005) than in nonlesional white matter with a normal MTR. A positive correlation was observed between the mean (18)F-PBR111 volume of distribution increase in lesions relative to nonlesional white matter with a normal MTR and the MS severity score (Spearman ρ = 0.62, P < 0.05). This study demonstrates that quantitative TSPO PET with a second-generation radioligand can be used to characterize innate immune responses in MS in vivo and provides further evidence supporting an association between the white matter TSPO PET signal in lesions and disease severity. Our approach is practical for extension to studies of the role of the innate immune response in MS for differentiation of antiinflammatory effects of new medicines and their longer term impact on clinical outcome. © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Impact of Strategically Located White Matter Hyperintensities on Cognition in Memory Clinic Patients with Small Vessel Disease.

PubMed

Biesbroek, J Matthijs; Weaver, Nick A; Hilal, Saima; Kuijf, Hugo J; Ikram, Mohammad Kamran; Xu, Xin; Tan, Boon Yeow; Venketasubramanian, Narayanaswamy; Postma, Albert; Biessels, Geert Jan; Chen, Christopher P L H

2016-01-01

Studies on the impact of small vessel disease (SVD) on cognition generally focus on white matter hyperintensity (WMH) volume. The extent to which WMH location relates to cognitive performance has received less attention, but is likely to be functionally important. We examined the relation between WMH location and cognition in a memory clinic cohort of patients with sporadic SVD. A total of 167 patients with SVD were recruited from memory clinics. Assumption-free region of interest-based analyses based on major white matter tracts and voxel-wise analyses were used to determine the association between WMH location and executive functioning, visuomotor speed and memory. Region of interest-based analyses showed that WMHs located particularly within the anterior thalamic radiation and forceps minor were inversely associated with both executive functioning and visuomotor speed, independent of total WMH volume. Memory was significantly associated with WMH volume in the forceps minor, independent of total WMH volume. An independent assumption-free voxel-wise analysis identified strategic voxels in these same tracts. Region of interest-based analyses showed that WMH volume within the anterior thalamic radiation explained 6.8% of variance in executive functioning, compared to 3.9% for total WMH volume; WMH volume within the forceps minor explained 4.6% of variance in visuomotor speed and 4.2% of variance in memory, compared to 1.8% and 1.3% respectively for total WMH volume. Our findings identify the anterior thalamic radiation and forceps minor as strategic white matter tracts in which WMHs are most strongly associated with cognitive impairment in memory clinic patients with SVD. WMH volumes in individual tracts explained more variance in cognition than total WMH burden, emphasizing the importance of lesion location when addressing the functional consequences of WMHs.

Associations between Proprioceptive Neural Pathway Structural Connectivity and Balance in People with Multiple Sclerosis

PubMed Central

Fling, Brett W.; Dutta, Geetanjali Gera; Schlueter, Heather; Cameron, Michelle H.; Horak, Fay B.

2014-01-01

Mobility and balance impairments are a hallmark of multiple sclerosis (MS), affecting nearly half of patients at presentation and resulting in decreased activity and participation, falls, injuries, and reduced quality of life. A growing body of work suggests that balance impairments in people with mild MS are primarily the result of deficits in proprioception, the ability to determine body position in space in the absence of vision. A better understanding of the pathophysiology of balance disturbances in MS is needed to develop evidence-based rehabilitation approaches. The purpose of the current study was to (1) map the cortical proprioceptive pathway in vivo using diffusion-weighted imaging and (2) assess associations between proprioceptive pathway white matter microstructural integrity and performance on clinical and behavioral balance tasks. We hypothesized that people with MS (PwMS) would have reduced integrity of cerebral proprioceptive pathways, and that reduced white matter microstructure within these tracts would be strongly related to proprioceptive-based balance deficits. We found poorer balance control on proprioceptive-based tasks and reduced white matter microstructural integrity of the cortical proprioceptive tracts in PwMS compared with age-matched healthy controls (HC). Microstructural integrity of this pathway in the right hemisphere was also strongly associated with proprioceptive-based balance control in PwMS and controls. Conversely, while white matter integrity of the right hemisphere’s proprioceptive pathway was significantly correlated with overall balance performance in HC, there was no such relationship in PwMS. These results augment existing literature suggesting that balance control in PwMS may become more dependent upon (1) cerebellar-regulated proprioceptive control, (2) the vestibular system, and/or (3) the visual system. PMID:25368564

Associations between Proprioceptive Neural Pathway Structural Connectivity and Balance in People with Multiple Sclerosis.

PubMed

Fling, Brett W; Dutta, Geetanjali Gera; Schlueter, Heather; Cameron, Michelle H; Horak, Fay B

2014-01-01

Mobility and balance impairments are a hallmark of multiple sclerosis (MS), affecting nearly half of patients at presentation and resulting in decreased activity and participation, falls, injuries, and reduced quality of life. A growing body of work suggests that balance impairments in people with mild MS are primarily the result of deficits in proprioception, the ability to determine body position in space in the absence of vision. A better understanding of the pathophysiology of balance disturbances in MS is needed to develop evidence-based rehabilitation approaches. The purpose of the current study was to (1) map the cortical proprioceptive pathway in vivo using diffusion-weighted imaging and (2) assess associations between proprioceptive pathway white matter microstructural integrity and performance on clinical and behavioral balance tasks. We hypothesized that people with MS (PwMS) would have reduced integrity of cerebral proprioceptive pathways, and that reduced white matter microstructure within these tracts would be strongly related to proprioceptive-based balance deficits. We found poorer balance control on proprioceptive-based tasks and reduced white matter microstructural integrity of the cortical proprioceptive tracts in PwMS compared with age-matched healthy controls (HC). Microstructural integrity of this pathway in the right hemisphere was also strongly associated with proprioceptive-based balance control in PwMS and controls. Conversely, while white matter integrity of the right hemisphere's proprioceptive pathway was significantly correlated with overall balance performance in HC, there was no such relationship in PwMS. These results augment existing literature suggesting that balance control in PwMS may become more dependent upon (1) cerebellar-regulated proprioceptive control, (2) the vestibular system, and/or (3) the visual system.

Education, occupation, leisure activities, and brain reserve: a population-based study.

PubMed

Foubert-Samier, Alexandra; Catheline, Gwenaelle; Amieva, Hélène; Dilharreguy, Bixente; Helmer, Catherine; Allard, Michèle; Dartigues, Jean-François

2012-02-01

The influence of education, occupation, and leisure activities on the passive and active components of reserve capacity remains unclear. We used the voxel-based morphometry (VBM) technique in a population-based sample of 331 nondemented people in order to investigate the relationship between these factors and the cerebral volume (a marker of brain reserve). The results showed a positive and significant association between education, occupation, and leisure activities and the cognitive performances on Isaac's set test. Among these factors, only education was significantly associated with a cerebral volume including gray and white matter (p = 0.01). In voxel-based morphometry analyses, the difference in gray matter volume was located in the temporoparietal lobes and in the orbitofrontal lobes bilaterally (a p-value corrected <0.05 by false discovery rate [FDR]). Although smaller, the education-related difference in white matter volume appeared in areas connected to the education-related difference in gray matter volume. Education, occupation attainment, and leisure activities were found to contribute differently to reserve capacity. Education could play a role in the constitution of cerebral reserve capacity. Copyright © 2012 Elsevier Inc. All rights reserved.

The association between white-matter tract abnormalities, and neuropsychiatric and cognitive symptoms in retired professional football players with multiple concussions.

PubMed

Multani, Namita; Goswami, Ruma; Khodadadi, Mozhgan; Ebraheem, Ahmed; Davis, Karen D; Tator, Charles H; Wennberg, Richard; Mikulis, David J; Ezerins, Leo; Tartaglia, Maria Carmela

2016-07-01

Retired professional athletes, who have suffered repetitive concussions, report symptoms of depression, anxiety, and memory impairment over time. Moreover, recent imaging data suggest chronic white-matter tract deterioration in sport-related concussion. The aim of this study is to evaluate the impact of repetitive concussions in retired professional football players on white-matter tracts, and relate these changes to neuropsychological function. All subjects (18 retired professional football players and 17 healthy controls) underwent imaging, neuropsychological assessment, and reported on concussion-related symptoms. Whole brain tract-based spatial statistics analysis revealed increased axial diffusivity in the right hemisphere of retired players in the (1) superior longitudinal fasciculus (SLF), (2) corticospinal tract, and (3) anterior thalamic radiations, suggesting chronic axonal degeneration in these tracts. Moreover, retired players report significantly higher neuropsychiatric and cognitive symptoms than healthy controls, and worsening of these symptoms since their last concussion. Loss of integrity in the right SLF significantly correlated with participants' visual learning ability. In sum, these results suggest that repetitive concussions in retired professional football players are associated with focal white-matter tract abnormalities that could explain some of the neuropsychiatric symptoms and cognitive deficits experienced by these retired athletes.

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.

Automated segmentation reveals silent radiographic progression in adult-onset vanishing white-matter disease.

PubMed

Huber, Thomas; Herwerth, Marina; Alberts, Esther; Kirschke, Jan S; Zimmer, Claus; Ilg, Ruediger

2017-02-01

Adult-onset vanishing white-matter disease (VWM) is a rare autosomal recessive disease with neurological symptoms such as ataxia and paraparesis, showing extensive white-matter hyperintensities (WMH) on magnetic resonance (MR) imaging. Besides symptom-specific scores like the International Cooperative Ataxia Rating Scale (ICARS), there is no established tool to monitor disease progression. Because of extensive WMH, visual comparison of MR images is challenging. Here, we report the results of an automated method of segmentation to detect alterations in T2-weighted fluid-attenuated-inversion-recovery (FLAIR) sequences in a one-year follow-up study of a clinically stable patient with genetically diagnosed VWM. Signal alterations in MR imaging were quantified with a recently published WMH segmentation method by means of extreme value distribution (EVD). Our analysis revealed progressive FLAIR alterations of 5.84% in the course of one year, whereas no significant WMH change could be detected in a stable multiple sclerosis (MS) control group. This result demonstrates that automated EVD-based segmentation allows a precise and rapid quantification of extensive FLAIR alterations like in VWM and might be a powerful tool for the clinical and scientific monitoring of degenerative white-matter diseases and potential therapeutic interventions.

Relationship between suicidality and impulsivity in bipolar I disorder: a diffusion tensor imaging study

PubMed Central

Mahon, Katie; Burdick, Katherine E; Wu, Jinghui; Ardekani, Babak A; Szeszko, Philip R

2012-01-01

Background Impulsivity is characteristic of individuals with bipolar disorder and may be a contributing factor to the high rate of suicide in patients with this disorder. Although white matter abnormalities have been implicated in the pathophysiology of bipolar disorder, their relationship to impulsivity and suicidality in this disorder has not been well-investigated. Methods Diffusion tensor imaging scans were acquired in 14 bipolar disorder patients with a prior suicide attempt, 15 bipolar disorder patients with no prior suicide attempt, and 15 healthy volunteers. Bipolar disorder patients received clinical assessments including measures of impulsivity, depression, mania, and anxiety. Images were processed using the Tract-Based Spatial Statistics method in the FSL software package. Results Bipolar disorder patients with a prior suicide attempt had lower fractional anisotropy (FA) within the left orbital frontal white matter (p < 0.05, corrected) and higher overall impulsivity compared to patients without a previous suicide attempt. Among patients with a prior suicide attempt, FA in the orbital frontal white matter region correlated inversely with motor impulsivity. Conclusions Abnormal orbital frontal white matter may play a role in impulsive and suicidal behavior among patients with bipolar disorder. PMID:22329475

Abnormal cholesterol is associated with prefrontal white matter abnormalities among obese adults, a diffusion tensor imaging study

PubMed Central

Cohen, Jessica I.; Cazettes, Fanny; Convit, Antonio

2011-01-01

The brain is the most cholesterol-rich organ in the body. Although most of the cholesterol in the brain is produced endogenously, some studies suggest that systemic cholesterol may be able to enter the brain. We investigated whether abnormal cholesterol profiles correlated with diffusion-tensor-imaging-based estimates of white matter microstructural integrity of lean and overweight/obese (o/o) adults. Twenty-two lean and 39 obese adults underwent magnetic resonance imaging, kept a 3-day food diary, and had a standardized assessment of fasting blood lipids. The lean group ate less cholesterol rich food than o/o although both groups ate equivalent servings of food per day. Voxelwise correlational analyses controlling for age, diabetes, and white matter hyperintensities, resulted in two significant clusters of negative associations between abnormal cholesterol profile and fractional anisotropy, located in the left and right prefrontal lobes. When the groups were split, the lean subjects showed no associations, whereas the o/o group expanded the association to three significant clusters, still in the frontal lobes. These findings suggest that cholesterol profile abnormalities may explain some of the reductions in white matter microstructural integrity that are reported in obesity. PMID:22163070

Language, aging, and cognition: frontal aslant tract and superior longitudinal fasciculus contribute toward working memory performance in older adults.

PubMed

Rizio, Avery A; Diaz, Michele T

2016-06-15

Previous research has documented change in white matter tract integrity with increasing age. Both interhemispheric and intrahemispheric tracts that underlie language processing are susceptible to these age-related changes. The aim of the current study was to explore age and white matter integrity in language-related tracts as predictors of cognitive task performance in younger and older adults. To this end, we carried out principal component analyses of white matter tracts and confirmatory factor analysis of neuropsychological measures. We next carried out a series of regression analyses that used white matter components to predict scores on each of the neuropsychological components. For both younger and older adults, age was a significant predictor of processing speed and working memory. However, white matter integrity did not contribute independently toward these models. In older adults only, both age and a white matter component that included the bilateral frontal aslant tract and left superior longitudinal fasciculus were significant predictors of working memory. Taken together, these results extend our understanding of the contributions of language-related white matter structure to cognitive processing and highlight the effects of age-related differences in both frontal and dorsal tracts.

Tissue signature characterisation of diffusion tensor abnormalities in cerebral gliomas.

PubMed

Price, Stephen J; Peña, Alonso; Burnet, Neil G; Jena, Raj; Green, Hadrian A L; Carpenter, T Adrian; Pickard, John D; Gillard, Jonathan H

2004-10-01

The inherent invasiveness of malignant cells is a major determinant of the poor prognosis of cerebral gliomas. Diffusion tensor MRI (DTI) can identify white matter abnormalities in gliomas that are not seen on conventional imaging. By breaking down DTI into its isotropic (p) and anisotropic (q) components, we can determine tissue diffusion "signatures". In this study we have characterised these abnormalities in peritumoural white matter tracts. Thirty-five patients with cerebral gliomas and seven normal volunteers were imaged with DTI and T2-weighted sequences at 3 T. Displaced, infiltrated and disrupted white matter tracts were identified using fractional anisotropy (FA) maps and directionally encoded colour maps and characterised using tissue signatures. The diffusion tissue signatures were normal in ROIs where the white matter was displaced. Infiltrated white matter was characterised by an increase in the isotropic component of the tensor (p) and a less marked reduction of the anisotropic component (q). In disrupted white matter tracts, there was a marked reduction in q and increase in p. The direction of water diffusion was grossly abnormal in these cases. Diffusion tissue signatures may be a useful method of assessing occult white matter infiltration. Copyright 2004 Springer-Verlag

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

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.

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.

Multisite longitudinal reliability of tract-based spatial statistics in diffusion tensor imaging of healthy elderly subjects.

PubMed

Jovicich, Jorge; Marizzoni, Moira; Bosch, Beatriz; Bartrés-Faz, David; Arnold, Jennifer; Benninghoff, Jens; Wiltfang, Jens; Roccatagliata, Luca; Picco, Agnese; Nobili, Flavio; Blin, Oliver; Bombois, Stephanie; Lopes, Renaud; Bordet, Régis; Chanoine, Valérie; Ranjeva, Jean-Philippe; Didic, Mira; Gros-Dagnac, Hélène; Payoux, Pierre; Zoccatelli, Giada; Alessandrini, Franco; Beltramello, Alberto; Bargalló, Núria; Ferretti, Antonio; Caulo, Massimo; Aiello, Marco; Ragucci, Monica; Soricelli, Andrea; Salvadori, Nicola; Tarducci, Roberto; Floridi, Piero; Tsolaki, Magda; Constantinidis, Manos; Drevelegas, Antonios; Rossini, Paolo Maria; Marra, Camillo; Otto, Josephin; Reiss-Zimmermann, Martin; Hoffmann, Karl-Titus; Galluzzi, Samantha; Frisoni, Giovanni B

2014-11-01

Large-scale longitudinal neuroimaging studies with diffusion imaging techniques are necessary to test and validate models of white matter neurophysiological processes that change in time, both in healthy and diseased brains. The predictive power of such longitudinal models will always be limited by the reproducibility of repeated measures acquired during different sessions. At present, there is limited quantitative knowledge about the across-session reproducibility of standard diffusion metrics in 3T multi-centric studies on subjects in stable conditions, in particular when using tract based spatial statistics and with elderly people. In this study we implemented a multi-site brain diffusion protocol in 10 clinical 3T MRI sites distributed across 4 countries in Europe (Italy, Germany, France and Greece) using vendor provided sequences from Siemens (Allegra, Trio Tim, Verio, Skyra, Biograph mMR), Philips (Achieva) and GE (HDxt) scanners. We acquired DTI data (2 × 2 × 2 mm(3), b = 700 s/mm(2), 5 b0 and 30 diffusion weighted volumes) of a group of healthy stable elderly subjects (5 subjects per site) in two separate sessions at least a week apart. For each subject and session four scalar diffusion metrics were considered: fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial (AD) diffusivity. The diffusion metrics from multiple subjects and sessions at each site were aligned to their common white matter skeleton using tract-based spatial statistics. The reproducibility at each MRI site was examined by looking at group averages of absolute changes relative to the mean (%) on various parameters: i) reproducibility of the signal-to-noise ratio (SNR) of the b0 images in centrum semiovale, ii) full brain test-retest differences of the diffusion metric maps on the white matter skeleton, iii) reproducibility of the diffusion metrics on atlas-based white matter ROIs on the white matter skeleton. Despite the differences of MRI scanner configurations across sites (vendors, models, RF coils and acquisition sequences) we found good and consistent test-retest reproducibility. White matter b0 SNR reproducibility was on average 7 ± 1% with no significant MRI site effects. Whole brain analysis resulted in no significant test-retest differences at any of the sites with any of the DTI metrics. The atlas-based ROI analysis showed that the mean reproducibility errors largely remained in the 2-4% range for FA and AD and 2-6% for MD and RD, averaged across ROIs. Our results show reproducibility values comparable to those reported in studies using a smaller number of MRI scanners, slightly different DTI protocols and mostly younger populations. We therefore show that the acquisition and analysis protocols used are appropriate for multi-site experimental scenarios. Copyright © 2014 Elsevier Inc. All rights reserved.

Ethnoracial differences in brain structure change and cognitive change.

PubMed

Gavett, Brandon E; Fletcher, Evan; Harvey, Danielle; Farias, Sarah Tomaszewski; Olichney, John; Beckett, Laurel; DeCarli, Charles; Mungas, Dan

2018-04-12

The purpose of this study was to examine longitudinal associations between structural MRI and cognition in a diverse sample. Older adults (n = 444; Mage = 74.5)-121 African Americans, 212 Whites, and 111 Hispanics-underwent an average of 5.3 annual study visits. Approximately half were cognitively normal at baseline (global Clinical Dementia Rating M = 0.5). Of the patients with dementia, most (79%) were diagnosed with Alzheimer's disease (AD). MRI measures of gray matter volume (baseline and change), and hippocampal and white matter hyperintensity (WMH) volumes (baseline), were used to predict change in global cognition. Multilevel latent variable modeling was used to test the hypothesis that brain effects on cognitive change differed across ethnoracial groups. In a multivariable model, global gray matter change was the strongest predictor of cognitive decline in Whites and African Americans and specific temporal lobe change added incremental explanatory power in Whites. Baseline WMH volume was the strongest predictor of cognitive decline in Hispanics and made an incremental contribution in Whites. We found ethnoracial group differences in associations of brain variables with cognitive decline. The unique patterns in Whites appeared to suggest a greater influence of AD in this group. In contrast, cognitive decline in African Americans and Hispanics was most uniquely attributable to global gray matter change and baseline WMH, respectively. Brain changes underlying cognitive decline in older adults are heterogeneous and depend on fixed and modifiable risk factors that differ based on ethnicity and race. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

The human cerebral cortex is neither one nor many: neuronal distribution reveals two quantitatively different zones in the gray matter, three in the white matter, and explains local variations in cortical folding

PubMed Central

Ribeiro, Pedro F. M.; Ventura-Antunes, Lissa; Gabi, Mariana; Mota, Bruno; Grinberg, Lea T.; Farfel, José M.; Ferretti-Rebustini, Renata E. L.; Leite, Renata E. P.; Filho, Wilson J.; Herculano-Houzel, Suzana

2013-01-01

The human prefrontal cortex has been considered different in several aspects and relatively enlarged compared to the rest of the cortical areas. Here we determine whether the white and gray matter of the prefrontal portion of the human cerebral cortex have similar or different cellular compositions relative to the rest of the cortical regions by applying the Isotropic Fractionator to analyze the distribution of neurons along the entire anteroposterior axis of the cortex, and its relationship with the degree of gyrification, number of neurons under the cortical surface, and other parameters. The prefrontal region shares with the remainder of the cerebral cortex (except for occipital cortex) the same relationship between cortical volume and number of neurons. In contrast, both occipital and prefrontal areas vary from other cortical areas in their connectivity through the white matter, with a systematic reduction of cortical connectivity through the white matter and an increase of the mean axon caliber along the anteroposterior axis. These two parameters explain local differences in the distribution of neurons underneath the cortical surface. We also show that local variations in cortical folding are neither a function of local numbers of neurons nor of cortical thickness, but correlate with properties of the white matter, and are best explained by the folding of the white matter surface. Our results suggest that the human cerebral cortex is divided in two zones (occipital and non-occipital) that differ in how neurons are distributed across their gray matter volume and in three zones (prefrontal, occipital, and non-occipital) that differ in how neurons are connected through the white matter. Thus, the human prefrontal cortex has the largest fraction of neuronal connectivity through the white matter and the smallest average axonal caliber in the white matter within the cortex, although its neuronal composition fits the pattern found for other, non-occipital areas. PMID:24032005

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.

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.

Mapping white-matter functional organization at rest and during naturalistic visual perception.

PubMed

Marussich, Lauren; Lu, Kun-Han; Wen, Haiguang; Liu, Zhongming

2017-02-01

Despite the wide applications of functional magnetic resonance imaging (fMRI) to mapping brain activation and connectivity in cortical gray matter, it has rarely been utilized to study white-matter functions. In this study, we investigated the spatiotemporal characteristics of fMRI data within the white matter acquired from humans both in the resting state and while watching a naturalistic movie. By using independent component analysis and hierarchical clustering, resting-state fMRI data in the white matter were de-noised and decomposed into spatially independent components, which were further assembled into hierarchically organized axonal fiber bundles. Interestingly, such components were partly reorganized during natural vision. Relative to resting state, the visual task specifically induced a stronger degree of temporal coherence within the optic radiations, as well as significant correlations between the optic radiations and multiple cortical visual networks. Therefore, fMRI contains rich functional information about the activity and connectivity within white matter at rest and during tasks, challenging the conventional practice of taking white-matter signals as noise or artifacts. Copyright © 2016 Elsevier Inc. All rights reserved.

Intrinsic gray-matter connectivity of the brain in adults with autism spectrum disorder

PubMed Central

Ecker, Christine; Ronan, Lisa; Feng, Yue; Daly, Eileen; Murphy, Clodagh; Ginestet, Cedric E.; Brammer, Michael; Fletcher, Paul C.; Bullmore, Edward T.; Suckling, John; Baron-Cohen, Simon; Williams, Steve; Loth, Eva; Murphy, Declan G. M.; Bailey, A. J.; Baron-Cohen, S.; Bolton, P. F.; Bullmore, E. T.; Carrington, S.; Chakrabarti, B.; Daly, E. M.; Deoni, S. C.; Ecker, C.; Happe, F.; Henty, J.; Jezzard, P.; Johnston, P.; Jones, D. K.; Lai, M. C.; Lombardo, M. V.; Madden, A.; Mullins, D.; Murphy, C. M.; Murphy, D. G.; Pasco, G.; Sadek, S.; Spain, D.; Steward, R.; Suckling, J.; Wheelwright, S.; Williams, S. C.

2013-01-01

Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions that are accompanied by atypical brain connectivity. So far, in vivo evidence for atypical structural brain connectivity in ASD has mainly been based on neuroimaging studies of cortical white matter. However, genetic studies suggest that abnormal connectivity in ASD may also affect neural connections within the cortical gray matter. Such intrinsic gray-matter connections are inherently more difficult to describe in vivo but may be inferred from a variety of surface-based geometric features that can be measured using magnetic resonance imaging. Here, we present a neuroimaging study that examines the intrinsic cortico-cortical connectivity of the brain in ASD using measures of “cortical separation distances” to assess the global and local intrinsic “wiring costs” of the cortex (i.e., estimated length of horizontal connections required to wire the cortex within the cortical sheet). In a sample of 68 adults with ASD and matched controls, we observed significantly reduced intrinsic wiring costs of cortex in ASD, both globally and locally. Differences in global and local wiring cost were predominantly observed in fronto-temporal regions and also significantly predicted the severity of social and repetitive symptoms (respectively). Our study confirms that atypical cortico-cortical “connectivity” in ASD is not restricted to the development of white-matter connections but may also affect the intrinsic gray-matter architecture (and connectivity) within the cortical sheet. Thus, the atypical connectivity of the brain in ASD is complex, affecting both gray and white matter, and forms part of the core neural substrates underlying autistic symptoms. PMID:23878213

Intrinsic gray-matter connectivity of the brain in adults with autism spectrum disorder.

PubMed

Ecker, Christine; Ronan, Lisa; Feng, Yue; Daly, Eileen; Murphy, Clodagh; Ginestet, Cedric E; Brammer, Michael; Fletcher, Paul C; Bullmore, Edward T; Suckling, John; Baron-Cohen, Simon; Williams, Steve; Loth, Eva; Murphy, Declan G M

2013-08-06

Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions that are accompanied by atypical brain connectivity. So far, in vivo evidence for atypical structural brain connectivity in ASD has mainly been based on neuroimaging studies of cortical white matter. However, genetic studies suggest that abnormal connectivity in ASD may also affect neural connections within the cortical gray matter. Such intrinsic gray-matter connections are inherently more difficult to describe in vivo but may be inferred from a variety of surface-based geometric features that can be measured using magnetic resonance imaging. Here, we present a neuroimaging study that examines the intrinsic cortico-cortical connectivity of the brain in ASD using measures of "cortical separation distances" to assess the global and local intrinsic "wiring costs" of the cortex (i.e., estimated length of horizontal connections required to wire the cortex within the cortical sheet). In a sample of 68 adults with ASD and matched controls, we observed significantly reduced intrinsic wiring costs of cortex in ASD, both globally and locally. Differences in global and local wiring cost were predominantly observed in fronto-temporal regions and also significantly predicted the severity of social and repetitive symptoms (respectively). Our study confirms that atypical cortico-cortical "connectivity" in ASD is not restricted to the development of white-matter connections but may also affect the intrinsic gray-matter architecture (and connectivity) within the cortical sheet. Thus, the atypical connectivity of the brain in ASD is complex, affecting both gray and white matter, and forms part of the core neural substrates underlying autistic symptoms.

Altered White Matter Microstructure in Children with Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Nagel, Bonnie J.; Bathula, Deepti; Herting, Megan; Schmitt, Colleen; Kroenke, Christopher D.; Fair, Damien; Nigg, Joel T.

2011-01-01

Objective: Identification of biomarkers is a priority for attention-deficit/hyperactivity disorder (ADHD). Studies have documented macrostructural brain alterations in ADHD, but few have examined white matter microstructure, particularly in preadolescent children. Given dramatic white matter maturation across childhood, microstructural differences…

Frontostriatal white matter integrity mediates adult age differences in probabilistic reward learning.

PubMed

Samanez-Larkin, Gregory R; Levens, Sara M; Perry, Lee M; Dougherty, Robert F; Knutson, Brian

2012-04-11

Frontostriatal circuits have been implicated in reward learning, and emerging findings suggest that frontal white matter structural integrity and probabilistic reward learning are reduced in older age. This cross-sectional study examined whether age differences in frontostriatal white matter integrity could account for age differences in reward learning in a community life span sample of human adults. By combining diffusion tensor imaging with a probabilistic reward learning task, we found that older age was associated with decreased reward learning and decreased white matter integrity in specific pathways running from the thalamus to the medial prefrontal cortex and from the medial prefrontal cortex to the ventral striatum. Further, white matter integrity in these thalamocorticostriatal paths could statistically account for age differences in learning. These findings suggest that the integrity of frontostriatal white matter pathways critically supports reward learning. The findings also raise the possibility that interventions that bolster frontostriatal integrity might improve reward learning and decision making.

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+ astrocytes with disrupted end-feet juxtaposed to microvessels. To explore whether this was associated with the disrupted gliovascular interactions or blood–brain barrier damage, we assessed the co-localization of GFAP and AQP4 immunoreactivities in post-mortem brains from adult baboons with cerebral hypoperfusive injury, induced by occlusion of three major vessels supplying blood to the brain. Analysis of the frontal white matter in perfused brains from the animals surviving 1–28 days after occlusion revealed that the highest intensity of fibrinogen immunoreactivity was at 14 days. At this survival time point, we also noted strikingly similar redistribution of AQP4 and GFAP+ astrocytes transformed into clasmatodendrocytes. Our findings suggest novel associations between irreversible astrocyte injury and disruption of gliovascular interactions at the blood–brain barrier in the frontal white matter and cognitive impairment in elderly post-stroke survivors. We propose that clasmatodendrosis is another pathological substrate, linked to white matter hyperintensities and frontal white matter changes, which may contribute to post-stroke or small vessel disease dementia. PMID:26667280

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.

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.

Identification of regions of normal grey matter and white matter from pathologic glioblastoma and necrosis in frozen sections using Raman imaging.

PubMed

Kast, Rachel; Auner, Gregory; Yurgelevic, Sally; Broadbent, Brandy; Raghunathan, Aditya; Poisson, Laila M; Mikkelsen, Tom; Rosenblum, Mark L; Kalkanis, Steven N

2015-11-01

In neurosurgical applications, a tool capable of distinguishing grey matter, white matter, and areas of tumor and/or necrosis in near-real time could greatly aid in tumor resection decision making. Raman spectroscopy is a non-destructive spectroscopic technique which provides molecular information about the tissue under examination based on the vibrational properties of the constituent molecules. With careful measurement and data processing, a spatial step and repeat acquisition of Raman spectra can be used to create Raman images. Forty frozen brain tissue sections were imaged in their entirety using a 300-µm-square measurement grid, and two or more regions of interest within each tissue were also imaged using a 25 µm-square step size. Molecular correlates for histologic features of interest were identified within the Raman spectra, and novel imaging algorithms were developed to compare molecular features across multiple tissues. In previous work, the relative concentration of individual biomolecules was imaged. Here, the relative concentrations of 1004, 1300:1344, and 1660 cm(-1), which correspond primarily to protein and lipid content, were simultaneously imaged across all tissues. This provided simple interpretation of boundaries between grey matter, white matter, and diseased tissue, and corresponded with findings from adjacent hematoxylin and eosin-stained sections. This novel, yet simple, multi-channel imaging technique allows clinically-relevant resolution with straightforward molecular interpretation of Raman images not possible by imaging any single peak. This method can be applied to either surgical or laboratory tools for rapid, non-destructive imaging of grey and white matter.

Brain anatomy differences in childhood stuttering.

PubMed

Chang, Soo-Eun; Erickson, Kirk I; Ambrose, Nicoline G; Hasegawa-Johnson, Mark A; Ludlow, Christy L

2008-02-01

Stuttering is a developmental speech disorder that occurs in 5% of children with spontaneous remission in approximately 70% of cases. Previous imaging studies in adults with persistent stuttering found left white matter deficiencies and reversed right-left asymmetries compared to fluent controls. We hypothesized that similar differences might be present indicating brain development differences in children at risk of stuttering. Optimized voxel-based morphometry compared gray matter volume (GMV) and diffusion tensor imaging measured fractional anisotropy (FA) in white matter tracts in 3 groups: children with persistent stuttering, children recovered from stuttering, and fluent peers. Both the persistent stuttering and recovered groups had reduced GMV from normal in speech-relevant regions: the left inferior frontal gyrus and bilateral temporal regions. Reduced FA was found in the left white matter tracts underlying the motor regions for face and larynx in the persistent stuttering group. Contrary to previous findings in adults who stutter, no increases were found in the right hemisphere speech regions in stuttering or recovered children and no differences in right-left asymmetries. Instead, a risk for childhood stuttering was associated with deficiencies in left gray matter volume while reduced white matter integrity in the left hemisphere speech system was associated with persistent stuttering. Anatomical increases in right hemisphere structures previously found in adults who stutter may have resulted from a lifetime of stuttering. These findings point to the importance of considering the role of neuroplasticity during development when studying persistent forms of developmental disorders in adults.

Brain Anatomy Differences in Childhood Stuttering

PubMed Central

Chang, Soo-Eun; Erickson, Kirk I.; Ambrose, Nicoline G.; Hasegawa-Johnson, Mark A.; Ludlow, Christy L.

2009-01-01

Stuttering is a developmental speech disorder that occurs in 5% of children with spontaneous remission in approximately 70% of cases. Previous imaging studies in adults with persistent stuttering found left white matter deficiencies and reversed right-left asymmetries compared to fluent controls. We hypothesized that similar differences might be present indicating brain development differences in children at risk of stuttering. Optimized voxel-based morphometry compared gray matter volume (GMV) and diffusion tensor imaging measured fractional anisotropy (FA) in white matter tracts in 3 groups: children with persistent stuttering, children recovered from stuttering, and fluent peers. Both the persistent stuttering and recovered groups had reduced GMV from normal in speech-relevant regions: the left inferior frontal gyrus, and bilateral temporal regions. Reduced FA was found in the left white matter tracts underlying the motor regions for face and larynx in the persistent stuttering group. Contrary to previous findings in adults who stutter, no increases were found in the right hemisphere speech regions in stuttering or recovered children and no differences in right-left asymmetries. Instead, a risk for childhood stuttering was associated with deficiencies in left gray matter volume while reduced white matter integrity in the left hemisphere speech system was associated with persistent stuttering. Anatomical increases in right hemisphere structures previously found in adults who stutter may have resulted from a life-time of stuttering. These findings point to the importance of considering the role of neuroplasticity during development when studying persistent forms of developmental disorders in adults. PMID:18023366

Raymond de Vieussens and his contribution to the study of white matter anatomy: historical vignette.

PubMed

Vergani, Francesco; Morris, Christopher M; Mitchell, Patrick; Duffau, Hugues

2012-12-01

In recent years, there has been a renewed interest in the study of white matter anatomy, both with the use of postmortem dissections and diffusion tensor imaging tractography. One of the precursors in the study of white matter anatomy was Raymond de Vieussens (1641-1716), a French anatomist born in Le Vigan. He studied medicine at the University of Montpellier in southern France, one of the most ancient and lively schools of medicine in Europe. In 1684 Vieussens published his masterpiece, the Neurographia Universalis, which is still considered one of the most complete and accurate descriptions of the nervous system provided in the 17th century. He described the white matter of the centrum ovale and was the first to demonstrate the continuity of the white matter fibers from the centrum ovale to the brainstem. He also described the dentate nuclei, the pyramids, and the olivary nuclei. According to the theory of Galen, Vieussens considered that the function of the white matter was to convey the "animal spirit" from the centrum ovale to the spinal cord. Although neglected, Vieussens' contribution to the study of white matter is relevant. His pioneering work showed that the white matter is not a homogeneous substance, but rather a complex structure rich in fibers that are interconnected with different parts of the brain. These initial results paved the way to advancements observed in later centuries that eventually led to modern hodology.

Financial literacy is associated with white matter integrity in old age.

PubMed

Han, S Duke; Boyle, Patricia A; Arfanakis, Konstantinos; Fleischman, Debra; Yu, Lei; James, Bryan D; Bennett, David A

2016-04-15

Financial literacy, the ability to understand, access, and utilize information in ways that contribute to optimal financial outcomes, is important for independence and wellbeing in old age. We previously reported that financial literacy is associated with greater functional connectivity between brain regions in old age. Here, we tested the hypothesis that higher financial literacy would be associated with greater white matter integrity in old age. Participants included 346 persons without dementia (mean age=81.36, mean education=15.39, male/female=79/267, mean MMSE=28.52) from the Rush Memory and Aging Project. Financial literacy was assessed using a series of questions imbedded as part of an ongoing decision making study. White matter integrity was assessed with diffusion anisotropy measured with diffusion tensor magnetic resonance imaging (DTI). We tested the hypothesis that higher financial literacy is associated with higher diffusion anisotropy in white matter, adjusting for the effects of age, education, sex, and white matter hyperintense lesions. We then repeated the analysis also adjusting for cognitive function. Analyses revealed regions with significant positive associations between financial literacy and diffusion anisotropy, and many remained significant after accounting for cognitive function. White matter tracts connecting right hemisphere temporal-parietal brain regions were particularly implicated. Greater financial literacy is associated with higher diffusion anisotropy in white matter of nondemented older adults after adjusting for important covariates. These results suggest that financial literacy is positively associated with white matter integrity in old age. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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.

Financial Literacy is Associated with White Matter Integrity in Old Age

PubMed Central

Han, S. Duke; Boyle, Patricia A.; Arfanakis, Konstantinos; Fleischman, Debra; Yu, Lei; James, Bryan D.; Bennett, David A.

2016-01-01

Financial literacy, the ability to understand, access, and utilize information in ways that contribute to optimal financial outcomes, is important for independence and wellbeing in old age. We previously reported that financial literacy is associated with greater functional connectivity between brain regions in old age. Here, we tested the hypothesis that higher financial literacy would be associated with greater white matter integrity in old age. Participants included 346 persons without dementia (mean age=81.36, mean education=15.39, male/female=79/267, mean MMSE=28.52) from the Rush Memory and Aging Project. Financial literacy was assessed using a series of questions imbedded as part of an ongoing decision making study. White matter integrity was assessed with diffusion anisotropy measured with diffusion tensor magnetic resonance imaging (DTI). We tested the hypothesis that higher financial literacy is associated with higher diffusion anisotropy in white matter, adjusting for the effects of age, education, sex, and white matter hyperintense lesions. We then repeated the analysis also adjusting for cognitive function. Analyses revealed regions with significant positive associations between financial literacy and diffusion anisotropy, and many remained significant after accounting for cognitive function. White matter tracts connecting right hemisphere temporal-parietal brain regions were particularly implicated. Greater financial literacy is associated with higher diffusion anisotropy in white matter of nondemented older adults after adjusting for important covariates. These results suggest that financial literacy is positively associated with white matter integrity in old age. PMID:26899784

Disconnected aging: cerebral white matter integrity and age-related differences in cognition.

PubMed

Bennett, I J; Madden, D J

2014-09-12

Cognition arises as a result of coordinated processing among distributed brain regions and disruptions to communication within these neural networks can result in cognitive dysfunction. Cortical disconnection may thus contribute to the declines in some aspects of cognitive functioning observed in healthy aging. Diffusion tensor imaging (DTI) is ideally suited for the study of cortical disconnection as it provides indices of structural integrity within interconnected neural networks. The current review summarizes results of previous DTI aging research with the aim of identifying consistent patterns of age-related differences in white matter integrity, and of relationships between measures of white matter integrity and behavioral performance as a function of adult age. We outline a number of future directions that will broaden our current understanding of these brain-behavior relationships in aging. Specifically, future research should aim to (1) investigate multiple models of age-brain-behavior relationships; (2) determine the tract-specificity versus global effect of aging on white matter integrity; (3) assess the relative contribution of normal variation in white matter integrity versus white matter lesions to age-related differences in cognition; (4) improve the definition of specific aspects of cognitive functioning related to age-related differences in white matter integrity using information processing tasks; and (5) combine multiple imaging modalities (e.g., resting-state and task-related functional magnetic resonance imaging; fMRI) with DTI to clarify the role of cerebral white matter integrity in cognitive aging. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Amyloid PET in pseudotumoral multiple sclerosis.

PubMed

Matías-Guiu, Jordi A; Cabrera-Martín, María Nieves; Cortés-Martínez, Ana; Pytel, Vanesa; Moreno-Ramos, Teresa; Oreja-Guevara, Celia; Carreras, José Luis; Matías-Guiu, Jorge

2017-07-01

Pseudotumoral multiple sclerosis is a rare form of demyelinating disease of the central nervous system. Positron emission tomography (PET) using amyloid-tracers has also been suggested as a marker of damage in white matter lesions in multiple sclerosis due to the nonspecific uptake of these tracers in white matter. We present the case of a 59 year-old woman with a pathological-confirmed pseudotumoral multiple sclerosis, who was studied with the amyloid tracer 18 F-florbetaben. The patient had developed word-finding difficulties and right hemianopia twelve years ago. In that time, MRI showed a lesion on the left hemisphere with an infiltrating aspect in frontotemporal lobes. Brain biopsy showed demyelinating areas and inflammation. During the following years, two new clinical relapses occurred. 18 F-florbetaben PET showed lower uptake in the white matter lesion visualized in the CT and MRI images. Decreased tracer uptake was also observed in a larger area of the left hemisphere beyond the lesions observed on MRI or CT. White matter lesion volume on FLAIR was 44.2mL, and tracer uptake change between damaged white matter and normal appearing white matter was - 40.5%. Standardized uptake value was inferior in the pseudotumoral lesion than in the other white matter lesions. We report the findings of amyloid PET in a patient with pseudotumoral multiple sclerosis. This case provides further evidence on the role of amyloid PET in the assessment of white matter and demyelinating diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Perilesional and contralateral white matter evolution and integrity in patients with periventricular nodular heterotopia and epilepsy: a longitudinal diffusion tensor imaging study.

PubMed

Liu, W; Yan, B; An, D; Niu, R; Tang, Y; Tong, X; Gong, Q; Zhou, D

2017-12-01

This study aimed to assess the evolution of perinodular and contralateral white matter abnormalities in patients with periventricular nodular heterotopia (PNH) and epilepsy. Diffusion tensor imaging (DTI) (64 directions) and 3 T structural magnetic resonance imaging were performed in 29 PNH patients (mean age 27.3 years), and 16 patients underwent a second scan (average time between the two scans 1.1 years). Fractional anisotropy and mean diffusivity were measured within the perilesional and contralateral white matter. Longitudinal analysis showed that white matter located 10 mm from the focal nodule displayed characteristics intermediate to tissue 5 mm away, and normal-appearing white matter (NAWM) also established evolution profiles of perinodular white matter in different cortical lobes. Compared to 29 age- and sex-matched healthy controls, significant decreased fractional anisotropy and elevated mean diffusivity values were observed in regions 5 and 10 mm from nodules (P < 0.01), whilst DTI metrics of the remaining NAWM did not differ significantly from controls. Additionally, normal DTI metrics were shown in the contralateral region in patients with unilateral PNH. Periventricular nodular heterotopia is associated with microstructural abnormalities within the perilesional white matter and the extent decreases with increasing distance from the nodule. In the homologous contralateral region, white matter diffusion metrics were unchanged in unilateral PNH. These findings have clinical implications with respect to the medical and surgical interventions of PNH-related epilepsy. © 2017 EAN.

Disconnected Aging: Cerebral White Matter Integrity and Age-Related Differences in Cognition

PubMed Central

Bennett, Ilana J.; Madden, David J.

2013-01-01

Cognition arises as a result of coordinated processing among distributed brain regions and disruptions to communication within these neural networks can result in cognitive dysfunction. Cortical disconnection may thus contribute to the declines in some aspects of cognitive functioning observed in healthy aging. Diffusion tensor imaging (DTI) is ideally suited for the study of cortical disconnection as it provides indices of structural integrity within interconnected neural networks. The current review summarizes results of previous DTI aging research with the aim of identifying consistent patterns of age-related differences in white matter integrity, and of relationships between measures of white matter integrity and behavioral performance as a function of adult age. We outline a number of future directions that will broaden our current understanding of these brain-behavior relationships in aging. Specifically, future research should aim to (1) investigate multiple models of age-brain-behavior relationships; (2) determine the tract-specificity versus global effect of aging on white matter integrity; (3) assess the relative contribution of normal variation in white matter integrity versus white matter lesions to age-related differences in cognition; (4) improve the definition of specific aspects of cognitive functioning related to age-related differences in white matter integrity using information processing tasks; and (5) combine multiple imaging modalities (e.g., resting-state and task-related functional magnetic resonance imaging; fMRI) with DTI to clarify the role of cerebral white matter integrity in cognitive aging. PMID:24280637

Characterising the grey matter correlates of leukoaraiosis in cerebral small vessel disease.

PubMed

Lambert, Christian; Sam Narean, Janakan; Benjamin, Philip; Zeestraten, Eva; Barrick, Thomas R; Markus, Hugh S

2015-01-01

Cerebral small vessel disease (SVD) is a heterogeneous group of pathological disorders that affect the small vessels of the brain and are an important cause of cognitive impairment. The ischaemic consequences of this disease can be detected using MRI, and include white matter hyperintensities (WMH), lacunar infarcts and microhaemorrhages. The relationship between SVD disease severity, as defined by WMH volume, in sporadic age-related SVD and cortical thickness has not been well defined. However, regional cortical thickness change would be expected due to associated phenomena such as underlying ischaemic white matter damage, and the observation that widespread cortical thinning is observed in the related genetic condition CADASIL (Righart et al., 2013). Using MRI data, we have developed a semi-automated processing pipeline for the anatomical analysis of individuals with cerebral small vessel disease and applied it cross-sectionally to 121 subjects diagnosed with this condition. Using a novel combined automated white matter lesion segmentation algorithm and lesion repair step, highly accurate warping to a group average template was achieved. The volume of white matter affected by WMH was calculated, and used as a covariate of interest in a voxel-based morphometry and voxel-based cortical thickness analysis. Additionally, Gaussian Process Regression (GPR) was used to assess if the severity of SVD, measured by WMH volume, could be predicted from the morphometry and cortical thickness measures. We found significant (Family Wise Error corrected p < 0.05) volumetric decline with increasing lesion load predominately in the parietal lobes, anterior insula and caudate nuclei bilaterally. Widespread significant cortical thinning was found bilaterally in the dorsolateral prefrontal, parietal and posterio-superior temporal cortices. These represent distinctive patterns of cortical thinning and volumetric reduction compared to ageing effects in the same cohort, which exhibited greater changes in the occipital and sensorimotor cortices. Using GPR, the absolute WMH volume could be significantly estimated from the grey matter density and cortical thickness maps (Pearson's coefficients 0.80 and 0.75 respectively). We demonstrate that SVD severity is associated with regional cortical thinning. Furthermore a quantitative measure of SVD severity (WMH volume) can be predicted from grey matter measures, supporting an association between white and grey matter damage. The pattern of cortical thinning and volumetric decline is distinctive for SVD severity compared to ageing. These results, taken together, suggest that there is a phenotypic pattern of atrophy associated with SVD severity.

Brain white matter fiber estimation and tractography using Q-ball imaging and Bayesian MODEL.

PubMed

Lu, Meng

2015-01-01

Diffusion tensor imaging allows for the non-invasive in vivo mapping of the brain tractography. However, fiber bundles have complex structures such as fiber crossings, fiber branchings and fibers with large curvatures that tensor imaging (DTI) cannot accurately handle. This study presents a novel brain white matter tractography method using Q-ball imaging as the data source instead of DTI, because QBI can provide accurate information about multiple fiber crossings and branchings in a single voxel using an orientation distribution function (ODF). The presented method also uses graph theory to construct the Bayesian model-based graph, so that the fiber tracking between two voxels can be represented as the shortest path in a graph. Our experiment showed that our new method can accurately handle brain white matter fiber crossings and branchings, and reconstruct brain tractograhpy both in phantom data and real brain data.

Association of Retinopathy and Retinal Microvascular Abnormalities with Stroke and Cerebrovascular Disease

PubMed Central

Hughes, Alun D; Falaschetti, Emanuela; Witt, Nicholas; Wijetunge, Sumangali; Thom, Simon A McG; Tillin, Therese; Aldington, Steve J; Chaturvedi, Nish

2016-01-01

Background and purpose Abnormalities of the retinal circulation may be associated with cerebrovascular disease. We investigated associations between retinal microvascular abnormalities and 1) strokes and subclinical cerebral infarcts and 2) cerebral white matter lesions in a UK-based tri-ethnic population-based cohort. Methods 1185 participants (age 68.8±6.1y; 77% male) underwent retinal imaging and cerebral MRI. Cerebral infarcts and white matter hyperintensities (WMH) were identified on MRI, retinopathy was graded and retinal vessels were measured. Results Higher retinopathy grade (odds ratio (OR) = 1.40 (1.16, 1.70)), narrower arteriolar diameter (OR = 0.98 (0.97, 0.99)), fewer symmetrical arteriolar bifurcations (OR = 0.84 (0.75, 0.95)), higher arteriolar optimality deviation (OR = 1.16 (1.00, 1.34)) and more tortuous venules (OR = 1.20(1.09, 1.32)) were associated with strokes/infarcts and WMH. Associations with quantitative retinal microvascular measures were independent of retinopathy. Conclusions Abnormalities of the retinal microvasculature are independently associated with stroke, cerebral infarcts and white matter lesions. PMID:27729577

Differential Contributions of Dorso-Ventral and Rostro-Caudal Prefrontal White Matter Tracts to Cognitive Control in Healthy Older Adults

PubMed Central

Strenziok, Maren; Greenwood, Pamela M.; Santa Cruz, Sophia A.; Thompson, James C.; Parasuraman, Raja

2013-01-01

Prefrontal cortex mediates cognitive control by means of circuitry organized along dorso-ventral and rostro-caudal axes. Along the dorso-ventral axis, ventrolateral PFC controls semantic information, whereas dorsolateral PFC encodes task rules. Along the rostro-caudal axis, anterior prefrontal cortex encodes complex rules and relationships between stimuli, whereas posterior prefrontal cortex encodes simple relationships between stimuli and behavior. Evidence of these gradients of prefrontal cortex organization has been well documented in fMRI studies, but their functional correlates have not been examined with regard to integrity of underlying white matter tracts. We hypothesized that (a) the integrity of specific white matter tracts is related to cognitive functioning in a manner consistent with the dorso-ventral and rostro-caudal organization of the prefrontal cortex, and (b) this would be particularly evident in healthy older adults. We assessed three cognitive processes that recruit the prefrontal cortex and can distinguish white matter tracts along the dorso-ventral and rostro-caudal dimensions –episodic memory, working memory, and reasoning. Correlations between cognition and fractional anisotropy as well as fiber tractography revealed: (a) Episodic memory was related to ventral prefrontal cortex-thalamo-hippocampal fiber integrity; (b) Working memory was related to integrity of corpus callosum body fibers subserving dorsolateral prefrontal cortex; and (c) Reasoning was related to integrity of corpus callosum body fibers subserving rostral and caudal dorsolateral prefrontal cortex. These findings confirm the ventrolateral prefrontal cortex's role in semantic control and the dorsolateral prefrontal cortex's role in rule-based processing, in accordance with the dorso-ventral prefrontal cortex gradient. Reasoning-related rostral and caudal superior frontal white matter may facilitate different levels of task rule complexity. This study is the first to demonstrate dorso-ventral and rostro-caudal prefrontal cortex processing gradients in white matter integrity. PMID:24312550

Disrupted White Matter Microstructure and Mood Disorders after Traumatic Brain Injury.

PubMed

Spitz, Gershon; Alway, Yvette; Gould, Kate Rachel; Ponsford, Jennie L

2017-02-15

Traumatic brain injury (TBI) is associated with an elevated frequency of mood disorders that may, in part, be explained by changes in white-matter microstructure. This study is the first to examine the relationship between mood disorders and white-matter pathology in a sample of patients with mild to severe TBI using a standardized psychiatric interview. This study reports on a sub-sample of 29 individuals recruited from a large prospective study that examined the evolution of psychiatric disorders following complicated, mild to severe TBI. Individuals with TBI were also compared with 23 healthy control participants. Individuals were invited to complete the Structured Clinical Interview for DSM-IV Disorders (SCID) to diagnose psychiatric disorders. Participants who developed a mood disorder within the first 3 years were categorized into a TBI-Mood group. Diffusion tensor tractography assessed white matter microstructure using atlas-based tract-averaged and along-tract approaches. Fractional anisotropy (FA) was used as the measure of white-matter microstructure. TBI participants with and without a mood disorder did not differ in regard to injury severity and other background factors. Nevertheless, TBI participants diagnosed with a mood disorder displayed significantly lower tract-averaged FA values for the right arcuate fasciculus (p = 0.011), right inferior longitudinal fasciculus (p = 0.009), and anterior segments I (p = 0.0004) and II (p = 0.007) of the corpus callosum, as well as the left (p = 0.014) and right (p = 0.015) fronto-occipital longitudinal fasciculi. The pattern of white matter disruption identified in the current study provides further support for a neurobiological basis of post-TBI mood disorders. Greater understanding of individuals' underlying neuropathology may enable better characterization and prediction of mood disorders. Integration of neuropathology may also inform the potential efficacy of pharmacological and psychological interventions.

Trait conscientiousness and the personality meta-trait stability are associated with regional white matter microstructure.

PubMed

Lewis, Gary J; Cox, Simon R; Booth, Tom; Muñoz Maniega, Susana; Royle, Natalie A; Valdés Hernández, Maria; Wardlaw, Joanna M; Bastin, Mark E; Deary, Ian J

2016-08-01

Establishing the neural bases of individual differences in personality has been an enduring topic of interest. However, while a growing literature has sought to characterize grey matter correlates of personality traits, little attention to date has been focused on regional white matter correlates of personality, especially for the personality traits agreeableness, conscientiousness and openness. To rectify this gap in knowledge we used a large sample (n > 550) of older adults who provided data on both personality (International Personality Item Pool) and white matter tract-specific fractional anisotropy (FA) from diffusion tensor MRI. Results indicated that conscientiousness was associated with greater FA in the left uncinate fasciculus (β = 0.17, P < 0.001). We also examined links between FA and the personality meta-trait 'stability', which is defined as the common variance underlying agreeableness, conscientiousness, and neuroticism/emotional stability. We observed an association between left uncinate fasciculus FA and stability (β = 0.27, P < 0.001), which fully accounted for the link between left uncinate fasciculus FA and conscientiousness. In sum, these results provide novel evidence for links between regional white matter microstructure and key traits of human personality, specifically conscientiousness and the meta-trait, stability. Future research is recommended to replicate and address the causal directions of these associations. © The Author (2016). Published by Oxford University Press.

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.

Neuroanatomy: The added value of the Klingler method.

PubMed

Silva, Susana M; Andrade, José Paulo

2016-11-01

Undergraduate neuroanatomy students are usually not able to achieve a clear comprehension of the spatial relationships existing between the white matter fiber tracts in spite of numerous neuroanatomy textbooks, atlases and multimedia tools. The objective of this paper is to show the educational value of the application of the Klingler fiber dissection technique and the use of these dissections in the understanding of the three-dimensional intrinsic anatomy of the brain white matter for medical students. Four formalin-fixed brains were dissected using the Klingler methodology in order to reveal the inner anatomical organization of the brain white matter. The most important fiber systems were dissected and their relationships to the cerebral and cerebellar gray matter structures visualized. These dissections were used as a learning tool in teaching the brain white matter structural and topographical connectivity. The white matter fiber systems were presented to undergraduate medical students during a neuroanatomy course. They observed and manipulated the dissected specimens leading to a thorough understanding of the configuration and location of the white matter fiber tracts, and their relationships to the ventricular system and gray matter structures. Subsequently, students were asked to answer a survey concerning the importance of the utilization of this material in their understanding of the three-dimensional intrinsic anatomy of the brain white matter. The knowledge acquired with this technique, complemented by conventional formalin-fixed sections may improve the neuroanatomical knowledge and future retention of medical students. Copyright © 2016 Elsevier GmbH. All rights reserved.

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 parallel pathology and behavior in the same mice. Copyright © 2011. Published by Elsevier Inc.

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 increased anisotropic diffusion in alternate brain regions suggest possible neuroadaptive processes and can be examined in future studies of connectivity to determine how aberrancies in specific tracts might influence efficient cognitive processing.

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…

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…

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…

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

ERIC Educational Resources Information Center

Sahyoun, Cherif 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…

Microstructural Abnormalities of Short-Distance White Matter Tracts in Autism Spectrum Disorder

ERIC Educational Resources Information Center

Shukla, Dinesh K.; Keehn, Brandon; Smylie, Daren M.; Muller, Ralph-Axel

2011-01-01

Recent functional connectivity magnetic resonance imaging and diffusion tensor imaging (DTI) studies have suggested atypical functional connectivity and reduced integrity of long-distance white matter fibers in autism spectrum disorder (ASD). However, evidence for short-distance white matter fibers is still limited, despite some speculation of…

Diffusion tensor imaging, white matter lesions, the corpus callosum, and gait in the elderly

USDA-ARS?s Scientific Manuscript database

Gait impairment is common in the elderly, especially affected by stroke and white matter hyper intensities found in conventional brain magnetic resonance imaging (MRI). Diffusion tensor imaging (DTI) is more sensitive to white matter damage than conventional MRI. The relationship between DTI measure...

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.

Diffusion tensor imaging in children with tuberous sclerosis complex: tract-based spatial statistics assessment of brain microstructural changes.

PubMed

Zikou, Anastasia K; Xydis, Vasileios G; Astrakas, Loukas G; Nakou, Iliada; Tzarouchi, Loukia C; Tzoufi, Meropi; Argyropoulou, Maria I

2016-07-01

There is evidence of microstructural changes in normal-appearing white matter of patients with tuberous sclerosis complex. To evaluate major white matter tracts in children with tuberous sclerosis complex using tract-based spatial statistics diffusion tensor imaging (DTI) analysis. Eight children (mean age ± standard deviation: 8.5 ± 5.5 years) with an established diagnosis of tuberous sclerosis complex and 8 age-matched controls were studied. The imaging protocol consisted of T1-weighted high-resolution 3-D spoiled gradient-echo sequence and a spin-echo, echo-planar diffusion-weighted sequence. Differences in the diffusion indices were evaluated using tract-based spatial statistics. Tract-based spatial statistics showed increased axial diffusivity in the children with tuberous sclerosis complex in the superior and anterior corona radiata, the superior longitudinal fascicle, the inferior fronto-occipital fascicle, the uncinate fascicle and the anterior thalamic radiation. No significant differences were observed in fractional anisotropy, mean diffusivity and radial diffusivity between patients and control subjects. No difference was found in the diffusion indices between the baseline and follow-up examination in the patient group. Patients with tuberous sclerosis complex have increased axial diffusivity in major white matter tracts, probably related to reduced axonal integrity.

Analysis of longitudinal diffusion-weighted images in healthy and pathological aging: An ADNI study.

PubMed

Kruggel, Frithjof; Masaki, Fumitaro; Solodkin, Ana

2017-02-15

The widely used framework of voxel-based morphometry for analyzing neuroimages is extended here to model longitudinal imaging data by exchanging the linear model with a linear mixed-effects model. The new approach is employed for analyzing a large longitudinal sample of 756 diffusion-weighted images acquired in 177 subjects of the Alzheimer's Disease Neuroimaging initiative (ADNI). While sample- and group-level results from both approaches are equivalent, the mixed-effect model yields information at the single subject level. Interestingly, the neurobiological relevance of the relevant parameter at the individual level describes specific differences associated with aging. In addition, our approach highlights white matter areas that reliably discriminate between patients with Alzheimer's disease and healthy controls with a predictive power of 0.99 and include the hippocampal alveus, the para-hippocampal white matter, the white matter of the posterior cingulate, and optic tracts. In this context, notably the classifier includes a sub-population of patients with minimal cognitive impairment into the pathological domain. Our classifier offers promising features for an accessible biomarker that predicts the risk of conversion to Alzheimer's disease. Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how to apply/ADNI Acknowledgement List.pdf. Significance statement This study assesses neuro-degenerative processes in the brain's white matter as revealed by diffusion-weighted imaging, in order to discriminate healthy from pathological aging in a large sample of elderly subjects. The analysis of time-series examinations in a linear mixed effects model allowed the discrimination of population-based aging processes from individual determinants. We demonstrate that a simple classifier based on white matter imaging data is able to predict the conversion to Alzheimer's disease with a high predictive power. Copyright © 2017 Elsevier B.V. All rights reserved.

Comprehensive Investigation of White Matter Tracts in Professional Chess Players and Relation to Expertise: Region of Interest and DMRI Connectometry.

PubMed

Mayeli, Mahsa; Rahmani, Farzaneh; Aarabi, Mohammad Hadi

2018-01-01

Purpose: Expertise is the product of training. Few studies have used functional connectivity or conventional diffusometric methods to identify neural underpinnings of chess expertise. Diffusometric variables of white matter might reflect these adaptive changes, along with changes in structural connectivity, which is a sensitive measure of microstructural changes. Method: Diffusometric variables of 29 professional chess players and 29 age-sex matched controls were extracted for white matter regions based on John Hopkin's Mori white matter atlas and partially correlated against professional training time and level of chess proficiency. Diffusion MRI connectometry was implemented to identify changes in structural connectivity in professional players compared to novices. Result: Compared to novices, higher planar anisotropy (CP) was observed in inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF) and cingulate gyrus, in professional chess players, which correlated with higher RPM score in this group. Higher fractional anisotropy (FA) was observed in ILF, uncinate fasciculus (UF) and hippocampus and correlated with better scores in Raven's progressive matrices (RPM) score and longer duration of chess training in professional players. Consistently, radial diffusivity in bilateral IFOF, bilateral ILF and bilateral SLF was inversely correlated with level of training in professional players. DMRI connectometry analysis identified increased connectivity in bilateral UF, bilateral IFOF, bilateral cingulum, and corpus callosum in chess player's compared to controls. Conclusion: Structural connectivity of major associational subcortical white matter fibers are increased in professional chess players. FA and CP of ILF, SLF and UF directly correlates with duration of professional training and RPM score, in professional chess players.

Comprehensive Investigation of White Matter Tracts in Professional Chess Players and Relation to Expertise: Region of Interest and DMRI Connectometry

PubMed Central

Mayeli, Mahsa; Rahmani, Farzaneh; Aarabi, Mohammad Hadi

2018-01-01

Purpose: Expertise is the product of training. Few studies have used functional connectivity or conventional diffusometric methods to identify neural underpinnings of chess expertise. Diffusometric variables of white matter might reflect these adaptive changes, along with changes in structural connectivity, which is a sensitive measure of microstructural changes. Method: Diffusometric variables of 29 professional chess players and 29 age-sex matched controls were extracted for white matter regions based on John Hopkin's Mori white matter atlas and partially correlated against professional training time and level of chess proficiency. Diffusion MRI connectometry was implemented to identify changes in structural connectivity in professional players compared to novices. Result: Compared to novices, higher planar anisotropy (CP) was observed in inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF) and cingulate gyrus, in professional chess players, which correlated with higher RPM score in this group. Higher fractional anisotropy (FA) was observed in ILF, uncinate fasciculus (UF) and hippocampus and correlated with better scores in Raven's progressive matrices (RPM) score and longer duration of chess training in professional players. Consistently, radial diffusivity in bilateral IFOF, bilateral ILF and bilateral SLF was inversely correlated with level of training in professional players. DMRI connectometry analysis identified increased connectivity in bilateral UF, bilateral IFOF, bilateral cingulum, and corpus callosum in chess player's compared to controls. Conclusion: Structural connectivity of major associational subcortical white matter fibers are increased in professional chess players. FA and CP of ILF, SLF and UF directly correlates with duration of professional training and RPM score, in professional chess players. PMID:29773973

Deviant white matter structure in adults with attention-deficit/hyperactivity disorder points to aberrant myelination and affects neuropsychological performance.

PubMed

Onnink, A Marten H; Zwiers, Marcel P; Hoogman, Martine; Mostert, Jeanette C; Dammers, Janneke; Kan, Cornelis C; Vasquez, Alejandro Arias; Schene, Aart H; Buitelaar, Jan; Franke, Barbara

2015-12-03

Attention-deficit/hyperactivity disorder (ADHD) in childhood is characterized by gray and white matter abnormalities in several brain areas. Considerably less is known about white matter microstructure in adults with ADHD and its relation with clinical symptoms and cognitive performance. In 107 adult ADHD patients and 109 gender-, age- and IQ-matched controls, we used diffusion tensor imaging (DTI) with tract-based spatial statistics (TBSS) to investigate whole-skeleton changes of fractional anisotropy (FA) and mean, axial, and radial diffusivity (MD, AD, RD). Additionally, we studied the relation of FA and MD values with symptom severity and cognitive performance on tasks measuring working memory, attention, inhibition, and delay discounting. In comparison to controls, participants with ADHD showed reduced FA in corpus callosum, bilateral corona radiata, and thalamic radiation. Higher MD and RD were found in overlapping and even more widespread areas in both hemispheres, also encompassing internal and external capsule, sagittal stratum, fornix, and superior lateral fasciculus. Values of FA and MD were not associated with symptom severity. However, within some white matter clusters that distinguished patients from controls, worse inhibition performance was associated with reduced FA and more impulsive decision making was associated with increased MD. This study shows widespread differences in white matter integrity between adults with persistent ADHD and healthy individuals. Changes in RD suggest aberrant myelination as a pathophysiological factor in persistent ADHD. The microstructural differences in adult ADHD may contribute to poor inhibition and greater impulsivity but appear to be independent of disease severity. Copyright © 2015. Published by Elsevier Inc.

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

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.

Quantification of diffusion tensor imaging in normal white matter maturation of early childhood using an automated processing pipeline.

PubMed

Loh, K B; Ramli, N; Tan, L K; Roziah, M; Rahmat, K; Ariffin, H

2012-07-01

The degree and status of white matter myelination can be sensitively monitored using diffusion tensor imaging (DTI). This study looks at the measurement of fractional anistropy (FA) and mean diffusivity (MD) using an automated ROI with an existing DTI atlas. Anatomical MRI and structural DTI were performed cross-sectionally on 26 normal children (newborn to 48 months old), using 1.5-T MRI. The automated processing pipeline was implemented to convert diffusion-weighted images into the NIfTI format. DTI-TK software was used to register the processed images to the ICBM DTI-81 atlas, while AFNI software was used for automated atlas-based volumes of interest (VOIs) and statistical value extraction. DTI exhibited consistent grey-white matter contrast. Triphasic temporal variation of the FA and MD values was noted, with FA increasing and MD decreasing rapidly early in the first 12 months. The second phase lasted 12-24 months during which the rate of FA and MD changes was reduced. After 24 months, the FA and MD values plateaued. DTI is a superior technique to conventional MR imaging in depicting WM maturation. The use of the automated processing pipeline provides a reliable environment for quantitative analysis of high-throughput DTI data. Diffusion tensor imaging outperforms conventional MRI in depicting white matter maturation. • DTI will become an important clinical tool for diagnosing paediatric neurological diseases. • DTI appears especially helpful for developmental abnormalities, tumours and white matter disease. • An automated processing pipeline assists quantitative analysis of high throughput DTI data.

Axonal disruption in white matter underlying cortical sulcus tau pathology in chronic traumatic encephalopathy.

PubMed

Holleran, Laurena; Kim, Joong Hee; Gangolli, Mihika; Stein, Thor; Alvarez, Victor; McKee, Ann; Brody, David L

2017-03-01

Chronic traumatic encephalopathy (CTE) is a progressive degenerative disorder associated with repetitive traumatic brain injury. One of the primary defining neuropathological lesions in CTE, based on the first consensus conference, is the accumulation of hyperphosphorylated tau in gray matter sulcal depths. Post-mortem CTE studies have also reported myelin loss, axonal injury and white matter degeneration. Currently, the diagnosis of CTE is restricted to post-mortem neuropathological analysis. We hypothesized that high spatial resolution advanced diffusion MRI might be useful for detecting white matter microstructural changes directly adjacent to gray matter tau pathology. To test this hypothesis, formalin-fixed post-mortem tissue blocks from the superior frontal cortex of ten individuals with an established diagnosis of CTE were obtained from the Veterans Affairs-Boston University-Concussion Legacy Foundation brain bank. Advanced diffusion MRI data was acquired using an 11.74 T MRI scanner at Washington University with 250 × 250 × 500 µm 3 spatial resolution. Diffusion tensor imaging, diffusion kurtosis imaging and generalized q-sampling imaging analyses were performed in a blinded fashion. Following MRI acquisition, tissue sections were tested for phosphorylated tau immunoreactivity in gray matter sulcal depths. Axonal disruption in underlying white matter was assessed using two-dimensional Fourier transform analysis of myelin black gold staining. A robust image co-registration method was applied to accurately quantify the relationship between diffusion MRI parameters and histopathology. We found that white matter underlying sulci with high levels of tau pathology had substantially impaired myelin black gold Fourier transform power coherence, indicating axonal microstructural disruption (r = -0.55, p = 0.0015). Using diffusion tensor MRI, we found that fractional anisotropy (FA) was modestly (r = 0.53) but significantly (p = 0.0012) correlated with axonal disruption, where lower FA was associated with greater axonal disruption in white matter directly adjacent to hyperphosphorylated tau positive sulci. In summary, our findings indicate that axonal disruption and tau pathology are closely associated, and high spatial resolution ex vivo diffusion MRI has the potential to detect microstructural alterations observed in CTE tissue. Future studies will be required to determine whether this approach can be applied to living people.

Automatic segmentation of white matter hyperintensities robust to multicentre acquisition and pathological variability

NASA Astrophysics Data System (ADS)

Samaille, T.; Colliot, O.; Cuingnet, R.; Jouvent, E.; Chabriat, H.; Dormont, D.; Chupin, M.

2012-02-01

White matter hyperintensities (WMH), commonly seen on FLAIR images in elderly people, are a risk factor for dementia onset and have been associated with motor and cognitive deficits. We present here a method to fully automatically segment WMH from T1 and FLAIR images. Iterative steps of non linear diffusion followed by watershed segmentation were applied on FLAIR images until convergence. Diffusivity function and associated contrast parameter were carefully designed to adapt to WMH segmentation. It resulted in piecewise constant images with enhanced contrast between lesions and surrounding tissues. Selection of WMH areas was based on two characteristics: 1) a threshold automatically computed for intensity selection, 2) main location of areas in white matter. False positive areas were finally removed based on their proximity with cerebrospinal fluid/grey matter interface. Evaluation was performed on 67 patients: 24 with amnestic mild cognitive impairment (MCI), from five different centres, and 43 with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoaraiosis (CADASIL) acquired in a single centre. Results showed excellent volume agreement with manual delineation (Pearson coefficient: r=0.97, p<0.001) and substantial spatial correspondence (Similarity Index: 72%+/-16%). Our method appeared robust to acquisition differences across the centres as well as to pathological variability.

Astrocytes Promote Oligodendrogenesis after White Matter Damage via Brain-Derived Neurotrophic Factor.

PubMed

Miyamoto, Nobukazu; Maki, Takakuni; Shindo, Akihiro; Liang, Anna C; Maeda, Mitsuyo; Egawa, Naohiro; Itoh, Kanako; Lo, Evan K; Lok, Josephine; Ihara, Masafumi; Arai, Ken

2015-10-14

Oligodendrocyte precursor cells (OPCs) in the adult brain contribute to white matter homeostasis. After white matter damage, OPCs compensate for oligodendrocyte loss by differentiating into mature oligodendrocytes. However, the underlying mechanisms remain to be fully defined. Here, we test the hypothesis that, during endogenous recovery from white matter ischemic injury, astrocytes support the maturation of OPCs by secreting brain-derived neurotrophic factor (BDNF). For in vitro experiments, cultured primary OPCs and astrocytes were prepared from postnatal day 2 rat cortex. When OPCs were subjected to chemical hypoxic stress by exposing them to sublethal CoCl2 for 7 d, in vitro OPC differentiation into oligodendrocytes was significantly suppressed. Conditioned medium from astrocytes (astro-medium) restored the process of OPC maturation even under the stressed conditions. When astro-medium was filtered with TrkB-Fc to remove BDNF, the BDNF-deficient astro-medium no longer supported OPC maturation. For in vivo experiments, we analyzed a transgenic mouse line (GFAP(cre)/BDNF(wt/fl)) in which BDNF expression is downregulated specifically in GFAP(+) astrocytes. Both wild-type (GFAP(wt)/BDNF(wt/fl) mice) and transgenic mice were subjected to prolonged cerebral hypoperfusion by bilateral common carotid artery stenosis. As expected, compared with wild-type mice, the transgenic mice exhibited a lower number of newly generated oligodendrocytes and larger white matter damage. Together, these findings demonstrate that, during endogenous recovery from white matter damage, astrocytes may promote oligodendrogenesis by secreting BDNF. The repair of white matter after brain injury and neurodegeneration remains a tremendous hurdle for a wide spectrum of CNS disorders. One potentially important opportunity may reside in the response of residual oligodendrocyte precursor cells (OPCs). OPCs may serve as a back-up for generating mature oligodendrocytes in damaged white matter. However, the underlying mechanisms are still mostly unknown. Here, we use a combination of cell biology and an animal model to report a new pathway in which astrocyte-derived BDNF supports oligodendrogenesis and regeneration after white matter damage. These findings provide new mechanistic insight into white matter physiology and pathophysiology, which would be broadly and clinically applicable to CNS disease. Copyright © 2015 the authors 0270-6474/15/3514002-07$15.00/0.

Brain Lesions in Children with Unilateral Spastic Cerebral Palsy.

PubMed

Hadzagic-Catibusic, Feriha; Avdagic, Edin; Zubcevic, Smail; Uzicanin, Sajra

2017-02-01

Unilateral spastic cerebral palsy (US CP) is the second most common subtype of cerebral palsy. The aim of the study was to analyze neuroimaging findings in children with unilateral spastic cerebral palsy. The study was hospital based, which has included 106 patients with US CP (boys 72/girls 34, term 82/preterm 24). Neuroimaging findings were classified into 5 groups: Brain maldevelopment, predominant white matter injury, predominant gray matter injury, non specific findings and normal neuroimaging findings. Predominant white matter lesions where the most frequent (48/106,45.28%; term 35/preterm 13), without statistically significant difference between term and preterm born children (x2=0.4357; p=0.490517). Predominant gray matter lesions had 32/106 children, 30.19%; (term 25/preterm 7, without statistically significant difference between term and preterm born children (x2=0.902; p=0.9862). Brain malformations had 10/106 children, 9.43%, and all of them were term born. Other finding had 2/106 children, 1.89%, both of them were term born. Normal neuroimaging findings were present in14/106 patients (13.21%). Neuroimaging may help to understand morphological background of motor impairment in children with US CP. Periventricular white matter lesions were the most frequent, then gray matter lesions.

Fast progressive lower motor neuron disease is an ALS variant: A two-centre tract of interest-based MRI data analysis.

PubMed

Müller, Hans-Peter; Agosta, Federica; Riva, Nilo; Spinelli, Edoardo G; Comi, Giancarlo; Ludolph, Albert C; Filippi, Massimo; Kassubek, Jan

2018-01-01

The criteria for assessing upper motor neuron pathology in pure lower motor neuron disease (LMND) still remain a major issue of debate with respect to the clinical classification as an amyotrophic lateral sclerosis (ALS) variant. The study was designed to investigate white matter damage by a hypothesis-guided tract-of-interest-based approach in patients with LMND compared with healthy controls and ´classical´ ALS patients in order to identify in vivo brain structural changes according to the neuropathologically defined ALS affectation pattern. Data were pooled from two previous studies at two different study sites (Ulm, Germany and Milano, Italy). DTI-based white matter integrity mapping was performed by voxelwise statistical comparison and by a tractwise analysis of fractional anisotropy (FA) maps according to the ALS-staging pattern for 65 LMND patients (clinically differentiated in fast and slow progressors) vs. 92 matched controls and 101 ALS patients with a 'classical' phenotype to identify white matter structural alterations. The analysis of white matter structural connectivity by regional FA reductions demonstrated the characteristic alteration patterns along the CST and also in frontal and prefrontal brain areas in LMND patients compared to controls and ALS. Fast progressing LMND showed substantial involvement, like in ALS, while slow progressors showed less severe alterations. In the tract-specific analysis according to the ALS-staging pattern, fast progressing LMND showed significant alterations of ALS-related tract systems as compared to slow progressors and controls. This study showed an affectation pattern for corticoefferent fibers in LMND with fast disease progression as defined for ALS, that way confirming the hypothesis that fast progressing LMND is a phenotypical variant of ALS.

Alterations of white matter structural networks in patients with non-neuropsychiatric systemic lupus erythematosus identified by probabilistic tractography and connectivity-based analyses.

PubMed

Xu, Man; Tan, Xiangliang; Zhang, Xinyuan; Guo, Yihao; Mei, Yingjie; Feng, Qianjin; Xu, Yikai; Feng, Yanqiu

2017-01-01

Systemic lupus erythematosus (SLE) is a chronic inflammatory female-predominant autoimmune disease that can affect the central nervous system and exhibit neuropsychiatric symptoms. In SLE patients without neuropsychiatric symptoms (non-NPSLE), recent diffusion tensor imaging studies showed white matter abnormalities in their brains. The present study investigated the entire brain white matter structural connectivity in non-NPSLE patients by using probabilistic tractography and connectivity-based analyses. Whole-brain structural networks of 29 non-NPSLE patients and 29 healthy controls (HCs) were examined. The structural networks were constructed with interregional probabilistic connectivity. Graph theory analysis was performed to investigate the topological properties, and network-based statistic was employed to assess the alterations of the interregional connections among non-NPSLE patients and controls. Compared with HCs, non-NPSLE patients demonstrated significantly decreased global and local network efficiencies and showed increased characteristic path length. This finding suggests that the global integration and local specialization were impaired. Moreover, the regional properties (nodal efficiency and degree) in the frontal, occipital, and cingulum regions of the non-NPSLE patients were significantly changed and negatively correlated with the disease activity index. The distribution pattern of the hubs measured by nodal degree was altered in the patient group. Finally, the non-NPSLE group exhibited decreased structural connectivity in the left median cingulate-centered component and increased connectivity in the left precuneus-centered component and right middle temporal lobe-centered component. This study reveals an altered topological organization of white matter networks in non-NPSLE patients. Furthermore, this research provides new insights into the structural disruptions underlying the functional and neurocognitive deficits in non-NPSLE patients.

White matter deficits assessed by diffusion tensor imaging and cognitive dysfunction in psychostimulant users with comorbid human immunodeficiency virus infection.

PubMed

Tang, Victor M; Lang, Donna J; Giesbrecht, Chantelle J; Panenka, William J; Willi, Taylor; Procyshyn, Ric M; Vila-Rodriguez, Fidel; Jenkins, Willough; Lecomte, Tania; Boyda, Heidi N; Aleksic, Ana; MacEwan, G William; Honer, William G; Barr, Alasdair M

2015-09-30

Psychostimulant drug use is commonly associated with drug-related infection, including the human immunodeficiency virus (HIV). Both psychostimulant use and HIV infection are known to damage brain white matter and impair cognition. To date, no study has examined white matter integrity using magnetic resonance imaging (MRI) diffusion tensor imaging (DTI) in chronic psychostimulant users with comorbid HIV infection, and determined the relationship of white matter integrity to cognitive function. Twenty-one subjects (mean age 37.5 ± 9.0 years) with a history of heavy psychostimulant use and HIV infection (8.7 ± 4.3 years) and 22 matched controls were scanned on a 3T MRI. Fractional anisotropy (FA) values were calculated with DTI software. Four regions of interest were manually segmented, including the genu of the corpus callosum, left and right anterior limbs of the internal capsule, and the anterior commissure. Subjects also completed a neurocognitive battery and questionnaires about physical and mental health. The psychostimulant using, HIV positive group displayed decreased white matter integrity, with significantly lower FA values for all white matter tracts (p < 0.05). This group also exhibited decreased cognitive performance on tasks that assessed cognitive set-shifting, fine motor speed and verbal memory. FA values for the white matter tracts correlated with cognitive performance on many of the neurocognitive tests. White matter integrity was thus impaired in subjects with psychostimulant use and comorbid HIV infection, which predicted worsened cognitive performance on a range of tests. Further study on this medical comorbidity is required.

White matter fiber integrity of the saccadic eye movement network differs between schizophrenia and healthy groups.

PubMed

Schaeffer, David J; Rodrigue, Amanda L; Burton, Courtney R; Pierce, Jordan E; Murphy, Megan N; Clementz, Brett A; McDowell, Jennifer E

2017-12-01

Recent diffusion tensor imaging (DTI) studies suggest that altered white matter fiber integrity is a pathophysiological feature of schizophrenia. Lower white matter integrity is associated with poor cognitive control, a characteristic of schizophrenia that can be measured using antisaccade tasks. Although the functional neural correlates of poor antisaccade performance have been well documented, fewer studies have investigated the extent to which white matter fibers connecting the functional nodes of this network contribute to antisaccade performance. The aim of the present study was to assess the white matter structural integrity of fibers connecting two functional nodes (putamen and medial frontal eye fields) of the saccadic eye movement network implicated in poor antisaccade performance in schizophrenia. To evaluate white matter integrity, DTI was acquired on subjects with schizophrenia and two comparison groups: (a) behaviorally matched healthy comparison subjects with low levels of cognitive control (LCC group), and (b) healthy subjects with high levels of cognitive control (HCC group). White matter fibers were tracked between functional regions of interest generated from antisaccade fMRI activation maps, and measures of diffusivity were quantified. The results demonstrated lower white matter integrity in the schizophrenia group than in the HCC group, but not the LCC group who showed similarly poor cognitive control performance. Overall, the results suggest that these alterations are not specific to the disease process of schizophrenia, but may rather be a function of uncontrolled cognitive factors that are concomitant with the disease but also observed in some healthy people. © 2017 Society for Psychophysiological Research.

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.

Exercise protects myelinated fibers of white matter in a rat model of depression.

PubMed

Xiao, Qian; Wang, Feifei; Luo, Yanmin; Chen, Linmu; Chao, Fenglei; Tan, Chuanxue; Gao, Yuan; Huang, Chunxia; Zhang, Lei; Liang, Xin; Tang, Jing; Qi, Yingqing; Jiang, Lin; Zhang, Yi; Zhou, Chunni; Tang, Yong

2018-02-15

The antidepressive effects of exercise have been a focus of research and are hypothesized to remodel the brain networks constructed by myelinated fibers. However, whether the antidepressant effects of exercise are dependent on changes in white matter myelination are unknown. Therefore, we chose chronic unpredictable stress (CUS) as a model of depression and designed an experiment. After a 4-week CUS period, 40 animals were tested using the sucrose preference test (SPT) and the open field test (OFT). The depressed rats then underwent 4-week running exercise. Next, electron microscopy and unbiased stereological methods were used to investigate white matter changes in the rats. After the 4-week CUS stimulation, body weight, sucrose preference and scores on the OFT were significantly lower in the depression rats than in the unstressed rats (p < .05). After undergoing a 4-week running exercise, the depression rats showed a significantly greater sucrose preference than the depression control rats without running exercise (p < .05). Furthermore, the white matter parameters of the depression rats (including the white matter volumes, the length and volumes of myelinated fibers, and the volumes and thickness of the myelin sheaths) were significantly reduced after the CUS period (p < .05). However, these white matter parameters were significantly increased after running exercise (p < .05). The present study is the first to provide evidence that running exercise has positive effects on white matter and the myelinated fibers of white matter in depressed rats, and this evidence might provide an important theoretical basis for the exercise-mediated treatment of depression. © 2017 Wiley Periodicals, Inc.

White matter abnormalities are associated with overall cognitive status in blast-related mTBI.

PubMed

Miller, Danielle R; Hayes, Jasmeet P; Lafleche, Ginette; Salat, David H; Verfaellie, Mieke

2017-08-01

Blast-related mild traumatic brain injury (mTBI) is a common injury of the Iraq and Afghanistan Wars. Research has suggested that blast-related mTBI is associated with chronic white matter abnormalities, which in turn are associated with impairment in neurocognitive function. However, findings are inconsistent as to which domains of cognition are affected by TBI-related white matter disruption. Recent evidence that white matter abnormalities associated with blast-related mTBI are spatially variable raises the possibility that the associated cognitive impairment is also heterogeneous. Thus, the goals of this study were to examine (1) whether mTBI-related white matter abnormalities are associated with overall cognitive status and (2) whether white matter abnormalities provide a mechanism by which mTBI influences cognition. Ninety-six Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OEF) veterans were assigned to one of three groups: no-TBI, mTBI without loss of consciousness (LOC) (mTBI-LOC), and mTBI with LOC (mTBI + LOC). Participants were given a battery of neuropsychological tests that were selected for their sensitivity to mTBI. Results showed that number of white matter abnormalities was associated with the odds of having clinically significant cognitive impairment. A mediation analysis revealed that mTBI + LOC was indirectly associated with cognitive impairment through its effect on white matter integrity. These results suggest that cognitive difficulties in blast-related mTBI can be linked to injury-induced neural changes when taking into account the variability of injury as well as the heterogeneity in cognitive deficits across individuals.

White matter atrophy and myelinated fiber disruption in a rat model of depression.

PubMed

Gao, Yuan; Ma, Jing; Tang, Jing; Liang, Xin; Huang, Chun-Xia; Wang, San-Rong; Chen, Lin-Mu; Wang, Fei-Fei; Tan, Chuan-Xue; Chao, Feng-Lei; Zhang, Lei; Qiu, Xuan; Luo, Yan-Min; Xiao, Qian; Du, Lian; Xiao, Qian; Tang, Yong

2017-06-01

Brain imaging and postmortem studies have indicated that white matter abnormalities may contribute to the pathology and pathogenesis of depression. However, until now, no study has quantitatively investigated white matter changes in depression in rats. The current study used the chronic unpredictable stress (CUS) model of depression. Body weight and sucrose preference test (SPT) scores were assessed weekly. Upon successfully establishing the CUS animal model, all animals were tested using the SPT and the open field test (OFT). Then, transmission electron microscopy and unbiased stereological methods were used to investigate white matter changes in the rats. Compared with the control group, the body weight and sucrose preference of the CUS rats were significantly decreased (p < .001, p < .001, respectively). In the OFT, the total time spent and the total distance traveled in the inner area by the CUS rats were significantly lower than those of the control group (p = .002, p = .001, respectively). The stereological results revealed that white matter volume, the total volume, and the total length and mean diameter of myelinated fibers in the white matter of the CUS rats were significantly decreased compared to the control rats (p = .042, p = .038, p = .035, p = .019, respectively). The results of this study suggested that white matter atrophy and disruption of myelinated fibers in the white matter may contribute to the pathophysiology underlying depression, which might provide new targets for the development of novel therapeutic interventions for depression. © 2017 Wiley Periodicals, Inc.

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 disrupted end-feet juxtaposed to microvessels. To explore whether this was associated with the disrupted gliovascular interactions or blood-brain barrier damage, we assessed the co-localization of GFAP and AQP4 immunoreactivities in post-mortem brains from adult baboons with cerebral hypoperfusive injury, induced by occlusion of three major vessels supplying blood to the brain. Analysis of the frontal white matter in perfused brains from the animals surviving 1-28 days after occlusion revealed that the highest intensity of fibrinogen immunoreactivity was at 14 days. At this survival time point, we also noted strikingly similar redistribution of AQP4 and GFAP+ astrocytes transformed into clasmatodendrocytes. Our findings suggest novel associations between irreversible astrocyte injury and disruption of gliovascular interactions at the blood-brain barrier in the frontal white matter and cognitive impairment in elderly post-stroke survivors. We propose that clasmatodendrosis is another pathological substrate, linked to white matter hyperintensities and frontal white matter changes, which may contribute to post-stroke or small vessel disease dementia. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

Depressive Symptoms in Adolescents: Associations with White Matter Volume and Marijuana Use

ERIC Educational Resources Information Center

Medina, Krista Lisdahl; Nagel, Bonnie J.; Park, Ann; McQueeny, Tim; Tapert, Susan F.

2007-01-01

Background: Depressed mood has been associated with decreased white matter and reduced hippocampal volumes. However, the relationship between brain structure and mood may be unique among adolescents who use marijuana heavily. The goal of this study was to examine the relationship between white matter and hippocampal volumes and depressive symptoms…

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…

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....

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.

Age-related white matter integrity differences in oldest-old without dementia.

PubMed

Bennett, Ilana J; Greenia, Dana E; Maillard, Pauline; Sajjadi, S Ahmad; DeCarli, Charles; Corrada, Maria M; Kawas, Claudia H

2017-08-01

Aging is known to have deleterious effects on cerebral white matter, yet little is known about these white matter alterations in advanced age. In this study, 94 oldest-old adults without dementia (90-103 years) underwent diffusion tensor imaging to assess relationships between chronological age and multiple measures of integrity in 18 white matter regions across the brain. Results revealed significant age-related declines in integrity in regions previously identified as being sensitive to aging in younger-old adults (corpus callosum, fornix, cingulum, external capsule). For the corpus callosum, the effect of age on genu fractional anisotropy was significantly weaker than the relationship between age and splenium fractional anisotropy. Importantly, age-related declines in white matter integrity did not differ in cognitively normal and cognitively impaired not demented oldest-old, suggesting that they were not solely driven by cognitive dysfunction or preclinical dementia in this advanced age group. Instead, white matter in these regions appears to remain vulnerable to normal aging processes through the 10th decade of life. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Neuroblast Distribution after Cortical Impact Is Influenced by White Matter Injury in the Immature Gyrencephalic Brain

PubMed Central

Taylor, Sabrina R.; Smith, Colin M.; Keeley, Kristen L.; McGuone, Declan; Dodge, Carter P.; Duhaime, Ann-Christine; Costine, Beth A.

2016-01-01

Cortical contusions are a common type of traumatic brain injury (TBI) in children. Current knowledge of neuroblast response to cortical injury arises primarily from studies utilizing aspiration or cryoinjury in rodents. In infants and children, cortical impact affects both gray and white matter and any neurogenic response may be complicated by the large expanse of white matter between the subventricular zone (SVZ) and the cortex, and the large number of neuroblasts in transit along the major white matter tracts to populate brain regions. Previously, we described an age-dependent increase of neuroblasts in the SVZ in response to cortical impact in the immature gyrencephalic brain. Here, we investigate if neuroblasts target the injury, if white matter injury influences repair efforts, and if postnatal population of brain regions are disrupted. Piglets received a cortical impact to the rostral gyrus cortex or sham surgery at postnatal day (PND) 7, BrdU 2 days prior to (PND 5 and 6) or after injury (PND 7 and 8), and brains were collected at PND 14. Injury did not alter the number of neuroblasts in the white matter between the SVZ and the rostral gyrus. In the gray matter of the injury site, neuroblast density was increased in cavitated lesions, and the number of BrdU+ neuroblasts was increased, but comprised less than 1% of all neuroblasts. In the white matter of the injury site, neuroblasts with differentiating morphology were densely arranged along the cavity edge. In a ventral migratory stream, neuroblast density was greater in subjects with a cavitated lesion, indicating that TBI may alter postnatal development of regions supplied by that stream. Cortical impact in the immature gyrencephalic brain produced complicated and variable lesions, increased neuroblast density in cavitated gray matter, resulted in potentially differentiating neuroblasts in the white matter, and may alter the postnatal population of brain regions utilizing a population of neuroblasts that were born prior to PND 5. This platform may be useful to continue to study potential complications of white matter injury and alterations of postnatal population of brain regions, which may contribute to the chronic effects of TBI in children. PMID:27601978

Left-Hemispheric Microstructural Abnormalities in Children With High Functioning Autism Spectrum Disorder

PubMed Central

Peterson, Daniel; Mahajan, Rajneesh; Crocetti, Deana; Mejia, Amanda; Mostofsky, Stewart

2014-01-01

Current theories of the neurobiological basis of Autism Spectrum Disorder (ASD) posit an altered pattern of connectivity in large-scale brain networks. Here we used Diffusion Tensor Imaging to investigate the microstructural properties of the white matter that mediates inter-regional connectivity in 36 high-functioning children with ASD (HF-ASD), as compared to 37 controls. By employing an atlas-based analysis using LDDMM registration, a widespread, but left-lateralized pattern of abnormalities was revealed. The Mean Diffusivity (MD) of water in the white matter of HF-ASD children was significantly elevated throughout the left hemisphere, particularly in the outer-zone cortical white matter. Across diagnostic groups there was a significant effect of age on left hemisphere MD, with a similar reduction in MD during childhood in both TD and HF-ASD children. The increased MD in children with HF-ASD suggests hypomyelination, and may reflect increased short-range cortico-cortical connections subsequent to early white matter overgrowth. These findings also highlight left hemispheric connectivity as relevant to the pathophysiology of ASD, and indicate that the spatial distribution of microstructural abnormalities in HF-ASD is widespread, and left-lateralized. This altered left-hemispheric connectivity may contribute to deficits in communication and praxis observed in ASD. PMID:25256103

Hypoxia during pregnancy in rats leads to the changes of the cerebral white matter in adult offspring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Lingxing; Cai, Ruowei; Lv, Guorong, E-mail: lxingwan502@gmail.com

The aim of the present study is to evaluate the effect of reduced fetal oxygen supply on cerebral white matter in the adult offspring and further assess its susceptibility to postnatal hypoxia and high-fat diet. Based on a 3 x 2 full factorial design consisting of three factors of maternal hypoxia, postnatal high-fat diet, and postnatal hypoxia, the ultrastructure of myelin, axon and capillaries were observed, and the expression of myelin basic protein (MBP), neurofilament-H+L(NF-H+L), and glial fibrillary acidic protein (GFAP) was analyzed in periventricular white matter of 16-month-old offspring. Demyelination, injured axon and damaged microvasculars were observed in maternalmore » hypoxia offspring. The main effect of maternal hypoxia lead to decreased expression of MBP or NF-H+L, and increased expression of GFAP (all P < 0.05). Moreover, there was positive three-way interaction among maternal hypoxia, high-fat diet and postnatal hypoxia on MBP, NF-H+L or GFAP expression (all P < 0.05). In summary, our results indicated that maternal hypoxia during pregnancy in rats lead to changes of periventricular white matter in adult offspring, including demyelination, damaged axon and proliferated astroglia. This effect was amplified by high-fat diet and postnatal hypoxia.« less

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

The association of mid-to late-life systemic inflammation with white matter structure in older adults: The Atherosclerosis Risk in Communities Study.

PubMed

Walker, Keenan A; Windham, B Gwen; Power, Melinda C; Hoogeveen, Ron C; Folsom, Aaron R; Ballantyne, Christie M; Knopman, David S; Selvin, Elizabeth; Jack, Clifford R; Gottesman, Rebecca F

2018-08-01

We examined whether the pattern of middle- to late-life systemic inflammation was associated with white matter (WM) structural abnormalities in older adults. A total of 1532 participants (age = 76.5; standard deviations = 5.4) underwent 3T brain magnetic resonance imaging to quantify white matter hyperintensity volume and whole-brain WM microstructural integrity (fractional anisotropy, mean diffusivity). High-sensitivity C-reactive protein (CRP), a marker of systemic inflammation, was measured at 3 visits (21 and 14 years before, and concurrent with, neuroimaging). Participants were categorized into 1 of 6 groups based on their 21-year pattern of low (<3 mg/L) versus elevated (≥3 mg/L) CRP. Compared to the group with low CRP at all 3 visits, the group that transitioned from low to elevated CRP during midlife demonstrated greatest white matter hyperintensity volume and poorest WM microstructural integrity, after adjusting for demographic variables and cardiovascular risk factors. Participants with high CRP at all visits also demonstrated greater WM structural abnormalities, but only after accounting for differential attrition. These results suggest that increasing and persistent inflammation in the decades spanning middle-to late-life may promote WM disease in older adults. Copyright © 2018 Elsevier Inc. All rights reserved.

Differences in integrity of white matter and changes with training in spelling impaired children: a diffusion tensor imaging study

PubMed Central

Gebauer, D.; Fink, A.; Filippini, N.; Johansen-Berg, H.; Reishofer, G.; Koschutnig, K.; Kargl, R.; Purgstaller, C.; Fazekas, F.; Enzinger, C.

2013-01-01

While the functional correlates of spelling impairment have been rarely investigated, to our knowledge no study exists regarding the structural characteristics of spelling impairment and potential changes with interventions. Using diffusion tensor imaging at 3.0 T, we here therefore sought to investigate (a) differences between children with poor spelling abilities (training group and waiting group) and controls, and (b) the effects of a morpheme- based spelling intervention in children with poor spelling abilities on DTI parameters. A baseline comparison of white matter indices revealed significant differences between controls and spelling-impaired children, mainly located in the right hemisphere (superior corona radiata (SCR), posterior limb of internal capsule, superior longitudinal fasciculus). After 5 weeks of training, spelling ability improved in the training group, along with increases in fractional anisotropy and decreases of radial diffusivity in the right hemisphere compared to controls. In addition, significantly higher decreases of mean diffusivity in the right SCR for the spelling-impaired training group compared to the waiting group were observed. Our results suggest that spelling impairment is associated with differences in white-matter integrity in the right hemisphere. We also provide first indications that white matter changes occur during successful training, but this needs to be more specifically addressed in future research. PMID:22198594

Differences in integrity of white matter and changes with training in spelling impaired children: a diffusion tensor imaging study.

PubMed

Gebauer, D; Fink, A; Filippini, N; Johansen-Berg, H; Reishofer, G; Koschutnig, K; Kargl, R; Purgstaller, C; Fazekas, F; Enzinger, C

2012-07-01

While the functional correlates of spelling impairment have been rarely investigated, to our knowledge no study exists regarding the structural characteristics of spelling impairment and potential changes with interventions. Using diffusion tensor imaging at 3.0 T, we here therefore sought to investigate (a) differences between children with poor spelling abilities (training group and waiting group) and controls, and (b) the effects of a morpheme-based spelling intervention in children with poor spelling abilities on DTI parameters. A baseline comparison of white matter indices revealed significant differences between controls and spelling-impaired children, mainly located in the right hemisphere (superior corona radiata (SCR), posterior limb of internal capsule, superior longitudinal fasciculus). After 5 weeks of training, spelling ability improved in the training group, along with increases in fractional anisotropy and decreases of radial diffusivity in the right hemisphere compared to controls. In addition, significantly higher decreases of mean diffusivity in the right SCR for the spelling-impaired training group compared to the waiting group were observed. Our results suggest that spelling impairment is associated with differences in white-matter integrity in the right hemisphere. We also provide first indications that white matter changes occur during successful training, but this needs to be more specifically addressed in future research.

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

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.

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.

Bivariate Heritability of Total and Regional Brain Volumes: the Framingham Study

PubMed Central

DeStefano, Anita L.; Seshadri, Sudha; Beiser, Alexa; Atwood, Larry D.; Massaro, Joe M.; Au, Rhoda; Wolf, Philip A.; DeCarli, Charles

2009-01-01

Heritability and genetic and environmental correlations of total and regional brain volumes were estimated from a large, generally healthy, community-based sample, to determine if there are common elements to the genetic influence of brain volumes and white matter hyperintensity volume. There were 1538 Framingham Heart Study participants with brain volume measures from quantitative magnetic resonance imaging (MRI) who were free of stroke and other neurological disorders that might influence brain volumes and who were members of families with at least two Framingham Heart Study participants. Heritability was estimated using variance component methodology and adjusting for the components of the Framingham stroke risk profile. Genetic and environmental correlations between traits were obtained from bivariate analysis. Heritability estimates ranging from 0.46 to 0.60, were observed for total brain, white matter hyperintensity, hippocampal, temporal lobe, and lateral ventricular volumes. Moderate, yet significant, heritability was observed for the other measures. Bivariate analyses demonstrated that relationships between brain volume measures, except for white matter hyperintensity, reflected both moderate to strong shared genetic and shared environmental influences. This study confirms strong genetic effects on brain and white matter hyperintensity volumes. These data extend current knowledge by showing that these two different types of MRI measures do not share underlying genetic or environmental influences. PMID:19812462

White matter changes in an untreated, newly diagnosed case of classical homocystinuria.

PubMed

Brenton, J Nicholas; Matsumoto, Julie A; Rust, Robert S; Wilson, William G

2014-01-01

The authors report the case of a 4-year-old boy who developed progressive unilateral weakness and developmental delays prior to his diagnosis of classical homocystinuria. Magnetic resonance imaging (MRI) of the brain demonstrated diffuse white matter changes, raising the concern for a secondary diagnosis causing leukoencephalopathy, since classical homocystinuria is not typically associated with these changes. Other inborn errors of the transsulfuration pathway have been reported as causing these changes. Once begun on therapy for his homocystinuria, his neurologic deficits resolved and his delays rapidly improved. Repeat MRI performed one year after instating therapy showed resolution of his white matter abnormalities. This case illustrates the need to consider homocystinuria and other amino acidopathies in the differential diagnosis of childhood white matter diseases and lends weight to the hypothesis that hypermethioninemia may induce white matter changes.

Acute Disseminated Encephalomyelitis: A Gray Distinction.

PubMed

Abu Libdeh, Amal; Goodkin, Howard P; Ramirez-Montealegre, Denia; Brenton, J Nicholas

2017-03-01

Acute disseminated encephalomyelitis (ADEM) is an immune-mediated, inflammatory acquired demyelinating syndrome predominantly affecting the white matter of the central nervous system. We describe a three-year-old boy whose clinical presentation was suspicious for ADEM but whose initial imaging abnormalities were confined to the deep gray matter (without evidence of white matter involvement). His clinical course was fluctuating and repeat imaging one week after presentation demonstrated interval development of characteristic white matter lesions. Treatment with adjunctive intravenous immunoglobulin and high-dose corticosteroids resulted in significant clinical improvement. Isolated deep gray matter involvement can precede the appearance of white matter abnormalities of ADEM, suggesting that repeat imaging is indicated in individuals whose findings are clinically suspicious for ADEM but who lack characteristic imaging findings. Copyright © 2017 Elsevier Inc. All rights reserved.

Prominent microglial activation in cortical white matter is selectively associated with cortical atrophy in primary progressive aphasia.

PubMed

Ohm, D T; Kim, G; Gefen, T; Rademaker, A; Weintraub, S; Bigio, E H; Mesulam, M-M; Rogalski, E; Geula, C

2018-04-21

Primary progressive aphasia (PPA) is a clinical syndrome characterized by selective language impairments associated with focal cortical atrophy favouring the language dominant hemisphere. PPA is associated with Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) and significant accumulation of activated microglia. Activated microglia can initiate an inflammatory cascade that may contribute to neurodegeneration, but their quantitative distribution in cortical white matter and their relationship with cortical atrophy remain unknown. We investigated white matter activated microglia and their association with grey matter atrophy in 10 PPA cases with either AD or FTLD-TDP pathology. Activated microglia were quantified with optical density measures of HLA-DR immunoreactivity in two regions with peak cortical atrophy, and one nonatrophied region within the language dominant hemisphere of each PPA case. Nonatrophied contralateral homologues of the language dominant regions were examined for hemispheric asymmetry. Qualitatively, greater densities of activated microglia were observed in cortical white matter when compared to grey matter. Quantitative analyses revealed significantly greater densities of activated microglia in the white matter of atrophied regions compared to nonatrophied regions in the language dominant hemisphere (P < 0.05). Atrophied regions of the language dominant hemisphere also showed significantly more activated microglia compared to contralateral homologues (P < 0.05). White matter activated microglia accumulate more in atrophied regions in the language dominant hemisphere of PPA. While microglial activation may constitute a response to neurodegenerative processes in white matter, the resultant inflammatory processes may also exacerbate disease progression and contribute to cortical atrophy. © 2018 British Neuropathological Society.

White matter lesions and brain atrophy in systemic lupus erythematosus patients: correlation to cognitive dysfunction in a cohort of systemic lupus erythematosus patients using different definition models for neuropsychiatric systemic lupus erythematosus.

PubMed

Cannerfelt, B; Nystedt, J; Jönsen, A; Lätt, J; van Westen, D; Lilja, A; Bengtsson, A; Nilsson, P; Mårtensson, J; Sundgren, P C

2018-06-01

Aim The aim of this study was to evaluate the extent of white matter lesions, atrophy of the hippocampus and corpus callosum, and their correlation with cognitive dysfunction (CD), in patients diagnosed with systemic lupus erythematosus (SLE). Methods Seventy SLE patients and 25 healthy individuals (HIs) were included in the study. To evaluate the different SLE and neuropsychiatric SLE (NPSLE) definition schemes, patients were grouped both according to the American College of Rheumatology (ACR) definition, as well as the more stringent ACR-Systemic Lupus International Collaborating Clinics definition. Patients and HIs underwent a 3 Tesla brain MRI and a standardized neuropsychological test. MRI data were evaluated for number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum. Differences between groups and subgroups were evaluated for significance. Number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum were correlated to cognitive dysfunction. Results The total volume of white matter lesions was significantly larger in SLE patients compared to HIs ( p = 0.004). However, no significant differences were seen between the different SLE subgroups. Atrophy of the bilateral hippocampus was significantly more pronounced in patients with NPSLE compared to those with non-NPSLE (right: p = 0.010; left p = 0.023). Significant negative correlations between cognitive test scores on verbal memory and number and volume of white matter lesions were present. Conclusion SLE patients have a significantly larger volume of white matter lesions on MRI compared to HIs and the degree of white matter lesion volume correlates to cognitive dysfunction, specifically to verbal memory. No significant differences in the number or volume of white matter lesions were identified between subgroups of SLE patients regardless of the definition model used.

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 4-27). We report and anatomically map lifespan changes related to cellular and extracellular microstructural components that are associated with white matter maturation and aging.

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 their term MRI appear to be spared many of the cognitive impairments commonly associated with preterm birth. Further follow-up will be important to assess whether this finding persists into the school years. PMID:23284800

White Matter Correlates of Auditory Comprehension Outcomes in Chronic Post-Stroke Aphasia

PubMed Central

Xing, Shihui; Lacey, Elizabeth H.; Skipper-Kallal, Laura M.; Zeng, Jinsheng; Turkeltaub, Peter E.

2017-01-01

Neuroimaging studies have shown that speech comprehension involves a number of widely distributed regions within the frontal and temporal lobes. We aimed to examine the differential contributions of white matter connectivity to auditory word and sentence comprehension in chronic post-stroke aphasia. Structural and diffusion MRI data were acquired on 40 patients with chronic post-stroke aphasia. A battery of auditory word and sentence comprehension tests were administered to all the patients. Tract-based spatial statistics were used to identify areas in which white matter integrity related to specific comprehension deficits. Relevant tracts were reconstructed using probabilistic tractography in healthy older participants, and the mean values of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of the entire tracts were examined in relation to comprehension scores. Anterior temporal white matter integrity loss and involvement of the uncinate fasciculus related to word-level comprehension deficits (RFA = 0.408, P = 0.012; RMD = −0.429, P = 0.008; RAD = −0.424, P = 0.009; RRD = −0.439, P = 0.007). Posterior temporal white matter integrity loss and involvement of the inferior longitudinal fasciculus related to sentence-level comprehension deficits (RFA = 0.382, P = 0.02; RMD = −0.461, P = 0.004; RAD = −0.457, P = 0.004; RRD = −0.453, P = 0.005). Loss of white matter integrity in the inferior fronto-occipital fasciculus related to both word- and sentence-level comprehension (word-level scores: RFA = 0.41, P = 0.012; RMD = −0.447, P = 0.006; RAD = −0.489, P = 0.002; RRD = −0.432, P = 0.008; sentence-level scores: RFA = 0.409, P = 0.012; RMD = −0.413, P = 0.011; RAD = −0.408, P = 0.012; RRD = −0.413, P = 0.011). Lesion overlap, but not white matter integrity, in the arcuate fasciculus related to sentence-level comprehension deficits. These findings suggest that word-level comprehension outcomes in chronic post-stroke aphasia rely primarily on anterior temporal lobe pathways, whereas sentence-level comprehension relies on more widespread pathways including the posterior temporal lobe. PMID:28275366

Complex Regional Pain Syndrome Type I Affects Brain Structure in Prefrontal and Motor Cortex

PubMed Central

Pleger, Burkhard; Draganski, Bogdan; Schwenkreis, Peter; Lenz, Melanie; Nicolas, Volkmar; Maier, Christoph; Tegenthoff, Martin

2014-01-01

The complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1) and motor cortex (M1) contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls) were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the “non-flipped” data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the “flipped” data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control. PMID:24416397

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.

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.

Sensitive biomarkers of alcoholism's effect on brain macrostructure: similarities and differences between France and the United States

PubMed Central

Le Berre, Anne-Pascale; Pitel, Anne-Lise; Chanraud, Sandra; Beaunieux, Hélène; Eustache, Francis; Martinot, Jean-Luc; Reynaud, Michel; Martelli, Catherine; Rohlfing, Torsten; Pfefferbaum, Adolf; Sullivan, Edith V.

2015-01-01

Alcohol consumption patterns and recognition of health outcomes related to hazardous drinking vary widely internationally, raising the question whether these national differences are reflected in brain damage observed in alcoholism. This retrospective analysis assessed variability of alcoholism's effects on brain cerebrospinal fluid (CSF) and white matter volumes between France and the United States (U.S.). MRI data from two French sites (Caen and Orsay) and a U.S. laboratory (SRI/Stanford University) were acquired on 1.5T imaging systems in 287 controls, 165 uncomplicated alcoholics (ALC), and 26 alcoholics with Korsakoff's Syndrome (KS). All data were analyzed at the U.S. site using atlas-based parcellation. Results revealed graded CSF volume enlargement from ALC to KS and white matter volume deficits in KS only. In ALC from France but not the U.S., CSF and white matter volumes correlated with lifetime alcohol consumption, alcoholism duration, and length of sobriety. MRI highlighted CSF volume enlargement in both ALC and KS, serving as a basis for an ex vacuo process to explain correlated gray matter shrinkage. By contrast, MRI provided a sensitive in vivo biomarker of white matter volume shrinkage in KS only, suggesting a specific process sensitive to mechanisms contributing to Wernicke's encephalopathy, the precursor of KS. Identified structural brain abnormalities may provide biomarkers underlying alcoholism's heterogeneity in and among nations and suggest a substrate of gray matter tissue shrinkage. Proposed are hypotheses for national differences in interpreting whether the severity of sequelae observe a graded phenomenon or a continuum from uncomplicated alcoholism to alcoholism complicated by KS. PMID:26157376

Creutzfeldt-Jakob disease with severe involvement of cerebral white matter and cerebellum.

PubMed

Berciano, J; Berciano, M T; Polo, J M; Figols, J; Ciudad, J; Lafarga, M

1990-01-01

We describe a patient with Creutzfeldt-Jakob disease (CJD) of the ataxic and panencephalopathic type. Postmortem examination revealed the characteristic lesions of CJD in the grey matter and profound white matter involvement was seen with immunocytochemical techniques. Ultrastructural white matter lesions were identical to those described in experimentally transmitted CJD. There was marked loss of cerebellar granule cells with virtual disappearance of parallel fibres, but Purkinje cells were only slightly reduced. Electron microscopic studies revealed extensive degenerative changes including cytoplasmic vacuoles in both cell types. Silver methods disclosed massive impregnation of white matter and striking abnormalities of Purkinje cells consisting of hypertrophy and flattening of thick dendritic branches, reduction in the number of terminal branchlets, segmentary loss of spines and polymorphic spines. These findings show the extensive involvement of all three cerebellar cortical layers and the reactive plasticity of Purkinje cells to deafferentiation. They favour the hypothesis that demyelination represents a primary lesion of the white matter.

Perinatal White Matter Injury: The Changing Spectrum of Pathology and Emerging Insights into Pathogenetic Mechanisms

ERIC Educational Resources Information Center

Back, Stephen A.

2006-01-01

Perinatal brain injury in survivors of premature birth has a unique and unexplained predilection for periventricular cerebral white matter. Periventricular white-matter injury (PWMI) is now the most common cause of brain injury in preterm infants and the leading cause of chronic neurological morbidity. The spectrum of chronic PWMI includes focal…

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 Compromise of Callosal and Subcortical Fiber Tracts in Children with Autism Spectrum Disorder: A Diffusion Tensor Imaging Study

ERIC Educational Resources Information Center

Shukla, Dinesh K.; Keehn, Brandon; Lincoln, Alan J.; Muller, Ralph-Axel

2010-01-01

Objective: Autism spectrum disorder (ASD) is increasingly viewed as a disorder of functional networks, highlighting the importance of investigating white matter and interregional connectivity. We used diffusion tensor imaging (DTI) to examine white matter integrity for the whole brain and for corpus callosum, internal capsule, and middle…

The association of cognitive impairment with gray matter atrophy and cortical lesion load in clinically isolated syndrome.

PubMed

Diker, Sevda; Has, Arzu Ceylan; Kurne, Aslı; Göçmen, Rahşan; Oğuz, Kader Karlı; Karabudak, Rana

2016-11-01

Multiple sclerosis can impair cognition from the early stages and has been shown to be associated with gray matter damage in addition to white matter pathology. To investigate the profile of cognitive impairment in clinically isolated syndrome (CIS), and the contribution of cortical inflammation, cortical and deep gray matter atrophy, and white matter lesions to cognitive decline. Thirty patients with clinically isolated syndrome and twenty demographically- matched healthy controls underwent neuropsychologic assessment through the Rao Brief Repeatable Battery, and brain magnetic resonance imaging with double inversion recovery using a 3T scanner. Patients with clinically isolated syndrome performed significantly worse than healthy controls on tests that evaluated verbal memory, visuospatial learning and memory, and verbal fluency. Significant deep gray matter atrophy was found in the patients but cortical volume was not lower than the controls. Visual memory tests correlated with the volume of the hippocampus, cerebral white matter and deep gray matter structures and with cerebellar cortical atrophy. Cortical or white matter lesion load did not affect cognitive test results. In our patients with CIS, it was shown that cognitive impairment was mainly related to cerebral white matter, cerebellar cortical and deep gray matter atrophy, but not with cortical inflammation, at least in the early stage of disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Tracking Brain Development and Dimensional Psychiatric Symptoms in Children: A Longitudinal Population-Based Neuroimaging Study.

PubMed

Muetzel, Ryan L; Blanken, Laura M E; van der Ende, Jan; El Marroun, Hanan; Shaw, Philip; Sudre, Gustavo; van der Lugt, Aad; Jaddoe, Vincent W V; Verhulst, Frank C; Tiemeier, Henning; White, Tonya

2018-01-01

Psychiatric symptomatology during childhood predicts persistent mental illness later in life. While neuroimaging methodologies are routinely applied cross-sectionally to the study of child and adolescent psychopathology, the nature of the relationship between childhood symptoms and the underlying neurodevelopmental processes remains unclear. The authors used a prospective population-based cohort to delineate the longitudinal relationship between childhood psychiatric problems and brain development. A total of 845 children participated in the study. Psychiatric symptoms were measured with the parent-rated Child Behavior Checklist at ages 6 and 10. MRI data were collected at ages 8 and 10. Cross-lagged panel models and linear mixed-effects models were used to determine the associations between psychiatric symptom ratings and quantitative anatomic and white matter microstructural measures over time. Higher ratings for externalizing and internalizing symptoms at baseline predicted smaller increases in both subcortical gray matter volume and global fractional anisotropy over time. The reverse relationship did not hold; thus, baseline measures of gray matter and white matter were not significantly related to changes in symptom ratings over time. Children presenting with behavioral problems at an early age show differential subcortical and white matter development. Most neuroimaging models tend to explain brain differences observed in psychopathology as an underlying (causal) neurobiological substrate. However, the present work suggests that future neuroimaging studies showing effects that are pathogenic in nature should additionally explore the possibility of the downstream effects of psychopathology on the brain.

Surface-based brain morphometry and diffusion tensor imaging in schizoaffective disorder.

PubMed

Landin-Romero, Ramón; Canales-Rodríguez, Erick J; Kumfor, Fiona; Moreno-Alcázar, Ana; Madre, Mercè; Maristany, Teresa; Pomarol-Clotet, Edith; Amann, Benedikt L

2017-01-01

The profile of grey matter abnormalities and related white-matter pathology in schizoaffective disorder has only been studied to a limited extent. The aim of this study was to identify grey- and white-matter abnormalities in patients with schizoaffective disorder using complementary structural imaging techniques. Forty-five patients meeting Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria and Research Diagnostic Criteria for schizoaffective disorder and 45 matched healthy controls underwent structural-T1 and diffusion magnetic resonance imaging to enable surface-based brain morphometry and diffusion tensor imaging analyses. Analyses were conducted to determine group differences in cortical volume, cortical thickness and surface area, as well as in fractional anisotropy and mean diffusivity. At a threshold of p = 0.05 corrected, all measures revealed significant differences between patients and controls at the group level. Spatial overlap of abnormalities was observed across the various structural neuroimaging measures. In grey matter, patients with schizoaffective disorder showed abnormalities in the frontal and temporal lobes, striatum, fusiform, cuneus, precuneus, lingual and limbic regions. White-matter abnormalities were identified in tracts connecting these areas, including the corpus callosum, superior and inferior longitudinal fasciculi, anterior thalamic radiation, uncinate fasciculus and cingulum bundle. The spatial overlap of abnormalities across the different imaging techniques suggests widespread and consistent brain pathology in schizoaffective disorder. The abnormalities were mainly detected in areas that have commonly been reported to be abnormal in schizophrenia, and to some extent in bipolar disorder, which may explain the clinical and aetiological overlap in these disorders.

Epigenetic Age Acceleration Assessed with Human White-Matter Images.

PubMed

Hodgson, Karen; Carless, Melanie A; Kulkarni, Hemant; Curran, Joanne E; Sprooten, Emma; Knowles, Emma E; Mathias, Samuel; Göring, Harald H H; Yao, Nailin; Olvera, Rene L; Fox, Peter T; Almasy, Laura; Duggirala, Ravi; Blangero, John; Glahn, David C

2017-05-03

The accurate estimation of age using methylation data has proved a useful and heritable biomarker, with acceleration in epigenetic age predicting a number of age-related phenotypes. Measures of white matter integrity in the brain are also heritable and highly sensitive to both normal and pathological aging processes across adulthood. We consider the phenotypic and genetic interrelationships between epigenetic age acceleration and white matter integrity in humans. Our goal was to investigate processes that underlie interindividual variability in age-related changes in the brain. Using blood taken from a Mexican-American extended pedigree sample ( n = 628; age = 23.28-93.11 years), epigenetic age was estimated using the method developed by Horvath (2013). For n = 376 individuals, diffusion tensor imaging scans were also available. The interrelationship between epigenetic age acceleration and global white matter integrity was investigated with variance decomposition methods. To test for neuroanatomical specificity, 16 specific tracts were additionally considered. We observed negative phenotypic correlations between epigenetic age acceleration and global white matter tract integrity (ρ pheno = -0.119, p = 0.028), with evidence of shared genetic (ρ gene = -0.463, p = 0.013) but not environmental influences. Negative phenotypic and genetic correlations with age acceleration were also seen for a number of specific white matter tracts, along with additional negative phenotypic correlations between granulocyte abundance and white matter integrity. These findings (i.e., increased acceleration in epigenetic age in peripheral blood correlates with reduced white matter integrity in the brain and shares common genetic influences) provide a window into the neurobiology of aging processes within the brain and a potential biomarker of normal and pathological brain aging. SIGNIFICANCE STATEMENT Epigenetic measures can be used to predict age with a high degree of accuracy and so capture acceleration in biological age, relative to chronological age. The white matter tracts within the brain are also highly sensitive to aging processes. We show that increased biological aging (measured using epigenetic data from blood samples) is correlated with reduced integrity of white matter tracts within the human brain (measured using diffusion tensor imaging) with data from a large sample of Mexican-American families. Given the family design of the sample, we are also able to demonstrate that epigenetic aging and white matter tract integrity also share common genetic influences. Therefore, epigenetic age may be a potential, and accessible, biomarker of brain aging. Copyright © 2017 the authors 0270-6474/17/374735-09$15.00/0.

Cortisol Reactivity to Stress and Its Association With White Matter Integrity in Adults With Schizophrenia.

PubMed

Nugent, Katie L; Chiappelli, Joshua; Sampath, Hemalatha; Rowland, Laura M; Thangavelu, Kavita; Davis, Beshaun; Du, Xiaoming; Muellerklein, Florian; Daughters, Stacey; Kochunov, Peter; Hong, L Elliot

2015-09-01

Although acute hypothalamic-pituitary-adrenal axis response to stress is often adaptive, prolonged responses may have detrimental effects. Many components of white matter structures are sensitive to prolonged cortisol exposure. We aimed to identify a behavioral laboratory assay for cortisol response related to brain pathophysiology in schizophrenia. We hypothesized that an abnormally prolonged cortisol response to stress may be linked to abnormal white matter integrity in patients with schizophrenia. Acute and prolonged salivary cortisol response was measured outside the scanner at pretest and then at 0, 20, and 40 minutes after a psychological stress task in patients with schizophrenia (n = 45) and controls (n = 53). Tract-averaged white matter was measured by 64-direction diffusion tensor imaging in a subset of patients (n = 30) and controls (n = 33). Patients who did not tolerate the psychological stress task and quit had greater acute (t = 2.52 [p = .016] and t = 3.51 [p = .001] at 0 and 20 minutes) and prolonged (t = 3.62 [p = .001] at 40 minutes) cortisol reactivity compared with patients who finished the task. Abnormally prolonged cortisol reactivity in patients was significantly associated with reduced white matter integrity (r = -0.468, p = .009). Regardless of task completion status, acute cortisol response was not related to the white matter measures in patients or controls. This paradigm was successful at identifying a subset of patients whose cortisol response was associated with brain pathophysiology. Abnormal cortisol response may adversely affect white matter integrity, partly explaining this pathology observed in schizophrenia. Prolonged stress responses may be targeted for intervention to test for protective effects against white matter damages.

Usefulness of the apparent diffusion coefficient for the evaluation of the white matter to differentiate between glioblastoma and brain metastases.

PubMed

Miquelini, L A; Pérez Akly, M S; Funes, J A; Besada, C H

2016-01-01

To determine whether there are significant differences in the apparent diffusion coefficient (ADC) between the apparently normal peritumor white matter surrounding glioblastomas and that surrounding brain metastases. We retrospectively reviewed 42 patients with histologically confirmed glioblastomas and 42 patients with a single cerebral metastasis. We measured the signal intensity in the apparently normal peritumor white matter and in the abnormal peritumor white matter on the ADC maps. We used mean ADC values in the contralateral occipital white matter as a reference from which to design normalized ADC indices. We compared mean values between the two tumor types. We calculated the area under the receiver operator characteristic curve and estimated the sensitivity and specificity of the measurements taken. Supratentorial lesions and compromise of the corpus callosum were more common in patients with glioblastoma than in patients with brain metastases. The maximum diameter of the enhanced area after injection of a contrast agent was greater in the glioblastomas (p<0.001). The minimum ADC value measured in the apparently normal peritumor white matter was higher for the glioblastomas than for the metastases (p=0.002). Significant differences in the ADC index were found only for the minimum ADC value in apparently normal peritumor white matter. The sensitivity and specificity were less than 70% for all variables analyzed. There are differences in the ADC values of apparently normal peritumor white matter between glioblastomas and cerebral metastases, but the magnitude of these differences is slight and the application of these differences in clinical practice is still limited. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

γδT cells but not αβT cells contribute to sepsis-induced white matter injury and motor abnormalities in mice.

PubMed

Zhang, Xiaoli; Rocha-Ferreira, Eridan; Li, Tao; Vontell, Regina; Jabin, Darakhshan; Hua, Sha; Zhou, Kai; Nazmi, Arshed; Albertsson, Anna-Maj; Sobotka, Kristina; Ek, Joakim; Thornton, Claire; Hagberg, Henrik; Mallard, Carina; Leavenworth, Jianmei W; Zhu, Changlian; Wang, Xiaoyang

2017-12-20

Infection and sepsis are associated with brain white matter injury in preterm infants and the subsequent development of cerebral palsy. In the present study, we used a neonatal mouse sepsis-induced white matter injury model to determine the contribution of different T cell subsets (αβT cells and γδT cells) to white matter injury and consequent behavioral changes. C57BL/6J wild-type (WT), T cell receptor (TCR) δ-deficient (Tcrd -/- , lacking γδT cells), and TCRα-deficient (Tcra -/- , lacking αβT cells) mice were administered with lipopolysaccharide (LPS) at postnatal day (PND) 2. Brain myelination was examined at PNDs 12, 26, and 60. Motor function and anxiety-like behavior were evaluated at PND 26 or 30 using DigiGait analysis and an elevated plus maze. White matter development was normal in Tcrd -/- and Tcrα -/- compared to WT mice. LPS exposure induced reductions in white matter tissue volume in WT and Tcrα -/- mice, but not in the Tcrd -/- mice, compared with the saline-treated groups. Neither LPS administration nor the T cell deficiency affected anxiety behavior in these mice as determined with the elevated plus maze. DigiGait analysis revealed motor function deficiency after LPS-induced sepsis in both WT and Tcrα -/- mice, but no such effect was observed in Tcrd -/- mice. Our results suggest that γδT cells but not αβT cells contribute to sepsis-induced white matter injury and subsequent motor function abnormalities in early life. Modulating the activity of γδT cells in the early stages of preterm white matter injury might represent a novel therapeutic strategy for the treatment of perinatal brain injury.

Right Fronto-Subcortical White Matter Microstructure Predicts Cognitive Control Ability on the Go/No-go Task in a Community Sample.

PubMed

Hinton, Kendra E; Lahey, Benjamin B; Villalta-Gil, Victoria; Boyd, Brian D; Yvernault, Benjamin C; Werts, Katherine B; Plassard, Andrew J; Applegate, Brooks; Woodward, Neil D; Landman, Bennett A; Zald, David H

2018-01-01

Go/no-go tasks are widely used to index cognitive control. This construct has been linked to white matter microstructure in a circuit connecting the right inferior frontal gyrus (IFG), subthalamic nucleus (STN), and pre-supplementary motor area. However, the specificity of this association has not been tested. A general factor of white matter has been identified that is related to processing speed. Given the strong processing speed component in successful performance on the go/no-go task, this general factor could contribute to task performance, but the general factor has often not been accounted for in past studies of cognitive control. Further, studies on cognitive control have generally employed small unrepresentative case-control designs. The present study examined the relationship between go/no-go performance and white matter microstructure in a large community sample of 378 subjects that included participants with a range of both clinical and subclinical nonpsychotic psychopathology. We found that white matter microstructure properties in the right IFG-STN tract significantly predicted task performance, and remained significant after controlling for dimensional psychopathology. The general factor of white matter only reached statistical significance when controlling for dimensional psychopathology. Although the IFG-STN and general factor tracts were highly correlated, when both were included in the model, only the IFG-STN remained a significant predictor of performance. Overall, these findings suggest that while a general factor of white matter can be identified in a young community sample, white matter microstructure properties in the right IFG-STN tract show a specific relationship to cognitive control. The findings highlight the importance of examining both specific and general correlates of cognition, especially in tasks with a speeded component.

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.

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.

Increased White Matter Inflammation in Aging- and Alzheimer's Disease Brain.

PubMed

Raj, Divya; Yin, Zhuoran; Breur, Marjolein; Doorduin, Janine; Holtman, Inge R; Olah, Marta; Mantingh-Otter, Ietje J; Van Dam, Debby; De Deyn, Peter P; den Dunnen, Wilfred; Eggen, Bart J L; Amor, Sandra; Boddeke, Erik

2017-01-01

Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer's disease (AD)-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis. Particularly in white matter microglia of 24-month-old mice, abundant expression of phagocytic markers including Mac-2, Axl, CD16/32, Dectin1, CD11c, and CD36 was detected. Interestingly, in white matter of human brain tissue the first signs of inflammatory activity were already detected during middle age. Thus quantification of microglial proteins, such as CD68 (commonly associated with phagocytosis) and HLA-DR (associated with antigen presentation), in postmortem human white matter brain tissue showed an age-dependent increase in immunoreactivity already in middle-aged people (53.2 ± 2.0 years). This early inflammation was also detectable by non-invasive positron emission tomography imaging using [ 11 C]-(R)-PK11195, a ligand that binds to activated microglia. Increased microglia activity was also prominently present in the white matter of human postmortem early-onset AD (EOAD) brain tissue. Interestingly, microglia activity in the white matter of late-onset AD (LOAD) CNS was similar to that of the aged clinically silent AD cases. These data indicate that microglia-induced neuroinflammation is predominant in the white matter of aging mice and humans as well as in EOAD brains. This white matter inflammation may contribute to the progression of neurodegeneration, and have prognostic value for detecting the onset and progression of aging and neurodegeneration.

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.

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

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.

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.

Functionally defined white matter reveals segregated pathways in human ventral temporal cortex associated with category-specific processing

PubMed Central

Gomez, Jesse; Pestilli, Franco; Witthoft, Nathan; Golarai, Golijeh; Liberman, Alina; Poltoratski, Sonia; Yoon, Jennifer; Grill-Spector, Kalanit

2014-01-01

Summary It is unknown if the white matter properties associated with specific visual networks selectively affect category-specific processing. In a novel protocol we combined measurements of white matter structure, functional selectivity, and behavior in the same subjects. We find two parallel white matter pathways along the ventral temporal lobe connecting to either face-selective or place-selective regions. Diffusion properties of portions of these tracts adjacent to face- and place-selective regions of ventral temporal cortex correlate with behavioral performance for face or place processing, respectively. Strikingly, adults with developmental prosopagnosia (face blindness) express an atypical structure-behavior relationship near face-selective cortex, suggesting that white matter atypicalities in this region may have behavioral consequences. These data suggest that examining the interplay between cortical function, anatomical connectivity, and visual behavior is integral to understanding functional networks and their role in producing visual abilities and deficits. PMID:25569351

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.

Origins of R2∗ and white matter

PubMed Central

Rudko, David A.; Klassen, L. Martyn; de Chickera, Sonali N.; Gati, Joseph S.; Dekaban, Gregory A.; Menon, Ravi S.

2014-01-01

Estimates of the apparent transverse relaxation rate () can be used to quantify important properties of biological tissue. Surprisingly, the mechanism of dependence on tissue orientation is not well understood. The primary goal of this paper was to characterize orientation dependence of in gray and white matter and relate it to independent measurements of two other susceptibility based parameters: the local Larmor frequency shift (fL) and quantitative volume magnetic susceptibility (Δχ). Through this comparative analysis we calculated scaling relations quantifying (reversible contribution to the transverse relaxation rate from local field inhomogeneities) in a voxel given measurements of the local Larmor frequency shift. is a measure of both perturber geometry and density and is related to tissue microstructure. Additionally, two methods (the Generalized Lorentzian model and iterative dipole inversion) for calculating Δχ were compared in gray and white matter. The value of Δχ derived from fitting the Generalized Lorentzian model was then connected to the observed orientation dependence using image-registered optical density measurements from histochemical staining. Our results demonstrate that the and fL of white and cortical gray matter are well described by a sinusoidal dependence on the orientation of the tissue and a linear dependence on the volume fraction of myelin in the tissue. In deep brain gray matter structures, where there is no obvious symmetry axis, and fL have no orientation dependence but retain a linear dependence on tissue iron concentration and hence Δχ. PMID:24374633

Anterior Cortical Development During Adolescence in Bipolar Disorder

PubMed Central

Najt, Pablo; Wang, Fei; Spencer, Linda; Johnston, Jennifer A.Y.; Cox Lippard, Elizabeth T.; Pittman, Brian P.; Lacadie, Cheryl; Staib, Lawrence H.; Papademetris, Xenophon; Blumberg, Hilary P.

2015-01-01

Background Increasing evidence supports a neurodevelopmental model for bipolar disorder (BD), with adolescence as a critical period in its development. Developmental abnormalities of anterior paralimbic and heteromodal frontal cortices, key structures in emotional regulation processes and central in BD, are implicated. However, few longitudinal studies have been conducted, limiting understanding of trajectory alterations in BD. In this study, we performed longitudinal neuroimaging of adolescents with and without BD and assessed volume changes over time, including changes in tissue overall and within gray and white matter. Larger decreases over time in anterior cortical volumes in the adolescents with BD were hypothesized. Gray matter decreases and white matter increases are typically observed during adolescence in anterior cortices. It was hypothesized that volume decreases over time in BD would reflect alterations in those processes, showing larger gray matter contraction and decreased white matter expansion. Methods Two high-resolution magnetic resonance imaging scans were obtained approximately two-years apart for 35 adolescents with BDI and 37 healthy adolescents. Differences over time between groups were investigated for volume overall and specifically for gray and white matter. Results Relative to healthy adolescents, adolescents with BDI showed greater volume contraction over time in a region including insula, and orbitofrontal, rostral and dorsolateral prefrontal cortices (P<.05, corrected), including greater gray matter contraction and decreased white matter expansion over time, in the BD compared to the healthy group. Conclusions: The findings support neurodevelopmental abnormalities during adolescence in BDI in anterior cortices, include altered developmental trajectories of anterior gray and white matter. PMID:26033826

Highways of the emotional intellect: white matter microstructural correlates of an ability-based measure of emotional intelligence.

PubMed

Pisner, Derek A; Smith, Ryan; Alkozei, Anna; Klimova, Aleksandra; Killgore, William D S

2017-06-01

Individuals differ in their ability to understand emotional information and apply that understanding to make decisions and solve problems effectively - a construct known as Emotional Intelligence (EI). While considerable evidence supports the importance of EI in social and occupational functioning, the neural underpinnings of this capacity are relatively unexplored. We used Tract-Based Spatial Statistics (TBSS) to determine the white matter correlates of EI as measured by the ability-based Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Participants included 32 healthy adults (16 men; 16 women), aged 18-45 years. White matter integrity in key tracts was positively correlated with the Strategic Area branches of the MSCEIT (Understanding Emotions and Managing Emotions), but not the Experiential branches (Perceiving and Facilitating Emotions). Specifically, the Understanding Emotions branch was associated with greater fractional anisotropy (FA) within somatosensory and sensory-motor fiber bundles, particularly those of the left superior longitudinal fasciculus and corticospinal tract. Managing Emotions was associated with greater FA within frontal-affective association tracts including the anterior forceps and right uncinate fasciculus, along with frontal-parietal cingulum and interhemispheric corpus callosum tracts. These findings suggest that specific components of EI are directly related to the structural microarchitecture of major axonal pathways.

Predictive classification of pediatric bipolar disorder using atlas-based diffusion weighted imaging and support vector machines.

PubMed

Mwangi, Benson; Wu, Mon-Ju; Bauer, Isabelle E; Modi, Haina; Zeni, Cristian P; Zunta-Soares, Giovana B; Hasan, Khader M; Soares, Jair C

2015-11-30

Previous studies have reported abnormalities of white-matter diffusivity in pediatric bipolar disorder. However, it has not been established whether these abnormalities are able to distinguish individual subjects with pediatric bipolar disorder from healthy controls with a high specificity and sensitivity. Diffusion-weighted imaging scans were acquired from 16 youths diagnosed with DSM-IV bipolar disorder and 16 demographically matched healthy controls. Regional white matter tissue microstructural measurements such as fractional anisotropy, axial diffusivity and radial diffusivity were computed using an atlas-based approach. These measurements were used to 'train' a support vector machine (SVM) algorithm to predict new or 'unseen' subjects' diagnostic labels. The SVM algorithm predicted individual subjects with specificity=87.5%, sensitivity=68.75%, accuracy=78.12%, positive predictive value=84.62%, negative predictive value=73.68%, area under receiver operating characteristic curve (AUROC)=0.7812 and chi-square p-value=0.0012. A pattern of reduced regional white matter fractional anisotropy was observed in pediatric bipolar disorder patients. These results suggest that atlas-based diffusion weighted imaging measurements can distinguish individual pediatric bipolar disorder patients from healthy controls. Notably, from a clinical perspective these findings will contribute to the pathophysiological understanding of pediatric bipolar disorder. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

White matter microstructural variability mediates the relation between obesity and cognition in healthy adults.

PubMed

Zhang, Rui; Beyer, Frauke; Lampe, Leonie; Luck, Tobias; Riedel-Heller, Steffi G; Loeffler, Markus; Schroeter, Matthias L; Stumvoll, Michael; Villringer, Arno; Witte, A Veronica

2018-05-15

Obesity has been linked with structural and functional brain changes. However, the impact of obesity on brain and cognition in aging remains debatable, especially for white matter. We therefore aimed to determine the effects of obesity on white matter microstructure and potential implications for cognition in a well-characterized large cohort of healthy adults. In total, 1255 participants (50% females, 19-80 years, BMI 16.8-50.2 kg/m 2 ) with diffusion-weighted magnetic resonance imaging at 3T were analysed. Tract-based spatial statistics (TBSS) probed whether body mass index (BMI) and waist-to-hip ratio (WHR) were related to fractional anisotropy (FA). We conducted partial correlations and mediation analyses to explore whether obesity or regional FA were related to cognitive performance. Analyses were adjusted for demographic, genetic, and obesity-associated confounders. Results showed that higher BMI and higher WHR were associated with lower FA in multiple white matter tracts (p < 0.05, FWE-corrected). Mediation analyses provided evidence for indirect negative effects of higher BMI and higher WHR on executive functions and processing speed through lower FA in fiber tracts connecting (pre)frontal, visual, and associative areas (indirect paths, |ß| ≥ 0.01; 99% |CI| > 0). This large cross-sectional study showed that obesity is correlated with lower FA in multiple white matter tracts in otherwise healthy adults, independent of confounders. Moreover, although effect sizes were small, mediation results indicated that visceral obesity was linked to poorer executive functions and lower processing speed through lower FA in callosal and associative fiber tracts. Longitudinal studies are needed to support this hypothesis. Copyright © 2018 Elsevier Inc. All rights reserved.

White Matter Damage Relates to Oxygen Saturation in Children With Sickle Cell Anemia Without Silent Cerebral Infarcts.

PubMed

Kawadler, Jamie M; Kirkham, Fenella J; Clayden, Jonathan D; Hollocks, Matthew J; Seymour, Emma L; Edey, Rosanna; Telfer, Paul; Robins, Andrew; Wilkey, Olu; Barker, Simon; Cox, Tim C S; Clark, Chris A

2015-07-01

Sickle cell anemia is associated with compromised oxygen-carrying capability of hemoglobin and a high incidence of overt and silent stroke. However, in children with no evidence of cerebral infarction, there are changes in brain morphometry relative to healthy controls, which may be related to chronic anemia and oxygen desaturation. A whole-brain tract-based spatial statistics analysis was carried out in 25 children with sickle cell anemia with no evidence of abnormality on T2-weighted magnetic resonance imaging (13 male, age range: 8-18 years) and 14 age- and race-matched controls (7 male, age range: 10-19 years) to determine the extent of white matter injury. The hypotheses that white matter damage is related to daytime peripheral oxygen saturation and steady-state hemoglobin were tested. Fractional anisotropy was found to be significantly lower in patients in the subcortical white matter (corticospinal tract and cerebellum), whereas mean diffusivity and radial diffusivity were higher in patients in widespread areas. There was a significant negative relationship between radial diffusivity and oxygen saturation (P<0.05) in the anterior corpus callosum and a trend-level negative relationship between radial diffusivity and hemoglobin (P<0.1) in the midbody of the corpus callosum. These data show widespread white matter abnormalities in a sample of asymptomatic children with sickle cell anemia, and provides for the first time direct evidence of a relationship between brain microstructure and markers of disease severity (eg, peripheral oxygen saturation and steady-state hemoglobin). This study suggests that diffusion tensor imaging metrics may serve as a biomarker for future trials of reducing hypoxic exposure. © 2015 American Heart Association, Inc.

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.

Left hemisphere fractional anisotropy increase in noise-induced tinnitus: a diffusion tensor imaging (DTI) study of white matter tracts in the brain.

PubMed

Benson, Randall R; Gattu, Ramtilak; Cacace, Anthony T

2014-03-01

Diffusion tensor imaging (DTI) is a contemporary neuroimaging modality used to study connectivity patterns and microstructure of white matter tracts in the brain. The use of DTI in the study of tinnitus is a relatively unexplored methodology with no studies focusing specifically on tinnitus induced by noise exposure. In this investigation, participants were two groups of adults matched for etiology, age, and degree of peripheral hearing loss, but differed by the presence or absence (+/-) of tinnitus. It is assumed that matching individuals on the basis of peripheral hearing loss, allows for differentiating changes in white matter microstructure due to hearing loss from changes due to the effects of chronic tinnitus. Alterations in white matter tracts, using the fractional anisotropy (FA) metric, which measures directional diffusion of water, were quantified using tract-based spatial statistics (TBSS) with additional details provided by in vivo probabilistic tractography. Our results indicate that 10 voxel clusters differentiated the two groups, including 9 with higher FA in the group with tinnitus. A decrease in FA was found for a single cluster in the group with tinnitus. However, seven of the 9 clusters with higher FA were in left hemisphere thalamic, frontal, and parietal white matter. These foci were localized to the anterior thalamic radiations and the inferior and superior longitudinal fasciculi. The two right-sided clusters with increased FA were located in the inferior fronto-occipital fasciculus and superior longitudinal fasciculus. The only decrease in FA for the tinnitus-positive group was found in the superior longitudinal fasciculus of the left parietal lobe. Copyright © 2013 Elsevier B.V. All rights reserved.

Longitudinal brain white matter alterations in minimal hepatic encephalopathy before and after liver transplantation.

PubMed

Lin, Wei-Che; Chou, Kun-Hsien; Chen, Chao-Long; Chen, Hsiu-Ling; Lu, Cheng-Hsien; Li, Shau-Hsuan; Huang, Chu-Chung; Lin, Ching-Po; Cheng, Yu-Fan

2014-01-01

Cerebral edema is the common pathogenic mechanism for cognitive impairment in minimal hepatic encephalopathy. Whether complete reversibility of brain edema, cognitive deficits, and their associated imaging can be achieved after liver transplantation remains an open question. To characterize white matter integrity before and after liver transplantation in patients with minimal hepatic encephalopathy, multiple diffusivity indices acquired via diffusion tensor imaging was applied. Twenty-eight patients and thirty age- and sex-matched healthy volunteers were included. Multiple diffusivity indices were obtained from diffusion tensor images, including mean diffusivity, fractional anisotropy, axial diffusivity and radial diffusivity. The assessment was repeated 6-12 month after transplantation. Differences in white matter integrity between groups, as well as longitudinal changes, were evaluated using tract-based spatial statistical analysis. Correlation analyses were performed to identify first scan before transplantation and interval changes among the neuropsychiatric tests, clinical laboratory tests, and diffusion tensor imaging indices. After transplantation, decreased water diffusivity without fractional anisotropy change indicating reversible cerebral edema was found in the left anterior cingulate, claustrum, postcentral gyrus, and right corpus callosum. However, a progressive decrease in fractional anisotropy and an increase in radial diffusivity suggesting demyelination were noted in temporal lobe. Improved pre-transplantation albumin levels and interval changes were associated with better recoveries of diffusion tensor imaging indices. Improvements in interval diffusion tensor imaging indices in the right postcentral gyrus were correlated with visuospatial function score correction. In conclusion, longitudinal voxel-wise analysis of multiple diffusion tensor imaging indices demonstrated different white matter changes in minimal hepatic encephalopathy patients. Transplantation improved extracellular cerebral edema and the results of associated cognition tests. However, white matter demyelination may advance in temporal lobe.

The myelinated fiber loss in the corpus callosum of mouse model of schizophrenia induced by MK-801.

PubMed

Xiu, Yun; Kong, Xiang-ru; Zhang, Lei; Qiu, Xuan; Gao, Yuan; Huang, Chun-xia; Chao, Feng-lei; Wang, San-rong; Tang, Yong

2015-04-01

Previous magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) investigations have shown that the white matter volume and fractional anisotropy (FA) were decreased in schizophrenia (SZ), which indicated impaired white matter integrity in SZ. However, the mechanism underlying these abnormalities has been less studied. The current study was designed to investigate the possible reasons for white matter abnormalities in the mouse model of SZ induced by NMDA receptor antagonist using the unbiased stereological methods and transmission electron microscope technique. We found that the mice treated with MK-801 demonstrated a series of schizophrenia-like behaviors including hyperlocomotor activity and more anxiety. The myelinated fibers in the corpus callosum (CC) of the mice treated with MK-801 were impaired with splitting lamellae of myelin sheaths and segmental demyelination. The CC volume and the total length of the myelinated fibers in the CC of the mice treated with MK-801 were significantly decreased by 9.4% and 16.8% when compared to those of the mice treated with saline. We further found that the loss of the myelinated fibers length was mainly due to the marked loss of the myelinated nerve fibers with the diameter of 0.4-0.5 μm. These results indicated that the splitting myelin sheaths, demyelination and the loss of myelinated fibers with small diameter might provide one of the structural bases for impaired white matter integrity of CC in the mouse model of SZ. These results might also provide a baseline for further studies searching for the treatment of SZ through targeting white matter. Copyright © 2015 Elsevier Ltd. All rights reserved.

Motor skill learning is associated with diffusion characteristics of white matter in individuals with chronic stroke.

PubMed

Borich, Michael R; Brown, Katlyn E; Boyd, Lara A

2014-07-01

Imaging advances allow investigation of white matter after stroke; a growing body of literature has shown links between diffusion-based measures of white matter microstructure and motor function. However, the relationship between these measures and motor skill learning has not been considered in individuals with stroke. The aim of this study was to investigate the relationships between posttraining white matter microstructural status, as indexed by diffusion tensor imaging within the ipsilesional posterior limb of the internal capsule (PLIC), and learning of a novel motor task in individuals with chronic stroke. A total of 13 participants with chronic stroke and 9 healthy controls practiced a visuomotor pursuit task across 5 sessions. Change in motor behavior associated with learning was indexed by comparing baseline performance with a delayed retention test. Fractional anisotropy (FA) indexed at the retention test was the primary diffusion tensor imaging-derived outcome measure. In individuals with chronic stroke, we discovered an association between posttraining ipsilesional PLIC FA and the magnitude of change associated with motor learning; hierarchical multiple linear regression analyses revealed that the combination of age, time poststroke, and ipsilesional PLIC FA posttraining was associated with motor learning-related change (R = 0.649; P = 0.02). Baseline motor performance was not related to posttraining ipsilesional PLIC FA. Diffusion characteristics of posttraining ipsilesional PLIC were linked to the magnitude of change in skilled motor behavior. These results imply that the microstructural properties of regional white matter indexed by diffusion behavior may be an important factor to consider when determining potential response to rehabilitation in persons with stroke. (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A59) for more insights from the authors.

Cerebral Mitochondrial Microangiopathy Leads to Leukoencephalopathy in Mitochondrial Neurogastrointestinal Encephalopathy.

PubMed

Gramegna, L L; Pisano, A; Testa, C; Manners, D N; D'Angelo, R; Boschetti, E; Giancola, F; Pironi, L; Caporali, L; Capristo, M; Valentino, M L; Plazzi, G; Casali, C; Dotti, M T; Cenacchi, G; Hirano, M; Giordano, C; Parchi, P; Rinaldi, R; De Giorgio, R; Lodi, R; Carelli, V; Tonon, C

2018-01-18

Mitochondrial neurogastrointestinal encephalopathy is a rare disorder due to recessive mutations in the thymidine phosphorylase gene, encoding thymidine phosphorylase protein required for mitochondrial DNA replication. Clinical manifestations include gastrointestinal dysmotility and diffuse asymptomatic leukoencephalopathy. This study aimed to elucidate the mechanisms underlying brain leukoencephalopathy in patients with mitochondrial neurogastrointestinal encephalopathy by correlating multimodal neuroradiologic features to postmortem pathology. Seven patients underwent brain MR imaging, including single-voxel proton MR spectroscopy and diffusion imaging. Absolute concentrations of metabolites calculated by acquiring unsuppressed water spectra at multiple TEs, along with diffusion metrics based on the tensor model, were compared with those of healthy controls using unpaired t tests in multiple white matters regions. Brain postmortem histologic, immunohistochemical, and molecular analyses were performed in 1 patient. All patients showed bilateral and nearly symmetric cerebral white matter hyperintensities on T2-weighted images, extending to the cerebellar white matter and brain stem in 4. White matter, N -acetylaspartate, creatine, and choline concentrations were significantly reduced compared with those in controls, with a prominent increase in the radial water diffusivity component. At postmortem examination, severe fibrosis of brain vessel smooth muscle was evident, along with mitochondrial DNA replication depletion in brain and vascular smooth-muscle and endothelial cells, without neuronal loss, myelin damage, or gliosis. Prominent periependymal cytochrome C oxidase deficiency was also observed. Vascular functional and histologic alterations account for leukoencephalopathy in mitochondrial neurogastrointestinal encephalopathy. Thymidine toxicity and mitochondrial DNA replication depletion may induce microangiopathy and blood-brain-barrier dysfunction, leading to increased water content in the white matter. Periependymal cytochrome C oxidase deficiency could explain prominent periventricular impairment. © 2018 by American Journal of Neuroradiology.

Combining Fiber Dissection, Plastination, and Tractography for Neuroanatomical Education: Revealing the Cerebellar Nuclei and Their White Matter Connections

ERIC Educational Resources Information Center

Arnts, Hisse; Kleinnijenhuis, Michiel; Kooloos, Jan G. M.; Schepens-Franke, Annelieke N.; van Cappellen van Walsum, Anne-Marie

2014-01-01

In recent years, there has been a growing interest in white matter anatomy of the human brain. With advances in brain imaging techniques, the significance of white matter integrity for brain function has been demonstrated in various neurological and psychiatric disorders. As the demand for interpretation of clinical and imaging data on white…

White Matter Maturation Supports the Development of Reasoning Ability through Its Influence on Processing Speed

ERIC Educational Resources Information Center

Ferrer, Emilio; Whitaker, Kirstie J.; Steele, Joel S.; Green, Chloe T.; Wendelken, Carter; Bunge, Silvia 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…

Impact of Strategically Located White Matter Hyperintensities on Cognition in Memory Clinic Patients with Small Vessel Disease

PubMed Central

Hilal, Saima; Kuijf, Hugo J.; Ikram, Mohammad Kamran; Xu, Xin; Tan, Boon Yeow; Venketasubramanian, Narayanaswamy; Postma, Albert; Biessels, Geert Jan; Chen, Christopher P. L. H.

2016-01-01

Background and Purpose Studies on the impact of small vessel disease (SVD) on cognition generally focus on white matter hyperintensity (WMH) volume. The extent to which WMH location relates to cognitive performance has received less attention, but is likely to be functionally important. We examined the relation between WMH location and cognition in a memory clinic cohort of patients with sporadic SVD. Methods A total of 167 patients with SVD were recruited from memory clinics. Assumption-free region of interest-based analyses based on major white matter tracts and voxel-wise analyses were used to determine the association between WMH location and executive functioning, visuomotor speed and memory. Results Region of interest-based analyses showed that WMHs located particularly within the anterior thalamic radiation and forceps minor were inversely associated with both executive functioning and visuomotor speed, independent of total WMH volume. Memory was significantly associated with WMH volume in the forceps minor, independent of total WMH volume. An independent assumption-free voxel-wise analysis identified strategic voxels in these same tracts. Region of interest-based analyses showed that WMH volume within the anterior thalamic radiation explained 6.8% of variance in executive functioning, compared to 3.9% for total WMH volume; WMH volume within the forceps minor explained 4.6% of variance in visuomotor speed and 4.2% of variance in memory, compared to 1.8% and 1.3% respectively for total WMH volume. Conclusions Our findings identify the anterior thalamic radiation and forceps minor as strategic white matter tracts in which WMHs are most strongly associated with cognitive impairment in memory clinic patients with SVD. WMH volumes in individual tracts explained more variance in cognition than total WMH burden, emphasizing the importance of lesion location when addressing the functional consequences of WMHs. PMID:27824925

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.

Executive dysfunctions in migraine with and without aura: what is the role of white matter lesions?

PubMed

Le Pira, Francesco; Reggio, Ester; Quattrocchi, Graziella; Sanfilippo, Cristina; Maci, Tiziana; Cavallaro, Tiziana; Zappia, Mario

2014-01-01

Executive dysfunctions and white matter lesions on magnetic resonance imaging have been reported in migraine. The aim of this study was to determine whether any correlation between these 2 variables exists. Forty-four subjects affected by migraine with or without aura were compared with 16 healthy subjects. A battery of neuropsychological tests assessing executive functions was administered to all subjects. Number and total volume of white matter lesions were assessed in the whole brain and in the frontal lobe. The performances of both groups of migraineurs, with and without aura, were significantly worse when compared with controls on Boston Scanning Test. Moreover, we found lower performances compared with controls respectively on Frontal Assessment Battery in patients with migraine with aura and on Controlled Oral Word Association Test in patients with migraine without aura. Nineteen patients (43.2%) and one control subject (6.2%) had white matter lesions. We did not find any significant correlation between white matter lesions load and neuropsychological performances. On the basis of our results, white matter lesions load on magnetic resonance imaging do not seem to contribute to neuropsychological performances deficit in migraineurs. © 2013 American Headache Society.

The visual white matter: The application of diffusion MRI and fiber tractography to vision science

PubMed Central

Rokem, Ariel; Takemura, Hiromasa; Bock, Andrew S.; Scherf, K. Suzanne; Behrmann, Marlene; Wandell, Brian A.; Fine, Ione; Bridge, Holly; Pestilli, Franco

2017-01-01

Visual neuroscience has traditionally focused much of its attention on understanding the response properties of single neurons or neuronal ensembles. The visual white matter and the long-range neuronal connections it supports are fundamental in establishing such neuronal response properties and visual function. This review article provides an introduction to measurements and methods to study the human visual white matter using diffusion MRI. These methods allow us to measure the microstructural and macrostructural properties of the white matter in living human individuals; they allow us to trace long-range connections between neurons in different parts of the visual system and to measure the biophysical properties of these connections. We also review a range of findings from recent studies on connections between different visual field maps, the effects of visual impairment on the white matter, and the properties underlying networks that process visual information supporting visual face recognition. Finally, we discuss a few promising directions for future studies. These include new methods for analysis of MRI data, open datasets that are becoming available to study brain connectivity and white matter properties, and open source software for the analysis of these data. PMID:28196374

Increased PK11195-PET binding in normal-appearing white matter in clinically isolated syndrome

PubMed Central

Politis, Marios; Su, Paul; Turkheimer, Federico E.; Malik, Omar; Keihaninejad, Shiva; Wu, Kit; Waldman, Adam; Reynolds, Richard; Nicholas, Richard; Piccini, Paola

2015-01-01

The most accurate predictor of the subsequent development of multiple sclerosis in clinically isolated syndrome is the presence of lesions at magnetic resonance imaging. We used in vivo positron emission tomography with 11C-(R)-PK11195, a biomarker of activated microglia, to investigate the normal-appearing white matter and grey matter of subjects with clinically isolated syndrome to explore its role in the development of multiple sclerosis. Eighteen clinically isolated syndrome and eight healthy control subjects were recruited. Baseline assessment included: history, neurological examination, expanded disability status scale, magnetic resonance imaging and PK11195-positron emission tomography scans. All assessments except the PK11195-positron emission tomography scan were repeated over 2 years. SUPERPK methodology was used to measure the binding potential relative to the non-specific volume, BPND. We show a global increase of normal-appearing white matter PK11195 BPND in clinically isolated syndrome subjects compared with healthy controls (P = 0.014). Clinically isolated syndrome subjects with T2 magnetic resonance imaging lesions had higher PK11195 BPND in normal-appearing white matter (P = 0.009) and their normal-appearing white matter PK11195 BPND correlated with the Expanded Disability Status Scale (P = 0.007; r = 0.672). At 2 years those who developed dissemination in space or multiple sclerosis, had higher PK11195 BPND in normal-appearing white matter at baseline (P = 0.007 and P = 0.048, respectively). Central grey matter PK11195 BPND was increased in subjects with clinically isolated syndrome compared to healthy controls but no difference was found in cortical grey matter PK11195 BPND. Microglial activation in clinically isolated syndrome normal-appearing white matter is diffusely increased compared with healthy control subjects and is further increased in those who have magnetic resonance imaging lesions. Furthermore microglial activation in clinically isolated syndrome normal-appearing white matter is also higher in those subjects who developed multiple sclerosis at 2 years. Our finding, if replicated in a larger study, could be of prognostic value and aid early treatment decisions in clinically isolated syndrome. PMID:25416179

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.

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

Diffusion-tensor imaging of white matter tracts in patients with cerebral neoplasm.

PubMed

Witwer, Brian P; Moftakhar, Roham; Hasan, Khader M; Deshmukh, Praveen; Haughton, Victor; Field, Aaron; Arfanakis, Konstantinos; Noyes, Jane; Moritz, Chad H; Meyerand, M Elizabeth; Rowley, Howard A; Alexander, Andrew L; Badie, Behnam

2002-09-01

Preserving vital cerebral function while maximizing tumor resection is a principal goal in surgical neurooncology. Although functional magnetic resonance imaging has been useful in the localization of eloquent cerebral cortex, this method does not provide information about the white matter tracts that may be involved in invasive, intrinsic brain tumors. Recently, diffusion-tensor (DT) imaging techniques have been used to map white matter tracts in the normal brain. The aim of this study was to demonstrate the role of DT imaging in preoperative mapping of white matter tracts in relation to cerebral neoplasms. Nine patients with brain malignancies (one pilocytic astrocytoma, five oligodendrogliomas, one low-grade oligoastrocytoma, one Grade 4 astrocytoma, and one metastatic adenocarcinoma) underwent DT imaging examinations prior to tumor excision. Anatomical information about white matter tract location, orientation, and projections was obtained in every patient. Depending on the tumor type and location, evidence of white matter tract edema (two patients), infiltration (two patients), displacement (five patients), and disruption (two patients) could be assessed with the aid of DT imaging in each case. Diffusion-tensor imaging allowed for visualization of white matter tracts and was found to be beneficial in the surgical planning for patients with intrinsic brain tumors. The authors' experience with DT imaging indicates that anatomically intact fibers may be present in abnormal-appearing areas of the brain. Whether resection of these involved fibers results in subtle postoperative neurological deficits requires further systematic study.

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

Destruction of white matter integrity in patients with mild cognitive impairment and Alzheimer disease.

PubMed

Sun, Xiaoyan; Salat, David; Upchurch, Kristen; Deason, Rebecca; Kowall, Neil; Budson, Andrew

2014-10-01

Accumulating evidence shows that gradual loss of white matter integrity plays an important role in the development of Alzheimer disease (AD). The aim of this research was to study the microstructural integrity of white matter in AD in vivo. Global fractional anisotropy, global axial diffusivity (AxD), and global radial diffusivity (RD) were analyzed in subjects with normal controls (NC), mild cognitive impairment (MCI), and AD using Alzheimer's Disease Neuroimaging Initiative data (total N = 210). We further compared specific white matter tracts among the 3 groups. Compared with the NC group, the MCI group had significantly increased global AxD and global RD. Compared with the NC and MCI groups, the AD group had significantly decreased global fractional anisotropy, increased global AxD, and increased global RD. With regard to specific white matter tracts, in the MCI group, we found increased AxD and increased RD in the external capsule, part of the lateral cholinergic pathway, in addition to the tracts connecting the limbic regions, predominantly in the left hemisphere. In the AD group, white matter abnormalities were widespread, including in the external capsule (cholinergic pathway) and limbic region tracts as well as tracts connecting anterior to posterior regions bilaterally. The radiographic manifestation of damaged white matter microstructural integrity in the cholinergic pathway in MCI patients may provide a rational basis for the use of cholinesterase inhibitor drugs in the MCI stage of AD.

Does APO ε4 correlate with MRI changes in Alzheimer's disease?

PubMed Central

Doody, R; Azher, S; Haykal, H; Dunn, J; Liao, T; Schneider, L

2000-01-01

OBJECTIVE—To assess the relation between APO E genotype and MRI white matter changes in Alzheimer's disease. The APO ε4 allele is correlated with amyloid angiopathy and other neuropathologies in Alzheimer's disease and could be associated with white matter changes. If so, there should be a dose effect.
METHODS—104 patients with probable Alzheimer's disease (NINCDS-ADRDA criteria) in this Alzheimer's Disease Research Centre were studied. Patients received MRI and APO E genotyping by standardised protocols. Axial MRI was scored (modified Schelten's scale) for the presence and degree of white matter changes and atrophy in several regions by a neuroradiologist blinded to genotype. Total white matter and total atrophy scores were also generated. Data analysis included Pearson's correlation for regional and total imaging scores and analysis of variance (ANOVA) (or Kruskal-Wallis) and χ2 for demographic and disease related variables.
RESULTS—30 patients had no ε4, 53 patients were heterozygous, and 21 patients were homozygous. The three groups did not differ in sex distribution, age of onset, age at MRI, MMSE, clinical dementia rating, or modified Hachinski ischaemia scores. There were no significant correlations between total or regional white matter scores and APO E genotype (Pearson correlation).
CONCLUSIONS—No correlation between total or regional white matter scores and APO E genotype was found. The pathogenesis of white matter changes in Alzheimer's disease may be independent of APO E genotype.

 PMID:11032626

Three-Dimensional Printed Modeling of Diffuse Low-Grade Gliomas and Associated White Matter Tract Anatomy.

PubMed

Thawani, Jayesh P; Singh, Nickpreet; Pisapia, Jared M; Abdullah, Kalil G; Parker, Drew; Pukenas, Bryan A; Zager, Eric L; Verma, Ragini; Brem, Steven

2017-04-01

Diffuse low-grade gliomas (DLGGs) represent several pathological entities that infiltrate and invade cortical and subcortical structures in the brain. To describe methods for rapid prototyping of DLGGs and surgically relevant anatomy. Using high-definition imaging data and rapid prototyping technologies, we were able to generate 3 patient DLGGs to scale and represent the associated white matter tracts in 3 dimensions using advanced diffusion tensor imaging techniques. This report represents a novel application of 3-dimensional (3-D) printing in neurosurgery and a means to model individualized tumors in 3-D space with respect to subcortical white matter tract anatomy. Faculty and resident evaluations of this technology were favorable at our institution. Developing an understanding of the anatomic relationships existing within individuals is fundamental to successful neurosurgical therapy. Imaging-based rapid prototyping may improve on our ability to plan for and treat complex neuro-oncologic pathology. Copyright © 2017 by the Congress of Neurological Surgeons

Normal gray and white matter volume after weight restoration in adolescents with anorexia nervosa.

PubMed

Lázaro, Luisa; Andrés, Susana; Calvo, Anna; Cullell, Clàudia; Moreno, Elena; Plana, M Teresa; Falcón, Carles; Bargalló, Núria; Castro-Fornieles, Josefina

2013-12-01

The aim of this study was to determine whether treated, weight-stabilized adolescents with anorexia nervosa (AN) present brain volume differences in comparison with healthy controls. Thirty-five adolescents with weight-recovered AN and 17 healthy controls were assessed by means of psychopathology scales and magnetic resonance imaging. Axial three-dimensional T1-weighted images were obtained in a 1.5 Tesla scanner and analyzed using optimized voxel-based morphometry (VBM). There were no significant differences between controls and weight-stabilized AN patients with regard to global volumes of either gray or white brain matter, or in the regional VBM study. Differences were not significant between patients with psychopharmacological treatment and without, between those with amenorrhea and without, as well as between patients with restrictive versus purgative AN. The present findings reveal no global or regional gray or white matter abnormalities in this sample of adolescents following weight restoration. Copyright © 2013 Wiley Periodicals, Inc.

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).

Manual dexterity and brain structure in patients with schizophrenia: A whole-brain magnetic resonance imaging study.

PubMed

Hidese, Shinsuke; Ota, Miho; Sasayama, Daimei; Matsuo, Junko; Ishida, Ikki; Hiraishi, Moeko; Teraishi, Toshiya; Hattori, Kotaro; Kunugi, Hiroshi

2018-04-14

The Purdue Pegboard Test (PPT) is a motor coordination task used to assess manual dexterity. Although several brain regions are thought to be involved in PPT performance, the relationship of the task with decreased insular volume has not been investigated. The PPT was administered to 83 subjects diagnosed with schizophrenia (mean ± standard deviation age: 38.6 ± 11.2 years; 47 males, 36 females) and 130 healthy controls (42.1 ± 15.2 years; 67 males, 63 females). All subjects were Japanese and right-handed. Gray matter volume was analyzed using voxel-based morphometry in statistical parametric mapping, while white matter measures were analyzed using diffusion tensor imaging in tract-based spatial statistics. For the patients with schizophrenia, the left-hand scores positively correlated with the right insular and bilateral operculum volumes, while the summation score (sum of left-, right-, and both-hands scores) positively correlated with the right insular volume, and the summation and assembly (number of assemblies completed) scores correlated with the diffuse white matter fractional anisotropy, axial diffusivity, and radial diffusivity values. In contrast, no significant correlations were found for the controls. These results suggested that decreased insular volume and white matter measures contributed to the impairments in manual dexterity observed in subjects with schizophrenia. Copyright © 2018 Elsevier B.V. All rights reserved.

Distinct white matter integrity in glutamic acid decarboxylase and voltage-gated potassium channel-complex antibody-associated limbic encephalitis.

PubMed

Wagner, Jan; Schoene-Bake, Jan-Christoph; Witt, Juri-Alexander; Helmstaedter, Christoph; Malter, Michael P; Stoecker, Winfried; Probst, Christian; Weber, Bernd; Elger, Christian E

2016-03-01

Autoantibodies against glutamic acid decarboxylase (GAD) and the voltage-gated potassium channel (VGKC) complex are associated with distinct subtypes of limbic encephalitis regarding clinical presentation, response to therapy, and outcome. The aim of this study was to investigate white matter changes in these two limbic encephalitis subtypes by means of diffusion tensor imaging (DTI). Diffusion data were obtained in 14 patients with GAD antibodies and 16 patients with VGKC-complex antibodies and compared with age- and gender-matched control groups. Voxelwise statistical analysis was carried out using tract-based spatial statistics. The results were furthermore compared with those of 15 patients with unilateral histologically confirmed hippocampal sclerosis and correlated with verbal and figural memory performance. We found widespread changes of fractional anisotropy and all diffusivity parameters in GAD-associated limbic encephalitis, whereas no changes were found in VGKC-complex-associated limbic encephalitis. The changes observed in the GAD group were even more extensive when compared against those of the hippocampal sclerosis group, although the disease duration was markedly shorter in patients with GAD antibodies. Correlation analysis revealed areas with a trend toward a negative correlation of diffusivity parameters with figural memory performance located mainly in the right temporal lobe in the GAD group as well. The present study provides further evidence that, depending on the associated antibody, limbic encephalitis features clearly distinct imaging characteristics by showing widespread white matter changes in GAD-associated limbic encephalitis and preserved white matter integrity in VGKC-complex-associated limbic encephalitis. Furthermore, our results contribute to a better understanding of the specific pathophysiologic properties in these two subforms of limbic encephalitis by revealing that patients with GAD antibodies show widespread affections of white matter across various regions of the brain. In contrast to this, the inflammatory process seems to be more localized in VGKC-complex-associated limbic encephalitis, primarily affecting mesiotemporal gray matter. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Labels Matter: Changing the Conversation From “-isms” to Privilege

NASA Astrophysics Data System (ADS)

Dancy, Melissa H.

2006-12-01

Whites typically view racism as discrimination and unfair judgment based on skin color. This view inhibits an end to race-based oppression because it names the issue in terms of the oppressed. A more accurate label is White Privilege. The concept of White privilege is very different from the concept of racism because it includes all Whites, not just those who hold explicit racist views. Acknowledging privilege can be threatening for those who hold a privileged status. However, it is necessary for those who are advantaged to have clarity about their status if the “isms” are to be overcome. In this talk I will discuss my personal struggle to acknowledge my own privileged status (White, American, straight, etc.) and will offer suggestions based on my own experiences for working with advantaged populations committed to overcoming all forms of oppression.

Correlation among body height, intelligence, and brain gray matter volume in healthy children.

PubMed

Taki, Yasuyuki; Hashizume, Hiroshi; Sassa, Yuko; Takeuchi, Hikaru; Asano, Michiko; Asano, Kohei; Kotozaki, Yuka; Nouchi, Rui; Wu, Kai; Fukuda, Hiroshi; Kawashima, Ryuta

2012-01-16

A significant positive correlation between height and intelligence has been demonstrated in children. Additionally, intelligence has been associated with the volume of gray matter in the brains of children. Based on these correlations, we analyzed the correlation among height, full-scale intelligence quotient (IQ) and gray matter volume applying voxel-based morphometry using data from the brain magnetic resonance images of 160 healthy children aged 5-18 years of age. As a result, body height was significantly positively correlated with brain gray matter volume. Additionally, the regional gray matter volume of several regions such as the bilateral prefrontal cortices, temporoparietal region, and cerebellum was significantly positively correlated with body height and that the gray matter volume of several of these regions was also significantly positively correlated with full-scale intelligence quotient (IQ) scores after adjusting for age, sex, and socioeconomic status. Our results demonstrate that gray and white matter volume may mediate the correlation between body height and intelligence in healthy children. Additionally, the correlations among gray and white matter volume, height, and intelligence may be at least partially explained by the effect of insulin-like growth factor-1 and growth hormones. Given the importance of the effect of environmental factors, especially nutrition, on height, IQ, and gray matter volume, the present results stress the importance of nutrition during childhood for the healthy maturation of body and brain. Copyright © 2011 Elsevier Inc. All rights reserved.

Increased cortical curvature reflects white matter atrophy in individual patients with early multiple sclerosis

PubMed Central

Deppe, Michael; Marinell, Jasmin; Krämer, Julia; Duning, Thomas; Ruck, Tobias; Simon, Ole J.; Zipp, Frauke; Wiendl, Heinz; Meuth, Sven G.

2014-01-01

Objective White matter atrophy occurs independently of lesions in multiple sclerosis. In contrast to lesion detection, the quantitative assessment of white matter atrophy in individual patients has been regarded as a major challenge. We therefore tested the hypothesis that white matter atrophy (WMA) is present at the very beginning of multiple sclerosis (MS) and in virtually each individual patient. To find a new sensitive and robust marker for WMA we investigated the relationship between cortical surface area, white matter volume (WMV), and whole-brain-surface-averaged rectified cortical extrinsic curvature. Based on geometrical considerations we hypothesized that cortical curvature increases if WMV decreases and the cortical surface area remains constant. Methods In total, 95 participants were enrolled: 30 patients with early and advanced relapsing–remitting MS; 30 age-matched control subjects; 30 patients with Alzheimer's disease (AD) and 5 patients with clinically isolated syndrome (CIS). Results 29/30 MS and 5/5 CIS patients showed lower WMV than expected from their intracranial volume (average reduction 13.0%, P < 10− 10), while the cortical surface area showed no significant differences compared with controls. The estimated WMV reductions were correlated with an increase in cortical curvature (R = 0.62, P = 0.000001). Discriminant analysis revealed that the curvature increase was highly specific for the MS and CIS groups (96.7% correct assignments between MS and control groups) and was significantly correlated with reduction of white matter fractional anisotropy, as determined by diffusion tensor imaging and the Expanded Disability Status Scale. As expected by the predominant gray and WM degeneration in AD, no systematic curvature increase was observed in AD. Conclusion Whole-brain-averaged cortical extrinsic curvature appears to be a specific and quantitative marker for a WMV–cortex disproportionality and allows us to assess “pure” WMA without being confounded by intracranial volume. WMA seems to be a characteristic symptom in early MS and can already occur in patients with CIS and should thus be considered in future MS research and clinical studies. PMID:25610761

Axon-glia Synapses Are Highly Vulnerable to White Matter Injury in the Developing Brain

PubMed Central

Shen, Yan; Liu, Xiao-Bo; Pleasure, David E.; Deng, Wenbin

2011-01-01

The biology of cerebral white matter injury is woefully understudied, in part due to the difficulty to reliably model this type of injury in rodents. Periventricular leukomalacia (PVL) is the predominant form of brain injury and the most common cause of cerebral palsy in premature infants. PVL is characterized by predominant white matter injury. No specific therapy for PVL is presently available because the pathogenesis is not well understood. Here we report that two types of mouse PVL models have been created by hypoxia-ischemia with or without systemic co-administration of lipopolysaccharide (LPS). LPS co-administration exacerbated hypoxic-ischemic white matter injury and led to enhanced microglial activation and astrogliosis. Drug trials with the anti-inflammatory agent minocycline, the anti-excitotoxic agent NBQX and the antioxidant agent edaravone showed various degrees of protection in the two models, indicating that excitotoxic, oxidative and inflammatory forms of injury are involved in the pathogenesis of injury to immature white matter. We then applied immune-electron microscopy to reveal fine structural changes in the injured white matter, and found that synapses between axons and oligodendroglial precursor cells (OPCs) are quickly and profoundly damaged. Hypoxia-ischemia caused a drastic decrease in the number of postsynaptic densities associated with the glutamatergic axon-OPC synapses defined by the expression of vesicular glutamate transporters, vGluT1 and vGluT2, on axon terminals that formed contacts with OPCs in the periventricular white matter, resulted in selective shrinkage of the postsynaptic OPCs contacted by vGluT2 labeled synapses, and led to excitotoxicity mediated by GluR2-lacking, Ca2+-permeable AMPA receptors. Taken together, the present study provides novel mechanistic insights into the pathogenesis of PVL, and reveals that axon-glia synapses are highly vulnerable to white matter injury in the developing brain. More broadly, the study of white matter development and injury has general implications for a variety of neurological diseases including PVL, stroke, spinal cord injury and multiple sclerosis. PMID:21812016

Early musical training is linked to gray matter structure in the ventral premotor cortex and auditory-motor rhythm synchronization performance.

PubMed

Bailey, Jennifer Anne; Zatorre, Robert J; Penhune, Virginia B

2014-04-01

Evidence in animals and humans indicates that there are sensitive periods during development, times when experience or stimulation has a greater influence on behavior and brain structure. Sensitive periods are the result of an interaction between maturational processes and experience-dependent plasticity mechanisms. Previous work from our laboratory has shown that adult musicians who begin training before the age of 7 show enhancements in behavior and white matter structure compared with those who begin later. Plastic changes in white matter and gray matter are hypothesized to co-occur; therefore, the current study investigated possible differences in gray matter structure between early-trained (ET; <7) and late-trained (LT; >7) musicians, matched for years of experience. Gray matter structure was assessed using voxel-wise analysis techniques (optimized voxel-based morphometry, traditional voxel-based morphometry, and deformation-based morphometry) and surface-based measures (cortical thickness, surface area and mean curvature). Deformation-based morphometry analyses identified group differences between ET and LT musicians in right ventral premotor cortex (vPMC), which correlated with performance on an auditory motor synchronization task and with age of onset of musical training. In addition, cortical surface area in vPMC was greater for ET musicians. These results are consistent with evidence that premotor cortex shows greatest maturational change between the ages of 6-9 years and that this region is important for integrating auditory and motor information. We propose that the auditory and motor interactions required by musical practice drive plasticity in vPMC and that this plasticity is greatest when maturation is near its peak.

Influence of White and Gray Matter Connections on Endogenous Human Cortical Oscillations

PubMed Central

Hawasli, Ammar H.; Kim, DoHyun; Ledbetter, Noah M.; Dahiya, Sonika; Barbour, Dennis L.; Leuthardt, Eric C.

2016-01-01

Brain oscillations reflect changes in electrical potentials summated across neuronal populations. Low- and high-frequency rhythms have different modulation patterns. Slower rhythms are spatially broad, while faster rhythms are more local. From this observation, we hypothesized that low- and high-frequency oscillations reflect white- and gray-matter communications, respectively, and synchronization between low-frequency phase with high-frequency amplitude represents a mechanism enabling distributed brain-networks to coordinate local processing. Testing this common understanding, we selectively disrupted white or gray matter connections to human cortex while recording surface field potentials. Counter to our original hypotheses, we found that cortex consists of independent oscillatory-units (IOUs) that maintain their own complex endogenous rhythm structure. IOUs are differentially modulated by white and gray matter connections. White-matter connections maintain topographical anatomic heterogeneity (i.e., separable processing in cortical space) and gray-matter connections segregate cortical synchronization patterns (i.e., separable temporal processing through phase-power coupling). Modulation of distinct oscillatory modules enables the functional diversity necessary for complex processing in the human brain. PMID:27445767

Whole-brain voxel-based morphometry in Kallmann syndrome associated with mirror movements.

PubMed

Koenigkam-Santos, M; Santos, A C; Borduqui, T; Versiani, B R; Hallak, J E C; Crippa, J A S; Castro, M

2008-10-01

There are 2 main hypotheses concerning the cause of mirror movements (MM) in Kallmann syndrome (KS): abnormal development of the primary motor system, involving the ipsilateral corticospinal tract; and lack of contralateral motor cortex inhibitory mechanisms, mainly through the corpus callosum. The purpose of our study was to determine white and gray matter volume changes in a KS population by using optimized voxel-based morphometry (VBM) and to investigate the relationship between the abnormalities and the presence of MM, addressing the 2 mentioned hypotheses. T1-weighted volumetric images from 21 patients with KS and 16 matched control subjects were analyzed with optimized VBM. Images were segmented and spatially normalized, and these deformation parameters were then applied to the original images before the second segmentation. Patients were divided into groups with and without MM, and a t test statistic was then applied on a voxel-by-voxel basis between the groups and controls to evaluate significant differences. When considering our hypothesis a priori, we found that 2 areas of increased gray matter volume, in the left primary motor and sensorimotor cortex, were demonstrated only in patients with MM, when compared with healthy controls. Regarding white matter alterations, no areas of altered volume involving the corpus callosum or the projection of the corticospinal tract were demonstrated. The VBM study did not show significant white matter changes in patients with KS but showed gray matter alterations in keeping with a hypertrophic response to a deficient pyramidal decussation in patients with MM. In addition, gray matter alterations were observed in patients without MM, which can represent more complex mechanisms determining the presence or absence of this symptom.

White Matter Hyperintensities on Brain Magnetic Resonance Imaging in People with Epilepsy: A Hospital-Based Study.

PubMed

Mao, Yi-Ting; Goh, Enid; Churilov, Leonid; McIntosh, Anne; Ren, Yi-Fan; O'Brien, Terence J; Davis, Stephen; Dong, Qiang; Yan, Bernard; Kwan, Patrick

2016-09-01

We aim to explore whether people with epilepsy have increased white matter hyperintensities (WMHs). Eligible patients were categorized into newly diagnosed epilepsy (NE) and chronic epilepsy (CE); the latter were subdivided to those treated with enzyme-inducing antiepileptic drugs (EIAEDs) with or without non-enzyme-inducing antiepileptic drugs (NEIAEDs) and those with NEIAEDs only. WMHs were measured using age-related white matter changes (ARWMC) scale and compared between patients and healthy control group. Higher scores indicate greater WMH changes. The strengths of associations were estimated as incidence rate ratios (IRRs) with 95% confidence interval (CI). A total of 217 patients were included in the analysis, of whom 67 had NE, 45 had CE treated with NEIAEDs, and 105 had CE treated with EIAEDs. Age was positively associated with ARWMC score (IRR per year, 1.03; 95%CI, 1.03-1.04, P < 0.001). Compared with the healthy control group (n = 23), all patient groups had higher ARWMC score (P < 0.05). The difference was greatest in patients receiving EIAEDs (IRR, 2.13; 95%CI, 1.22-3.70, P = 0.007). WMHs tended to be observed in people with epilepsy, especially in those treated with EIAEDs. People with epilepsy with white matter changes should be evaluated for stroke risk, particularly if they are receiving EIAEDs. © 2016 John Wiley & Sons Ltd.

Collateral Flow and White Matter Disease in Patients with Internal Carotid Artery Occlusion.

PubMed

Ishikawa, Mami; Sugawara, Hitoshi; Nagai, Mutsumi; Kusaka, Gen; Tanaka, Yuichi; Naritaka, Heiji

2017-01-01

When an internal carotid artery (ICA) occludes, a patient may develop cerebral infarction (CI). We investigated whether CI caused by ICA occlusion (ICAO) is associated with collateral flow through the anterior and posterior communicating arteries (ACoA and PCoA). In 100 patients with ICAO, we investigated CI and white matter disease by performing an MRI and the anatomy of the ACoA and PCoA were investigated by performing magnetic resonance angiography. All patients were divided into the symptomatic CI group or the no-CI group. The collateral flow pathway was estimated by the anterior cerebral artery (ACA)-PCoA score and the collateral flow volume after ICAO was estimated by the middle cerebral artery (MCA) flow score, based on how well the MCA was visualized. Of 100 patients with ICAO, the symptomatic CI group included 36 patients. ACA-PCoA score and white matter disease grades were significantly higher in the CI group (indicating poor collateral flow). More than 80% of patients with an ACA-PCoA score of 4 (poor collateral) experienced symptomatic CI. Thirty-one symptomatic CI patients (86%) had an MCA flow score of 1 or 2 (decreased MCA flow). The ACA-PCoA score and white matter disease grade may suggest an increased risk of CI following ICAO. © 2016 S. Karger AG, Basel.

Exploring the neural substrates of attentional control and human intelligence: Diffusion tensor imaging of prefrontal white matter tractography in healthy cognition.

PubMed

Ohtani, Toshiyuki; Nestor, Paul G; Bouix, Sylvain; Newell, Dominick; Melonakos, Eric D; McCarley, Robert W; Shenton, Martha E; Kubicki, Marek

2017-01-26

We combined diffusion tension imaging (DTI) of prefrontal white matter integrity and neuropsychological measures to examine the functional neuroanatomy of human intelligence. Healthy participants completed the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) along with neuropsychological tests of attention and executive control, as measured by Trail Making Test (TMT) and Wisconsin Card Sorting Test (WCST). Stochastic tractography, considered the most effective DTI method, quantified white matter integrity of the medial orbital frontal cortex (mOFC) and rostral anterior cingulate cortex (rACC) circuitry. Based on prior studies, we hypothesized that posterior mOFC-rACC connections may play a key structural role linking attentional control processes and intelligence. Behavioral results provided strong support for this hypothesis, specifically linking attentional control processes, measured by Trails B and WCST perseverative errors, to intelligent quotient (IQ). Hierarchical regression results indicated left posterior mOFC-rACC fractional anisotropy (FA) and Trails B performance time, but not WCST perseverative errors, each contributed significantly to IQ, accounting for approximately 33.95-51.60% of the variance in IQ scores. These findings suggested that left posterior mOFC-rACC white matter connections may play a key role in supporting the relationship of executive functions of attentional control and general intelligence in healthy cognition. Copyright © 2016. Published by Elsevier Ltd.