Sample records for white matter region

  1. Midlife measurements of white matter microstructure predict subsequent regional white matter atrophy in healthy adults

    PubMed Central

    Ly, Martina; Canu, Elisa; Xu, Guofan; Oh, Jennifer; McLaren, Donald G; Dowling, N. Maritza; Alexander, Andrew L; Sager, Mark A; Johnson, Sterling C; Bendlin, Barbara B

    2013-01-01

    Objectives While age-related brain changes are becoming better understood, midlife patterns of change are still in need of characterization, and longitudinal studies are lacking. The aim of this study was to determine if baseline fractional anisotropy (FA), obtained from diffusion tensor imaging (DTI) predicts volume change over a four-year interval. Experimental design Forty-four cognitively healthy middle-age adults underwent baseline DTI and longitudinal T1-weighted magnetic resonance imaging. Tensor Based Morphometry methods were used to evaluate volume change over time. FA values were extracted from regions of interest that included the cingulum, entorhinal white matter, and the genu and splenium of the corpus callosum. Baseline FA was used as a predictor variable, while gray and white matter atrophy rates as indexed by Tensor Based Morphometry were the dependent variables. Principal observations Over a four-year period, participants showed significant contraction of white matter, especially in frontal, temporal, and cerebellar regions (p<0.05, corrected for multiple comparisons). Baseline FA in entorhinal white matter, genu, and splenium, was associated with longitudinal rates of atrophy in regions that included the superior longitudinal fasciculus, anterior corona radiata, temporal stem, and white matter of the inferior temporal gyrus (p<0.001, uncorrected for multiple comparisons). Conclusions Brain change with aging is characterized by extensive shrinkage of white matter. Baseline white matter microstructure as indexed by DTI was associated with some of the observed regional volume loss. The findings suggest that both white matter volume loss and microstructural alterations should be considered more prominently in models of aging and neurodegenerative diseases. PMID:23861348

  2. Global, Regional, and Local Development of Gray and White Matter Volume in Normal Children

    PubMed Central

    Wilke, Marko; Holland, Scott K.; Krägeloh-Mann, Ingeborg

    2006-01-01

    Objective Surprisingly little is known about normal brain development in healthy children. Over the last decade, non-invasive and high-resolution magnetic resonance imaging has allowed investigating this process in more details. However, much is still not known in this context, especially with regard to regional differences in brain morphology between genders. Design We conducted a large-scale study utilizing fully automated analysis-approaches, using high-resolution MR-imaging data from 200 normal children and aimed at providing reference data for future neuroimaging studies. Global, regional, and local aspects of normal development of gray and white matter volume were investigated as a function of age and gender while covarying for known nuisance variables. Results Global developmental patterns were apparent in both gray and white matter, with gray matter decreasing and white matter increasing significantly with age in all brain areas. Gray matter loss was most pronounced in the parietal lobes and least in the cingulate and in posterior temporal regions. White matter gains were almost uniform, with an accentuation of the pyramidal tract. Gender influences were pronounced for both gray and white matter. A number of regional measures also showed a strong influence of gender. The analysis of local effects confirmed significant differences in brain morphology between genders, like a larger amygdala in boys or a larger caudate in girls, in line with and extending earlier studies. Conclusion We could demonstrate profound influences of both age and gender on normal brain morphology, confirming and extending earlier studies. The knowledge of such influence allows for the consideration of age- and gender-effects in future pediatric neuroimaging studies. PMID:17051378

  3. Regional cortical white matter reductions in velocardiofacial syndrome: a volumetric MRI analysis

    Microsoft Academic Search

    Wendy R Kates; Courtney P Burnette; Ethylin W Jabs; Julie Rutberg; Anne M Murphy; Marco Grados; Michael Geraghty; Walter E Kaufmann; Godfrey D Pearlson

    2001-01-01

    Background: Velocardiofacial syndrome, caused by a microdeletion on chromosome 22q.11, is associated with craniofacial anomalies, cardiac defects, learning disabilities, and psychiatric disorders. To understand how the 22q.11 deletion affects brain development, this study examined gray and white matter volumes in major lobar brain regions of children with velocardiofacial syndrome relative to control subjects.Methods: Subjects were ten children with velocardiofacial syndrome

  4. Regional Gray Matter, White Matter, and Cerebrospinal Fluid Distributions in Schizophrenic Patients, Their Siblings, and Controls

    Microsoft Academic Search

    Tyrone D. Cannon; Theo G. M. van Erp; Matti Huttunen; Jouko Lonnqvist; Oili Salonen; Leena Valanne; Veli-Pekka Poutanen; Raquel E. Gur; Michelle Yan

    1998-01-01

    ter volume and significant increases in ventricular CSF volume. Regional effects were most robust when com- ponent volumes were expressed as percentages of over- all regional volumes; in this case, for patient and sibling groups, gray matter volume reductions and sulcal CSF volume increases were significantly more pronounced in the frontal and temporal lobes than in the remainder of the

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

    PubMed

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

    2015-07-01

    Lifelong bilingualism is associated with the delayed diagnosis of dementia, suggesting bilingual experience is relevant to brain health in aging. While the effects of bilingualism on cognitive functions across the lifespan are well documented, less is known about the neural substrates underlying differential behaviour. It is clear that bilingualism affects brain regions that mediate language abilities and that these regions are at least partially overlapping with those that exhibit age-related decline. Moreover, the behavioural advantages observed in bilingualism are generally found in executive function performance, suggesting that the frontal lobes may also be sensitive to bilingualism, which exhibit volume reductions with age. The current study investigated structural differences in the brain of lifelong bilingual older adults (n=14, mean age=70.4) compared with older monolinguals (n=14, mean age=70.6). We employed two analytic approaches: 1) we examined global differences in grey and white matter volumes; and, 2) we examined local differences in volume and cortical thickness of specific regions of interest previously implicated in bilingual/monolingual comparisons (temporal pole) or in aging (entorhinal cortex and hippocampus). We expected bilinguals would exhibit greater volume of the frontal lobe and temporal lobe (grey and white matter), given the importance of these regions in executive and language functions, respectively. We further hypothesized that regions in the medial temporal lobe, which demonstrate early changes in aging and exhibit neural pathology in dementia, would be more preserved in the bilingual group. As predicted, bilinguals exhibit greater frontal lobe white matter compared with monolinguals. Moreover, increasing age was related to decreasing temporal pole cortical thickness in the monolingual group, but no such relationship was observed for bilinguals. Finally, Stroop task performance was positively correlated with frontal lobe white matter, emphasizing the importance of preserved white matter in maintaining executive function in aging. These results underscore previous findings implicating an association between bilingualism and preserved frontal and temporal lobe function in aging. This article is part of a Special Issue entitled SI: Memory Ĺ. PMID:25725380

  6. 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.

  7. Potential interactions between pericytes and oligodendrocyte precursor cells in perivascular regions of cerebral white matter.

    PubMed

    Maki, Takakuni; Maeda, Mitsuyo; Uemura, Maiko; Lo, Evan K; Terasaki, Yasukazu; Liang, Anna C; Shindo, Akihiro; Choi, Yoon Kyung; Taguchi, Akihiko; Matsuyama, Tomohiro; Takahashi, Ryosuke; Ihara, Masafumi; Arai, Ken

    2015-06-15

    Pericytes are embedded within basal lamina and play multiple roles in the perivascular niche in brain. Recently, oligodendrocyte precursor cells (OPCs) have also been reported to associate with cerebral endothelium. Is it possible that within this gliovascular locus, there may also exist potential spatial and functional interactions between pericytes and OPCs? Here, we demonstrated that in the perivascular region of cerebral white matter, pericytes and OPCs may attach and support each other. Immunostaining showed that pericytes and OPCs are localized in close contact with each other in mouse white matter at postnatal days 0, 60 and 240. Electron microscopic analysis confirmed that pericytes attached to OPCs via basal lamina in the perivascular region. The close proximity between these two cell types was also observed in postmortem human brains. Functional interaction between pericytes and OPCs was assessed by in vitro media transfer experiments. When OPC cultures were treated with pericyte-conditioned media, OPC number increased. Similarly, pericyte number increased when pericytes were maintained in OPC-conditioned media. Taken together, our data suggest a potential anatomical and functional interaction between pericytes and OPCs in cerebral white matter. PMID:25936593

  8. Regional white matter hyperintensity volume, not hippocampal atrophy, predicts incident Alzheimer disease in the community.

    PubMed

    Brickman, Adam M; Provenzano, Frank A; Muraskin, Jordan; Manly, Jennifer J; Blum, Sonja; Apa, Zoltan; Stern, Yaakov; Brown, Truman R; Luchsinger, José A; Mayeux, Richard

    2012-12-01

    BACKGROUND New-onset Alzheimer disease (AD) is often attributed to degenerative changes in the hippocampus. However, the contribution of regionally distributed small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMHs) on magnetic resonance imaging, remains unclear. OBJECTIVE To determine whether regional WMHs and hippocampal volume predict incident AD in an epidemiological study. DESIGN A longitudinal community-based epidemiological study of older adults from northern Manhattan, New York. SETTING The Washington Heights/Inwood Columbia Aging Project. PARTICIPANTS Between 2005 and 2007, 717 participants without dementia received magnetic resonance imaging scans. A mean (SD) of 40.28 (9.77) months later, 503 returned for follow-up clinical examination and 46 met criteria for incident dementia (45 with AD). Regional WMHs and relative hippocampal volumes were derived. Three Cox proportional hazards models were run to predict incident dementia, controlling for relevant variables. The first included all WMH measurements; the second included relative hippocampal volume; and the third combined the 2 measurements. MAIN OUTCOME MEASURE Incident AD. RESULTS White matter hyperintensity volume in the parietal lobe predicted time to incident dementia (hazard ratio [HR] = 1.194; P = .03). Relative hippocampal volume did not predict incident dementia when considered alone (HR = 0.419; P = .77) or with the WMH measures included in the model (HR = 0.302; P = .70). Including hippocampal volume in the model did not notably alter the predictive utility of parietal lobe WMHs (HR = 1.197; P = .049). CONCLUSIONS The findings highlight the regional specificity of the association of WMHs with AD. It is not clear whether parietal WMHs solely represent a marker for cerebrovascular burden or point to distinct injury compared with other regions. Future work should elucidate pathogenic mechanisms linking WMHs and AD pathology. PMID:22945686

  9. Apathy is associated with white matter abnormalities in anterior, medial brain regions in persons with HIV infection

    PubMed Central

    Kamat, Rujvi; Brown, Gregory G.; Bolden, Khalima; Fennema-Notestine, Christine; Archibald, Sarah; Marcotte, Thomas D.; Letendre, Scott L.; Ellis, Ronald J.; Woods, Steven Paul; Grant, Igor; Heaton, Robert K.

    2015-01-01

    Apathy is a relatively common psychiatric syndrome in HIV infection, but little is known about its neural correlates. In the present study, we examined the associations between apathy and diffusion tensor imaging (DTI) indices in key frontal white matter regions in the thalamocorticostriatal circuit that has been implicated in the expression of apathy. Nineteen participants with HIV infection and 19 demographically comparable seronegative comparison subjects completed the Apathy subscale of the Frontal Systems Behavioral Scale as a part of a comprehensive neuropsychiatric research evaluation. When compared to the seronegative participants, the HIV+ group had significantly more frontal white matter abnormalities. Within HIV+ persons, and as predicted, higher ratings of apathy were associated with greater white matter alterations in the anterior corona radiata, genu, and orbital medial prefrontal cortex. The associations between white matter alterations and apathy were independent of depression and were stronger among participants with lower current CD4 counts. All told, these findings indicate that apathy is independently associated with white matter abnormalities in anterior, medial brain regions in persons infected with HIV, particularly in the setting of lower current immune functioning, which may have implications for antiretroviral therapy. PMID:25275424

  10. A cryogenic device for reversibly blocking transmission through small regions of the spinal cord white matter

    Microsoft Academic Search

    A. Vania Apkarian; C HODGEJR; Robert J. Martin; Richard T. Stevens

    1989-01-01

    A simple cryogenic device is described. This device is capable of cooling neural tissue in contact with the probe and maintaining the tissue at the desired temperature for extended periods of time. The cold probe can thereby reversibly block neural transmission through small portions of the spinal cord white matter. Interruption of axonal transmission is achieved by placing the tip

  11. Verbal Working Memory Performance Correlates with Regional White Matter Structures in the Frontoparietal Regions

    ERIC Educational Resources Information Center

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

    2011-01-01

    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…

  12. Regression coefficient maps showing that Nadir CD4+ count is correlated with regional white matter volumes (FDR q=0.05, critical P=0.03)

    E-print Network

    Thompson, Paul

    brain volumes and (1) demographic variables: age, sex (2) immune system measures: current and nadir CD4 in the frontal white matter are correlated with regional white matter volumes (FDR q=0.05, critical P=0.03) Brain, but the brain changes underlying this cognitive decline are still poorly understood. In patients with HIV

  13. A cryogenic device for reversibly blocking transmission through small regions of the spinal cord white matter.

    PubMed

    Apkarian, A V; Hodge, C J; Martin, R J; Stevens, R T

    1989-08-01

    A simple cryogenic device is described. This device is capable of cooling neural tissue in contact with the probe and maintaining the tissue at the desired temperature for extended periods of time. The cold probe can thereby reversibly block neural transmission through small portions of the spinal cord white matter. Interruption of axonal transmission is achieved by placing the tip of the device in contact with the exposed surface of the spinal cord and cooling the tip of the probe to -1 to +2 degrees C. The investigator monitors the tip temperature and adjusts the pump rate to maintain a constant tip temperature. The cross-sectional area under the probe where effective transmission block is achieved is about 1.5 mm2 which approximates the size of a single funiculus in the cat thoracic spinal cord. The cryogenic device was constructed for less than $700. The properties of this device were studied in physiologic experiments in cats. This device reversibly, selectively and repeatedly blocked the ascending mass action potential in the dorsolateral funiculus, transmission through ascending spinal axons in the dorsal columns, transmission through axons of spinal dorsal horn cells, the descending inhibitory input to the dorsal horn and the activity of thalamic nociceptive neurons. The reversible cold block effects on single units were observed for the duration of the experiments (up to 18 h) with no detectable damage to the underlying tissue. The physiologic effects of the cold block were usually reversed a few minutes after rewarming, although in some cases it took up to 40 min for the complete reversal of the cold block. This cryogenic device is useful for studying spinal cord pathways. PMID:2549308

  14. Regionally-specific alterations in myelin proteins in nonhuman primate white matter following prolonged cocaine self-administration

    PubMed Central

    Smith, Hilary R.; Beveridge, Thomas J.R.; Nader, Michael A.; Porrino, Linda J.

    2014-01-01

    Background Neuroimaging studies of cocaine users have demonstrated white matter abnormalities associated with behavioral measures of impulsivity and decision-making deficits. The underlying bases for this dysregulation in white matter structure and function have yet to be determined. The aim of the present studies was to investigate the influence of prolonged cocaine self-administration on the levels of myelin-associated proteins and mRNAs in nonhuman primate white matter. Methods Rhesus monkeys (n=4) self-administered cocaine (0.3 mg/kg/inj, 30 reinforcers per session) for 300 sessions. Control animals (n=4) responded for food. Following the final session monkeys were euthanized and white matter tissue at three brain levels was processed for immunoblotting analysis of proteolipid protein (PLP) and myelin basic protein (MBP), as well as for in situ hybridization histochemical analysis of PLP and MBP mRNAs. Results Both MBP and PLP immunoreactivities in white matter at the level of the precommissural striatum were significantly lower in tissue from monkeys self-administering cocaine as compared to controls. No significant differences were seen for either protein at the levels of the prefrontal cortex or postcommissural striatum. In addition, no differences were observed in expression of mRNA for either protein. Conclusions These preliminary findings, in a nonhuman model of prolonged cocaine self-administration, provide further evidence that compromised myelin may underlie the deficits in white matter integrity described in studies of human cocaine users. PMID:24529965

  15. Frontoparietal white matter diffusion properties predict mental arithmetic skills in children

    E-print Network

    Wandell, Brian A.

    Frontoparietal white matter diffusion properties predict mental arithmetic skills in children about the relationship between white matter properties and performance on mental calculation tasks oxygen level­dependent signals in the parietal and frontal regions. We tested whether white matter

  16. Canavan Disease: A White Matter Disorder

    ERIC Educational Resources Information Center

    Kumar, Shalini; Mattan, Natalia S.; de Vellis, Jean

    2006-01-01

    Breakdown of oligodendrocyte-neuron interactions in white matter (WM), such as the loss of myelin, results in axonal dysfunction and hence a disruption of information processing between brain regions. The major feature of leukodystrophies is the lack of proper myelin formation during early development or the onset of myelin loss late in life.…

  17. Regional electric field induced by electroconvulsive therapy in a realistic finite element head model: Influence of white matter anisotropic conductivity

    PubMed Central

    Lee, Won Hee; Deng, Zhi-De; Kim, Tae-Seong; Laine, Andrew F.; Lisanby, Sarah H.; Peterchev, Angel V.

    2012-01-01

    We present the first computational study investigating the electric field (E-field) strength generated by various electroconvulsive therapy (ECT) electrode configurations in specific brain regions of interest (ROIs) that have putative roles in the therapeutic action and/or adverse side effects of ECT. This study also characterizes the impact of the white matter (WM) conductivity anisotropy on the E-field distribution. A finite element head model incorporating tissue heterogeneity and WM anisotropic conductivity was constructed based on structural magnetic resonance imaging (MRI) and diffusion tensor MRI data. We computed the spatial E-field distributions generated by three standard ECT electrode placements including bilateral (BL), bifrontal (BF), and right unilateral (RUL) and an investigational electrode configuration for focal electrically administered seizure therapy (FEAST). The key results are that (1) the median E-field strength over the whole brain is 3.9, 1.5, 2.3, and 2.6 V/cm for the BL, BF, RUL, and FEAST electrode configurations, respectively, which coupled with the broad spread of the BL E-field suggests a biophysical basis for observations of superior efficacy of BL ECT compared to BF and RUL ECT; (2) in the hippocampi, BL ECT produces a median E-field of 4.8 V/cm that is 1.5–2.8 times stronger than that for the other electrode configurations, consistent with the more pronounced amnestic effects of BL ECT; and (3) neglecting the WM conductivity anisotropy results in E-field strength error up to 18% overall and up to 39% in specific ROIs, motivating the inclusion of the WM conductivity anisotropy in accurate head models. This computational study demonstrates how the realistic finite element head model incorporating tissue conductivity anisotropy provides quantitative insight into the biophysics of ECT, which may shed light on the differential clinical outcomes seen with various forms of ECT, and may guide the development of novel stimulation paradigms with improved risk/benefit ratio. PMID:22032945

  18. Microvasculature of the human cerebral white matter: arteries of the deep white matter.

    PubMed

    Nonaka, Hiroko; Akima, Michio; Hatori, Tsutomu; Nagayama, Tadashi; Zhang, Zean; Ihara, Fumie

    2003-06-01

    The vascular architecture of the human cerebral deep white matter was studied using soft X-ray and diaphanized specimens, achieved by intra-arterial injection of barium and vascular stain respectively, and also by electron microscopic examination of the corrosion cast of arteries in normal adult brains. The deep white matter arteries passed through the cerebral cortex with a few branches to the cortex and ran straight through the white matter. The arteries concentrated ventriculopetally to the white matter around the lateral ventricle. Anastomoses were noted around the ventricular wall at the terminals of the deep white matter arteries. No centrifugal branches irrigating the periventricular white matter from the lenticulo-striate arteries were observed in the present study. The presence of anastomoses among the terminal branches of deep white matter arteries protects against ischemic change or infarction in this area from an occlusion of a single deep white matter artery. This may lead to development of terminal zone infarction from ischemia or vascular diseases, affecting multiple deep white matter arteries. The subcortical and deep white matter arteries had thick adventitial sheaths and large adventitial spaces in the white matter but not in the cortex. The presence or absence of the adventitial space is regarded as another characteristic difference between the arteries in the white matter and cortex. This difference may influence pathological changes in vascular lesions in these respective areas. PMID:12777099

  19. White matter abnormalities in methcathinone abusers with an extrapyramidal syndrome.

    PubMed

    Stepens, Ainars; Stagg, Charlotte Jane; Platkajis, Ardis; Boudrias, Marie-Hélčne; Johansen-Berg, Heidi; Donaghy, Michael

    2010-12-01

    We examined white matter abnormalities in patients with a distinctive extrapyramidal syndrome due to intravenous methcathinone (ephedrone) abuse. We performed diffusion tensor imaging in 10 patients and 15 age-matched controls to assess white matter structure across the whole brain. Diffuse significant decreases in white matter fractional anisotropy, a diffusion tensor imaging metric reflecting microstructural integrity, occurred in patients compared with controls. In addition, we identified two foci of severe white matter abnormality underlying the right ventral premotor cortex and the medial frontal cortex, two cortical regions involved in higher-level executive control of motor function. Paths connecting different cortical regions with the globus pallidus, the nucleus previously shown to be abnormal on structural imaging in these patients, were generated using probabilistic tractography. The fractional anisotropy within all these tracts was lower in the patient group than in controls. Finally, we tested for a relationship between white matter integrity and clinical outcome. We identified a region within the left corticospinal tract in which lower fractional anisotropy was associated with greater functional deficit, but this region did not show reduced fractional anisotropy in the overall patient group compared to controls. These patients have widespread white matter damage with greatest severity of damage underlying executive motor areas. PMID:21036949

  20. White Matter Pathway Asymmetry Underlies Functional Lateralization

    Microsoft Academic Search

    Thomas R. Barrick; I. Nigel Lawes; Clare E. Mackay; Chris A. Clark

    2006-01-01

    Structural and functional asymmetry of the human brain has been well documented using techniques such as magnetic resonance imaging (MRI). However, asymmetry of underlying white matter connections is less well understood. We applied an MRI technique known as diffusion tensor tractography to reveal the morphology of the white matter in vivo by mapping directions of maximum water diffusion in brain

  1. 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.

  2. The contribution of regional gray/white matter volume in preclinical depression assessed by the Automatic Thoughts Questionnaire: a voxel-based morphometry study.

    PubMed

    Cun, Lingli; Wang, Yanqiu; Zhang, Songyan; Wei, Dongtao; Qiu, Jiang

    2014-09-10

    Negative automatic thought is a characteristic of depression that contributes toward the risk for episodes of depression. Evidence suggests that gray and white matter abnormalities are linked with depression, but little is known about the association between the negative cognitive experience and brain structure in preclinical depression. We examined the correlation between negative thought and gray (GMV)/white matter volume (WMV) in healthy individuals with preclinical depression. The participants were 309 university students with preclinical depression, as measured by their Automatic Thoughts Questionnaire (ATQ) scores. We collected brain MRIs and used voxel-based morphometry to analyze the correlation of regional GMV/WMV with the ATQ scores. The voxel-based morphometry results showed that the GMV of the right parahippocampal gyrus and fusiform gyrus and the WMV of the right superior temporal pole increased with the severity of depression. Furthermore, the corpus callosum volume decreased with the ATQ scores. This study implied that GMV increase and corpus callosum volume reduction may be associated with negative thought in nonclinical individuals, even at a preclinical depressed level. PMID:24999908

  3. Medial Frontal White and Gray Matter Contributions to General Intelligence

    PubMed Central

    Bouix, Sylvain; 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. PMID:25551572

  4. Cortical white matter: beyond the pale

    E-print Network

    Rockland, Kathleen

    The tracts within the subcortical white matter and corpus callosum provide an anatomical connectivity that is essential for normal cognitive functioning. These structures are predominantly made up of axons that are myelinated ...

  5. Cerebral white matter analysis using diffusion imaging

    E-print Network

    O'Donnell, Lauren Jean

    2006-01-01

    In this thesis we address the whole-brain tractography segmentation problem. Diffusion magnetic resonance imaging can be used to create a representation of white matter tracts in the brain via a process called tractography. ...

  6. Cardiorespiratory fitness is associated with white matter integrity in aging

    PubMed Central

    Hayes, Scott M; Salat, David H; Forman, Daniel E; Sperling, Reisa A; Verfaellie, Mieke

    2015-01-01

    Objective Aging is associated with reduced neural integrity, yet there are remarkable individual differences in brain health among older adults (OA). One factor that may attenuate age-related neural decline is cardiorespiratory fitness (CRF). The primary aim of this study was to link CRF to neural white matter microstructure using diffusion tensor imaging in OA. Methods Young adults (YA; n = 32) and OA (n = 27) completed a graded maximal exercise test to evaluate CRF and diffusion tensor magnetic resonance imaging to examine neural white matter integrity. Results As expected, pervasive age-related declines in white matter integrity were observed when OA were compared to YA. Further, peak VO2 was positively associated with fractional anisotropy (FA), an indicator of white matter integrity, in multiple brain regions in OA, but not YA. In multiple posterior regions such as the splenium, sagittal stratum, posterior corona radiata, and superior parietal white matter, FA values were similar in YA and OA classified as higher fit, with both groups having greater FA than lower fit OA. However, age-related differences in FA values remained in other regions, including the body and genu of the corpus callosum, precuneus, and superior frontal gyrus. Interpretation CRF is positively associated with neural white matter microstructure in aging. The relationship between peak VO2 and FA appears to be tract-specific, as equivalent FA values were observed in higher fit OA and YA in some white matter tracts, but not others. Further, the association between peak VO2 and FA appears to be age-dependent.

  7. Clinically relevant intronic splicing enhancer mutation in myelin proteolipid protein leads to progressive microglia and astrocyte activation in white and gray matter regions of the brain

    PubMed Central

    2013-01-01

    Introduction Mutations in proteolipid protein (PLP), the most abundant myelin protein in the CNS, cause the X-linked dysmyelinating leukodystrophies, Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia type 2 (SPG2). Point mutations, deletion, and duplication of the PLP1 gene cause PMD/SPG2 with varying clinical presentation. Deletion of an intronic splicing enhancer (ISEdel) within intron 3 of the PLP1 gene is associated with a mild form of PMD. Clinical and preclinical studies have indicated that mutations in myelin proteins, including PLP, can induce neuroinflammation, but the temporal and spatial onset of the reactive glia response in a clinically relevant mild form of PMD has not been defined. Methods A PLP-ISEdel knockin mouse was used to examine the behavioral and neuroinflammatory consequences of a deletion within intron 3 of the PLP gene, at two time points (two and four months old) early in the pathological progression. Mice were characterized functionally using the open field task, elevated plus maze, and nesting behavior. Quantitative neuropathological analysis was for markers of astrocytes (GFAP), microglia (IBA1, CD68, MHCII) and axons (APP). The Aperio ScanScope was used to generate a digital, high magnification photomicrograph of entire brain sections. These digital slides were used to quantify the immunohistochemical staining in ten different brain regions to assess the regional heterogeneity in the reactive astrocyte and microglial response. Results The PLP-ISEdel mice exhibited behavioral deficits in the open field and nesting behavior at two months, which did not worsen by four months of age. A marker of axonal injury (APP) increased from two months to four months of age. Striking was the robust reactive astrocyte and microglia response which was also progressive. In the two-month-old mice, the astrocyte and microglia reactivity was most apparent in white matter rich regions of the brain. By four months of age the gliosis had become widespread and included both white as well as gray matter regions of the brain. Conclusions Our results indicate, along with other preclinical models of PMD, that an early reactive glia response occurs following mutations in the PLP gene, which may represent a potentially clinically relevant, oligodendrocyte-independent therapeutic target for PMD. PMID:24314267

  8. ORIGINAL CONTRIBUTION White Matter Hyperintensities and

    E-print Network

    syndrome. The impact of small- vessel cerebrovascular disease, visualized as white mat- terORIGINAL CONTRIBUTION White Matter Hyperintensities and Cerebral Amyloidosis Necessary PIB-positive subjects, those diag- nosed as having AD had greater WMH volume than nor- mal control

  9. White Matter Microstructure in Idiopathic Craniocervical Dystonia

    PubMed Central

    Pinheiro, Giordanna L. S.; Guimarăes, Rachel P.; Piovesana, Luiza G.; Campos, Brunno M.; Campos, Lidiane S.; Azevedo, Paula C.; Torres, Fabio R.; Amato-Filho, Augusto C.; França, Marcondes C.; Lopes-Cendes, Iscia; Cendes, Fernando; D’Abreu, Anelyssa

    2015-01-01

    Background Dystonias are hyperkinetic movement disorders characterized by involuntary muscle contractions resulting in abnormal torsional movements and postures. Recent neuroimaging studies in idiopathic craniocervical dystonia (CCD) have uncovered the involvement of multiple areas, including cortical ones. Our goal was to evaluate white matter (WM) microstructure in subjects with CCD using diffusion tensor imaging (DTI) analysis. Methods We compared 40 patients with 40 healthy controls. Patients were then divided into subgroups: cervical dystonia, blepharospasm, blepharospasm + oromandibular dystonia, blepharospasm + oromandibular dystonia + cervical dystonia, using tract-based spatial statistics. We performed a region of interest-based analysis and tractography as confirmatory tests. Results There was no significant difference in the mean fractional anisotropy (FA) and mean diffusivity (MD) between the groups in any analysis. Discussion The lack of DTI changes in CCD suggests that the WM tracts are not primarily affected.

  10. 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. PMID:15739047

  11. 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. PMID:23929545

  12. White matter morphometric changes uniquely predict children's reading acquisition.

    PubMed

    Myers, Chelsea A; Vandermosten, Maaike; Farris, Emily A; Hancock, Roeland; Gimenez, Paul; Black, Jessica M; Casto, Brandi; Drahos, Miroslav; Tumber, Mandeep; Hendren, Robert L; Hulme, Charles; Hoeft, Fumiko

    2014-10-01

    This study examined whether variations in brain development between kindergarten and Grade 3 predicted individual differences in reading ability at Grade 3. Structural MRI measurements indicated that increases in the volume of two left temporo-parietal white matter clusters are unique predictors of reading outcomes above and beyond family history, socioeconomic status, and cognitive and preliteracy measures at baseline. Using diffusion MRI, we identified the left arcuate fasciculus and superior corona radiata as key fibers within the two clusters. Bias-free regression analyses using regions of interest from prior literature revealed that volume changes in temporo-parietal white matter, together with preliteracy measures, predicted 56% of the variance in reading outcomes. Our findings demonstrate the important contribution of developmental differences in areas of left dorsal white matter, often implicated in phonological processing, as a sensitive early biomarker for later reading abilities, and by extension, reading difficulties. PMID:25212581

  13. White Matter Abnormalities and Animal Models Examining a Putative Role of Altered White Matter in Schizophrenia

    PubMed Central

    Xu, Haiyun; Li, Xin-Min

    2011-01-01

    Schizophrenia is a severe mental disorder affecting about 1% of the population worldwide. Although the dopamine (DA) hypothesis is still keeping a dominant position in schizophrenia research, new advances have been emerging in recent years, which suggest the implication of white matter abnormalities in schizophrenia. In this paper, we will briefly review some of recent human studies showing white matter abnormalities in schizophrenic brains and altered oligodendrocyte-(OL-) and myelin-related genes in patients with schizophrenia and will consider abnormal behaviors reported in patients with white matter diseases. Following these, we will selectively introduce some animal models examining a putative role of white matter abnormalities in schizophrenia. The emphasis will be put on the cuprizone (CPZ) model. CPZ-fed mice show demyelination and OLs loss, display schizophrenia-related behaviors, and have higher DA levels in the prefrontal cortex. These features suggest that the CPZ model is a novel animal model of schizophrenia. PMID:22937274

  14. Does functional MRI detect activation in white matter? A review of emerging evidence, issues, and future directions

    PubMed Central

    Gawryluk, Jodie R.; Mazerolle, Erin L.; D'Arcy, Ryan C. N.

    2014-01-01

    Functional magnetic resonance imaging (fMRI) is a non-invasive technique that allows for visualization of activated brain regions. Until recently, fMRI studies have focused on gray matter. There are two main reasons white matter fMRI remains controversial: (1) the blood oxygen level dependent (BOLD) fMRI signal depends on cerebral blood flow and volume, which are lower in white matter than gray matter and (2) fMRI signal has been associated with post-synaptic potentials (mainly localized in gray matter) as opposed to action potentials (the primary type of neural activity in white matter). Despite these observations, there is no direct evidence against measuring fMRI activation in white matter and reports of fMRI activation in white matter continue to increase. The questions underlying white matter fMRI activation are important. White matter fMRI activation has the potential to greatly expand the breadth of brain connectivity research, as well as improve the assessment and diagnosis of white matter and connectivity disorders. The current review provides an overview of the motivation to investigate white matter fMRI activation, as well as the published evidence of this phenomenon. We speculate on possible neurophysiologic bases of white matter fMRI signals, and discuss potential explanations for why reports of white matter fMRI activation are relatively scarce. We end with a discussion of future basic and clinical research directions in the study of white matter fMRI. PMID:25152709

  15. Original Article Electrophysiological changes in isolated spinal cord white matter

    E-print Network

    Shi, Riyi

    Original Article Electrophysiological changes in isolated spinal cord white matter in response pig spinal cord white matter. Objectives: To determine whether lack of oxygen can cause irreversible of reoxygenation, mammalian spinal cord white matter can partially recover electrical impulse conduction. However

  16. Grading white matter lesions on CT and MRI: a simple scale

    Microsoft Academic Search

    J C van Swieten; A Hijdra; P J Koudstaal; J van Gijn

    1990-01-01

    We developed and tested a simple three-point scale for grading white matter lesions in anterior and posterior regions of the brain. Twenty four CT scans and 24 MRI scans were separately judged by 11 and five observers, respectively, on the presence and severity of white matter lesions. The observers were radiologists and neurologists. For CT scans, these periventricular changes were

  17. DTI Fiber Tract-Oriented Quantitative and Visual Analysis of White Matter Integrity

    E-print Network

    Zhang, Jun

    DTI Fiber Tract-Oriented Quantitative and Visual Analysis of White Matter Integrity Xuwei Liang@cs.uky.edu. Abstract. A new fiber tract-oriented quantitative and visual analysis scheme using diffusion tensor imaging (DTI) is developed to study the regional micro structural white matter changes along major fiber bun

  18. Abnormal gray and white matter volume in delusional infestation.

    PubMed

    Wolf, Robert Christian; Huber, Markus; Depping, Malte Sebastian; Thomann, Philipp Arthur; Karner, Martin; Lepping, Peter; Freudenmann, Roland W

    2013-10-01

    Little is known about the neural basis of delusional infestation (DI), the delusional belief to be infested with pathogens. Case series and the response to anti-dopaminergic medication indicate disruptions in dopaminergic neurotransmission in the striatum (caudate, putamen), but did not allow for population-based inference. Here, we report the first whole-brain structural neuroimaging study to investigate gray and white matter abnormalities in DI compared to controls. In this study, we used structural magnetic resonance imaging and voxel-based morphometry to investigate gray and white matter volume in 16 DI patients and 16 matched healthy controls. Lower gray matter volume in DI patients compared to controls was found in left medial, lateral and right superior frontal cortices, left anterior cingulate cortex, bilateral insula, left thalamus, right striatal areas and in lateral and medial temporal cortical regions (p<0.05, cluster-corrected). Higher white matter volume in DI patients compared to controls was found in right middle cingulate, left frontal opercular and bilateral striatal regions (p<0.05, cluster-corrected). This study shows that structural changes in prefrontal, temporal, insular, cingulate and striatal brain regions are associated with DI, supporting a neurobiological model of disrupted prefrontal control over somato-sensory representations. PMID:23791615

  19. 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 (??). 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 ?? were compared in gray and white matter. The value of ?? 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 ??. PMID:24374633

  20. Microglia of prefrontal white matter in suicide.

    PubMed

    Schnieder, Tatiana P; Trencevska, Iskra; Rosoklija, Gorazd; Stankov, Aleksandr; Mann, J John; Smiley, John; Dwork, Andrew J

    2014-09-01

    Immune functions in the brain are associated with psychiatric illness and temporary alteration of mental state. Microglia, the principal brain immunologic cells, respond to changes in the internal brain milieu through a sequence of activated states, each with characteristic function and morphology. To assess a possible association of frontal white matter pathology with suicide, we stained autopsy brain tissue samples from 11 suicide and 25 nonsuicide subjects for ionized calcium-binding adapter molecule 1, cluster of differentiation 68, and myelin. Groups were matched by age, sex, and psychiatric diagnosis. We classified ionized calcium-binding adapter molecule 1-immunoreactive cells based on shape, immunoreactivity to cluster of differentiation 68, and association with blood vessels to obtain stereologic estimates of densities of resting microglia, activated phagocytes, and perivascular cells. We found no effect of psychiatric diagnosis but 2 statistically significant effects of suicide: 1) The dorsal-ventral difference in activated microglial density was reversed such that, with suicide, the density was greater in ventral prefrontal white matter than in dorsal prefrontal white matter, whereas in the absence of suicide, the opposite was true; and 2) with suicide, there was a greater density of ionized calcium-binding adapter molecule 1-immunoreactive cells within or in contact with blood vessel walls in dorsal prefrontal white matter. These observations could reflect a mechanism for the stress/diathesis (state/trait) model of suicide, whereby an acute stress activates a reactive process in the brain, either directly or by compromising the blood-brain barrier, and creates a suicidal state in an individual at risk. They also indicate the theoretical potential of imaging studies in living vulnerable individuals for the assessment of suicide risk. Further studies are needed to investigate specific phenotypes of perivascular cells and blood-brain barrier changes associated with suicide. PMID:25101704

  1. Pediatric neurodegenerative white matter processes: leukodystrophies and beyond

    Microsoft Academic Search

    Jonathan A. Phelan; Lisa H. Lowe; Charles M. Glasier

    2008-01-01

    Pediatric neurodegenerative white matter processes are complex, numerous and result from a vast array of causes ranging from\\u000a white matter injury or inflammation to congenital metabolic disorders. When faced with a neurodegenerative white matter process\\u000a on neuroimaging, the first step for the radiologist is to determine whether the findings represent a congenital metabolic\\u000a leukodystrophy or one of various other white

  2. 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. PMID:25454416

  3. Whole-brain voxel-based statistical analysis of gray matter and white matter in temporal lobe epilepsy

    Microsoft Academic Search

    N. Bernasconi; S. Duchesne; A. Janke; J. Lerch; D. L. Collins; A. Bernasconi

    2004-01-01

    Volumetric MRI studies based on manual labeling of selected anatomical structures have provided in vivo evidence that brain abnormalities associated with temporal lobe epilepsy (TLE) extend beyond the hippocampus. Voxel-based morphometry (VBM) is a fully automated image analysis technique allowing identification of regional differences in gray matter (GM) and white matter (WM) between groups of subjects without a prior region

  4. White matter integrity in small vessel disease is related to cognition

    PubMed Central

    Tuladhar, Anil M.; van Norden, Anouk G.W.; de Laat, Karlijn F.; Zwiers, Marcel P.; van Dijk, Ewoud J.; Norris, David G.; de Leeuw, Frank-Erik

    2015-01-01

    Cerebral small vessel disease, including white matter hyperintensities (WMH) and lacunes of presumed vascular origin, is common in elderly people and is related to cognitive impairment and dementia. One possible mechanism could be the disruption of white matter tracts (both within WMH and normal-appearing white matter) that connect distributed brain regions involved in cognitive functions. Here, we investigated the relation between microstructural integrity of the white matter and cognitive functions in patients with small vessel disease. The Radboud University Nijmegen Diffusion tensor and Magnetic resonance Cohort study is a prospective cohort study among 444 independently living, non-demented elderly with cerebral small vessel disease, aged between 5500 and 85 years. All subjects underwent magnetic resonance imaging and diffusion tensor imaging scanning and an extensive neuropsychological assessment. We showed that loss of microstructural integrity of the white matter at specific locations was related to specific cognitive disturbances, which was mainly located in the normal-appearing white matter (p < 0.05, FWE-corrected for multiple comparisons). The microstructural integrity in the genu and splenium showed the highest significant relation with global cognitive function and executive functions, in the cingulum bundle with verbal memory performance. Associations between diffusion tensor imaging parameters and most cognitive domains remained present after adjustment for WMH and lacunes. In conclusion, cognitive disturbances in subjects with cerebral small vessel disease are related to microstructural integrity of multiple white matter fibers (within WMH and normal-appearing white matter) connecting different cortical and subcortical regions. PMID:25737960

  5. Altered white matter microstructure in adolescent substance users

    PubMed Central

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

    2009-01-01

    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. Diffusion parameters fractional anisotropy (FA) and mean diffusivity (MD) were subjected to whole-brain voxelwise group comparisons using tract-based spatial statistics (Smith et al., 2006). 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 suggests possible neuroadaptive processes and can be examined in future studies of connectivity to determine how aberrancies in specific tracts might influence efficient cognitive processing. PMID:19699064

  6. Diffusion tensor imaging in studying white matter complexity: a gap junction hypothesis.

    PubMed

    Abdallah, Chadi G; Tang, Cheuk Y; Mathew, Sanjay J; Martinez, Jose; Hof, Patrick R; Perera, Tarique D; Shungu, Dikoma C; Gorman, Jack M; Coplan, Jeremy D

    2010-05-21

    The role of the prefrontal cortex as an executive oversight of posterior brain regions raises the question of the extent to which the anterior regions of the brain interconnect with the posterior regions. The aim of this study is to test the complexity of rostral white matter tracts, which connect anterior and posterior brain regions, in comparison to caudal white matter tracts and the corpus callosum. Diffusion tensor imaging (DTI) is a modality that measures fractional anisotropy (FA). Higher white matter complexity could result in a decrease of FA, possibly through denser intersection of fiber tracts. DTI was used to determine regional FA in 9 healthy bonnet macaques (Macaca radiata). Four regions of interest were included: anterior and posterior limbs of the internal capsule, the occipital lobe white matter, and the corpus callosum. FA of the anterior limbs of the internal capsule was lowest compared to all other regions of interest (Newman-Keuls (N-K); p<0.0001), whereas FA of the corpus callosum was highest (N-K; p<0.0001). The posterior limbs of the internal capsule and the occipital white matter were not distinguishable but exhibited intermediate FA in comparison to the former (N-K; p<0.0001) and the latter (N-K; p<0.0001). The current study demonstrates that FA, a measure of white matter complexity, can vary markedly as a function of region of interest. Moreover, validation of these findings using neurohistological studies and replication in human samples appears warranted. PMID:20371267

  7. Diffusion tensor imaging in studying white matter complexity: A gap junction hypothesis

    PubMed Central

    Abdallah, Chadi G.; Tang, Cheuk Y.; Mathew, Sanjay J.; Martinez, Jose; Hof, Patrick R.; Perera, Tarique D.; Shungu, Dikoma C.; Gorman, Jack M.; Coplan, Jeremy D.

    2010-01-01

    The role of the prefrontal cortex as an executive oversight of posterior brain regions raises the question of the extent to which the anterior regions of the brain interconnect with the posterior regions. The aim of this study is to test the complexity of rostral white matter tracts, which connect anterior and posterior brain regions, in comparison to caudal white matter tracts and the corpus callosum. Diffusion tensor imaging (DTI) is a modality that measures fractional anisotropy (FA). Higher white matter complexity could result in a decrease of FA, possibly through denser intersection of fiber tracts. DTI was used to determine regional FA in 9 healthy bonnet macaques (Macaca radiata). Four regions of interest were included: anterior and posterior limbs of the internal capsule, the occipital lobe white matter, and the corpus callosum. FA of the anterior limbs of the internal capsule was lowest compared to all other regions of interest (Newman-Keuls (N-K); p < 0.0001), whereas FA of the corpus callosum was highest (N-K; p < 0.0001). The posterior limbs of the internal capsule and the occipital white matter were not distinguishable but exhibited intermediate FA in comparison to the former (N-K; p < 0.0001) and the latter (N-K; p < 0.0001). The current study demonstrates that FA, a measure of white matter complexity, can vary markedly as a function of region of interest. Moreover, validation of these findings using neurohistological studies and replication in human samples appears warranted. PMID:20371267

  8. Evaluation of white matter myelin water fraction in chronic stroke?

    PubMed Central

    Borich, M.R.; MacKay, A.L.; Vavasour, I.M.; Rauscher, A.; Boyd, L.A.

    2013-01-01

    Multi-component T2 relaxation imaging (MCRI) provides specific in vivo measurement of myelin water content and tissue water environments through myelin water fraction (MWF), intra/extra-cellular water fraction (I/EWF) and intra/extracellular and global geometric mean T2 (GMT2) times. Quantitative MCRI assessment of tissue water environments has provided new insights into the progression and underlying white matter pathology in neural disorders such as multiple sclerosis. It has not previously been applied to investigate changes in white matter in the stroke-affected brain. Thus, the purposes of this study were to 1) use MCRI to index myelin water content and tissue water environments in the brain after stroke 2) evaluate relationships between MWF and diffusion behavior indexed by diffusion tensor imaging-based metrics and 3) examine the relationship between white matter status (MWF and fractional anisotropy) and motor behavior in the chronic phase of stroke recovery. Twenty individuals with ischemic stroke and 12 matched healthy controls participated. Excellent to good test/re-test and inter-rater reliability was observed for region of interest-based voxelwise MWF data. Reduced MWF was observed in whole-cerebrum white matter (p < 0.001) and in the ipsilesional (p = 0.017) and contralesional (p = 0.037) posterior limb of internal capsule (PLIC) after stroke compared to whole-cerebrum and bilateral PLIC MWF in healthy controls. The stroke group also demonstrated increased I/EWF, I/E GMT2 and global GMT2 times for whole-cerebrum white matter. Measures of diffusion behavior were also significantly different in the stroke group across each region investigated (p < 0.001). MWF was not significantly correlated with specific tensor-based measures of diffusion in the PLIC for either group. Fractional anisotropy in the ipsilesional PLIC correlated with motor behavior in chronic stroke. These results provide novel insights into tissue-specific changes within white matter after stroke that may have important applications for the understanding of the neuropathology of stroke. PMID:24179808

  9. Organising white matter in a brain without corpus callosum fibres.

    PubMed

    Bénézit, Audrey; Hertz-Pannier, Lucie; Dehaene-Lambertz, Ghislaine; Monzalvo, Karla; Germanaud, David; Duclap, Delphine; Guevara, Pamela; Mangin, Jean-François; Poupon, Cyril; Moutard, Marie-Laure; Dubois, Jessica

    2015-02-01

    Isolated corpus callosum dysgenesis (CCD) is a congenital malformation which occurs during early development of the brain. In this study, we aimed to identify and describe its consequences beyond the lack of callosal fibres, on the morphology, microstructure and asymmetries of the main white matter bundles with diffusion imaging and fibre tractography. Seven children aged between 9 and 13 years old and seven age- and gender-matched control children were studied. First, we focused on bundles within the mesial region of the cerebral hemispheres: the corpus callosum, Probst bundles and cingulum which were selected using a conventional region-based approach. We demonstrated that the Probst bundles have a wider connectivity than the previously described rostrocaudal direction, and a microstructure rather distinct from the cingulum but relatively close to callosal remnant fibres. A sigmoid bundle was found in two partial ageneses. Second, the corticospinal tract, thalamic radiations and association bundles were extracted automatically via an atlas of adult white matter bundles to overcome bias resulting from a priori knowledge of the bundles' anatomical morphology and trajectory. Despite the lack of callosal fibres and the colpocephaly observed in CCD, all major white matter bundles were identified with a relatively normal morphology, and preserved microstructure (i.e. fractional anisotropy, mean diffusivity) and asymmetries. Consequently the bundles' organisation seems well conserved in brains with CCD. These results await further investigations with functional imaging before apprehending the cognition variability in children with isolated dysgenesis. PMID:25282054

  10. Probing the brain’s white matter with diffusion MRI and a tissue dependent diffusion model 

    E-print Network

    Piatkowski, Jakub Przemyslaw

    2014-06-27

    While diffusion MRI promises an insight into white matter microstructure in vivo, the axonal pathways that connect different brain regions together can only partially be segmented using current methods. Here we present ...

  11. Microstructural White Matter Changes in Primary Torsion Dystonia

    PubMed Central

    Carbon, Maren; Kingsley, Peter B.; Tang, Chengke; Bressman, Susan; Eidelberg, David

    2015-01-01

    Primary torsion dystonia (PTD) has been conceptualized as a disorder of the basal ganglia. However, recent data suggest a widespread pathology involving motor control pathways. In this report, we explored whether PTD is associated with abnormal anatomical connectivity within motor control pathways. We used diffusion tensor magnetic resonance imaging (DT-MRI) to assess the microstructure of white matter. We found that fractional anisotropy, a measure of axonal integrity and coherence, was significantly reduced in PTD patients in the pontine brainstem in the vicinity of the left superior cerebellar peduncle and bilaterally in the white matter of the sensorimotor region. Our data thus support the possibility of a disturbance in cerebello-thalamo-cortical pathways as a cause of the clinical manifestations of PTD. PMID:17999428

  12. Localisation of increased prefrontal white matter in pathological liars.

    PubMed

    Yang, Yaling; Raine, Adrian; Narr, Katherine L; Lencz, Todd; LaCasse, Lori; Colletti, Patrick; Toga, Arthur W

    2007-02-01

    We examined white matter volumes in four prefrontal subregions using structural magnetic resonance imaging in 10 pathological liars, 14 antisocial controls, and 20 normal controls. Liars showed a relatively widespread increase in white matter (23-36%) in orbitofrontal, middle and inferior, but not superior, frontal gyri compared with antisocial and normal controls. This white matter increase may predispose some individuals to pathological lying. PMID:17267937

  13. Explicating the Face Perception Network with White Matter Connectivity

    PubMed Central

    Pyles, John A.; Verstynen, Timothy D.; Schneider, Walter; Tarr, Michael J.

    2013-01-01

    A network of multiple brain regions is recruited in face perception. Our understanding of the functional properties of this network can be facilitated by explicating the structural white matter connections that exist between its functional nodes. We accomplished this using functional MRI (fMRI) in combination with fiber tractography on high angular resolution diffusion weighted imaging data. We identified the three nodes of the core face network: the “occipital face area” (OFA), the “fusiform face area” (mid-fusiform gyrus or mFus), and the superior temporal sulcus (STS). Additionally, a region of the anterior temporal lobe (aIT), implicated as being important for face perception was identified. Our data suggest that we can further divide the OFA into multiple anatomically distinct clusters – a partitioning consistent with several recent neuroimaging results. More generally, structural white matter connectivity within this network revealed: 1) Connectivity between aIT and mFus, and between aIT and occipital regions, consistent with studies implicating this posterior to anterior pathway as critical to normal face processing; 2) Strong connectivity between mFus and each of the occipital face-selective regions, suggesting that these three areas may subserve different functional roles; 3) Almost no connectivity between STS and mFus, or between STS and the other face-selective regions. Overall, our findings suggest a re-evaluation of the “core” face network with respect to what functional areas are or are not included in this network. PMID:23630602

  14. Obsessive-compulsive disorder associated with parietal white matter multiple sclerosis plaques.

    PubMed

    Douzenis, Athanassios; Michalopoulou, Panayiota G; Voumvourakis, Constantine; Typaldou, Maria; Michopoulos, Ioannis; Lykouras, Lefteris

    2009-01-01

    We report the case of a patient who developed obsessive-compulsive symptoms after being diagnosed with multiple sclerosis. In this patient, obsessive-compulsive symptoms deteriorated with the emergence of a right parietal white matter multiple sclerosis plaque. The involvement of parietal white matter abnormalities in the pathophysiology of obsessive-compulsive disorder remains largely unexplored. Our case report raises the possibility that parietal lobe white matter microstructure plays a role in mediating obsessions and compulsions through disruptions of the functional connectivity between cortical-cortical and/or cortical-subcortical brain regions implicated in the pathophysiology of obsessive-compulsive disorder. PMID:19995223

  15. Belief Propagation Based Segmentation of White Matter Tracts in DTI

    PubMed Central

    Bazin, Pierre-Louis; Bogovic, John; Reich, Daniel; Prince, Jerry L.; Pham, Dzung L.

    2011-01-01

    This paper presents a belief propagation approach to the segmentation of the major white matter tracts in diffusion tensor images of the human brain. Unlike tractography methods that sample multiple fibers to be bundled together, we define a Markov field directly on the diffusion tensors to separate the main fiber tracts at the voxel level. A prior model of shape and direction guides a full segmentation of the brain into known fiber tracts; additional, unspecified fibers; and isotropic regions. The method is evaluated on various data sets from an atlasing project, healthy subjects, and multiple sclerosis patients. PMID:20426079

  16. 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…

  17. STUDY PROTOCOL Open Access Multimodal neuroimaging of frontal white matter

    E-print Network

    white matter, in a vulnerable brain. Methods/Design: Young adults with schizophrenia at the early stage phase schizophrenia: the impact of early adolescent cannabis use Denise Bernier1* , Jacob Cookey1 symptoms and cognitive dysfunctions observed in schizophrenia. White matter, which comprises axons

  18. Selective reduction of diffusion anisotropy in white matter of Alzheimer disease brains measured by 3.0 Tesla magnetic resonance imaging

    Microsoft Academic Search

    Satoshi Takahashi; Hisashi Yonezawa; Junko Takahashi; Masako Kudo; Takashi Inoue; Hideo Tohgi

    2002-01-01

    Alzheimer disease (AD) is pathologically characterized by cortical atrophy. Changes in the white matter and their relation to the pathogenesis of AD remain to be studied. To quantitatively investigate the integrity and organization of white matter fiber tracts in patients with AD, we used diffusion tensor (DT) imaging to study the diffusion anisotropy of white matter regions. DT imaging was

  19. White matter abnormalities revealed by diffusion tensor imaging in non-demented and demented HIV+ patients

    PubMed Central

    Chen, Yasheng; An, Hongyu; Zhu, Hongtu; Stone, Taylor; Smith, J. Keith; Hall, Colin; Bullitt, Elizabeth; Shen, Dinggang; Lin, Weili

    2015-01-01

    HIV associated dementia (HAD) is the most advanced stage of central nervous system disease caused by HIV infection. Previous studies have demonstrated that patients with HAD exhibit greater cerebral and basal ganglia atrophy than non-demented HIV+ (HND) patients. However, the extent to which white matter is affected in HAD patients compared to HND patients remains elusive. This study is designed to address the potential white matter abnormalities through the utilization of diffusion tensor imaging (DTI) in both HND and HAD patients. DTI and T1-weighted images were acquired from 18 healthy controls, 21 HND and 8 HAD patients. T1 image-based registration was performed to 1) parcellate the whole brain white matter into major white matter regions, including frontal, parietal, temporal and occipital white matter, corpus callosum and internal capsule for statistical comparisons of the mean DTI values, and 2) warp all DTI parametric images towards the common template space for voxel-based analysis. The statistical comparisons were performed with four DTI parameters including fractional anisotropy (FA), mean (MD), axial (AD), and radial (RD) diffusivities. With Whitney U tests on the mean DTI values, both HND and HAD demonstrated significant differences from the healthy control in multiple white matter regions. In addition, HAD patients exhibited significantly elevated MD and RD in the parietal white matter when compared to HND patients. In the voxel-based analysis, widespread abnormal regions were identified for both HND and HAD patients, although a much larger abnormal volume was observed in HAD patients for all four DTI parameters. Furthermore, both region of interest (ROI) based and voxel-based analyses revealed that RD was affected to a much greater extent than AD by HIV infection, which may suggest that demyelination is the prominent disease progression in white matter. PMID:19376246

  20. Neurocognitive Correlates of White Matter Quality in Adolescent Substance Users

    PubMed Central

    Bava, Sunita; Jacobus, Joanna; Mahmood, Omar; Yang, Tony T.; Tapert, Susan F.

    2009-01-01

    Background Progressive myelination during adolescence implicates an increased vulnerability to neurotoxic substances and enduring neurocognitive consequences. This study examined the cognitive manifestations of altered white matter microstructure in chronic marijuana and alcohol-using (MJ+ALC) adolescents. Methods Thirty-six MJ+ALC adolescents (ages 16-19) and 36 demographically similar controls were evaluated with diffusion tensor imaging (Bava et al., 2009) and neurocognitive tests. Regions of group difference in fractional anisotropy (FA) and mean diffusivity (MD) were analyzed in relation to cognitive performance. Results In users, lower FA in temporal areas related to poorer performance on attention, working memory, and speeded processing tasks. Among regions where users had higher FA than controls, occipital FA was positively associated with working memory and complex visuomotor sequencing, whereas FA in anterior regions was negatively associated with verbal memory performance. Conclusions Findings suggest differential influences of white matter development on cognition in MJ+ALC using adolescents than in non-using peers. Neuroadaptation may reflect additive and subtractive responses to substance use that are complicated by competing maturational processes. PMID:19932550

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

    PubMed Central

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

    2015-01-01

    White matter hyperintensities (WMH) of presumed vascular origin are a common finding in brain magnetic resonance imaging of older individuals and contribute to cognitive and functional decline. It is unknown how WMH form, although white matter degeneration is characterized pathologically by demyelination, axonal loss, and rarefaction, often attributed to ischemia. Changes within normal-appearing white matter (NAWM) in subjects with WMH have also been reported but have not yet been fully characterized. Here, we describe the in vivo imaging signatures of both NAWM and WMH in a large group of community-dwelling older people of similar age using biomarkers derived from magnetic resonance imaging that collectively reflect white matter integrity, myelination, and brain water content. Fractional anisotropy (FA) and magnetization transfer ratio (MTR) were significantly lower, whereas mean diffusivity (MD) and longitudinal relaxation time (T1) were significantly higher, in WMH than NAWM (p < 0.0001), with MD providing the largest difference between NAWM and WMH. Receiver operating characteristic analysis on each biomarker showed that MD differentiated best between NAWM and WMH, identifying 94.6% of the lesions using a threshold of 0.747 × 10?9 m2s?1 (area under curve, 0.982; 95% CI, 0.975–0.989). Furthermore, the level of deterioration of NAWM was strongly associated with the severity of WMH, with MD and T1 increasing and FA and MTR decreasing in NAWM with increasing WMH score, a relationship that was sustained regardless of distance from the WMH. These multimodal imaging data indicate that WMH have reduced structural integrity compared with surrounding NAWM, and MD provides the best discriminator between the 2 tissue classes even within the mild range of WMH severity, whereas FA, MTR, and T1 only start reflecting significant changes in tissue microstructure as WMH become more severe. PMID:25457555

  2. The Classical Pathways of Occipital Lobe Epileptic Propagation Revised in the Light of White Matter Dissection

    PubMed Central

    Latini, Francesco; Hjortberg, Mats; Aldskogius, Hĺkan; Ryttlefors, Mats

    2015-01-01

    The clinical evidences of variable epileptic propagation in occipital lobe epilepsy (OLE) have been demonstrated by several studies. However the exact localization of the epileptic focus sometimes represents a problem because of the rapid propagation to frontal, parietal, or temporal regions. Each white matter pathway close to the supposed initial focus can lead the propagation towards a specific direction, explaining the variable semiology of these rare epilepsy syndromes. Some new insights in occipital white matter anatomy are herein described by means of white matter dissection and compared to the classical epileptic patterns, mostly based on the central position of the primary visual cortex. The dissections showed a complex white matter architecture composed by vertical and longitudinal bundles, which are closely interconnected and segregated and are able to support specific high order functions with parallel bidirectional propagation of the electric signal. The same sublobar lesions may hyperactivate different white matter bundles reemphasizing the importance of the ictal semiology as a specific clinical demonstration of the subcortical networks recruited. Merging semiology, white matter anatomy, and electrophysiology may lead us to a better understanding of these complex syndromes and tailored therapeutic options based on individual white matter connectivity. PMID:26063964

  3. Breastfeeding and early white matter development: A cross-sectional study?

    PubMed Central

    Deoni, Sean C.L.; Dean, Douglas C.; Piryatinsky, Irene; O'Muircheartaigh, Jonathan; Waskiewicz, Nicole; Lehman, Katie; Han, Michelle; Dirks, Holly

    2013-01-01

    Does breastfeeding alter early brain development? The prevailing consensus from large epidemiological studies posits that early exclusive breastfeeding is associated with improved measures of IQ and cognitive functioning in later childhood and adolescence. Prior morphometric brain imaging studies support these findings, revealing increased white matter and sub-cortical gray matter volume, and parietal lobe cortical thickness, associated with IQ, in adolescents who were breastfed as infants compared to those who were exclusively formula-fed. Yet it remains unknown when these structural differences first manifest and when developmental differences that predict later performance improvements can be detected. In this study, we used quiet magnetic resonance imaging (MRI) scans to compare measures of white matter microstructure (mcDESPOT measures of myelin water fraction) in 133 healthy children from 10 months through 4 years of age, who were either exclusively breastfed a minimum of 3 months; exclusively formula-fed; or received a mixture of breast milk and formula. We also examined the relationship between breastfeeding duration and white matter microstructure. Breastfed children exhibited increased white matter development in later maturing frontal and association brain regions. Positive relationships between white matter microstructure and breastfeeding duration are also exhibited in several brain regions, that are anatomically consistent with observed improvements in cognitive and behavioral performance measures. While the mechanisms underlying these structural differences remains unclear, our findings provide new insight into the earliest developmental advantages associated with breastfeeding, and support the hypothesis that breast milk constituents promote healthy neural growth and white matter development. PMID:23721722

  4. Frontal White Matter and Cingulum Diffusion Tensor Imaging Deficits in Alcoholism

    PubMed Central

    Harris, Gordon J.; Jaffin, Sharon Kim; Hodge, Steven M.; Kennedy, David; Caviness, Verne S.; Marinkovic, Ksenija; Papadimitriou, George M.; Makris, Nikos; Oscar-Berman, Marlene

    2014-01-01

    Background Alcoholism-related deficits in cognition and emotion point toward frontal and limbic dysfunction, particularly in the right hemisphere. Prefrontal and anterior cingulate cortices are involved in cognitive and emotional functions and play critical roles in the oversight of the limbic reward system. In the present study, we examined the integrity of white matter tracts that are critical to frontal and limbic connectivity. Methods Diffusion tensor magnetic resonance imaging (DT-MRI) was used to assess functional anisotropy (FA), a measure of white matter integrity, in 15 abstinent long-term chronic alcoholic and 15 demographically equivalent control men. Voxel-based and region-based analyses of group FA differences were applied to these scans. Results Alcoholic subjects had diminished frontal lobe FA in the right superior longitudinal fascicles II and III, orbitofrontal cortex white matter, and cingulum bundle, but not in corresponding left hemisphere regions. These right frontal and cingulum white matter regional FA measures provided 97% correct group discrimination. Working Memory scores positively correlated with superior longitudinal fascicle III FA measures in control subjects only. Conclusions The findings demonstrate white matter microstructure deficits in abstinent alcoholic men in several right hemisphere tracts connecting prefrontal and limbic systems. These white matter deficits may contribute to underlying dysfunction in memory, emotion, and reward response in alcoholism. PMID:18422840

  5. AGREEMENT BETWEEN THE WHITE MATTER CONNECTIVITY BASED ON THE TENSOR-BASED MORPHOMETRY AND THE VOLUMETRIC WHITE MATTER

    E-print Network

    Chung, Moo K.

    . Pollak3,6 1 Department of Brain and Cognitive Sciences, 2 Department of Nuclear Medicine, 3 Institute and Medical Informatics, 5 Waisman Laboratory for Brain Imaging and Behavior, 6 Department of Psychology-based white matter atlas. As an application, altered white matter connectivity in a clinical population

  6. White Matter Microstructure Alterations: A Study of Alcoholics with and without Post-Traumatic Stress Disorder

    PubMed Central

    Durkee, Caitlin A.; Sarlls, Joelle E.; Hommer, Daniel W.; Momenan, Reza

    2013-01-01

    Many brain imaging studies have demonstrated reductions in gray and white matter volumes in alcoholism, with fewer investigators using diffusion tensor imaging (DTI) to examine the integrity of white matter pathways. Among various medical conditions, alcoholism and post-traumatic stress disorder (PTSD) are two comorbid diseases that have similar degenerative effects on the white matter integrity. Therefore, understanding and differentiating these effects would be very important in characterizing alcoholism and PTSD. Alcoholics are known to have neurocognitive deficits in decision-making, particularly in decisions related to emotionally-motivated behavior, while individuals with PTSD have deficits in emotional regulation and enhanced fear response. It is widely believed that these types of abnormalities in both alcoholism and PTSD are related to fronto-limbic dysfunction. In addition, previous studies have shown cortico-limbic fiber degradation through fiber tracking in alcoholism. DTI was used to measure white matter fractional anisotropy (FA), which provides information about tissue microstructure, possibly indicating white matter integrity. We quantitatively investigated the microstructure of white matter through whole brain DTI analysis in healthy volunteers (HV) and alcohol dependent subjects without PTSD (ALC) and with PTSD (ALC+PTSD). These data show significant differences in FA between alcoholics and non-alcoholic HVs, with no significant differences in FA between ALC and ALC+PTSD in any white matter structure. We performed a post-hoc region of interest analysis that allowed us to incorporate multiple covariates into the analysis and found similar results. HV had higher FA in several areas implicated in the reward circuit, emotion, and executive functioning, suggesting that there may be microstructural abnormalities in white matter pathways that contribute to neurocognitive and executive functioning deficits observed in alcoholics. Furthermore, our data do not reveal any differences between ALC and ALC+PTSD, suggesting that the effect of alcohol on white matter microstructure may be more significant than any effect caused by PTSD. PMID:24260518

  7. Drawing connections between white matter and numerical and mathematical cognition: a literature review.

    PubMed

    Matejko, Anna A; Ansari, Daniel

    2015-01-01

    In this review we examine white matter tracts that may support numerical and mathematical abilities and whether abnormalities in these pathways are associated with deficits in numerical and mathematical abilities. Diffusion tensor imaging (DTI) yields indices of white matter integrity and can provide information about the axonal organization of the brain. A growing body of research is using DTI to investigate how individual differences in brain microstructures relate to different numerical and mathematical abilities. Several tracts have been associated with numerical and mathematical abilities such as the superior longitudinal fasciculus, the posterior segment of the corpus callosum, inferior longitudinal fasciculus, corona radiata, and the corticospinal tract. Impairments in mathematics tend to be associated with atypical white matter structures within similar regions, especially in inferior parietal and temporal tracts. This systematic review summarizes and critically examines the current literature on white matter correlates of numerical and mathematical abilities, and provides directions for future research. PMID:25446952

  8. Probing white-matter microstructure with higher-order diffusion tensors and susceptibility tensor MRI

    PubMed Central

    Liu, Chunlei; Murphy, Nicole E.; Li, Wei

    2012-01-01

    Diffusion MRI has become an invaluable tool for studying white matter microstructure and brain connectivity. The emergence of quantitative susceptibility mapping and susceptibility tensor imaging (STI) has provided another unique tool for assessing the structure of white matter. In the highly ordered white matter structure, diffusion MRI measures hindered water mobility induced by various tissue and cell membranes, while susceptibility sensitizes to the molecular composition and axonal arrangement. Integrating these two methods may produce new insights into the complex physiology of white matter. In this study, we investigated the relationship between diffusion and magnetic susceptibility in the white matter. Experiments were conducted on phantoms and human brains in vivo. Diffusion properties were quantified with the diffusion tensor model and also with the higher order tensor model based on the cumulant expansion. Frequency shift and susceptibility tensor were measured with quantitative susceptibility mapping and susceptibility tensor imaging. These diffusion and susceptibility quantities were compared and correlated in regions of single fiber bundles and regions of multiple fiber orientations. Relationships were established with similarities and differences identified. It is believed that diffusion MRI and susceptibility MRI provide complementary information of the microstructure of white matter. Together, they allow a more complete assessment of healthy and diseased brains. PMID:23507987

  9. Performances of diffusion kurtosis imaging and diffusion tensor imaging in detecting white matter abnormality in schizophrenia.

    PubMed

    Zhu, Jiajia; Zhuo, Chuanjun; Qin, Wen; Wang, Di; Ma, Xiaomei; Zhou, Yujing; Yu, Chunshui

    2015-01-01

    Diffusion kurtosis imaging (DKI) is an extension of diffusion tensor imaging (DTI), exhibiting improved sensitivity and specificity in detecting developmental and pathological changes in neural tissues. However, little attention was paid to the performances of DKI and DTI in detecting white matter abnormality in schizophrenia. In this study, DKI and DTI were performed in 94 schizophrenia patients and 91 sex- and age-matched healthy controls. White matter integrity was assessed by fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), mean kurtosis (MK), axial kurtosis (AK) and radial kurtosis (RK) of DKI and FA, MD, AD and RD of DTI. Group differences in these parameters were compared using tract-based spatial statistics (TBSS) (P < 0.01, corrected). The sensitivities in detecting white matter abnormality in schizophrenia were MK (34%) > AK (20%) > RK (3%) and RD (37%) > FA (24%) > MD (21%) for DKI, and RD (43%) > FA (30%) > MD (21%) for DTI. DKI-derived diffusion parameters (RD, FA and MD) were sensitive to detect abnormality in white matter regions (the corpus callosum and anterior limb of internal capsule) with coherent fiber arrangement; however, the kurtosis parameters (MK and AK) were sensitive to reveal abnormality in white matter regions (the juxtacortical white matter and corona radiata) with complex fiber arrangement. In schizophrenia, the decreased AK suggests axonal damage; however, the increased RD indicates myelin impairment. These findings suggest that diffusion and kurtosis parameters could provide complementary information and they should be jointly used to reveal pathological changes in schizophrenia. PMID:25610778

  10. Evaluating the Accuracy of Diffusion MRI Models in White Matter

    PubMed Central

    Rokem, Ariel; Yeatman, Jason D.; Pestilli, Franco; Kay, Kendrick N.; Mezer, Aviv; van der Walt, Stefan; Wandell, Brian A.

    2015-01-01

    Models of diffusion MRI within a voxel are useful for making inferences about the properties of the tissue and inferring fiber orientation distribution used by tractography algorithms. A useful model must fit the data accurately. However, evaluations of model-accuracy of commonly used models have not been published before. Here, we evaluate model-accuracy of the two main classes of diffusion MRI models. The diffusion tensor model (DTM) summarizes diffusion as a 3-dimensional Gaussian distribution. Sparse fascicle models (SFM) summarize the signal as a sum of signals originating from a collection of fascicles oriented in different directions. We use cross-validation to assess model-accuracy at different gradient amplitudes (b-values) throughout the white matter. Specifically, we fit each model to all the white matter voxels in one data set and then use the model to predict a second, independent data set. This is the first evaluation of model-accuracy of these models. In most of the white matter the DTM predicts the data more accurately than test-retest reliability; SFM model-accuracy is higher than test-retest reliability and also higher than the DTM model-accuracy, particularly for measurements with (a) a b-value above 1000 in locations containing fiber crossings, and (b) in the regions of the brain surrounding the optic radiations. The SFM also has better parameter-validity: it more accurately estimates the fiber orientation distribution function (fODF) in each voxel, which is useful for fiber tracking. PMID:25879933

  11. The effects of type 1 diabetes on cerebral white matter

    Microsoft Academic Search

    K. Weinger; A. M. Jacobson; G. Musen; I. K. Lyoo; C. M. Ryan; D. C. Jimerson; P. F. Renshaw

    2008-01-01

    Aim\\/hypothesis  Studies investigating the structure, neurophysiology and functional outcomes of white matter among type 1 diabetes patients\\u000a have given conflicting results. Our aim was to investigate the relationship between type 1 diabetes and white matter hyperintensities.\\u000a \\u000a \\u000a \\u000a Method  We assessed white matter integrity (using magnetic resonance imaging), depressive symptoms and neuropsychological function\\u000a in 114 type 1 diabetes patients and 58 age-matched non-diabetic controls.

  12. Deep White Matter in Huntington's Disease

    PubMed Central

    Phillips, Owen; Squitieri, Ferdinando; Sanchez-Castaneda, Cristina; Elifani, Francesca; Caltagirone, Carlo; Sabatini, Umberto; Di Paola, Margherita

    2014-01-01

    White matter (WM) abnormalities have already been shown in presymptomatic (Pre-HD) and symptomatic HD subjects using Magnetic Resonance Imaging (MRI). In the present study, we examined the microstructure of the long-range large deep WM tracts by applying two different MRI approaches: Diffusion Tensor Imaging (DTI) -based tractography, and T2*weighted (iron sensitive) imaging. We collected Pre-HD subjects (n?=?25), HD patients (n?=?25) and healthy control subjects (n?=?50). Results revealed increased axial (AD) and radial diffusivity (RD) and iron levels in Pre-HD subjects compared to controls. Fractional anisotropy decreased between the Pre-HD and HD phase and AD/RD increased and although impairment was pervasive in HD, degeneration occurred in a pattern in Pre-HD. Furthermore, iron levels dropped for HD patients. As increased iron levels are associated with remyelination, the data suggests that Pre-HD subjects attempt to repair damaged deep WM years before symptoms occur but this process fails with disease progression. PMID:25340651

  13. White Matter Hyperintensities and Hypobaric Exposure

    PubMed Central

    McGuire, Stephen A.; Sherman, Paul M.; Wijtenburg, S. Andrea; Rowland, Laura M.; Grogan, Patrick M.; Sladky, John H.; Robinson, Andrew Y.; Kochunov, Peter V.

    2014-01-01

    Objective Demonstrate that occupational exposure to nonhypoxic hypobaria is associated with subcortical white matter hyperintensities (WMHs) on fluid-attenuated inversion recovery magnetic resonance imaging (MRI). Methods Eighty-three altitude chamber personnel (PHY), 105 U-2 pilots (U2P), and 148 age- controlled and health-matched doctorate degree controls (DOC) underwent high-resolution MRI. Subcortical WMH burden was quantified as count and volume of subcortical WMH lesions after transformation of images to the Talairach atlas–based stereo-tactic frame. Results Subcortical WMHs were more prevalent in PHY (volume p = 0.011/count p = 0.019) and U2P (volume p<0.001/count p<0.001) when compared to DOC, whereas PHY were not significantly different than U2P. Interpretation This study provides strong evidence that nonhypoxic hypobaric exposure may induce subcortical WMHs in a young, healthy population lacking other risk factors for WMHs and adds this occupational exposure to other environmentally related potential causes of WMHs. PMID:25164539

  14. Constrained by Our Connections: White Matter's Key Role in Interindividual Variability in Visual Working Memory Capacity

    PubMed Central

    Golestani, Ali M.; Miles, Laura; Babb, James; Castellanos, F. Xavier; Malaspina, Dolores

    2014-01-01

    Visual working memory (VWM) plays an essential role in many perceptual and higher-order cognitive processes. Despite its reliance on a broad network of brain regions, VWM has a capacity limited to a few objects. This capacity varies substantially across individuals and relates closely to measures of overall cognitive function (Luck and Vogel, 2013). The mechanisms underlying these properties are not completely understood, although the amplitude of neural signal oscillations (Vogel and Machizawa, 2004) and brain activation in specific cortical regions (Todd and Marois, 2004) have been implicated. Variability in VWM performance may also reflect variability in white matter structural properties. However, data based primarily on diffusion tensor imaging approaches remain inconclusive. Here, we investigate the relationship between white matter and VWM capacity in human subjects using an advanced diffusion imaging technique, diffusion kurtosis imaging. Diffusion kurtosis imaging provides several novel quantitative white mater metrics, among them the axonal water fraction (faxon), an index of axonal density and caliber. Our results show that 59% of individual variability in VWM capacity may be explained by variations in faxon within a widely distributed network of white matter tracts. Increased faxon associates with increased VWM capacity. An additional 12% in VWM capacity variance may be explained by diffusion properties of the extra-axonal space. These data demonstrate, for the first time, the key role of white matter in limiting VWM capacity in the healthy adult brain and suggest that white matter may represent an important therapeutic target in disorders of impaired VWM and cognition. PMID:25378158

  15. Valproic acid increases white matter repair and neurogenesis after stroke

    PubMed Central

    Liu, Xian Shuang; Chopp, Michael; Kassis, Haifa; Jia, Long Fei; Hozeska-Solgot, Ann; Zhang, Rui Lan; Chen, Charlie; Cui, Yi Sheng; Zhang, Zheng Gang

    2012-01-01

    Acute treatment of stroke with HDAC inhibitors has been shown to reduce ischemic cell damage; however, it is unclear whether delayed treatment with HDAC inhibitors will contribute to the brain repair and plasticity. In the present study, we investigated the effects of delayed treatment of stroke with a pan HDAC inhibitor, valproic acid (VPA), on white matter injury and neurogenesis during stroke recovery. Administration of VPA at a dose of 100 mg/kg for 7 days starting 24 hours after middle cerebral artery occlusion (MCAo) in rats significantly improved neurological outcome measured 7 to 28 days post-MCAo. In addition, the VPA treatment significantly increased oligodendrocyte survival and newly generated oligodendrocytes, which was associated with elevation of myelinated axonal density in the ischemic boundary 28 days after MCAo. VPA treatment also increased the expression of glutamate transporter 1 (GLT1) in the ischemic boundary after stroke, and increased acetylated histone H4 expression in neuroblasts and the number of new neurons in striatal ischemic boundary region. This study provides new evidence that the delayed VPA treatment enhances white matter repair and neurogenesis in ischemic brain, which may contribute to improved functional outcome. PMID:22704966

  16. Valproic acid increases white matter repair and neurogenesis after stroke.

    PubMed

    Liu, X S; Chopp, M; Kassis, H; Jia, L F; Hozeska-Solgot, A; Zhang, R L; Chen, C; Cui, Y S; Zhang, Z G

    2012-09-18

    Acute treatment of stroke with histone deacetylase (HDAC) inhibitors has been shown to reduce ischemic cell damage; however, it is unclear whether delayed treatment with HDAC inhibitors will contribute to the brain repair and plasticity. In the present study, we investigated the effects of delayed treatment of stroke with a pan HDAC inhibitor, valproic acid (VPA), on white matter injury and neurogenesis during stroke recovery. Administration of VPA at a dose of 100mg/kg for 7 days starting 24h after middle cerebral artery occlusion (MCAo) in rats significantly improved neurological outcome measured 7-28 days post-MCAo. In addition, the VPA treatment significantly increased oligodendrocyte survival and newly generated oligodendrocytes, which was associated with elevation of myelinated axonal density in the ischemic boundary 28 days after MCAo. VPA treatment also increased the expression of glutamate transporter 1 (GLT1) in the ischemic boundary after stroke, and increased acetylated histone H4 expression in neuroblasts and the number of new neurons in striatal ischemic boundary region. This study provides new evidence that the delayed VPA treatment enhances white matter repair and neurogenesis in ischemic brain, which may contribute to improved functional outcome. PMID:22704966

  17. Development of white matter pathways in typically developing preadolescent children

    PubMed Central

    Muftuler, L. Tugan; Davis, Elysia Poggi; Buss, Claudia; Solodkin, Ana; Su, Min Ying; Head, Kevin M.; Hasso, Anton N.; Sandman, Curt A.

    2012-01-01

    The first phase of major neuronal rearrangements in the brain takes place during the prenatal period. While the brain continues maturation throughout childhood, a critical second phase of synaptic overproduction and elimination takes place during the preadolescent period. Despite the importance of this developmental phase, few studies have evaluated neural changes taking place during this period. In this study, MRI Diffusion Tensor Imaging data from a normative sample of 126 preadolescent children (59 girls and 67 boys) between the ages of 6 and 10 years were analyzed in order to characterize age-relationships in the white matter microstructure. Tract Based Spatial Statistics (TBSS) method was used for whole brain analysis of white matter tracts without a priori assumption about the location of age associated differences. Our results demonstrate significant age-associated differences in most of the major fiber tracts bilaterally and along the whole body of the tracts. In contrast, developmental differences in the cingulum at the level of the parahippocampal region were only observed in the right hemisphere. We suggest that these age-relationships with a widespread distribution seen during the preadolescent years maybe relevant for the implementation of cognitive and social behaviors needed for a normal development into adulthood. PMID:22634375

  18. 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

  19. DCDC2 polymorphism is associated with left temporoparietal gray and white matter structures during development.

    PubMed

    Darki, Fahimeh; Peyrard-Janvid, Myriam; Matsson, Hans; Kere, Juha; Klingberg, Torkel

    2014-10-22

    Three genes, DYX1C1, DCDC2, and KIAA0319, have been previously associated with dyslexia, neuronal migration, and ciliary function. Three polymorphisms within these genes, rs3743204 (DYX1C1), rs793842 (DCDC2), and rs6935076 (KIAA0319) have also been linked to normal variability of left temporoparietal white matter volume connecting the middle temporal cortex to the angular and supramarginal gyri. Here, we assessed whether these polymorphisms are also related to the cortical thickness of the associated regions during childhood development using a longitudinal dataset of 76 randomly selected children and young adults who were scanned up to three times each, 2 years apart. rs793842 in DCDC2 was significantly associated with the thickness of left angular and supramarginal gyri as well as the left lateral occipital cortex. The cortex was significantly thicker for T-allele carriers, who also had lower white matter volume and lower reading comprehension scores. There was a negative correlation between white matter volume and cortical thickness, but only white matter volume predicted reading comprehension 2 years after scanning. These results show how normal variability in reading comprehension is related to gene, white matter volume, and cortical thickness in the inferior parietal lobe. Possibly, the variability of gray and white matter structures could both be related to the role of DCDC2 in ciliary function, which affects both neuronal migration and axonal outgrowth. PMID:25339756

  20. Cerebral Hemodynamics and White Matter Hyperintensities in CADASIL

    Microsoft Academic Search

    Rivka van den Boom; Saskia A. Lesnik Oberstein; Aart Spilt; Faiza Behloul; Michel D. Ferrari; Joost Haan; Rudi G. Westendorp; Mark A. van Buchem

    2003-01-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small-vessel disease caused by mutations in the NOTCH3 gene on chromosome 19. On magnetic resonance imaging (MRI), subcortical white matter hyperintensities and lacunar infarcts are visualized. It is unknown whether a decrease in cerebral blood flow or cerebrovascular reactivity is primarily responsible for the development of white

  1. Structure-Specific Statistical Mapping of White Matter Tracts

    Microsoft Academic Search

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

    We present a new model-based framework for the statistical analysis of diffusion imaging data associated with specific white\\u000a matter tracts. The framework takes advantage of the fact that several of the major white matter tracts are thin sheet-like\\u000a structures that can be effectively modeled by medial representations. The approach involves segmenting major tracts and fitting\\u000a them with deformable geometric medial

  2. White Matter and Cognition in Adults Who Were Born Preterm

    Microsoft Academic Search

    Matthew P. G. Allin; Dimitris Kontis; Muriel Walshe; John Wyatt; Gareth J. Barker; Richard A. A. Kanaan; Philip McGuire; Larry Rifkin; Robin M. Murray; Chiara Nosarti; Joseph Najbauer

    2011-01-01

    Background and PurposeIndividuals born very preterm (before 33 weeks of gestation, VPT) are at risk of damage to developing white matter, which may affect later cognition and behaviour.MethodsWe used diffusion tensor MRI (DT-MRI) to assess white matter microstructure (fractional anisotropy; FA) in 80 VPT and 41 term-born individuals (mean age 19.1 years, range 17–22, and 18.5 years, range17–22 years, respectively).

  3. White Matter Protection in Congenital Heart Surgery

    PubMed Central

    Ishibashi, Nobuyuki; Scafidi, Joseph; Murata, Akira; Korotcova, Ludmila; Zurakowski, David; Gallo, Vittorio; Jonas, Richard A.

    2012-01-01

    Background Neurodevelopmental delays in motor skills and white matter (WM) injury have been documented in congenital heart disease (CHD) and after pediatric cardiac surgery. The lack of a suitable animal model has hampered our understanding of the cellular mechanisms underlying WM injury in these patients. Our aim is to identify an optimal surgical strategy for WM protection to reduce neurological injury in CHD patients. Methods and Results We developed a porcine cardiopulmonary bypass (CPB) model, which displays area dependent WM maturation. In this model, WM injury was identified following CPB-induced ischemia-reperfusion injury. The degree of injury was inversely correlated with the maturation stage, indicating maturation-dependent vulnerability of WM. Within different oligodendrocyte (OL) developmental stages, we show selective vulnerability of O4+ pre-OLs, while OL progenitor cells (OPCs) were resistant to insults. This indicates that immature WM is vulnerable to CPB-induced injury, but has an intrinsic potential for recovery mediated by endogenous OPCs. OPC number decreased with age, suggesting that earlier repair allows successful WM development. OPC proliferation was observed within a few days after CPB-induced ischemia-reperfusion injury; however by four weeks arrested OL maturation and delayed myelination were detected. Logistic model confirmed that maintaining higher oxygenation and reducing inflammation were effective in minimizing the risk of injury at immature stages of WM development. Conclusions Primary repair in neonates and young infants potentially provides successful WM development in CHD patients. Cardiac surgery during this susceptible period should avoid ischemia-reperfusion injury and minimize inflammation to prevent long-term WM-related neurological impairment. PMID:22247493

  4. Genetic white matter fiber tractography with global optimization.

    PubMed

    Wu, Xi; Xu, Qing; Xu, Lei; Zhou, Jiliu; Anderson, Adam W; Ding, Zhaohua

    2009-11-15

    Diffusion tensor imaging (DTI) tractography is a novel technique that can delineate the trajectories between cortical region of the human brain non-invasively. In this paper, a novel DTI based white matter fiber tractography using genetic algorithm is presented. Adapting the concepts from evolutionary biology which include selection, recombination and mutation, globally optimized fiber pathways are generated iteratively. Global optimality of the fiber tracts is evaluated using Bayes decision rule, which simultaneously considers both the fiber geometric smoothness and consistency with the tensor field. This global optimality assigns the tracking fibers great immunity to random image noise and other local image artifacts, thus avoiding the detrimental effects of cumulative noise on fiber tracking. Experiments with synthetic and in vivo human DTI data have demonstrated the feasibility and robustness of this new fiber tracking technique, and an improved performance over commonly used probabilistic fiber tracking. PMID:19666052

  5. Evaluation of Atlas-Based White Matter Segmentation with Eve

    PubMed Central

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

    2015-01-01

    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. PMID:25914503

  6. White matter integrity in hair-pulling disorder (trichotillomania).

    PubMed

    Roos, Annerine; Fouche, Jean-Paul; Stein, Dan J; Lochner, Christine

    2013-03-30

    Hair-pulling disorder (trichotillomania, HPD) is a disabling condition that is characterized by repetitive hair-pulling resulting in hair loss. Although there is evidence of structural grey matter abnormalities in HPD, there is a paucity of data on white matter integrity. The aim of this study was to explore white matter integrity using diffusion tensor imaging (DTI) in subjects with HPD and healthy controls. Sixteen adult female subjects with HPD and 13 healthy female controls underwent DTI. Hair-pulling symptom severity, anxiety and depressive symptoms were also assessed. Tract-based spatial statistics were used to analyze data on fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). There were no differences in DTI measures between HPD subjects and healthy controls. However, there were significant associations of increased MD in white matter tracts of the fronto-striatal-thalamic pathway with longer HPD duration and increased HPD severity. Our findings suggest that white matter integrity in fronto-striatal-thalamic pathways in HPD is related to symptom duration and severity. The molecular basis of measures of white matter integrity in HPD deserves further exploration. PMID:23149033

  7. Reduced White Matter Integrity in Sibling Pairs Discordant for Bipolar Disorder

    PubMed Central

    Sprooten, Emma; Brumbaugh, Margaret S.; Knowles, Emma E.M.; McKay, D. Reese; Lewis, John; Barrett, Jennifer; Landau, Stefanie; Cyr, Lindsay; Kochunov, Peter; Winkler, Anderson M.; Pearlson, Godfrey D.; Glahn, David C.

    2014-01-01

    Objective Several lines of evidence indicate that white matter integrity is compromised in bipolar disorder, but the nature, extent, and biological causes remain elusive. To determine the extent to which white matter deficits in bipolar disorder are familial, the authors investigated white matter integrity in a large sample of bipolar patients, unaffected siblings, and healthy comparison subjects. Method The authors collected diffusion imaging data for 64 adult bipolar patients, 60 unaffected siblings (including 54 discordant sibling pairs), and 46 demographically matched comparison subjects. Fractional anisotropy was compared between the groups using voxel-wise tract-based spatial statistics and by extracting mean fractional anisotropy from 10 regions of interest. Additionally, intra-class correlation coefficients were calculated between the sibling pairs as an index of familiality. Results Widespread fractional anisotropy reductions in bipolar patients (>40,000 voxels) and more subtle reductions in their siblings, mainly restricted to the corpus callosum, posterior thalamic radiations, and left superior longitudinal fasciculus (>2,000 voxels) were observed. Similarly, region-of-interest analysis revealed significant reductions in most white matter regions in patients. In siblings, fractional anisotropy in the posterior thalamic radiation and the forceps was nominally reduced. Significant between-sibling correlations were found for mean fractional anisotropy across the tract-based spatial statistic skeleton, within significant clusters, and within nearly all regions of interest. Conclusions These findings emphasize the relevance of white matter to neuropathology and familiality of bipolar disorder and encourage further use of white matter integrity markers as endophenotypes in genetic studies. PMID:24185242

  8. Spatial Characteristics of White Matter Abnormalities in Schizophrenia

    PubMed Central

    White, Tonya

    2013-01-01

    There is considerable evidence implicating brain white matter (WM) abnormalities in the pathophysiology of schizophrenia; however, the spatial localization of WM abnormalities reported in the existing studies is heterogeneous. Thus, the goal of this study was to quantify the spatial characteristics of WM abnormalities in schizophrenia. One hundred and fourteen patients with schizophrenia and 138 matched controls participated in this multisite study involving the Universities of Iowa, Minnesota, and New Mexico, and the Massachusetts General Hospital. We measured fractional anisotropy (FA) in brain WM regions extracted using 3 different image-processing algorithms: regions of interest, tract-based spatial statistics, and the pothole approach. We found that FA was significantly lower in patients using each of the 3 image-processing algorithms. The region-of-interest approach showed multiple regions with lower FA in patients with schizophrenia, with overlap at all 4 sites in the corpus callosum and posterior thalamic radiation. The tract-based spatial statistic approach showed (1) global differences in 3 of the 4 cohorts and (2) lower frontal FA at the Iowa site. Finally, the pothole approach showed a significantly greater number of WM potholes in patients compared to controls at each of the 4 sites. In conclusion, the spatial characteristics of WM abnormalities in schizophrenia reflect a combination of a global low-level decrease in FA, suggesting a diffuse process, coupled with widely dispersed focal reductions in FA that vary spatially among individuals (ie, potholes). PMID:22987296

  9. Abnormalities of cortical thickness, subcortical shapes, and white matter integrity in subcortical vascular cognitive impairment.

    PubMed

    Thong, Jamie Yu Jin; Du, Jia; Ratnarajah, Nagulan; Dong, Yanhong; Soon, Hock Wei; Saini, Monica; Tan, Ming Zhen; Ta, Anh Tuan; Chen, Christopher; Qiu, Anqi

    2014-05-01

    Subcortical vascular cognitive impairment (sVCI) is caused by lacunar infarcts or extensive and/or diffuse lesions in the white matter that may disrupt the white matter circuitry connecting cortical and subcortical regions and result in the degeneration of neurons in these regions. This study used structural magnetic resonance imaging (MRI) and high angular resolution diffusion imaging (HARDI) techniques to examine cortical thickness, subcortical shapes, and white matter integrity in mild vascular cognitive impairment no dementia (VCIND Mild) and moderate-to-severe VCI (MSVCI). Our study found that compared to controls (n = 25), VCIND Mild (n = 25), and MSVCI (n = 30) showed thinner cortex predominantly in the frontal cortex. The cortex in MSVCI was thinner in the parietal and lateral temporal cortices than that in VCIND Mild. Moreover, compared to controls, VCIND Mild and MSVCI showed smaller shapes (i.e., volume reduction) in the thalamus, putamen, and globus pallidus and ventricular enlargement. Finally, compared to controls, VCIND Mild, and MSVCI showed an increased mean diffusivity in the white matter, while decreased generalized fractional anisotropy was only found in the MSVCI subjects. The major axonal bundles involved in the white matter abnormalities were mainly toward the frontal regions, including the internal capsule/corona radiata, uncinate fasciculus, and anterior section of the inferior fronto-occipital fasciculus, and were anatomically connected to the affected cortical and subcortical structures. Our findings suggest that abnormalities in cortical, subcortical, and white matter morphology in sVCI occur in anatomically connected structures, and that abnormalities progress along a similar trajectory from the mild to moderate and severe conditions. PMID:23861356

  10. 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

  11. Neuroscience Letters 424 (2007) 127132 Diffusion tensor imaging of white matter in the superior temporal

    E-print Network

    Chung, Moo K.

    2007-01-01

    A prevalent hypothesis is that brain connectivity in autism is aberrant (e.g. [6,11]). Regional abnormalities temporal gyrus and temporal stem in autism Jee Eun Leea, Erin D. Biglere,f,g,k, Andrew L. Alexandera in autism. In this study, diffusion tensor imaging (DTI) measurements of white matter in the STG and the TS

  12. White matter structures associated with creativity: Evidence from diffusion tensor imaging

    Microsoft Academic Search

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

    2010-01-01

    Creativity has been essential to the development of human civilization and plays a crucial role in cultural life. However, despite literature that has proposed the importance of structural connectivity in the brain for creativity, the relationship between regional white matter integrity and creativity has never been directly investigated. In this study, we used diffusion tensor imaging and a behavioral creativity

  13. Susceptibility induced gray–white matter MRI contrast in the human brain

    Microsoft Academic Search

    Christian Langkammer; Nikolaus Krebs; Walter Goessler; Eva Scheurer; Kathrin Yen; Franz Fazekas; Stefan Ropele

    MR phase images have shown significantly improved contrast between cortical gray and white matter regions compared to magnitude images obtained with gradient echo sequences. A variety of underlying biophysical mechanisms (including iron, blood, myelin content, macromolecular chemical exchange, and fiber orientation) have been suggested to account for this observation but assessing the individual contribution of these factors is limited in

  14. 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

  15. Susceptibility-Weighted Imaging Provides Insight into White Matter Damage in Amyotrophic Lateral Sclerosis

    PubMed Central

    Prell, Tino; Hartung, Viktor; Tietz, Florian; Penzlin, Susanne; Ilse, Benjamin; Schweser, Ferdinand; Deistung, Andreas; Bokemeyer, Martin; Reichenbach, Jürgen R.; Witte, Otto W.; Grosskreutz, Julian

    2015-01-01

    Background Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disorder, characterised by widespread white matter damage. There is growing evidence that disturbances in iron metabolism contribute to white matter alterations. Materials & Methods We analysed the data of susceptibility-weighted imaging (SWI) of white matter in a cohort of 27 patients with ALS and 30 healthy age-matched controls. Results Signal alterations were found on SWI in the corpus callosum; along the corticospinal tract (subcortical motor cortex, posterior limb of the internal capsule and brainstem levels) and in the subgyral regions of frontal, parietal, temporal, occipital and limbic lobes. Alterations of white matter in the corpus callosum correlated with disease severity as assessed by the revised ALS functional rating scale. Conclusion SWI is capable of indicating iron and myelin disturbances in white matter of ALS patients. The SWI patterns observed in this study suggest that widespread alterations due to iron disturbances occur in patients with ALS and correlate with disease severity. PMID:26110427

  16. White matter fractional anisotropy is inversely related to anxious symptoms in older adults with atherosclerosis

    PubMed Central

    Bijanki, Kelly C. R.; Stillman, Ashley N.; Arndt, Stephan; Magnotta, Vincent A.; Fiedorowicz, Jess G.; Haynes, William G.; Matsui, Joy T.; Johnson, Hans J.; Moser, David J.

    2013-01-01

    Objective Clinical anxiety disorders are associated with white matter hyperintensities and diffusion abnormalities measured using diffusion tensor imaging (DTI). However, it is not known if this association extends into individuals with mild anxious symptoms without formal diagnosis, in those who are older, or in those who have atherosclerosis. The current study explored whether white matter integrity and/or organization significantly associates with anxious symptoms in older adults with and without atherosclerosis. Methods We recruited older adults (ages 55–90); 35 with clinically diagnosed atherosclerotic vascular disease (AVD) and 22 without AVD. Anxious symptoms were measured using the validated Symptom Checklist-90-Revised. Fractional anisotropy (FA), a proxy for white matter organization and health, was measured in the white matter globally, by lobe, and in several smaller regions of interest suggested by the literature. Partial correlations between anxious symptoms and FA were calculated, controlling for significant covariates. Results Participants with and without AVD did not differ in severity of anxious symptom endorsement. There was a unique inverse relationship between white matter health and anxious symptoms in the AVD participants, but not in healthy comparisons. Significant relationships were observed in the superior longitudinal fasciculus (r=?.476, df=32, p=.004), as well as the cingulum bundle, the frontal lobes, and the parietal lobes. Conclusions Anxiety symptoms uniquely correlated with low fractional anisotropy in older adults with atherosclerosis. These findings may have implications for future research on the topic of anxiety in aging and vascular disease and warrant replication. PMID:23348834

  17. Genetic variation in homocysteine metabolism, cognition, and white matter lesions.

    PubMed

    de Lau, Lonneke M L; van Meurs, Joyce B J; Uitterlinden, André G; Smith, A David; Refsum, Helga; Johnston, Carole; Breteler, Monique M B

    2010-11-01

    Several studies have shown an association between homocysteine concentration and cognitive performance or cerebral white matter lesions. However, variations in genes encoding for enzymes and other proteins that play a role in homocysteine metabolism have hardly been evaluated in relation to these outcome measures. In the population-based Rotterdam Scan Study, we examined the association of seven polymorphisms of genes involved in homocysteine metabolism (MTHFR 677C>T, MTHFR 1298A>C, RFC 80G>A, TC 776C>G, MTR 2756A>G, MTRR 66A>G, and CBS 844ins68) with plasma total homocysteine, cognitive performance, and cerebral white matter lesions among 1011 non-demented elderly participants. Of all the studied polymorphisms, only MTHFR 677C>T was associated with homocysteine concentration. No significant relationship was observed for any of the polymorphisms with cognitive performance or severity of cerebral white matter lesions. PMID:19019492

  18. Snake-based brain white matter fiber reconstruction.

    PubMed

    Lu, Meng; Di, Jia

    2014-01-01

    Diffusion tensor imaging (DTI) is a tractography algorithm that provides the only means of mapping white matter fibers. Furthermore, because of its wealth of applications, diffusion MRI tractography is gaining importance in clinical and neuroscience research. This paper presents a novel brain white matter fiber reconstruction method based on the snake model by minimizing the energy function, which is composed of both external energy and internal energy. Internal energy represents the assembly of the interaction potential between connected segments, whereas external energy represents the differences between predicted DTI signals and measured DTI signals. Through comparing the proposed method with other tractography algorithms in the Fiber Cup test, the present method was shown to perform superiorly to the majority of the other methods. In fact, the proposed test performed the third best out of the ten available methods, which demonstrates that present method can accurately formulate the brain white matter fiber reconstruction. PMID:25227001

  19. Fiber tract-based atlas of human white matter anatomy.

    PubMed

    Wakana, Setsu; Jiang, Hangyi; Nagae-Poetscher, Lidia M; van Zijl, Peter C M; Mori, Susumu

    2004-01-01

    Two- and three-dimensional (3D) white matter atlases were created on the basis of high-spatial-resolution diffusion tensor magnetic resonance (MR) imaging and 3D tract reconstruction. The 3D trajectories of 17 prominent white matter tracts could be reconstructed and depicted. Tracts were superimposed on coregistered anatomic MR images to parcel the white matter. These parcellation maps were then compared with coregistered diffusion tensor imaging color maps to assign visible structures. The results showed (a). which anatomic structures can be identified on diffusion tensor images and (b). where these anatomic units are located at each section level and orientation. The atlas may prove useful for educational and clinical purposes. PMID:14645885

  20. Analysis of White Dwarfs with Strange-Matter Cores

    E-print Network

    G. J. Mathews; I. -S. Suh; B. O'Gorman; N. Q. Lan; W. Zech; K. Otsuki; F. Weber

    2006-04-17

    We summarize masses and radii for a number of white dwarfs as deduced from a combination of proper motion studies, Hipparcos parallax distances, effective temperatures, and binary or spectroscopic masses. A puzzling feature of these data is that some stars appear to have radii which are significantly smaller than that expected for a standard electron-degenerate white-dwarf equations of state. We construct a projection of white-dwarf radii for fixed effective mass and conclude that there is at least marginal evidence for bimodality in the radius distribution forwhite dwarfs. We argue that if such compact white dwarfs exist it is unlikely that they contain an iron core. We propose an alternative of strange-quark matter within the white-dwarf core. We also discuss the impact of the so-called color-flavor locked (CFL) state in strange-matter core associated with color superconductivity. We show that the data exhibit several features consistent with the expected mass-radius relation of strange dwarfs. We identify eight nearby white dwarfs which are possible candidates for strange matter cores and suggest observational tests of this hypothesis.

  1. Mechanisms of white matter change induced by meditation training

    PubMed Central

    Posner, Michael I.; Tang, Yi-Yuan; Lynch, Gary

    2014-01-01

    Training can induce changes in specific brain networks and changes in brain state. In both cases it has been found that the efficiency of white matter as measured by diffusion tensor imaging is increased, often after only a few hours of training. In this paper we consider a plausible molecular mechanism for how state change produced by meditation might lead to white matter change. According to this hypothesis frontal theta induced by meditation produces a molecular cascade that increases myelin and improves connectivity. PMID:25386155

  2. Scalable brain network construction on white matter fibers

    NASA Astrophysics Data System (ADS)

    Chung, Moo K.; Adluru, Nagesh; Dalton, Kim M.; Alexander, Andrew L.; Davidson, Richard J.

    2011-03-01

    DTI offers a unique opportunity to characterize the structural connectivity of the human brain non-invasively by tracing white matter fiber tracts. Whole brain tractography studies routinely generate up to half million tracts per brain, which serves as edges in an extremely large 3D graph with up to half million edges. Currently there is no agreed-upon method for constructing the brain structural network graphs out of large number of white matter tracts. In this paper, we present a scalable iterative framework called the ?-neighbor method for building a network graph and apply it to testing abnormal connectivity in autism.

  3. Body mass and white matter integrity: the influence of vascular and inflammatory markers.

    PubMed

    Bettcher, Brianne Magouirk; Walsh, Christine M; Watson, Christa; Miller, Joshua W; Green, Ralph; Patel, Nihar; Miller, Bruce L; Neuhaus, John; Yaffe, Kristine; Kramer, Joel H

    2013-01-01

    High adiposity is deleteriously associated with brain health, and may disproportionately affect white matter integrity; however, limited information exists regarding the mechanisms underlying the association between body mass (BMI) and white matter integrity. The present study evaluated whether vascular and inflammatory markers influence the relationship between BMI and white matter in healthy aging. We conducted a cross-sectional evaluation of white matter integrity, BMI, and vascular/inflammatory factors in a cohort of 138 healthy older adults (mean age: 71.3 years). Participants underwent diffusion tensor imaging, provided blood samples, and participated in a health evaluation. Vascular risk factors and vascular/inflammatory blood markers were assessed. The primary outcome measure was fractional anisotropy (FA) of the genu, body, and splenium (corpus callosum); exploratory measures included additional white matter regions, based on significant associations with BMI. Regression analyses indicated that higher BMI was associated with lower FA in the corpus callosum, cingulate, and fornix (p<.001). Vascular and inflammatory factors influenced the association between BMI and FA. Specifically, BMI was independently associated with the genu [?=-.21; B=-.0024; 95% CI, -.0048 to -.0000; p=.05] and cingulate fibers [?=-.39; B=-.0035; 95% CI,-.0056 to -.0015; p<.001], even after controlling for vascular/inflammatory risk factors and blood markers. In contrast, BMI was no longer significantly associated with the fornix and middle/posterior regions of the corpus callosum after controlling for these markers. Results partially support a vascular/inflammatory hypothesis, but also suggest a more complex relationship between BMI and white matter characterized by potentially different neuroanatomic vulnerability. PMID:24147070

  4. Body Mass and White Matter Integrity: The Influence of Vascular and Inflammatory Markers

    PubMed Central

    Bettcher, Brianne Magouirk; Walsh, Christine M.; Watson, Christa; Miller, Joshua W.; Green, Ralph; Patel, Nihar; Miller, Bruce L.; Neuhaus, John; Yaffe, Kristine; Kramer, Joel H.

    2013-01-01

    High adiposity is deleteriously associated with brain health, and may disproportionately affect white matter integrity; however, limited information exists regarding the mechanisms underlying the association between body mass (BMI) and white matter integrity. The present study evaluated whether vascular and inflammatory markers influence the relationship between BMI and white matter in healthy aging. We conducted a cross-sectional evaluation of white matter integrity, BMI, and vascular/inflammatory factors in a cohort of 138 healthy older adults (mean age: 71.3 years). Participants underwent diffusion tensor imaging, provided blood samples, and participated in a health evaluation. Vascular risk factors and vascular/inflammatory blood markers were assessed. The primary outcome measure was fractional anisotropy (FA) of the genu, body, and splenium (corpus callosum); exploratory measures included additional white matter regions, based on significant associations with BMI. Regression analyses indicated that higher BMI was associated with lower FA in the corpus callosum, cingulate, and fornix (p<.001). Vascular and inflammatory factors influenced the association between BMI and FA. Specifically, BMI was independently associated with the genu [?=-.21; B=-.0024; 95% CI, -.0048 to -.0000; p=.05] and cingulate fibers [?=-.39; B=-.0035; 95% CI,-.0056 to -.0015; p<.001], even after controlling for vascular/inflammatory risk factors and blood markers. In contrast, BMI was no longer significantly associated with the fornix and middle/posterior regions of the corpus callosum after controlling for these markers. Results partially support a vascular/inflammatory hypothesis, but also suggest a more complex relationship between BMI and white matter characterized by potentially different neuroanatomic vulnerability. PMID:24147070

  5. Tissue plasminogen activator prevents white matter damage following stroke

    PubMed Central

    Correa, Fernando; Gauberti, Maxime; Parcq, Jérôme; Macrez, Richard; Hommet, Yannick; Obiang, Pauline; Hernangómez, Miriam; Montagne, Axel; Liot, Géraldine; Guaza, Carmen; Maubert, Eric; Ali, Carine; Vivien, Denis

    2011-01-01

    Tissue plasminogen activator (tPA) is the only available treatment for acute stroke. In addition to its vascular fibrinolytic action, tPA exerts various effects within the brain, ranging from synaptic plasticity to control of cell fate. To date, the influence of tPA in the ischemic brain has only been investigated on neuronal, microglial, and endothelial fate. We addressed the mechanism of action of tPA on oligodendrocyte (OL) survival and on the extent of white matter lesions in stroke. We also investigated the impact of aging on these processes. We observed that, in parallel to reduced levels of tPA in OLs, white matter gets more susceptible to ischemia in old mice. Interestingly, tPA protects murine and human OLs from apoptosis through an unexpected cytokine-like effect by the virtue of its epidermal growth factor–like domain. When injected into aged animals, tPA, although toxic to the gray matter, rescues white matter from ischemia independently of its proteolytic activity. These studies reveal a novel mechanism of action of tPA and unveil OL as a target cell for cytokine effects of tPA in brain diseases. They show overall that tPA protects white matter from stroke-induced lesions, an effect which may contribute to the global benefit of tPA-based stroke treatment. PMID:21576385

  6. The nature of white matter abnormalities in blast-related mild traumatic brain injury

    PubMed Central

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

    2015-01-01

    Blast-related traumatic brain injury (TBI) has been a common injury among returning troops due to the widespread use of improvised explosive devices in the Iraq and Afghanistan Wars. As most of the TBIs sustained are in the mild range, brain changes may not be detected by standard clinical imaging techniques such as CT. Furthermore, the functional significance of these types of injuries is currently being debated. However, accumulating evidence suggests that diffusion tensor imaging (DTI) is sensitive to subtle white matter abnormalities and may be especially useful in detecting mild TBI (mTBI). The primary aim of this study was to use DTI to characterize the nature of white matter abnormalities following blast-related mTBI, and in particular, examine the extent to which mTBI-related white matter abnormalities are region-specific or spatially heterogeneous. In addition, we examined whether mTBI with loss of consciousness (LOC) was associated with more extensive white matter abnormality than mTBI without LOC, as well as the potential moderating effect of number of blast exposures. A second aim was to examine the relationship between white matter integrity and neurocognitive function. Finally, a third aim was to examine the contribution of PTSD symptom severity to observed white matter alterations. One hundred fourteen OEF/OIF veterans underwent DTI and neuropsychological examination and were divided into three groups including a control group, blast-related mTBI without LOC (mTBI - LOC) group, and blast-related mTBI with LOC (mTBI + LOC) group. Hierarchical regression models were used to examine the extent to which mTBI and PTSD predicted white matter abnormalities using two approaches: 1) a region-specific analysis and 2) a measure of spatial heterogeneity. Neurocognitive composite scores were calculated for executive functions, attention, memory, and psychomotor speed. Results showed that blast-related mTBI + LOC was associated with greater odds of having spatially heterogeneous white matter abnormalities. Region-specific reduction in fractional anisotropy (FA) in the left retrolenticular part of the internal capsule was observed in the mTBI + LOC group as the number of blast exposures increased. A mediation analysis revealed that mTBI + LOC indirectly influenced verbal memory performance through its effect on white matter integrity. PTSD was not associated with spatially heterogeneous white matter abnormalities. However, there was a suggestion that at higher levels of PTSD symptom severity, LOC was associated with reduced FA in the left retrolenticular part of the internal capsule. These results support postmortem reports of diffuse axonal injury following mTBI and suggest that injuries with LOC involvement may be particularly detrimental to white matter integrity. Furthermore, these results suggest that LOC-associated white matter abnormalities in turn influence neurocognitive function.

  7. Cognitive Intraindividual Variability and White Matter Integrity in Aging

    PubMed Central

    2013-01-01

    The intraindividual variability (IIV) of cognitive performance has been shown to increase with aging. While brain research has generally focused on mean performance, little is known about neural correlates of cognitive IIV. Nevertheless, some studies suggest that IIV relates more strongly than mean level of performance to the quality of white matter (WM). Our study aims to explore the relation between WM integrity and cognitive IIV by combining functional (fMRI) and structural (diffusion tensor imaging, DTI) imaging. Twelve young adults (aged 18–30 years) and thirteen older adults (61–82 years) underwent a battery of neuropsychological tasks, along with fMRI and DTI imaging. Their behavioral data were analyzed and correlated with the imaging data at WM regions of interest defined on the basis of (1) the fMRI-activated areas and (2) the Johns Hopkins University (JHU) WM tractography atlas. For both methods, fractional anisotropy, along with the mean, radial, and axial diffusivity parameters, was computed. In accord with previous studies, our results showed that the DTI parameters were more related to IIV than to mean performance. Results also indicated that age differences in the DTI parameters were more pronounced in the regions activated primarily by young adults during a choice reaction-time task than in those also activated in older adults. PMID:24174913

  8. White Matter Volume Abnormalities and Associations with Symptomatology in Schizophrenia

    PubMed Central

    Makris, N.; Seidman, L. J.; Ahern, T.; Kennedy, D. N.; Caviness, V. S.; Tsuang, M. T.; Goldstein, J. M.

    2010-01-01

    The cerebral white matter (WM) is critically involved in many bio-behavioral functions impaired in schizophrenia. However, the specific neural systems underlying symptomatology in schizophrenia are not well known. By comparing the volume of all brain fiber systems between chronic patients with DSM-III-R schizophrenia (n = 88) and matched healthy community controls (n = 40), we found that a set of a priori WM regions of local and distal associative fiber systems were significantly different in patients with schizophrenia. There were significant positive correlations between volumes (larger) in anterior callosal, cingulate and temporal deep WM regions (related to distal connections) with positive symptoms, such as hallucinations, delusions and bizarre behavior, and significant negative correlation between volumes (smaller) in occipital and paralimbic superficial WM (related to local connections) and posterior callosal fiber systems with higher negative symptoms, such as alogia. Furthermore, the temporal sagittal system showed significant rightward asymmetry between patients and controls. These observations suggest a pattern of volume WM alterations associated with symptomatology in schizophrenia that may be related in part to predisposition to schizophrenia. PMID:20538438

  9. 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

  10. Differences in Function and Structure of the Capillary Endothelium in Gray Matter, White Matter and a Circumventricular Organ of Rat Brain

    Microsoft Academic Search

    Paul M. Gross; Nadine M. Sposito; Susan E. Pettersen; Joseph D. Fenstermacher

    1986-01-01

    Physiological and morphometric studies were conducted on the microvascular endothelium of four individual cerebral structures having different neural activities – the inferior colliculus, sensorimotor cortex (both gray matter regions), genu of the corpus callosum (white matter), and the subfornical organ (a circumventricular organ) of rats. The physiological data, obtained by quantitative autoradiography, produced new findings: (1) the rate of blood-to-tissue

  11. Improving White Matter Tractography by Resolving the Challenges of Edema

    E-print Network

    Paris-Sud XI, Université de

    Improving White Matter Tractography by Resolving the Challenges of Edema Jérémy Lecoeur1 , Emmanuel Tractography Challenge. Although the data was single shell, b = 1000s/mm2 , we were able to successfully fit, published in "MICCAI 2013 DTI Tractography Challenge (2013)" #12;this lowered anisotropy. While high order

  12. White dwarf stars as strange quark matter detectors

    Microsoft Academic Search

    O G Benvenuto

    2005-01-01

    We show that the presence of a strange matter core inside a white dwarf (WD) star produces a drastic change in the spectrum of non-radial oscillations in the range of periods corresponding to gravity modes. The distinctive, observable signal for such a core is a very short period spacing between consecutive modes, far shorter than in the case of pulsating

  13. Neurocognitive Correlates of White Matter Quality in Adolescent Substance Users

    ERIC Educational Resources Information Center

    Bava, Sunita; Jacobus, Joanna; Mahmood, Omar; Yang, Tony T.; Tapert, Susan F.

    2010-01-01

    Background: Progressive myelination during adolescence implicates an increased vulnerability to neurotoxic substances and enduring neurocognitive consequences. This study examined the cognitive manifestations of altered white matter microstructure in chronic marijuana and alcohol-using (MJ + ALC) adolescents. Methods: Thirty-six MJ + ALC…

  14. Compression behavior of porcine spinal cord white matter

    Microsoft Academic Search

    Carolyn J. Sparrey; Tony M. Keaveny

    2011-01-01

    Spinal cord injury often results from a compressive load; however, the compression behavior of spinal cord white matter has not been clearly established. Quantifying the compression behavior is important for advancing our understanding of spinal cord injury mechanics and facilitating the use of finite element models to study injury. The objective of this study was to characterize the unconfined compression

  15. PROGRESSIVE WHITE MATTER ABNORMALITIES IN AUTOSOMAL-DOMINANT

    E-print Network

    Thompson, Paul

    P4-154 PROGRESSIVE WHITE MATTER ABNORMALITIES IN AUTOSOMAL-DOMINANT ALZHEIMER'S DISEASE: RESULTS for Alzheimer's Disease Research, Los Angeles, California, United States; 5University of California, Los Angeles States; 12Neuroscience Research Australia, Newcastle, Australia; 13The National Hospital for Neurology

  16. White matter abnormalities in mobility-impaired older persons

    Microsoft Academic Search

    C. R. G. Guttmann; R. Benson; S. Warfield; X. Wei; M. C. Anderson; C. B. Hall; K. Abu-Hasaballah; L. Wolfson

    2000-01-01

    Objective: To investigate the relationship between white matter abnormalities and impairment of gait and balance in older persons. Methods: We used quantitative MRI to evaluate the brain tissue compartments of 28 older individuals separated into normal and impaired groups on the basis of mobility performance testing using the Short Physical Performance Battery (SPPB). In addition, individuals were tested on six

  17. Anomalous White Matter Morphology in Adults Who Stutter

    ERIC Educational Resources Information Center

    Cieslak, Matthew; Ingham, Rojer J.; Ingham, Janis C.; Grafton, Scott T.

    2015-01-01

    Aims: Developmental stuttering is now generally considered to arise from genetic determinants interacting with neurologic function. Changes within speech-motor white matter (WM) connections may also be implicated. These connections can now be studied in great detail by high-angular-resolution diffusion magnetic resonance imaging. Therefore,…

  18. Comparative Aspects of Microglia Reaction in White and Gray Matter

    PubMed Central

    C?t?lin, B.; Mitran, Smaranda; Albu, Carmen; Ianc?u, Maria

    2013-01-01

    Objectives: Microglia are considered as the primary immune effector cells in the brain and have a critical role in all brain lesions. We wanted to find out if there is any difference in the way that white and gray matter microglia react to the same type of lesion. Material and Method: We used 14-16 weeks old single transgenic CX3CR1-EGFP mice, whereon microglia were labeled by expression of the green fluorescent protein EGFP and the L1-L2 dorsal spinal columns were exposed. After 10 min of continuous base line image acquisition, we made a micro-lesion by focusing and raising the power of the laser and, than, we monitored it for an additional hour. Laser-lesion and image recording were also made in the right somato-sensory cortex. We quantified microglial response and compared white vs. grey matter. Results: 5-10 min after the lesion, microglia already showed signs of polarization by extending their processes both in white and gray matter. Processes were sent by the microglial bodies situated at a distance of 50 to 100 µm, depending on the lesion size. Microglial processes did not display a preferred target site from the lesion; in contrast, they formed a uniform “shielding” ring around the lesion. Conclusions: Microglia showed targeted responses to acute injuries in grey and white matter also; no major differences were observed besides the speed of the process, due probably to particular cortex and spine architecture. PMID:24778858

  19. The Properties of Matter in White Dwarfs and Neutron Stars

    Microsoft Academic Search

    Shmuel Balberg; Stuart L. Shapiro

    2000-01-01

    White dwarfs and neutron stars are stellar objects with masses comparable to that of our sun. However, as the endpoint stages of stellar evolution, these objects do not sustain any thermonuclear burning and therefore can no longer support the gravitational load of their own mass by generating thermal pressure. Rather, matter in their interiors is compressed to much higher densities

  20. White Matter Damage and Cognitive Impairment after Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Kinnunen, Kirsi Maria; Greenwood, Richard; Powell, Jane Hilary; Leech, Robert; Hawkins, Peter Charlie; Bonnelle, Valerie; Patel, Maneesh Chandrakant; Counsell, Serena Jane; Sharp, David James

    2011-01-01

    White matter disruption is an important determinant of cognitive impairment after brain injury, but conventional neuroimaging underestimates its extent. In contrast, diffusion tensor imaging provides a validated and sensitive way of identifying the impact of axonal injury. The relationship between cognitive impairment after traumatic brain injury…

  1. Mechanisms of white matter changes induced by meditation.

    PubMed

    Tang, Yi-Yuan; Lu, Qilin; Fan, Ming; Yang, Yihong; Posner, Michael I

    2012-06-26

    Using diffusion tensor imaging, several recent studies have shown that training results in changes in white matter efficiency as measured by fractional anisotropy (FA). In our work, we found that a form of mindfulness meditation, integrative body-mind training (IBMT), improved FA in areas surrounding the anterior cingulate cortex after 4-wk training more than controls given relaxation training. Reductions in radial diffusivity (RD) have been interpreted as improved myelin but reductions in axial diffusivity (AD) involve other mechanisms, such as axonal density. We now report that after 4-wk training with IBMT, both RD and AD decrease accompanied by increased FA, indicating improved efficiency of white matter involves increased myelin as well as other axonal changes. However, 2-wk IBMT reduced AD, but not RD or FA, and improved moods. Our results demonstrate the time-course of white matter neuroplasticity in short-term meditation. This dynamic pattern of white matter change involving the anterior cingulate cortex, a part of the brain network related to self-regulation, could provide a means for intervention to improve or prevent mental disorders. PMID:22689998

  2. Magnetic resonance imaging of white matter diseases of prematurity.

    PubMed

    Rutherford, Mary A; Supramaniam, Veena; Ederies, Ashraf; Chew, Andrew; Bassi, Laura; Groppo, Michela; Anjari, Mustafa; Counsell, Serena; Ramenghi, Luca A

    2010-06-01

    Periventricular leucomalacia (PVL) and parenchymal venous infarction complicating germinal matrix/intraventricular haemorrhage have long been recognised as the two significant white matter diseases responsible for the majority of cases of cerebral palsy in survivors of preterm birth. However, more recent studies using magnetic resonance imaging to assess the preterm brain have documented two new appearances, adding to the spectrum of white matter disease of prematurity: punctate white matter lesions, and diffuse excessive high signal intensity (DEHSI). These appear to be more common than PVL but less significant in terms of their impact on individual neurodevelopment. They may, however, be associated with later cognitive and behavioural disorders known to be common following preterm birth. It remains unclear whether PVL, punctate lesions, and DEHSI represent a continuum of disorders occurring as a result of a similar injurious process to the developing white matter. This review discusses the role of MR imaging in investigating these three disorders in terms of aetiology, pathology, and outcome. PMID:20422407

  3. White Matter Tract Damage in the Behavioral Variant of Frontotemporal and Corticobasal Dementia Syndromes

    PubMed Central

    Tovar-Moll, Fernanda; de Oliveira-Souza, Ricardo; Bramati, Ivanei Edson; Zahn, Roland; Cavanagh, Alyson; Tierney, Michael; Moll, Jorge; Grafman, Jordan

    2014-01-01

    The phenotypes of the behavioral variant of frontotemporal dementia and the corticobasal syndrome present considerable clinical and anatomical overlap. The respective patterns of white matter damage in these syndromes have not been directly contrasted. Beyond cortical involvement, damage to white matter pathways may critically contribute to both common and specific symptoms in both conditions. Here we assessed patients with the behavioral variant of frontotemporal dementia and corticobasal syndrome with whole-brain diffusion tensor imaging to identify the white matter networks underlying these pathologies. Twenty patients with the behavioral variant of frontotemporal dementia, 19 with corticobasal syndrome, and 15 healthy controls were enrolled in the study. Differences in tract integrity between (i) patients and controls, and (ii) patients with the corticobasal syndrome and the behavioral variant of frontotemporal dementia were assessed with whole brain tract-based spatial statistics and analyses of regions of interest. Behavioral variant of frontotemporal dementia and the corticobasal syndrome shared a pattern of bilaterally decreased white matter integrity in the anterior commissure, genu and body of the corpus callosum, corona radiata and in the long intrahemispheric association pathways. Patients with the behavioral variant of frontotemporal dementia showed greater damage to the uncinate fasciculus, genu of corpus callosum and forceps minor. In contrast, corticobasal syndrome patients had greater damage to the midbody of the corpus callosum and perirolandic corona radiata. Whereas several compact white matter pathways were damaged in both the behavioral variant of frontotemporal dementia and corticobasal syndrome, the distribution and degree of white matter damage differed between them. These findings concur with the distinctive clinical manifestations of these conditions and may improve the in vivo neuroanatomical and diagnostic characterization of these disorders. PMID:25054218

  4. Adolescent Toluene Inhalation in Rats Affects White Matter Maturation with the Potential for Recovery Following Abstinence

    PubMed Central

    Egan, Gary; Kolbe, Scott; Gavrilescu, Maria; Wright, David; Lubman, Dan Ian; Lawrence, Andrew John

    2012-01-01

    Inhalant misuse is common during adolescence, with ongoing chronic misuse associated with neurobiological and cognitive abnormalities. While human imaging studies consistently report white matter abnormalities among long-term inhalant users, longitudinal studies have been lacking with limited data available regarding the progressive nature of such abnormalities, including the potential for recovery following periods of sustained abstinence. We exposed adolescent male Wistar rats (postnatal day 27) to chronic intermittent inhaled toluene (3,000 ppm) for 1 hour/day, 3 times/week for 8 weeks to model abuse patterns observed in adolescent and young adult human users. This dosing regimen resulted in a significant retardation in weight gain during the exposure period (p<0.05). In parallel, we performed longitudinal magnetic resonance imaging (T2-weighted) and diffusion tensor imaging prior to exposure, and after 4 and 8 weeks, to examine the integrity of white matter tracts, including the anterior commissure and corpus callosum. We also conducted imaging after 8 weeks of abstinence to assess for potential recovery. Chronic intermittent toluene exposure during adolescence and early adulthood resulted in white matter abnormalities, including a decrease in axial (p<0.05) and radial (p<0.05) diffusivity. These abnormalities appeared region-specific, occurring in the anterior commissure but not the corpus callosum and were not present until after at least 4 weeks of exposure. Toluene-induced effects on both body weight and white matter parameters recovered following abstinence. Behaviourally, we observed a progressive decrease in rearing activity following toluene exposure but no difference in motor function, suggesting cognitive function may be more sensitive to the effects of toluene. Furthermore, deficits in rearing were present by 4 weeks suggesting that toluene may affect behaviour prior to detectable white matter abnormalities. Consequently, exposure to inhalants that contain toluene during adolescence and early adulthood appear to differentially affect white matter maturation and behavioural outcomes, although recovery can occur following abstinence. PMID:23028622

  5. Individual differences in white matter anatomy predict dissociable components of reading skill in adults.

    PubMed

    Welcome, Suzanne E; Joanisse, Marc F

    2014-08-01

    We used diffusion tensor imaging (DTI) to investigate relationships between white matter anatomy and different reading subskills in typical-reading adults. A series of analytic approaches revealed that phonological decoding ability is associated with anatomical markers that do not relate to other reading-related cognitive abilities. Thus, individual differences in phonological decoding might relate to connectivity between a network of cortical regions, while skills like sight word reading might rely less strongly on integration across regions. Specifically, manually-drawn ROIs and probabilistic tractography revealed an association between the volume and integrity of white matter underlying primary auditory cortex and nonword reading ability. In a related finding, more extensive cross-hemispheric connections through the isthmus of the corpus callosum predicted better phonological decoding. Atlas-based white matter ROIs demonstrated that relationships with nonword reading were strongest in the inferior fronto-occipital fasciculus and uncinate fasciculus that connect occipital and anterior temporal cortex with inferior frontal cortex. In contrast, tract volume underlying the left angular gyrus was related to nonverbal IQ. Finally, connectivity underlying functional ROIs that are differentially active during phonological and semantic processing predicted nonword reading and reading comprehension, respectively. Together, these results provide important insights into how white matter anatomy may relate to both typical reading subskills, and perhaps a roadmap for understanding neural connectivity in individuals with reading impairments. PMID:24704456

  6. Metabolic syndrome and localization of white matter hyperintensities in the elderly population

    E-print Network

    Metabolic syndrome and localization of white matter hyperintensities in the elderly population Background: Metabolic syndrome (MetS) is defined as a clustering of metabolic disorders: abdom- inal obesity reserved. Keywords: Epidemiology; Observational study; Elderly; Metabolic syndrome; White matter

  7. White matter tract integrity and intelligence in patients with mental retardation and healthy adults

    E-print Network

    Jiang,Tianzi

    White matter tract integrity and intelligence in patients with mental retardation and healthy of brain white matter tracts and intelligence in patients with mental retardation (MR) and healthy adults; Fractional anisotropy; Mental retardation; Intelligence Introduction Researchers have long attempted

  8. ASSOCIATION BETWEEN WHITE MATTER MICROSTRUCTURE, EXECUTIVE FUNCTIONS AND PROCESSING SPEED IN OLDER ADULTS: THE IMPACT OF VASCULAR HEALTH

    PubMed Central

    Jacobs, Heidi I.L.; Leritz, Elizabeth C.; Williams, Victoria J.; Van Boxtel, Martin P.J.; van der Elst, Wim; Jolles, Jelle; Verhey, Frans R. J.; McGlinchey, Regina E.; Milberg, William P.; Salat, David H.

    2013-01-01

    Cerebral white matter damage is a commonly reported consequence of healthy aging, but is also associated with cognitive decline and dementia. The aetiology of this damage is unclear, however, individuals with hypertension have a greater burden of white matter signal abnormalities (WMSA) on MR imaging than those without hypertension. It is therefore possible that elevated blood pressure (BP) impacts white matter tissue structure which in turn has a negative impact on cognition. However, little information exists about whether vascular health indexed by BP mediates the relationship between cognition and white matter tissue structure. We used diffusion tensor imaging to examine the impact of vascular health on regional associations between white matter integrity and cognition in healthy older adults spanning the normotensive to moderate-severe hypertensive BP range (43–87 years; N=128). We examined how white matter structure was associated with performance on tests of two cognitive domains, executive functioning (EF) and processing speed (PS), and how patterns of regional associations were modified by BP and WMSA. Multiple linear regression and structural equation models demonstrated associations between tissue structure, EF and PS in frontal, temporal, parietal and occipital white matter regions. Radial diffusivity was more prominently associated with performance than axial diffusivity. BP only minimally influenced the relationship between white matter integrity, EF and PS. However, WMSA volume had a major impact on neurocognitive associations. This suggests that, although BP and WMSA are causally related, these differential metrics of vascular health may act via independent pathways to influence brain structure, EF and PS. PMID:21954054

  9. The Properties of Matter in White Dwarfs and Neutron Stars

    E-print Network

    Shmuel Balberg; Stuart L. Shapiro

    2000-04-24

    White dwarfs and neutron stars are stellar objects with masses comparable to that of our sun. However, as the endpoint stages of stellar evolution, these objects do not sustain any thermonuclear burning and therefore can no longer support the gravitational load of their own mass by generating thermal pressure. Rather, matter in their interiors is compressed to much higher densities than commonly found in normal stars, and pressure is created by degenerate fermion kinetic energy and particle interactions. As a result, white dwarfs and neutron stars offer unique cosmic laboratories for studying matter at very high densities. In this review we discuss the basic properties of condensed matter at extreme densities and summarize the extent to which these properties can be examined by observations of compact objects.

  10. Retinal nerve fibre layer thickness correlates with brain white matter damage in multiple sclerosis: a combined optical coherence tomography and diffusion tensor imaging study.

    PubMed

    Scheel, Michael; Finke, Carsten; Oberwahrenbrock, Timm; Freing, Alina; Pech, Luisa-Maria; Schlichting, Jeremias; Sömmer, Carina; Wuerfel, Jens; Paul, Friedemann; Brandt, Alexander U

    2014-12-01

    We investigated the association of retinal nerve fibre layer thickness (RNFL) with white matter damage assessed by diffusion tensor imaging (DTI). Forty-four MS patients and 30 healthy subjects underwent optical coherence tomography. DTI was analysed with a voxel-based whole brain and region-based analysis of optic radiation, corpus callosum and further white matter. Correlations between RNFL, fractional anisotropy (FA) and other DTI-based parameters were assessed in patients and controls. RNFL correlated with optic radiation FA, but also with corpus callosum and remaining white matter FA. Our findings demonstrate that RNFL changes indicate white matter damage exceeding the visual pathway. PMID:24842962

  11. White Matter Ischemic Changes in Hyperacute Ischemic Stroke

    PubMed Central

    Trouard, Theodore P; Lafleur, Scott R.; Krupinski, Elizabeth A.; Salamon, Noriko; Kidwell, Chelsea S.

    2015-01-01

    Background and Purpose— The purpose of this study was to evaluate changes in fractional anisotropy (FA), as measured by diffusion tensor imaging, of white matter (WM) infarction and hypoperfusion in patients with acute ischemic stroke using a quantitative voxel-based analysis. Methods— In this prospective study, diffusion tensor imaging and dynamic susceptibility contrast perfusion sequences were acquired in 21 patients with acute ischemic stroke who presented within 6 hours of symptom onset. The coregistered FA, apparent diffusion coefficient, and dynamic susceptibility contrast time to maximum (Tmax) maps were used for voxel-based quantification using a region of interest approach in the ipsilateral affected side and in the homologous contralateral WM. The regions of WM infarction versus hypoperfusion were segmented using a threshold method. Data were analyzed by regression and ANOVA. Results— There was an overall significant mean difference (P<0.001) for the apparent diffusion coefficient, Tmax, and FA values between the normal, hypoperfused, and infarcted WM. The mean±SD of FA was significantly higher (P<0.001) in hypoperfused WM (0.397±0.019) and lower (P<0.001) in infarcted WM (0.313±0.037) when compared with normal WM (0.360±0.020). Regression tree analysis of hypoperfused WM showed the largest mean FA difference at Tmax above versus below 5.4 s with a mean difference of 0.033 (P=0.0096). Conclusions— Diffusion tensor imaging-FA was decreased in regions of WM infarction and increased in hypoperfused WM in patients with hyperacute acute ischemic stroke. The significantly increased FA values in the hypoperfused WM with Tmax?5.4 s are suggestive of early ischemic microstructural changes. PMID:25523053

  12. Differential Developmental Trajectories of Magnetic Susceptibility in Human Brain Gray and White Matter Over the Lifespan

    PubMed Central

    Li, Wei; Wu, Bing; Batrachenko, Anastasia; Bancroft-Wu, Vivian; Morey, Rajendra A.; Shashi, Vandana; Langkammer, Christian; De Bellis, Michael D.; Ropele, Stefan; Song, Allen W.; Liu, Chunlei

    2014-01-01

    As indicated by several recent studies, magnetic susceptibility of the brain is influenced mainly by myelin in the white matter and by iron deposits in the deep nuclei. Myelination and iron deposition in the brain evolve both spatially and temporally. This evolution reflects an important characteristic of normal brain development and ageing. In this study, we assessed the changes of regional susceptibility in the human brain in vivo by examining the developmental and ageing process from 1 to 83 years of age. The evolution of magnetic susceptibility over this lifespan was found to display differential trajectories between the gray and the white matter. In both cortical and subcortical white matter, an initial decrease followed by a subsequent increase in magnetic susceptibility was observed, which could be fitted by a Poisson curve. In the gray matter, including the cortical gray matter and the iron-rich deep nuclei, magnetic susceptibility displayed a monotonic increase that can be described by an exponential growth. The rate of change varied according to functional and anatomical regions of the brain. For the brain nuclei, the age-related changes of susceptibility were in good agreement with the findings from R2* measurement. Our results suggest that magnetic susceptibility may provide valuable information regarding the spatial and temporal patterns of brain myelination and iron deposition during brain maturation and ageing. PMID:24038837

  13. 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…

  14. A tract-specific framework for white matter morphometry combining macroscopic and microscopic tract features

    E-print Network

    Utah, University of

    measures of microstructural tissue properties of white matter. In this paper, we describe a novel tractA tract-specific framework for white matter morphometry combining macroscopic and microscopic tract: Available online 26 May 2010 Keywords: White matter Tract-specific morphometry Shape analysis Diffusion

  15. IEEE TRANSACTIONS ON MEDICAL IMAGING 1 White Matter Fiber Tractography Via Anisotropic

    E-print Network

    Zhang, Jun

    IEEE TRANSACTIONS ON MEDICAL IMAGING 1 White Matter Fiber Tractography Via Anisotropic Diffusion approach to noninvasively tracing brain white matter fiber tracts is presented using diffusion tensor. It is shown that the synthetic tracts are accurately replicated, and several major white matter fiber pathways

  16. IEEE TRANSACTIONS ON VISUALIZATION AND COMPUTER GRAPHICS 1 Exploring Connectivity of the Brain's White Matter

    E-print Network

    Stanford University

    's White Matter with Dynamic Queries Anthony Sherbondy, David Akers, Rachel Mackenzie, Robert Dougherty imaging method that can be used to measure local information about the structure of white matter within estimate the locations and sizes of nerve bundles (white matter pathways) that course through the human

  17. Shape Modeling and Clustering of White Matter Fiber Tracts Using Fourier Descriptors

    E-print Network

    Zhang, Jun

    Shape Modeling and Clustering of White Matter Fiber Tracts Using Fourier Descriptors Xuwei Liang, Qi Zhuang, Ning Cao, and Jun Zhang Abstract-- Reliable shape modeling and clustering of white matter) tractography techniques. In this work we present a novel scheme to model the shape of white matter fiber tracts

  18. Structure-Specific Statistical Mapping of White Matter Tracts using the Continuous Medial Representation

    Microsoft Academic Search

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

    2007-01-01

    This paper describes a new statistical analysis framework for diffusion-based white matter studies. The framework is based on a recent unbiased normalization algorithm for diffusion tensor images. Taking advantage of the fact that most human white matter tracts are thin sheet-like structures, this framework uses deformable medial models to represent six of the major tracts in a white matter atlas

  19. Fronto-temporal white matter connectivity predicts reversal learning errors

    PubMed Central

    Alm, Kylie H.; Rolheiser, Tyler; Mohamed, Feroze B.; Olson, Ingrid R.

    2015-01-01

    Each day, we make hundreds of decisions. In some instances, these decisions are guided by our innate needs; in other instances they are guided by memory. Probabilistic reversal learning tasks exemplify the close relationship between decision making and memory, as subjects are exposed to repeated pairings of a stimulus choice with a reward or punishment outcome. After stimulus–outcome associations have been learned, the associated reward contingencies are reversed, and participants are not immediately aware of this reversal. Individual differences in the tendency to choose the previously rewarded stimulus reveal differences in the tendency to make poorly considered, inflexible choices. Lesion studies have strongly linked reversal learning performance to the functioning of the orbitofrontal cortex, the hippocampus, and in some instances, the amygdala. Here, we asked whether individual differences in the microstructure of the uncinate fasciculus, a white matter tract that connects anterior and medial temporal lobe regions to the orbitofrontal cortex, predict reversal learning performance. Diffusion tensor imaging and behavioral paradigms were used to examine this relationship in 33 healthy young adults. The results of tractography revealed a significant negative relationship between reversal learning performance and uncinate axial diffusivity, but no such relationship was demonstrated in a control tract, the inferior longitudinal fasciculus. Our findings suggest that the uncinate might serve to integrate associations stored in the anterior and medial temporal lobes with expectations about expected value based on feedback history, computed in the orbitofrontal cortex.

  20. White matter injury after cerebral ischemia in ovine fetuses.

    PubMed

    Petersson, Katherine H; Pinar, Halit; Stopa, Edward G; Faris, Ronald A; Sadowska, Grazyna B; Hanumara, R Choudry; Stonestreet, Barbara S

    2002-06-01

    The effects of cerebral ischemia on white matter changes in ovine fetuses were examined after exposure to bilateral carotid artery occlusion. Fetal sheep were exposed to 30 min of ischemia followed by 48 (I/R-48, n = 8) or 72 (I/R-72, n = 10) h of reperfusion or control sham treatment (control, n = 4). Serial coronal sections stained with Luxol fast blue/hematoxylin and eosin were scored for white matter, cerebral cortical, and hippocampal lesions. All areas received graded pathologic scores of 0 to 5, reflecting the degree of injury where 0 = 0%, 1 = 1% to 25%, 2 = 26% to 50%, 3 = 51% to 75%, 4 = 76% to 95%, and 5 = 96% to 100% of the area damaged. Dual-label immunofluorescence using antibodies against glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) were used to characterize white matter lesions. Basic fibroblast growth factor (FGF-2) was measured in the frontal cortex by ELISA. Results of the pathologic scores showed that the white matter of the I/R-72 (2.74 +/- 0.53, mean +/- SEM) was more (p < 0.05) damaged when compared with the control (0.80 +/- 0.33) group. Cortical lesions were greater (p < 0.05) in the I/R-48 (2.12 +/- 0.35) than the control (0.93 +/- 0.09) group. White matter lesions were characterized by reactive GFAP-positive astrocytes and a loss of MBP in oligodendrocytes. The ratio of MBP to GFAP decreased (p < 0.05) as a function of ischemia, indicative of a proportionally greater loss of MBP than GFAP. FGF-2 concentrations were higher (p < 0.05) in the I/R-72 than the control group and there was a direct correlation between the pathologic scores (PS) and FGF-2 concentrations (FGF-2 = e((1.6 PS-0.90)) + 743, n = 17, r = 0.73, p < 0.001). We conclude that carotid artery occlusion results in quantifiable white matter lesions that are associated with a loss of MBP from myelin, and that FGF-2, a purported mediator of recovery from brain injury in adult subjects, increases in concentration in proportion to the severity of brain damage in the fetus. PMID:12032276

  1. White matter microstructure correlates of inhibition and task-switching in adolescents

    PubMed Central

    Mackiewicz Seghete, Kristen L.; Herting, Megan M.; Nagel, Bonnie J.

    2013-01-01

    Although protracted prefrontal grey matter development is associated with concomitant executive function (EF) development in adolescents, few studies have explored the relationship between white matter and EF. This study examined the relationship between white matter microstructure and two aspects of EF, inhibition and task-switching, in a sample of 84 adolescents using diffusion tensor imaging (DTI). Tract-Based Spatial Statistics (TBSS) were used to examine fractional anisotropy (FA) and mean diffusivity (MD). Adolescents completed the Color-Word Interference task from the Delis-Kaplan Executive Function System, a modification of the Stroop task. Inhibition and task-switching performance were group normalized and measured using both reaction time and errors. Performance and the interaction of age and performance were regressed on FA and MD white matter skeletons, controlling for age and IQ, separately for inhibition and task-switching. Follow up analyses examined the relative contributions of axial and radial diffusivities. Greater FA in the anterior corona radiata (ACR) was associated with better inhibition, independent of age. Greater FA in the SCR and precentral gyrus white matter were associated with better task-switching, regardless of age, whereas an association between FA in the ACR and task-switching was dependent on age. There were no significant associations between MD and performance. Results suggest better inhibition and task-switching are associated with greater integrity of white matter microstructure in regions supporting cross-cortical and cortical-subcortical connections stemming from the prefrontal cortex. These findings are consistent with functional studies of cognitive control and models of EF that propose separate, yet related, latent factors. PMID:23811486

  2. Premyelinated central axons express neurotoxic NMDA receptors: relevance to early developing white-matter injury.

    PubMed

    Huria, Tahani; Beeraka, Narasimha Murthy; Al-Ghamdi, Badrah; Fern, Robert

    2015-04-01

    Ischemic-type injury to developing white matter is associated with the significant clinical condition cerebral palsy and with the cognitive deficits associated with premature birth. Premyelinated axons are the major cellular component of fetal white matter and loss of axon function underlies the disability, but the cellular mechanisms producing ischemic injury to premyelinated axons have not previously been described. Injury was found to require longer periods of modelled ischemia than at latter developmental points. Ischemia produced initial hyperexcitability in axons followed by loss of function after Na(+) and Ca(2+) influx. N-methyl-D-aspartate- (NMDA) type glutamate receptor (GluR) agonists potentiated axon injury while antagonists were protective. The NMDA GluR obligatory Nr1 subunit colocalized with markers of small premyelinated axons and expression was found at focal regions of axon injury. Ischemic injury of glial cells present in early developing white matter was NMDA GluR independent. Axons in human postconception week 18 to 23 white matter had a uniform prediameter expansion phenotype and postembedded immuno-gold labelling showed Nr1 subunit expression on the membrane of these axons, demonstrating a shared key neuropathologic feature with the rodent model. Premyelinated central axons therefore express high levels of functional NMDA GluRs that confer sensitivity to ischemic injury. PMID:25515212

  3. Cigarette Smoking and White Matter Microstructure in Schizophrenia

    PubMed Central

    Cullen, Kathryn R.; Wallace, Stuart; Magnotta, Vincent A.; Bockholt, Jeremy; Erlich, Stephan; Gollub, Randy L.; Manoach, Dara; Ho, Beng C.; Clark, Vincent P.; Lauriello, John; Bustillo, Juan R.; Schulz, S. Charles; Andreasen, Nancy C.; Calhoun, Vince D.; Lim, Kelvin O.; White, Tonya

    2011-01-01

    The majority of patients with schizophrenia smoke cigarettes. Both nicotine use and schizophrenia have been associated with alterations in brain white matter microstructure as measured by diffusion tensor imaging (DTI). The purpose of this study was to examine fractional anisotropy (FA) in smoking and non-smoking patients with schizophrenia and in healthy volunteers. A total of 43 patients (28 smoking and 15 non-smoking) with schizophrenia and 40 healthy, non-smoking participants underwent DTI. Mean FA was calculated in four global regions of interest (ROIs) (whole brain, cerebellum, brainstem, and total cortical) as well as in four regional ROIs (frontal, temporal, parietal and occipital lobes). The non-smoking patient group had a significantly higher IQ compared to the patients who smoked and our results depended on whether IQ was included as a covariate. Without IQ correction, significant between-group effects for FA were found in four ROIs: total brain, total cortical, frontal lobe and the occipital lobe. In all cases the FA was lower among the smoking patient group, and highest in the control group. Smoking patients differed significantly from non-smoking patients in the frontal lobe ROI. However, these differences were no longer significant after IQ correction. FA differences between non-smoking patients and controls were not significant. Among smoking and non-smoking patients with schizophrenia but not healthy controls, FA was correlated with IQ. In conclusion, group effects of smoking on FA in schizophrenia might be mediated by IQ. Further, low FA in specific brain areas may be a neural marker for complex pathophysiology and risk for diverse problems such as schizophrenia, low IQ, and nicotine addiction. PMID:22386966

  4. Diffusion Tensor Magnetic Resonance Imaging Finding of Discrepant Fractional Anisotropy Between the Frontal and Parietal Lobes After Whole-Brain Irradiation in Childhood Medulloblastoma Survivors: Reflection of Regional White Matter Radiosensitivity?

    SciTech Connect

    Qiu Deqiang [Department of Diagnostic Radiology, Queen Mary Hospital, University of Hong Kong, Hong Kong (China); Kwong, Dora [Department of Clinical Oncology, Queen Mary Hospital, University of Hong Kong, Hong Kong (China); Chan, Godfrey [Department of Pediatric and Adolescent Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong (China); Leung, Lucullus [Department of Oncology, Princess Margaret Hospital, Hong Kong (China); Khong, P.-L. [Department of Diagnostic Radiology, Queen Mary Hospital, University of Hong Kong, Hong Kong (China)], E-mail: plkhong@hkucc.hku.hk

    2007-11-01

    Purpose: To test the hypothesis that fractional anisotropy (FA) is more severely reduced in white matter of the frontal lobe compared with the parietal lobe after receiving the same whole-brain irradiation dose in a cohort of childhood medulloblastoma survivors. Methods and Materials: Twenty-two medulloblastoma survivors (15 male, mean [{+-} SD] age = 12.1 {+-} 4.6 years) and the same number of control subjects (15 male, aged 12.0 {+-} 4.2 years) were recruited for diffusion tensor magnetic resonance imaging scans. Using an automated tissue classification method and the Talairach Daemon atlas, FA values of frontal and parietal lobes receiving the same radiation dose, and the ratio between them were quantified and denoted as FFA, PFA, and FA{sub f/p}, respectively. The Mann-Whitney U test was used to test for significant differences of FFA, PFA, and FA{sub f/p} between medulloblastoma survivors and control subjects. Results: Frontal lobe and parietal lobe white matter FA were found to be significantly less in medulloblastoma survivors compared with control subjects (frontal p = 0.001, parietal p = 0.026). Moreover, these differences were found to be discrepant, with the frontal lobe having a significantly larger difference in FA compared with the parietal lobe. The FA{sub f/p} of control and medulloblastoma survivors was 1.110 and 1.082, respectively (p = 0.029). Conclusion: Discrepant FA changes after the same irradiation dose suggest radiosensitivity of the frontal lobe white matter compared with the parietal lobe. Special efforts to address the potentially vulnerable frontal lobe after treatment with whole-brain radiation may be needed so as to balance disease control and treatment-related morbidity.

  5. Local White Matter Geometry from Diffusion Tensor Gradients

    PubMed Central

    Savadjiev, Peter; Kindlmann, Gordon L.; Bouix, Sylvain; Shenton, Martha E.; Westin, Carl-Fredrik

    2010-01-01

    We introduce a mathematical framework for computing geometrical properties of white matter fibres directly from diffusion tensor fields. The key idea is to isolate the portion of the gradient of the tensor field corresponding to local variation in tensor orientation, and to project it onto a coordinate frame of tensor eigenvectors. The resulting eigenframe-centered representation then makes it possible to define scalar indices (or measures) that describe the local white matter geometry directly from the diffusion tensor field and its gradient, without requiring prior tractography. We derive new scalar indices of (1) fibre dispersion and (2) fibre curving, and we demonstrate them on synthetic and in vivo data. Finally, we illustrate their applicability to a group study on schizophrenia. PMID:20426006

  6. Memory binding and white matter integrity in familial Alzheimer's disease.

    PubMed

    Parra, Mario A; Saarimäki, Heini; Bastin, Mark E; Londońo, Ana C; Pettit, Lewis; Lopera, Francisco; Della Sala, Sergio; Abrahams, Sharon

    2015-05-01

    Binding information in short-term and long-term memory are functions sensitive to Alzheimer's disease. They have been found to be affected in patients who meet criteria for familial Alzheimer's disease due to the mutation E280A of the PSEN1 gene. However, only short-term memory binding has been found to be affected in asymptomatic carriers of this mutation. The neural correlates of this dissociation are poorly understood. The present study used diffusion tensor magnetic resonance imaging to investigate whether the integrity of white matter structures could offer an account. A sample of 19 patients with familial Alzheimer's disease, 18 asymptomatic carriers and 21 non-carrier controls underwent diffusion tensor magnetic resonance imaging, neuropsychological and memory binding assessment. The short-term memory binding task required participants to detect changes across two consecutive screens displaying arrays of shapes, colours, or shape-colour bindings. The long-term memory binding task was a Paired Associates Learning Test. Performance on these tasks were entered into regression models. Relative to controls, patients with familial Alzheimer's disease performed poorly on both memory binding tasks. Asymptomatic carriers differed from controls only in the short-term memory binding task. White matter integrity explained poor memory binding performance only in patients with familial Alzheimer's disease. White matter water diffusion metrics from the frontal lobe accounted for poor performance on both memory binding tasks. Dissociations were found in the genu of corpus callosum which accounted for short-term memory binding impairments and in the hippocampal part of cingulum bundle which accounted for long-term memory binding deficits. The results indicate that white matter structures in the frontal and temporal lobes are vulnerable to the early stages of familial Alzheimer's disease and their damage is associated with impairments in two memory binding functions known to be markers for Alzheimer's disease. PMID:25762465

  7. Structural gray and white matter changes in patients with HIV

    Microsoft Academic Search

    Michael KuperK; K. Rabe; S. Esser; E. R. Gizewski; I. W. Husstedt; M. Maschke; M. Obermann

    2011-01-01

    In this cross-sectional study we used magnetic resonance imaging (MRI)-based voxel based morphometry (VBM) in a sample of\\u000a HIV positive patients to detect structural gray and white matter changes. Forty-eight HIV positive subjects with (n = 28) or without (n = 20) cognitive deficits (mean age 48.5 ± 9.6 years) and 48 age- and sex-matched HIV negative controls underwent MRI for\\u000a VBM analyses. Clinical testing in HIV

  8. 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. PMID:24333926

  9. White matter abnormalities in bipolar disorder: insights from diffusion tensor imaging studies

    Microsoft Academic Search

    Serene Heng; Allen W. Song; Kang Sim

    2010-01-01

    Diffusion tensor imaging (DTI) is a neuroimaging technique with the potential to elucidate white matter abnormalities. Recently,\\u000a it has been applied to help in better understanding of the pathophysiology of bipolar disorder (BD). This review sought to\\u000a synthesise existing literature on DTI studies in BD, summarise current findings and highlight brain regions that have consistently\\u000a been implicated in BD, as

  10. White Matter Hyperintensities among Older Adults Are Associated with Futile Increase in Frontal Activation and Functional Connectivity during Spatial Search

    PubMed Central

    Lockhart, Samuel N.; Luck, Steven J.; Geng, Joy; Beckett, Laurel; Disbrow, Elizabeth A.; Carmichael, Owen; DeCarli, Charles

    2015-01-01

    The mechanisms by which aging and other processes can affect the structure and function of brain networks are important to understanding normal age-related cognitive decline. Advancing age is known to be associated with various disease processes, including clinically asymptomatic vascular and inflammation processes that contribute to white matter structural alteration and potential injury. The effects of these processes on the function of distributed cognitive networks, however, are poorly understood. We hypothesized that the extent of magnetic resonance imaging white matter hyperintensities would be associated with visual attentional control in healthy aging, measured using a functional magnetic resonance imaging search task. We assessed cognitively healthy older adults with search tasks indexing processing speed and attentional control. Expanding upon previous research, older adults demonstrate activation across a frontal-parietal attentional control network. Further, greater white matter hyperintensity volume was associated with increased activation of a frontal network node independent of chronological age. Also consistent with previous research, greater white matter hyperintensity volume was associated with anatomically specific reductions in functional magnetic resonance imaging functional connectivity during search among attentional control regions. White matter hyperintensities may lead to subtle attentional network dysfunction, potentially through impaired frontal-parietal and frontal interhemispheric connectivity, suggesting that clinically silent white matter biomarkers of vascular and inflammatory injury can contribute to differences in search performance and brain function in aging, and likely contribute to advanced age-related impairments in cognitive control. PMID:25793922

  11. Distinctive disruption patterns of white matter tracts in Alzheimer's disease with full diffusion tensor characterization.

    PubMed

    Huang, Hao; Fan, Xin; Weiner, Myron; Martin-Cook, Kristin; Xiao, Guanghua; Davis, Jeannie; Devous, Michael; Rosenberg, Roger; Diaz-Arrastia, Ramon

    2012-09-01

    To characterize the white matter structural changes at the tract level and tract group level, comprehensive analysis with 4 metrics derived from diffusion tensor imaging (DTI), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AxD) and radial diffusivity (RD), was conducted. Tract groups, namely limbic, commissural, association, and projection tracts, include white matter tracts of similar functions. Diffusion tensor imaging data were acquired from 61 subjects (26 Alzheimer's disease [AD], 11 subjects with amnestic mild cognitive impairment [aMCI], and 24 age-matched controls). An atlas-based approach was used to survey 30 major cerebral white matter tracts with the measurements of FA, MD, AxD, and RD. Regional cortical atrophy and cognitive functions of AD patients were also measured to correlate with the structural changes of white matter. Synchronized structural changes of cingulum bundle and fornix, both of which are part of limbic tract group, were revealed. Widespread yet distinctive structural changes were found in limbic, commissural, association, and projection tract groups between control and AD subjects. Specifically, FA, MD, and RD of limbic tracts, FA, MD, AxD, and RD of commissural tracts, MD, AxD, and RD of association tracts, and MD and AxD of projection tracts are significantly different between AD patients and control subjects. In contrast, the comparison between aMCI and control subjects shows disruption only in the limbic and commissural tract groups of aMCI subjects. MD values of all tract groups of AD patients are significantly correlated to cognitive functions. Difference between AD and control and that between aMCI and control indicates a progression pattern of white matter disruption from limbic and commissural tract group to other tract groups. High correlation between FA, MD, and RD measurements from limbic tracts and cortical atrophy suggests the disruption of the limbic tract group is caused by the neuronal damage. PMID:21872362

  12. MRI Markers for Mild Cognitive Impairment: Comparisons between White Matter Integrity and Gray Matter Volume Measurements

    PubMed Central

    Zhang, Yu; Schuff, Norbert; Camacho, Monica; Chao, Linda L.; Fletcher, Thomas P.; Yaffe, Kristine; Woolley, Susan C.; Madison, Catherine; Rosen, Howard J.; Miller, Bruce L.; Weiner, Michael W.

    2013-01-01

    The aim of the study was to evaluate the value of assessing white matter integrity using diffusion tensor imaging (DTI) for classification of mild cognitive impairment (MCI) and prediction of cognitive impairments in comparison to brain atrophy measurements using structural MRI. Fifty-one patients with MCI and 66 cognitive normal controls (CN) underwent DTI and T1-weighted structural MRI. DTI measures included fractional anisotropy (FA) and radial diffusivity (DR) from 20 predetermined regions-of-interest (ROIs) in the commissural, limbic and association tracts, which are thought to be involved in Alzheimer's disease; measures of regional gray matter (GM) volume included 21 ROIs in medial temporal lobe, parietal cortex, and subcortical regions. Significant group differences between MCI and CN were detected by each MRI modality: In particular, reduced FA was found in splenium, left isthmus cingulum and fornix; increased DR was found in splenium, left isthmus cingulum and bilateral uncinate fasciculi; reduced GM volume was found in bilateral hippocampi, left entorhinal cortex, right amygdala and bilateral thalamus; and thinner cortex was found in the left entorhinal cortex. Group classifications based on FA or DR was significant and better than classifications based on GM volume. Using either DR or FA together with GM volume improved classification accuracy. Furthermore, all three measures, FA, DR and GM volume were similarly accurate in predicting cognitive performance in MCI patients. Taken together, the results imply that DTI measures are as accurate as measures of GM volume in detecting brain alterations that are associated with cognitive impairment. Furthermore, a combination of DTI and structural MRI measurements improves classification accuracy. PMID:23762488

  13. White Matter Abnormalities and Structural Hippocampal Disconnections in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease

    PubMed Central

    Rowley, Jared; Fonov, Vladimir; Wu, Ona; Eskildsen, Simon Fristed; Schoemaker, Dorothee; Wu, Liyong; Mohades, Sara; Shin, Monica; Sziklas, Viviane; Cheewakriengkrai, Laksanun; Shmuel, Amir; Dagher, Alain; Gauthier, Serge; Rosa-Neto, Pedro

    2013-01-01

    The purpose of this project was to evaluate white matter degeneration and its impact on hippocampal structural connectivity in patients with amnestic mild cognitive impairment, non-amnestic mild cognitive impairment and Alzheimer’s disease. We estimated white matter fractional anisotropy, mean diffusivity and hippocampal structural connectivity in two independent cohorts. The ADNI cohort included 108 subjects [25 cognitively normal, 21 amnestic mild cognitive impairment, 47 non-amnestic mild cognitive impairment and 15 Alzheimer’s disease]. A second cohort included 34 subjects [15 cognitively normal and 19 amnestic mild cognitive impairment] recruited in Montreal. All subjects underwent clinical and neuropsychological assessment in addition to diffusion and T1 MRI. Individual fractional anisotropy and mean diffusivity maps were generated using FSL-DTIfit. In addition, hippocampal structural connectivity maps expressing the probability of connectivity between the hippocampus and cortex were generated using a pipeline based on FSL-probtrackX. Voxel-based group comparison statistics of fractional anisotropy, mean diffusivity and hippocampal structural connectivity were estimated using Tract-Based Spatial Statistics. The proportion of abnormal to total white matter volume was estimated using the total volume of the white matter skeleton. We found that in both cohorts, amnestic mild cognitive impairment patients had 27-29% white matter volume showing higher mean diffusivity but no significant fractional anisotropy abnormalities. No fractional anisotropy or mean diffusivity differences were observed between non-amnestic mild cognitive impairment patients and cognitively normal subjects. Alzheimer’s disease patients had 66.3% of normalized white matter volume with increased mean diffusivity and 54.3% of the white matter had reduced fractional anisotropy. Reduced structural connectivity was found in the hippocampal connections to temporal, inferior parietal, posterior cingulate and frontal regions only in the Alzheimer’s group. The severity of white matter degeneration appears to be higher in advanced clinical stages, supporting the construct that these abnormalities are part of the pathophysiological processes of Alzheimer’s disease. PMID:24086371

  14. 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

  15. Quantitative MR assessment of structural changes in white matter of children treated for ALL

    NASA Astrophysics Data System (ADS)

    Reddick, Wilburn E.; Glass, John O.; Mulhern, Raymond K.

    2001-07-01

    Our research builds on the hypothesis that white matter damage resulting from therapy spans a continuum of severity that can be reliably probed using non-invasive MR technology. This project focuses on children treated for ALL with a regimen containing seven courses of high-dose methotrexate (HDMTX) which is known to cause leukoencephalopathy. Axial FLAIR, T1-, T2-, and PD-weighted images were acquired, registered and then analyzed with a hybrid neural network segmentation algorithm to identify normal brain parenchyma and leukoencephalopathy. Quantitative T1 and T2 maps were also analyzed at the level of the basal ganglia and the centrum semiovale. The segmented images were used as mask to identify regions of normal appearing white matter (NAWM) and leukoencephalopathy in the quantitative T1 and T2 maps. We assessed the longitudinal changes in volume, T1 and T2 in NAWM and leukoencephalopathy for 42 patients. The segmentation analysis revealed that 69% of patients had leukoencephalopathy after receiving seven courses of HDMTX. The leukoencephalopathy affected approximately 17% of the patients' white matter volume on average (range 2% - 38%). Relaxation rates in the NAWM were not significantly changed between the 1st and 7th courses. Regions of leukoencephalopathy exhibited a 13% elevation in T1 and a 37% elevation in T2 relaxation rates.

  16. White Matter Changes of Neurite Density and Fiber Orientation Dispersion during Human Brain Maturation

    PubMed Central

    Chang, Yi Shin; Owen, Julia P.; Pojman, Nicholas J.; Thieu, Tony; Bukshpun, Polina; Wakahiro, Mari L. J.; Berman, Jeffrey I.; Roberts, Timothy P. L.; Nagarajan, Srikantan S.; Sherr, Elliott H.; Mukherjee, Pratik

    2015-01-01

    Diffusion tensor imaging (DTI) studies of human brain development have consistently shown widespread, but nonlinear increases in white matter anisotropy through childhood, adolescence, and into adulthood. However, despite its sensitivity to changes in tissue microstructure, DTI lacks the specificity to disentangle distinct microstructural features of white and gray matter. Neurite orientation dispersion and density imaging (NODDI) is a recently proposed multi-compartment biophysical model of brain microstructure that can estimate non-collinear properties of white matter, such as neurite orientation dispersion index (ODI) and neurite density index (NDI). In this study, we apply NODDI to 66 healthy controls aged 7–63 years to investigate changes of ODI and NDI with brain maturation, with comparison to standard DTI metrics. Using both region-of-interest and voxel-wise analyses, we find that NDI exhibits striking increases over the studied age range following a logarithmic growth pattern, while ODI rises following an exponential growth pattern. This novel finding is consistent with well-established age-related changes of FA over the lifespan that show growth during childhood and adolescence, plateau during early adulthood, and accelerating decay after the fourth decade of life. Our results suggest that the rise of FA during the first two decades of life is dominated by increasing NDI, while the fall in FA after the fourth decade is driven by the exponential rise of ODI that overcomes the slower increases of NDI. Using partial least squares regression, we further demonstrate that NODDI better predicts chronological age than DTI. Finally, we show excellent test—retest reliability of NODDI metrics, with coefficients of variation below 5% in all measured regions of interest. Our results support the conclusion that NODDI reveals biologically specific characteristics of brain development that are more closely linked to the microstructural features of white matter than are the empirical metrics provided by DTI. PMID:26115451

  17. Disentangling the relation between left temporoparietal white matter and reading: A spherical deconvolution tractography study.

    PubMed

    Vanderauwera, Jolijn; Vandermosten, Maaike; Dell'Acqua, Flavio; Wouters, Jan; Ghesquičre, Pol

    2015-08-01

    Diffusion tensor imaging (DTI) studies have shown that left temporoparietal white matter is related to phonological aspects of reading. However, DTI lacks the sensitivity to disentangle whether phonological processing is sustained by intrahemispheric connections, interhemispheric connections, or projection tracts. Spherical deconvolution (SD) is a nontensor model which enables a more accurate estimation of multiple fiber directions in crossing fiber regions. Hence, this study is the first to investigate whether the observed relation with reading aspects in left temporoparietal white matter is sustained by a particular pathway by applying a nontensor model. Second, measures of degree of diffusion anisotropy, which indirectly informs about white matter organization, were compared between DTI and SD tractography. In this study, 71 children (5-6 years old) participated. Intrahemispheric, interhemispheric, and projection pathways were delineated using DTI and SD tractography. Anisotropy indices were extracted, that is, fractional anisotropy (FA) in DTI and quantitative hindrance modulated orientational anisotropy (HMOA) in SD. DTI results show that diffusion anisotropy in both the intrahemispheric and projection tracts was positively correlated to phonological awareness; however, the effect was confounded by subjects' motion. In SD, the relation was restricted to the left intrahemispheric connections. A model comparison suggested that FA was, relatively to HMOA, more confounded by fiber crossings; however, anisotropy indices were highly related. In sum, this study shows the potential of SD to quantify white matter microstructure in regions containing crossing fibers. More specifically, SD analyses show that phonological awareness is sustained by left intrahemispheric connections and not interhemispheric or projection tracts. Hum Brain Mapp 36:3273-3287, 2015. © 2015 Wiley Periodicals, Inc. PMID:26037303

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

    Microsoft Academic Search

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

    1990-01-01

    Summary 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

  19. White matter integrity of the whole brain is disrupted in rst-episode schizophrenia

    E-print Network

    Jiang,Tianzi

    White matter integrity of the whole brain is disrupted in ˘rst-episode schizophrenia Yihui Haoa; revised 8 November 2005; accepted 9 November 2005 Diˇusion tensor imaging studies in schizophrenia have matter integrity.We have examined whether white matter is abnormal in ˘rst-episode schizophrenia by using

  20. Longitudinal relaxographic imaging of white matter hyperintensities in the elderly

    PubMed Central

    2014-01-01

    Background Incidental white matter hyperintensities (WMHs) are common findings on T2-weighted magnetic resonance images of the aged brain and have been associated with cognitive decline. While a variety of pathogenic mechanisms have been proposed, the origin of WMHs and the extent to which lesions in the deep and periventricular white matter reflect distinct etiologies remains unclear. Our aim was to quantify the fractional blood volume (vb) of small WMHs in vivo using a novel magnetic resonance imaging (MRI) approach and examine the contribution of blood–brain barrier disturbances to WMH formation in the deep and periventricular white matter. Methods Twenty-three elderly volunteers (aged 59–82 years) underwent 7 Tesla relaxographic imaging and fluid-attenuated inversion recovery (FLAIR) MRI. Maps of longitudinal relaxation rate constant (R1) were prepared before contrast reagent (CR) injection and throughout CR washout. Voxelwise estimates of vb were determined by fitting temporal changes in R1 values to a two-site model that incorporates the effects of transendothelial water exchange. Average vb values in deep and periventricular WMHs were determined after semi-automated segmentation of FLAIR images. Ventricular permeability was estimated from the change in CSF R1 values during CR washout. Results In the absence of CR, the total water fraction in both deep and periventricular WMHs was increased compared to normal appearing white matter (NAWM). The vb of deep WMHs was 1.8?±?0.6 mL/100 g and was significantly reduced compared to NAWM (2.4?±?0.8 mL/100 g). In contrast, the vb of periventricular WMHs was unchanged compared to NAWM, decreased with ventricular volume and showed a positive association with ventricular permeability. Conclusions Hyperintensities in the deep WM appear to be driven by vascular compromise, while those in the periventricular WM are most likely the result of a compromised ependyma in which the small vessels remain relatively intact. These findings support varying contributions of blood–brain barrier and brain-CSF interface disturbances in the pathophysiology of deep and periventricular WMHs in the aged human brain. PMID:25379172

  1. White matter abnormalities associated with military PTSD in the context of blast TBI.

    PubMed

    Davenport, Nicholas D; Lim, Kelvin O; Sponheim, Scott R

    2015-03-01

    Mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) are common among recent military veterans and involve substantial symptom overlap, making clinical distinction and effective intervention difficult. Emerging evidence of cerebral white matter abnormalities associated with mTBI may provide a biological measure to inform diagnosis and treatment, but the potentially confounding effects between PTSD and mTBI have largely gone unexamined. We collected diffusion imaging data from 133 recently-deployed American service members who developed PTSD and/or sustained mTBI, or had neither condition. Effects of PTSD and mTBI on traditional tensor-based measures of cerebral white matter integrity (fractional anisotropy [FA] and mean diffusivity [MD]) were compared in anatomical regions of interest and individual voxels throughout the brain. Generalized FA (GFA), which allows for multiple fiber orientations per voxel, was also included to improve sensitivity in white matter areas containing crossing or diverging axon bundles. PTSD was consistently associated with high GFA in select brain regions, greater likelihood of regions and voxels with abnormally low MD, and a greater number of voxels with abnormally high FA, while mTBI was associated with fewer high MD regions. Overall, PTSD was associated with more restricted diffusion (low MD) and greater anisotropy (high GFA) in regions of crossing/diverging fibers poorly characterized by a single tensor (FA), suggesting that interstitial fibers may be involved. Contrary to earlier results in a sample without PTSD, mTBI was not associated with anisotropy abnormalities, perhaps indicating the cooccurrence of PTSD and mTBI requires special consideration with regard to structural brain connectivity. PMID:25387950

  2. Effect of clozapine on white matter integrity in patients with schizophrenia: a diffusion tensor imaging study.

    PubMed

    Ozcelik-Eroglu, Elcin; Ertugrul, Aygun; Oguz, Kader Karli; Has, Arzu Ceylan; Karahan, Sevilay; Yazici, Mumin Kazim

    2014-09-30

    Several diffusion tensor imaging (DTI) studies have reported disturbed white matter integrity in various brain regions in patients with schizophrenia, whereas only a few studied the effect of antipsychotics on DTI measures. The aim of this study was to investigate the effect of 12 weeks of clozapine treatment on DTI findings in patients with schizophrenia, and to compare the findings with those in unaffected controls. The study included 16 patients with schizophrenia who were assessed with the Positive and Negative Syndrome Scale, a neurocognitive test battery, and DTI at baseline and 12 weeks after the initiation of clozapine treatment. Eight unaffected controls were assessed once with the neurocognitive test battery and DTI. Voxel-wise analysis of DTI data was performed via tract-based spatial statistics (TBSS). Compared with the control group, the patient group exhibited lower fractional anisotropy (FA) in 16 brain regions, including the bilateral superior longitudinal fasciculi, inferior fronto-occipital fasciculi, superior and inferior parietal lobules, cingulate bundles, cerebellum, middle cerebellar peduncles, and left inferior longitudinal fasciculus, whereas the patients had higher FA in six regions, including the right parahippocampus, left anterior thalamic radiation, and right posterior limb of the internal capsule before clozapine treatment. After 12 weeks of treatment with clozapine, white matter FA was increased in widespread brain regions. In two of the regions where FA had initially been lower in patients compared with controls (left inferior fronto-occipital fasciculus and superior parietal lobule), clozapine appeared to increase FA. An improvement in semantic fluency was correlated with the increase in FA value in the left inferior fronto-occipital fasciculus. An increase in FA following 12 weeks of treatment with clozapine suggests that this treatment alters white matter microstructural integrity in patients with schizophrenia previously treated with typical and/or atypical antipsychotics and, in some locations, reverses a previous deficit. PMID:25012780

  3. Computer-aided evaluation method of white matter hyperintensities related to subcortical vascular dementia based on magnetic resonance imaging

    Microsoft Academic Search

    Yasuo Kawata; Hidetaka Arimura; Yasuo Yamashita; Taiki Magome; Masafumi Ohki; Fukai Toyofuku; Yoshiharu Higashida; Kazuhiro Tsuchiya

    2010-01-01

    It has been reported that the severity of subcortical vascular dementia (VaD) correlated with an area ratio of white matter hyperintensity (WMH) regions to the brain parenchyma (WMH area ratio). The purpose of this study was to develop a computer-aided evaluation method of WMH regions for diagnosis of subcortical VaD based on magnetic resonance (MR) images. A brain parenchymal region

  4. Retinal arteriolar geometry is associated with cerebral white matter hyperintensities on MRI 

    E-print Network

    Doubal, F.N.; de Haan, R; MacGillivray, T.J.; Cohn-Hokke, P.; Dhillon, B.; Dennis, M.S.; Wardlaw, J.M.

    Background. Cerebral small vessel disease (lacunar stroke and cerebral white matter hyperintensities) is caused by vessel abnormalities of unknown aetiology. Retinal vessels show developmental and pathophysiological ...

  5. White matter changes linked to visual recovery after nerve decompression

    PubMed Central

    Paul, David A.; Gaffin-Cahn, Elon; Hintz, Eric B.; Adeclat, Giscard J.; Zhu, Tong; Williams, Zoë R.; Vates, G. Edward; Mahon, Bradford Z.

    2015-01-01

    The relationship between the integrity of white matter tracts and cortical function in the human brain remains poorly understood. Here we use a model of reversible white matter injury, compression of the optic chiasm by tumors of the pituitary gland, to study the structural and functional changes that attend spontaneous recovery of cortical function and visual abilities after surgical tumor removal and subsequent decompression of the nerves. We show that compression of the optic chiasm leads to demyelination of the optic tracts, which reverses as quickly as 4 weeks after nerve decompression. Furthermore, variability across patients in the severity of demyelination in the optic tracts predicts visual ability and functional activity in early cortical visual areas, and pre-operative measurements of myelination in the optic tracts predicts the magnitude of visual recovery after surgery. These data indicate that rapid regeneration of myelin in the human brain is a significant component of the normalization of cortical activity, and ultimately the recovery of sensory and cognitive function, after nerve decompression. More generally, our findings demonstrate the utility of diffusion tensor imaging as an in vivo measure of myelination in the human brain. PMID:25504884

  6. Age differences in periventricular and deep white matter lesions.

    PubMed

    Nyquist, Paul A; Bilgel, Murat; Gottesman, Rebecca; Yanek, Lisa R; Moy, Taryn F; Becker, Lewis C; Cuzzocreo, Jennifer L; Prince, Jerry; Wasserman, Bruce A; Yousem, David M; Becker, Diane M; Kral, Brian G; Vaidya, Dhananjay

    2015-04-01

    Deep white matter hyperintensity (DWMH) and periventricular (PV) white matter lesion volumes are associated with age and subsequent stroke. We studied age differences in these volumes accounting for collinearity and risk factors. Subjects were 563 healthy family members of early-onset coronary artery disease patients. Using 3T magnetic resonance imaging, lesions were classified as DWMH or PV. Age association with lesion classification was analyzed using random effects Tobit regression, adjusting for intracranial volume (ICV) and risk factors. Subjects were 60% women, 36% African-American, mean age 51 ± 11 years. In multivariable analysis adjusted for PV and ICV, DWMH was associated with age (p < 0.001) and female sex (p = 0.003). PV, adjusted for DWMH and ICV, was age associated (p < 0.001). For each age decade, DWMH showed 0.07 log units/decade greater volume (95% CI = 0.04-0.11); PV was 0.18 log units/decade greater (95% CI = 0.14-0.23); slope differences (p < 0.001). In people with a family history of coronary artery disease, PV and DWMH are independently and differentially associated with age controlling for traditional risk factors. PMID:25659858

  7. Differential Development of Human Brain White Matter Tracts

    PubMed Central

    Imperati, Davide; Colcombe, Stan; Kelly, Clare; Di Martino, Adriana; Zhou, Juan; Castellanos, F. Xavier; Milham, Michael P.

    2011-01-01

    Neuroscience is increasingly focusing on developmental factors related to human structural and functional connectivity. Unfortunately, to date, diffusion-based imaging approaches have only contributed modestly to these broad objectives, despite the promise of diffusion-based tractography. Here, we report a novel data-driven approach to detect similarities and differences among white matter tracts with respect to their developmental trajectories, using 64-direction diffusion tensor imaging. Specifically, using a cross-sectional sample comprising 144 healthy individuals (7 to 48 years old), we applied k-means cluster analysis to separate white matter voxels based on their age-related trajectories of fractional anisotropy. Optimal solutions included 5-, 9- and 14-clusters. Our results recapitulate well-established tracts (e.g., internal and external capsule, optic radiations, corpus callosum, cingulum bundle, cerebral peduncles) and subdivisions within tracts (e.g., corpus callosum, internal capsule). For all but one tract identified, age-related trajectories were curvilinear (i.e., inverted ‘U-shape’), with age-related increases during childhood and adolescence followed by decreases in middle adulthood. Identification of peaks in the trajectories suggests that age-related losses in fractional anisotropy occur as early as 23 years of age, with mean onset at 30 years of age. Our findings demonstrate that data-driven analytic techniques may be fruitfully applied to extant diffusion tensor imaging datasets in normative and neuropsychiatric samples. PMID:21909351

  8. A Voxel-Based Method for the Statistical Analysis of Gray and White Matter Density Applied to Schizophrenia

    Microsoft Academic Search

    I. C. Wright; P. K. McGuire; J.-B. Poline; J. M. Travere; R. M. Murray; C. D. Frith; R. S. J. Frackowiak; K. J. Friston

    1995-01-01

    We describe a novel technique for characterizing regional cerebral gray and white matter differences in structural magnetic resonance images by the application of methods derived from functional imaging. The technique involves automatic scalp-editing of images followed by segmentation, smoothing, and spatial normalization to a symmetrical template brain in stereotactic Talairach space. The basic idea is (i) to convert structural magnetic

  9. White matter abnormalities in skin picking disorder: a diffusion tensor imaging study.

    PubMed

    Grant, Jon E; Odlaug, Brian L; Hampshire, Adam; Schreiber, Liana R N; Chamberlain, Samuel R

    2013-04-01

    Skin picking disorder (SPD) is characterized by the repetitive and compulsive picking of skin, resulting in tissue damage. Neurocognitive findings in SPD implicate difficulty with response inhibition (suppression of pre-potent motor responses). This function is dependent on the integrity of the right frontal gyrus and the anterior cingulate cortices, and white-matter tracts connecting such neural nodes. It was hypothesized that SPD would be associated with reduced fractional anisotropy in regions implicated in top-down response suppression, particularly white-matter tracts in proximity of the bilateral anterior cingulate and right frontal (especially orbitofrontal and inferior frontal) cortices. 13-subjects meeting proposed SPD criteria for DSM-5 free from other current psychiatric comorbidities, and 12 healthy comparison subjects underwent MRI with a 3-T system. Between-group comparisons of imaging data underwent voxelwise analysis with permutation modeling and cluster correction. Fractional anisotropy (measured using diffusion tensor imaging) was the primary outcome measure. Subjects with SPD exhibited significantly reduced fractional anisotropy in tracts distributed bilaterally, which included the anterior cingulate cortices. Fractional anisotropy did not correlate significantly with SPD disease severity, or depressive or anxiety scores. These findings implicate disorganization of white-matter tracts involved in motor generation and suppression in the pathophysiology of SPD, findings remarkably similar to those previously reported in trichotillomania. This study adds considerable support to the notion that-in addition to the phenomenological and comorbid overlap between SPD and trichotillomania-these disorders likely share overlapping neurobiology. PMID:23303052

  10. Hypertension-Related Alterations in White Matter Microstructure Detectable in Middle Age.

    PubMed

    McEvoy, Linda K; Fennema-Notestine, Christine; Eyler, Lisa T; Franz, Carol E; Hagler, Donald J; Lyons, Michael J; Panizzon, Matthew S; Rinker, Daniel A; Dale, Anders M; Kremen, William S

    2015-08-01

    Most studies examining associations between hypertension and brain white matter microstructure have focused on older adults or on cohorts with a large age range. Because hypertension effects on the brain may vary with age, it is important to focus on middle age, when hypertension becomes more prevalent. We used linear mixed-effect models to examine differences in white matter diffusion metrics as a function of hypertension in a well-characterized cohort of middle-aged men (n=316; mean, 61.8 years; range, 56.7-65.6). Diffusion metrics were examined in 9 tracts reported to be sensitive to hypertension in older adults. Relative to normotensive individuals, individuals with long-standing hypertension (>5.6 years) showed reduced fractional anisotropy or increased diffusivity in most tracts. Effects were stronger among carriers than among noncarriers of the apolipoprotein E ?4 allele for 2 tracts connecting frontal regions with other brain areas. Significant differences were observed even after adjustment for potentially related lifestyle and cardiovascular risk factors. Shorter duration of hypertension or better blood pressure control among hypertensive individuals did not lessen the adverse effects. These findings suggest that microstructural white matter alterations appear early in the course of hypertension and may persist despite adequate treatment. Although longitudinal studies are needed to confirm these findings, the results suggest that prevention-rather than management-of hypertension may be vital to preserving brain health in aging. PMID:26056337

  11. White matter plasticity in the corticospinal tract of musicians: a diffusion tensor imaging study.

    PubMed

    Imfeld, Adrian; Oechslin, Mathias S; Meyer, Martin; Loenneker, Thomas; Jancke, Lutz

    2009-07-01

    With the advent of diffusion tensor imaging (DTI), the study of plastic changes in white matter architecture due to long-term practice has attracted increasing interest. Professional musicians provide an ideal model for investigating white matter plasticity because of their early onset of extensive auditory and sensorimotor training. We performed fiber tractography and subsequent voxelwise analysis, region of interest (ROI) analysis, and detailed slicewise analysis of diffusion parameters in the corticospinal tract (CST) on 26 professional musicians and a control group of 13 participants. All analyses resulted in significantly lower fractional anisotropy (FA) values in both the left and the right CST in the musician group. Furthermore, a right-greater-than-left asymmetry of FA was observed regardless of group. In the musician group, diffusivity was negatively correlated with the onset of musical training in childhood. A subsequent median split into an early and a late onset musician group (median=7 years) revealed increased diffusivity in the CST of the early onset group as compared to both the late onset group and the controls. In conclusion, these DTI-based findings might indicate plastic changes in white matter architecture of the CST in professional musicians. Our results imply that training-induced changes in diffusion characteristics of the axonal membrane may lead to increased radial diffusivity as reflected in decreased FA values. PMID:19264144

  12. Recent findings on the role of white matter pathology in bipolar disorder.

    PubMed

    Benedetti, Francesco; Bollettini, Irene

    2014-01-01

    Patients with bipolar disorder (BD) experience difficulties in information processing and in the cognitive control of emotions. Mood-congruent biases, which parallel illness episodes, find a neural correlate in abnormal reactivity to stimuli in specific brain regions, and in disrupted functional connectivity among brain areas pertaining to corticolimbic circuitries. It is suggested that a reduced integrity of white matter tracts could underpin dysfunctions in networks implicated in the generation and control of affect. Recent studies using diffusion tensor imaging techniques found that (1) independent of drug treatment, patients with BD show widespread signs of disrupted white matter microstructure, suggesting significant demyelination/dysmyelination without axonal loss, and (2) effective long-term treatment with lithium is associated with increased axial connectivity, proportional to the duration of treatment. These findings suggest that changes of white matter microstructure in specific brain networks could parallel disrupted neural connectivity during illness episodes in BD and that these changes might play a major role in the mechanistic explanation of the biological underpinnings of BD psychopathology. PMID:25377606

  13. Diffusion properties of major white matter tracts in young, typically developing children

    PubMed Central

    Johnson, Ryan T.; Yeatman, Jason D.; Wandell, Brian A.; Buonocore, Michael H.; Amaral, David G.; Nordahl, Christine W.

    2013-01-01

    Brain development occurs rapidly during the first few years of life involving region-specific changes in both gray and white matter. Due to the inherent difficulties in acquiring magnetic resonance imaging data in young children, little is known about the properties of white matter in typically developing toddlers. In the context of an ongoing study of young children with autism spectrum disorder, we collected diffusion-weighted imaging data during natural nocturnal sleep in a sample of young (mean age = 35 months) typically developing male and female (n = 41 and 25, respectively) children. Axial diffusivity, radial diffusivity, mean diffusivity and fractional anisotropy were measured at 99 points along the length of 18 major brain tracts. Influences of hemisphere, age, sex, and handedness were examined. We find that diffusion properties vary significantly along the length of the majority of tracks. We also identify hemispheric and sex differences in diffusion properties in several tracts. Finally, we find the relationship between age and diffusion parameters changes along the tract length illustrating variability in age-related white-matter development at the tract level. PMID:24269274

  14. The accretion and spreading of matter on white dwarfs

    E-print Network

    Fisker, J L; Bürger, T; Fisker, Jacob Lund; Balsara, Dinshaw S.; Burger, Tom

    2005-01-01

    For a slowly rotating non-magnetized white dwarf the accretion disk extends all the way to the star. Here the matter impacts and spreads towards the poles as new matter continuously piles up behind it. We have solved the 3d compressible Navier-Stokes equations on an axisymmetric grid to determine the structure of this boundary layer for different viscosities corresponding to different accretion rates. The high viscosity cases show a spreading BL which sets off a gravity wave in the surface matter. The accretion flow moves supersonically over the cusp making it susceptible to the rapid development of gravity wave and/or Kelvin-Helmholtz instabilities. This BL is optically thick and extends more than 30 degrees to either side of the disk plane after 3/4 of a Keplerian rotation period (t=19s). The low viscosity cases also show a spreading BL, but here the accretion flow does not set off gravity waves and it is optically thin.

  15. Diffusion Tensor Imaging of White Matter Networks in Individuals with Current and Remitted Alcohol Use Disorders and Comorbid Conditions

    PubMed Central

    Monnig, Mollie A.; Caprihan, Arvind; Yeo, Ronald A.; Gasparovic, Charles; Ruhl, David A.; Lysne, Per; Bogenschutz, Michael P.; Hutchison, Kent E.; Thoma, Robert J.

    2012-01-01

    Individuals with alcohol use disorders show white matter abnormality relative to normal samples, yet differences in white matter profiles have not yet been investigated as a function of abstinence. Individuals with current alcohol use disorders (AUD-C; n = 10), individuals with alcohol use disorders in remission for at least one year (AUD-R; n = 9), and healthy control participants (HC; n = 15) matched to alcohol groups on age and smoking status underwent magnetic resonance imaging (MRI). Diffusion tensor imaging (DTI) data were analyzed using tract-based spatial statistics (TBSS). Compared to HC, AUD-C showed reduced axial diffusivity in bilateral frontal and temporal white matter. In AUD-R, lower fractional anisotropy relative to HC was widespread in bilateral parietal regions. A combined AUD-C and AUD-R group had decreased fractional anisotropy primarily in the fornix and thalamus. In conclusion, AUD-R manifested damage in parietal regions integral to processing of visuospatial information and self-awareness, whereas AUD-C showed abnormal diffusivity in fronto-temporal regions that regulate impulsivity, attention, and memory. As a combined group, AUD individuals exhibited abnormality in subcortical areas associated with sensory processing and memory. White matter differences in individuals with AUD may be attributable to premorbid vulnerability or persisting effects of alcohol abuse, but the pattern of abnormality across groups suggests that these abnormalities may be secondary to alcohol use. PMID:22352699

  16. Superficial white matter fiber systems impede detection of long-range cortical connections in diffusion MR tractography.

    PubMed

    Reveley, Colin; Seth, Anil K; Pierpaoli, Carlo; Silva, Afonso C; Yu, David; Saunders, Richard C; Leopold, David A; Ye, Frank Q

    2015-05-26

    In vivo tractography based on diffusion magnetic resonance imaging (dMRI) has opened new doors to study structure-function relationships in the human brain. Initially developed to map the trajectory of major white matter tracts, dMRI is used increasingly to infer long-range anatomical connections of the cortex. Because axonal projections originate and terminate in the gray matter but travel mainly through the deep white matter, the success of tractography hinges on the capacity to follow fibers across this transition. Here we demonstrate that the complex arrangement of white matter fibers residing just under the cortical sheet poses severe challenges for long-range tractography over roughly half of the brain. We investigate this issue by comparing dMRI from very-high-resolution ex vivo macaque brain specimens with histological analysis of the same tissue. Using probabilistic tracking from pure gray and white matter seeds, we found that ?50% of the cortical surface was effectively inaccessible for long-range diffusion tracking because of dense white matter zones just beneath the infragranular layers of the cortex. Analysis of the corresponding myelin-stained sections revealed that these zones colocalized with dense and uniform sheets of axons running mostly parallel to the cortical surface, most often in sulcal regions but also in many gyral crowns. Tracer injection into the sulcal cortex demonstrated that at least some axonal fibers pass directly through these fiber systems. Current and future high-resolution dMRI studies of the human brain will need to develop methods to overcome the challenges posed by superficial white matter systems to determine long-range anatomical connections accurately. PMID:25964365

  17. Superficial white matter fiber systems impede detection of long-range cortical connections in diffusion MR tractography

    PubMed Central

    Reveley, Colin; Seth, Anil K.; Pierpaoli, Carlo; Silva, Afonso C.; Yu, David; Saunders, Richard C.; Leopold, David A.; Ye, Frank Q.

    2015-01-01

    In vivo tractography based on diffusion magnetic resonance imaging (dMRI) has opened new doors to study structure–function relationships in the human brain. Initially developed to map the trajectory of major white matter tracts, dMRI is used increasingly to infer long-range anatomical connections of the cortex. Because axonal projections originate and terminate in the gray matter but travel mainly through the deep white matter, the success of tractography hinges on the capacity to follow fibers across this transition. Here we demonstrate that the complex arrangement of white matter fibers residing just under the cortical sheet poses severe challenges for long-range tractography over roughly half of the brain. We investigate this issue by comparing dMRI from very-high-resolution ex vivo macaque brain specimens with histological analysis of the same tissue. Using probabilistic tracking from pure gray and white matter seeds, we found that ?50% of the cortical surface was effectively inaccessible for long-range diffusion tracking because of dense white matter zones just beneath the infragranular layers of the cortex. Analysis of the corresponding myelin-stained sections revealed that these zones colocalized with dense and uniform sheets of axons running mostly parallel to the cortical surface, most often in sulcal regions but also in many gyral crowns. Tracer injection into the sulcal cortex demonstrated that at least some axonal fibers pass directly through these fiber systems. Current and future high-resolution dMRI studies of the human brain will need to develop methods to overcome the challenges posed by superficial white matter systems to determine long-range anatomical connections accurately. PMID:25964365

  18. Tractography reveals diffuse white matter abnormalities in Myotonic Dystrophy Type 1

    PubMed Central

    Wozniak, Jeffrey R.; Mueller, Bryon A.; Lim, Kelvin O.; Hemmy, Laura S.; Day, John W.

    2014-01-01

    Cerebral involvement in Myotonic Dystrophy Type 1 (DM1) is well-established but not well characterized. This study applied new Diffusion Tensor Imaging (DTI) tractography to characterize white matter disturbance in adults with DM1. Forty-five participants with DM1 and 44 control participants had MRIs on a Siemens 3T TIM Trio scanner. Data were processed with TRActs Constrained by UnderLying Anatomy (TRACULA) and 7 tracts were evaluated. Bilateral disturbances in white matter integrity were seen in all tracts in participants with DM1 compared to controls. There were no right-left hemisphere differences. The resulting DTI metrics were correlated with cognitive functioning, particularly working memory and processing speed. Motor speed was not significantly correlated with white matter microstructural integrity and, thus, was not the core explanation for the working memory and processing speed findings. White matter integrity was correlated with important clinical variables including the muscular impairment rating scale (MIRS). CTG repeat length was moderately associated with white matter status in corticospinal tract and cingulum. Sleepiness (Epworth Sleepiness Scale) was moderately associated with white matter status in the superior longitudinal fasciculus and cingulum. Overall, the results add to an emerging literature showing widespread white matter disturbances in both early-onset and adult-onset DM1. Results suggest that further investigation of white matter pathology is warranted in DM1 and that non-invasive measures such as DTI have potentially important clinical value in characterizing the status of individuals with DM1. PMID:24768314

  19. Tractography reveals diffuse white matter abnormalities in Myotonic Dystrophy Type 1.

    PubMed

    Wozniak, Jeffrey R; Mueller, Bryon A; Lim, Kelvin O; Hemmy, Laura S; Day, John W

    2014-06-15

    Cerebral involvement in Myotonic Dystrophy Type 1 (DM1) is well-established but not well characterized. This study applied new Diffusion Tensor Imaging (DTI) tractography to characterize white matter disturbance in adults with DM1. Forty-five participants with DM1 and 44 control participants had MRIs on a Siemens 3T TIM Trio scanner. Data were processed with TRActs Constrained by UnderLying Anatomy (TRACULA) and 7 tracts were evaluated. Bilateral disturbances in white matter integrity were seen in all tracts in participants with DM1 compared to controls. There were no right-left hemisphere differences. The resulting DTI metrics were correlated with cognitive functioning, particularly working memory and processing speed. Motor speed was not significantly correlated with white matter microstructural integrity and, thus, was not the core explanation for the working memory and processing speed findings. White matter integrity was correlated with important clinical variables including the muscular impairment rating scale (MIRS). CTG repeat length was moderately associated with white matter status in corticospinal tract and cingulum. Sleepiness (Epworth Sleepiness Scale) was moderately associated with white matter status in the superior longitudinal fasciculus and cingulum. Overall, the results add to an emerging literature showing widespread white matter disturbances in both early-onset and adult-onset DM1. Results suggest that further investigation of white matter pathology is warranted in DM1 and that non-invasive measures such as DTI have a potentially important clinical value in characterizing the status of individuals with DM1. PMID:24768314

  20. 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…

  1. White Matter Lesions and Brain Atrophy: More than Shared Risk Factors? A Systematic Review

    Microsoft Academic Search

    Auke P. A. Appelman; Lieza G. Exalto; Yolanda van der Graaf; Geert Jan Biessels; Willem P. T. M. Mali; Mirjam I. Geerlings

    2009-01-01

    Background: White matter lesions (WML) and brain atrophy are often found on MRI in the elderly. Shared vascular risk factors may be an explanation for their concomitance. However, disturbances of white matter integrity could also be involved in the pathogenesis of brain atrophy. Our objective was to systematically review studies that investigated the relation between WML and brain atrophy on

  2. Asynchrony of the Early Maturation of White Matter Bundles in Healthy Infants: Quantitative

    E-print Network

    Dehaene-Lambertz, Ghislaine

    Asynchrony of the Early Maturation of White Matter Bundles in Healthy Infants: Quantitative with the structural maturation of underlying functional networks. Postmortem stud- ies and, more recently, structural of white matter myelination. However, in vivo quantification of the maturation phases of fiber bundles

  3. Transient Lectin Binding by White Matter Tract Border Zone Microglia in the Foetal Rabbit Brain

    Microsoft Academic Search

    W. Thomas Bass; Gerard A. Singer; Francis J. Liuzzi

    1998-01-01

    Axonal growth cones of developing white matter tracts are guided through the cerebrum by interactions with cell surface and extracellular matrix molecules expressed by glial cells that mediate cell adhesion and contact-dependent inhibition. Specific carbohydrates are considered essential for the proper functioning of these molecular complexes. We studied developmental aspects of complex carbohydrate expression by white matter glia in the

  4. Leukoencephalopathy with vanishing white matter: report of four cases from three unrelated Brazilian families

    Microsoft Academic Search

    Sergio Rosemberg; Claudia da Costa Leite; Fernando Norio Arita; Suzana Ely Kliemann; Maria Teresa Carvalho Lacerda

    2002-01-01

    Four patients with leukoencephalopathy with vanishing white matter from three unrelated Brazilian families are reported. In all cases the initial symptoms occurred in the three first years of life. In three cases the onset was acute and at least in two patients the involvement of the white matter preceded the clinical symptoms. Only cerebellar and pyramidal signs were present and

  5. A developmental study of the structural integrity of white matter in autism

    E-print Network

    A developmental study of the structural integrity of white matter in autism Timothy A. Keller in Autism (CPEA) Grant HD35469 from the National Institute of Child Health and Human Development. Received in the organization of white matter in a large sample of male participants with autism and controls between the ages

  6. CAFFEINE, COGNITIVE FUNCTIONING AND WHITE MATTER LESIONS IN THE ELDERLY: ESTABLISHING CAUSALITY FROM EPIDEMIOLOGICAL EVIDENCE

    E-print Network

    Paris-Sud XI, Université de

    Ritchie 1 CAFFEINE, COGNITIVE FUNCTIONING AND WHITE MATTER LESIONS IN THE ELDERLY: ESTABLISHING of interest. Running title : caffeine and white matter lesions inserm-00457699,version1-19Feb2010 Author for a causal relationship between caffeine consumption and cognitive deterioration in the elderly. Methods

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  8. Experimentally induced intrauterine infection causes fetal brain white matter lesions in rabbits

    Microsoft Academic Search

    Bo Hyun Yoon; Chong Jai Kim; Roberto Romero; Jong Kwan Jun; Kyo Hoon Park; Seok Tae Choi; Je G. Chi

    1997-01-01

    OBJECTIVE: Periventricular leukomalacia, a common brain white matter lesion in preterm neonates, is a major risk factor for cerebral palsy. Epidemiologic studies have demonstrated an association between infection and periventricular leukomalacia. The purpose of this study was to determine whether ascending intrauterine infection could cause brain white matter lesions in the fetal rabbit.STUDY DESIGN: Rabbits with timed pregnancies underwent hysteroscopy

  9. Brain virtual dissection and white matter 3D visualization.

    PubMed

    Serres, Barthélemy; Zemmoura, Ilyess; Andersson, Frédéric; Tauber, Clovis; Destrieux, Christophe; Venturini, Gilles

    2013-01-01

    This paper presents an immersive visualization tool that helps anatomists to establish a ground truth for brain white matter fiber bundles. Each step of a progressive anatomical dissection of human brain hemisphere is acquired using a high resolution 3D laser scanner and a photographic device. Each resulting surface is textured with a high resolution image and registered into a common 3D space using fiducial landmarks. Surfaces can be visualized using stereoscopic hardware and are interactively selectable. The tool allows the user to identify specific fiber bundle parts. Extracted fiber bundles are stacked together and rendered in stereoscopy with the corresponding MR volume. Surgeons have validated this tool for creating ground truth in medical imaging with the perspective of validating tractography algorithms. PMID:23400190

  10. Declines in inflammation predict greater white matter microstructure in older adults.

    PubMed

    Bettcher, Brianne Magouirk; Yaffe, Kristine; Boudreau, Robert M; Neuhaus, John; Aizenstein, Howard; Ding, Jingzhong; Kritchevsky, Stephen B; Launer, Lenore J; Liu, Yongmei; Satterfield, Suzanne; Rosano, Caterina

    2015-02-01

    Protracted systemic inflammation has been associated with adverse effects on cognition and brain structure and may accelerate neurodegenerative disease processes; however, it is less clear whether changes in inflammation are associated with brain structure. We studied 276 black and white older adults (mean age = 83 years at time of imaging) enrolled in a prospective study of aging. Inflammation (measured with c-reactive protein, CRP) was assessed repeatedly over 6 years (i.e., year 2, 4, 6, and 8). Brain magnetic resonance imaging (MRIs) were obtained at years 10-11 with diffusion tensor imaging; regions of interest included late-myelinating areas vulnerable to aging, including frontal-parietal (superior longitudinal fasciculus [SLF]-dorsal) and temporal (SLF-temporal; uncinate) white matter tracts. Mean CRP values significantly declined (t = -5.54, p < 0.0001) over 6 years, and subject-specific slopes (best linear unbiased predictors of slopes) all showed a decline (mean = -0.57, standard deviation = 0.53) for our participant sample. More than 50% of study participants were still in the moderate to high cardiovascular risk range based on CRP values at year 8. After controlling for demographics, vascular risk factors and MRI white matter hyperintensities, larger decreases in CRP values over time were significantly associated with higher fractional anisotropy in the SLF-dorsal (beta = -0.0052, standard error [SE] = 0.003; 95% confidence interval [CI] = -0.0103 to -0.0025, p = 0.04), SLF-temporal (beta = -0.0109, SE = 0.004; 95% CI = -0.0189 to -0.0029, p = 0.008), and uncinate (beta = -0.0067, SE = 0.003; 95% CI = -0.0132 to -0.0001, p = 0.05) fasciculi. Results suggest that in a prospective cohort of older individuals, faster declines in inflammation over time are related to indicators of white matter health, even after accounting for vascular risk factors. PMID:25554492

  11. Microstructural Correlations of White Matter Tracts in the Human Brain

    PubMed Central

    Wahl, Michael; Li, Yi-Ou; Ng, Joshua; LaHue, Sara C.; Cooper, Shelly R.; Sherr, Elliott H.; Mukherjee, Pratik

    2010-01-01

    The purpose of this study is to investigate whether specific patterns of correlation exist in diffusion tensor imaging (DTI) parameters across white matter tracts in the normal human brain, and whether the relative strengths of these putative microstructural correlations might reflect phylogenetic and functional similarities between tracts. We performed quantitative DTI fiber tracking on 44 healthy adult volunteers to obtain tract-based measures of mean diffusivity (MD), fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) from four homologous pairs of neocortical association pathways (arcuate fasciculi, inferior fronto-occipital fasciculi, inferior longitudinal fasciculi, and uncinate fasciculi bilaterally), a homologous pair of limbic association pathways (left and right dorsal cingulum bundles), and a homologous pair of cortical-subcortical projection pathways (left and right corticospinal tracts). From the resulting inter-tract correlation matrices, we show that there are statistically significant correlations of DTI parameters between tracts, and that there are statistically significant variations among these inter-tract correlations. Furthermore, we observe that many, but by no means all, of the strongest correlations were between homologous tracts in the left and right hemispheres. Even among homologous pairs of tracts, there were wide variations in the degree of coupling. Finally, we generate a data-driven hierarchical clustering of the fiber pathways based on pairwise FA correlations to demonstrate that the neocortical association pathways tended to group separately from the limbic pathways at trend-level statistical significance, and that the projection pathways of the left and right corticospinal tracts comprise the most distant outgroup with high confidence (p<0.01). Hence, specific patterns of microstructural correlation exist between tracts and may reflect phylogenetic and functional similarities between tracts. The study of these microstructural relationships between white matter pathways might aid research on the genetic basis and on the behavioral effects of axonal connectivity, as well as provide a revealing new perspective with which to investigate neurological and psychiatric disorders. PMID:20206699

  12. Detection of white matter lesions in cerebral small vessel disease

    NASA Astrophysics Data System (ADS)

    Riad, Medhat M.; Platel, Bram; de Leeuw, Frank-Erik; Karssemeijer, Nico

    2013-02-01

    White matter lesions (WML) are diffuse white matter abnormalities commonly found in older subjects and are important indicators of stroke, multiple sclerosis, dementia and other disorders. We present an automated WML detection method and evaluate it on a dataset of small vessel disease (SVD) patients. In early SVD, small WMLs are expected to be of importance for the prediction of disease progression. Commonly used WML segmentation methods tend to ignore small WMLs and are mostly validated on the basis of total lesion load or a Dice coefficient for all detected WMLs. Therefore, in this paper, we present a method that is designed to detect individual lesions, large or small, and we validate the detection performance of our system with FROC (free-response ROC) analysis. For the automated detection, we use supervised classification making use of multimodal voxel based features from different magnetic resonance imaging (MRI) sequences, including intensities, tissue probabilities, voxel locations and distances, neighborhood textures and others. After preprocessing, including co-registration, brain extraction, bias correction, intensity normalization, and nonlinear registration, ventricle segmentation is performed and features are calculated for each brain voxel. A gentle-boost classifier is trained using these features from 50 manually annotated subjects to give each voxel a probability of being a lesion voxel. We perform ROC analysis to illustrate the benefits of using additional features to the commonly used voxel intensities; significantly increasing the area under the curve (Az) from 0.81 to 0.96 (p<0.05). We perform the FROC analysis by testing our classifier on 50 previously unseen subjects and compare the results with manual annotations performed by two experts. Using the first annotator results as our reference, the second annotator performs at a sensitivity of 0.90 with an average of 41 false positives per subject while our automated method reached the same level of sensitivity at approximately 180 false positives per subject.

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

    PubMed Central

    Mao, Hui

    2015-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. PMID:26147736

  14. Altered Topological Organization of White Matter Structural Networks in Patients with Neuromyelitis Optica

    PubMed Central

    Liu, Yaou; Duan, Yunyun; He, Yong; Wang, Jun; Xia, Mingrui; Yu, Chunshui; Dong, Huiqing; Ye, Jing; Butzkueven, Helmut; Li, Kuncheng; Shu, Ni

    2012-01-01

    Objective To investigate the topological alterations of the whole-brain white-matter (WM) structural networks in patients with neuromyelitis optica (NMO). Methods The present study involved 26 NMO patients and 26 age- and sex-matched healthy controls. WM structural connectivity in each participant was imaged with diffusion-weighted MRI and represented in terms of a connectivity matrix using deterministic tractography method. Graph theory-based analyses were then performed for the characterization of brain network properties. A multiple linear regression analysis was performed on each network metric between the NMO and control groups. Results The NMO patients exhibited abnormal small-world network properties, as indicated by increased normalized characteristic path length, increased normalized clustering and increased small-worldness. Furthermore, largely similar hub distributions of the WM structural networks were observed between NMO patients and healthy controls. However, regional efficiency in several brain areas of NMO patients was significantly reduced, which were mainly distributed in the default-mode, sensorimotor and visual systems. Furthermore, we have observed increased regional efficiency in a few brain regions such as the orbital parts of the superior and middle frontal and fusiform gyri. Conclusion Although the NMO patients in this study had no discernible white matter T2 lesions in the brain, we hypothesize that the disrupted topological organization of WM networks provides additional evidence for subtle, widespread cerebral WM pathology in NMO. PMID:23144994

  15. Reduced white matter connectivity in the corpus callosum of children with Tourette syndrome

    PubMed Central

    Plessen, Kerstin J.; Grüner, Renate; Lundervold, Arvid; Hirsch, Jochen G.; Xu, Dongrong; Bansal, Ravi; Hammar, Ĺsa; Lundervold, Astri J.; Wentzel-Larsen, Tore; Lie, Stein Atle; Gass, Achim; Peterson, Bradley S.; Hugdahl, Kenneth

    2008-01-01

    Background Brain imaging studies have revealed anatomical anomalies in the brains of individuals with Tourette syndrome (TS). Prefrontal regions have been found to be larger and the corpus callosum (CC) area smaller in children and young adults with TS compared with healthy control subjects, and these anatomical features have been understood to reflect neural plasticity that helps to attenuate the severity of tics. Method CC white matter connectivity, as measured by the Fractional Anisotropy (FA) index from diffusion tensor images, was assessed in 20 clinically well-defined boys with Tourette syndrome and 20 age- and gender-matched controls. Results The hypothesis that children with TS would show reduced measures of connectivity in CC fibers was confirmed for all subregions of the CC. There was no significant interaction of TS and region. Reductions in FA in CC regions may reflect either fewer interhemispheric fibers or reduced axonal myelination. FA values did not correlate significantly with the severity of tic symptoms. Group differences in measures of connectivity did not seem to be attributable to the presence of comorbid ADHD or OCD, to medication exposure, or group differences in IQ. Conclusion Our findings of a reduced interhemispheral white matter connectivity add to the understanding of neural connectivity and plasticity in the brains of children who have TS. PMID:17073980

  16. Multi-label segmentation of white matter structures: application to neonatal brains.

    PubMed

    Ratnarajah, Nagulan; Qiu, Anqi

    2014-11-15

    Accurate and consistent segmentation of brain white matter bundles at neonatal stage plays an important role in understanding brain development and detecting white matter abnormalities for the prediction of psychiatric disorders. Due to the complexity of white matter anatomy and the spatial resolution of diffusion-weighted MR imaging, multiple fiber bundles can pass through one voxel. The goal of this study is to assign one or multiple anatomical labels of white matter bundles to each voxel to reflect complex white matter anatomy of the neonatal brain. For this, we develop a supervised multi-label k-nearest neighbor (ML-kNN) classification algorithm in Riemannian diffusion tensor spaces. Our ML-kNN considers diffusion tensors lying on the Log-Euclidean Riemannian manifold of symmetric positive definite (SPD) matrices and their corresponding vector space as feature space. The ML-kNN utilizes the maximum a posteriori (MAP) principle to make the prediction of white matter labels by reasoning with the labeling information derived from the neighbors without assuming any probabilistic distribution of the features. We show that our approach automatically learns the number of white matter bundles at a location and provides anatomical annotation of the neonatal white matter. In addition, our approach also provides the binary mask for individual white matter bundles to facilitate tract-based statistical analysis in clinical studies. We apply this method to automatically segment 13 white matter bundles of the neonatal brain and examine the segmentation accuracy against semi-manual labels derived from tractography. PMID:25111473

  17. 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

  18. GRIN2B Gene and Associated Brain Cortical White Matter Changes in Bipolar Disorder: A Preliminary Combined Platform Investigation

    PubMed Central

    Thng, Christopher Ren Zhi; Zhang, Yi Bin; Nowinski, Wieslaw Lucjan; Low, Chian Ming

    2013-01-01

    Abnormalities in glutamate signaling and glutamate toxicity are thought to be important in the pathophysiology of bipolar disorder (BD). Whilst previous studies have found brain white matter changes in BD, there is paucity of data about how glutamatergic genes affect brain white matter integrity in BD. Based on extant neuroimaging data, we hypothesized that GRIN2B risk allele is associated with reductions of brain white matter integrity in the frontal, parietal, temporal, and occipital regions and cingulate gyrus in BD. Fourteen patients with BD and 22 healthy controls matched in terms of age, gender and handedness were genotyped using blood samples and underwent diffusion tensor imaging. Compared to G allele, brain FA values were significantly lower in BD patients with risk T allele in left frontal region (P = 0.001), right frontal region (P = 0.002), left parietal region (P = 0.001), left occipital region (P = 0.001), right occipital region (P < 0.001), and left cingulate gyrus (P = 0.001). Further elucidation of the interactions between different glutamate genes and their relationships with such structural, functional brain substrates will enhance our understanding of the link between dysregulated glutamatergic neurotransmission and neuroimaging endophenotypes in BD. PMID:24490167

  19. Variation in Blood Pressure is Associated with White Matter Microstructure but not Cognition in African Americans

    PubMed Central

    Leritz, Elizabeth C.; Salat, David H.; Milberg, William P.; Williams, Victoria J.; Chapman, Caroline E.; Grande, Laura J.; Rudolph, James L.; Schnyer, David M.; Barber, Colleen E.; Lipsitz, Lewis; Fischl, Bruce; McGlinchey, Regina E.

    2010-01-01

    Although hypertension is a major risk factor for cerebrovascular disease (CVD) and is highly prevalent in African Americans, little is known about how blood pressure (BP) affects brain behavior relationships in this population. In predominantly Caucasian populations, high BP is associated with alterations in frontal-subcortical white matter and in executive functioning aspects of cognition. We investigated associations among BP, brain structure, and neuropsychological functioning in 52 middle-older aged African Americans without diagnosed history of CVD. All participants underwent diffusion tensor imaging (DTI) for examination of white matter integrity, indexed by fractional anisotropy (FA). Three regions of interest (ROI's) were derived in the anterior corpus callosum (genu), posterior corpus callosum (splenium), and across the whole brain. A brief neuropsychological battery was administered from which composite scores of executive function and memory were derived. Blood pressure was characterized by mean arterial blood pressure (MABP), an indicator of end-organ perfusion pressure. When controlling for age, higher MABP was associated with lower FA in the genu, and there was a trend for this sample relationship with regard to whole brain FA. When the sample was broken into groups based on treatment for BP regulation (medicated / nonmedicated), MABP was related to genu and whole-brain FA only in the non-medicated group. There were no associations in those individuals who reported taking medication to control blood pressure. Neither MABP nor FA was significantly related to either neuropsychological composite score regardless of medication use. These data provide important evidence that variation in BP may contribute to significant alterations in specific neural regions of white matter in non-medicated individuals without symptoms of overt CVD. PMID:20230114

  20. White matter damage in frontotemporal lobar degeneration spectrum.

    PubMed

    Agosta, F; Scola, E; Canu, E; Marcone, A; Magnani, G; Sarro, L; Copetti, M; Caso, F; Cerami, C; Comi, G; Cappa, S F; Falini, A; Filippi, M

    2012-12-01

    White matter (WM) tract damage was assessed in patients with the behavioral variant frontotemporal dementia (bvFTD) and the 3 primary progressive aphasia (PPA) variants and compared with the corresponding brain atrophy patterns. Thirteen bvFTD and 20 PPA patients were studied. Tract-based spatial statistics and voxel-based morphometry were used. Patients with bvFTD showed widespread diffusion tensor magnetic resonance imaging (DT MRI) abnormalities affecting most of the WM bilaterally. In PPA patients, WM damage was more focal and varied across the 3 syndromes: left frontotemporoparietal in nonfluent, left frontotemporal in semantic, and left frontoparietal in logopenic patients. In each syndrome, DT MRI changes extended beyond the topography of gray matter loss. Left uncinate damage was the best predictor of frontotemporal lobar degeneration diagnosis versus controls. DT MRI measures of the anterior corpus callosum and left superior longitudinal fasciculus differentiated bvFTD from nonfluent cases. The best predictors of semantic PPA compared with both bvFTD and nonfluent cases were diffusivity abnormalities of the left uncinate and inferior longitudinal fasciculus. This study provides insights into the similarities and differences of WM damage in bvFTD and PPA variants. DT MRI metrics hold promise to serve as early markers of WM integrity loss that only at a later stage may be detectable by volumetric measures. PMID:21988828

  1. Pathological changes in the white matter after spinal contusion injury in the rat.

    PubMed

    Ek, C Joakim; Habgood, Mark D; Dennis, Ross; Dziegielewska, Katarzyna M; Mallard, Carina; Wheaton, Benjamin; Saunders, Norman R

    2012-01-01

    It has been shown previously that after spinal cord injury, the loss of grey matter is relatively faster than loss of white matter suggesting interventions to save white matter tracts offer better therapeutic possibilities. Loss of white matter in and around the injury site is believed to be the main underlying cause for the subsequent loss of neurological functions. In this study we used a series of techniques, including estimations of the number of axons with pathology, immunohistochemistry and mapping of distribution of pathological axons, to better understand the temporal and spatial pathological events in white matter following contusion injury to the rat spinal cord. There was an initial rapid loss of axons with no detectable further loss beyond 1 week after injury. Immunoreactivity for CNPase indicated that changes to oligodendrocytes are rapid, extending to several millimetres away from injury site and preceding much of the axonal loss, giving early prediction of the final volume of white matter that survived. It seems that in juvenile rats the myelination of axons in white matter tracts continues for some time, which has an important bearing on interpretation of our, and previous, studies. The amount of myelin debris and axon pathology progressively decreased with time but could still be observed at 10 weeks after injury, especially at more distant rostral and caudal levels from the injury site. This study provides new methods to assess injuries to spinal cord and indicates that early interventions are needed for the successful sparing of white matter tracts following injury. PMID:22952690

  2. Pathological Changes in the White Matter after Spinal Contusion Injury in the Rat

    PubMed Central

    Ek, C. Joakim; Habgood, Mark D.; Dennis, Ross; Dziegielewska, Katarzyna M.; Mallard, Carina; Wheaton, Benjamin; Saunders, Norman R.

    2012-01-01

    It has been shown previously that after spinal cord injury, the loss of grey matter is relatively faster than loss of white matter suggesting interventions to save white matter tracts offer better therapeutic possibilities. Loss of white matter in and around the injury site is believed to be the main underlying cause for the subsequent loss of neurological functions. In this study we used a series of techniques, including estimations of the number of axons with pathology, immunohistochemistry and mapping of distribution of pathological axons, to better understand the temporal and spatial pathological events in white matter following contusion injury to the rat spinal cord. There was an initial rapid loss of axons with no detectable further loss beyond 1 week after injury. Immunoreactivity for CNPase indicated that changes to oligodendrocytes are rapid, extending to several millimetres away from injury site and preceding much of the axonal loss, giving early prediction of the final volume of white matter that survived. It seems that in juvenile rats the myelination of axons in white matter tracts continues for some time, which has an important bearing on interpretation of our, and previous, studies. The amount of myelin debris and axon pathology progressively decreased with time but could still be observed at 10 weeks after injury, especially at more distant rostral and caudal levels from the injury site. This study provides new methods to assess injuries to spinal cord and indicates that early interventions are needed for the successful sparing of white matter tracts following injury. PMID:22952690

  3. White Matter Atrophy and Cognitive Dysfunctions in Neuromyelitis Optica

    PubMed Central

    Blanc, Frederic; Noblet, Vincent; Jung, Barbara; Rousseau, François; Renard, Felix; Bourre, Bertrand; Longato, Nadine; Cremel, Nadjette; Di Bitonto, Laure; Kleitz, Catherine; Collongues, Nicolas; Foucher, Jack; Kremer, Stephane; Armspach, Jean-Paul; de Seze, Jerome

    2012-01-01

    Neuromyelitis optica (NMO) is an inflammatory disease of central nervous system characterized by optic neuritis and longitudinally extensive acute transverse myelitis. NMO patients have cognitive dysfunctions but other clinical symptoms of brain origin are rare. In the present study, we aimed to investigate cognitive functions and brain volume in NMO. The study population consisted of 28 patients with NMO and 28 healthy control subjects matched for age, sex and educational level. We applied a French translation of the Brief Repeatable Battery (BRB-N) to the NMO patients. Using SIENAx for global brain volume (Grey Matter, GM; White Matter, WM; and whole brain) and VBM for focal brain volume (GM and WM), NMO patients and controls were compared. Voxel-level correlations between diminished brain concentration and cognitive performance for each tests were performed. Focal and global brain volume of NMO patients with and without cognitive impairment were also compared. Fifteen NMO patients (54%) had cognitive impairment with memory, executive function, attention and speed of information processing deficits. Global and focal brain atrophy of WM but not Grey Matter (GM) was found in the NMO patients group. The focal WM atrophy included the optic chiasm, pons, cerebellum, the corpus callosum and parts of the frontal, temporal and parietal lobes, including superior longitudinal fascicle. Visual memory, verbal memory, speed of information processing, short-term memory and executive functions were correlated to focal WM volumes. The comparison of patients with, to patients without cognitive impairment showed a clear decrease of global and focal WM, including brainstem, corticospinal tracts, corpus callosum but also superior and inferior longitudinal fascicles. Cognitive impairment in NMO patients is correlated to the decreased of global and focal WM volume of the brain. Further studies are needed to better understand the precise origin of cognitive impairment in NMO patients, particularly in the WM. PMID:22509264

  4. Anatomical Abnormalities in Gray and White Matter of the Cortical Surface in Persons with Schizophrenia

    PubMed Central

    Colibazzi, Tiziano; Wexler, Bruce E.; Bansal, Ravi; Hao, Xuejun; Liu, Jun; Sanchez-Peńa, Juan; Corcoran, Cheryl; Lieberman, Jeffrey A.; Peterson, Bradley S.

    2013-01-01

    Background Although schizophrenia has been associated with abnormalities in brain anatomy, imaging studies have not fully determined the nature and relative contributions of gray matter (GM) and white matter (WM) disturbances underlying these findings. We sought to determine the pattern and distribution of these GM and WM abnormalities. Furthermore, we aimed to clarify the contribution of abnormalities in cortical thickness and cortical surface area to the reduced GM volumes reported in schizophrenia. Methods We recruited 76 persons with schizophrenia and 57 healthy controls from the community and obtained measures of cortical and WM surface areas, of local volumes along the brain and WM surfaces, and of cortical thickness. Results We detected reduced local volumes in patients along corresponding locations of the brain and WM surfaces in addition to bilateral greater thickness of perisylvian cortices and thinner cortex in the superior frontal and cingulate gyri. Total cortical and WM surface areas were reduced. Patients with worse performance on the serial-position task, a measure of working memory, had a higher burden of WM abnormalities. Conclusions Reduced local volumes along the surface of the brain mirrored the locations of abnormalities along the surface of the underlying WM, rather than of abnormalities of cortical thickness. Moreover, anatomical features of white matter, but not cortical thickness, correlated with measures of working memory. We propose that reductions in WM and smaller total cortical surface area could be central anatomical abnormalities in schizophrenia, driving, at least partially, the reduced regional GM volumes often observed in this illness. PMID:23418459

  5. Quantifying cerebellum grey matter and white matter perfusion using pulsed arterial spin labeling.

    PubMed

    Li, Xiufeng; Sarkar, Subhendra N; Purdy, David E; Briggs, Richard W

    2014-01-01

    To facilitate quantification of cerebellum cerebral blood flow (CBF), studies were performed to systematically optimize arterial spin labeling (ASL) parameters for measuring cerebellum perfusion, segment cerebellum to obtain separate CBF values for grey matter (GM) and white matter (WM), and compare FAIR ASST to PICORE. Cerebellum GM and WM CBF were measured with optimized ASL parameters using FAIR ASST and PICORE in five subjects. Influence of volume averaging in voxels on cerebellar grey and white matter boundaries was minimized by high-probability threshold masks. Cerebellar CBF values determined by FAIR ASST were 43.8 ± 5.1 mL/100 g/min for GM and 27.6 ± 4.5 mL/100 g/min for WM. Quantitative perfusion studies indicated that CBF in cerebellum GM is 1.6 times greater than that in cerebellum WM. Compared to PICORE, FAIR ASST produced similar CBF estimations but less subtraction error and lower temporal, spatial, and intersubject variability. These are important advantages for detecting group and/or condition differences in CBF values. PMID:24949416

  6. Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-1?, and tumor necrosis factor-?), neonatal brain white matter lesions, and cerebral palsy

    Microsoft Academic Search

    Bo Hyun Yoon; Jong Kwan Jun; Roberto Romero; Kyo Hoon Park; Ricardo Gomez; Jung-Hwan Choi

    1997-01-01

    OBJECTIVE: Ultrasonographically detectable neonatal brain white matter lesions are the most important identifiable risk factor for cerebral palsy. Inflammatory cytokines released during the course of intrauterine infections have been implicated in the genesis of brain white matter lesions and subsequent cerebral palsy. This study was undertaken to determine whether fetuses who subsequently were diagnosed to have periventricular brain white matter

  7. White matter hyperintensities on MRI in high-altitude U-2 pilots

    PubMed Central

    Sherman, Paul; Profenna, Leonardo; Grogan, Patrick; Sladky, John; Brown, Anthony; Robinson, Andrew; Rowland, Laura; Hong, Elliot; Patel, Beenish; Tate, David; Kawano, Elaine S.; Fox, Peter; Kochunov, Peter

    2013-01-01

    Objective: To demonstrate that U-2 pilot occupational exposure to hypobaria leads to increased incidence of white matter hyperintensities (WMH) with a more uniform distribution throughout the brain irrespective of clinical neurologic decompression sickness history. Methods: We evaluated imaging findings in 102 U-2 pilots and 91 controls matched for age, health, and education levels. Three-dimensional, T2-weighted, high-resolution (1-mm isotropic) imaging data were collected using fluid-attenuated inversion recovery sequence on a 3-tesla MRI scanner. Whole-brain and regional WMH volume and number were compared between groups using a 2-tailed Wilcoxon rank sum test. Results: U-2 pilots demonstrated an increase in volume (394%; p = 0.004) and number (295%; p < 0.001) of WMH. Analysis of regional distribution demonstrated WMH more uniformly distributed throughout the brain in U-2 pilots compared with mainly frontal distribution in controls. Conclusion: Pilots with occupational exposure to hypobaria showed a significant increase in WMH lesion volume and number. Unlike the healthy controls with predominantly WMH in the frontal white matter, WMH in pilots were more uniformly distributed throughout the brain. This is consistent with our hypothesized pattern of damage produced by interaction between microemboli and cerebral tissue, leading to thrombosis, coagulation, inflammation, and/or activation of innate immune response, although further studies will be necessary to clarify the pathologic mechanisms responsible. PMID:23960192

  8. Dirty-appearing white matter in multiple sclerosis: preliminary observations of myelin phospholipid and axonal loss.

    PubMed

    Moore, G R W; Laule, C; Mackay, A; Leung, E; Li, D K B; Zhao, G; Traboulsee, A L; Paty, D W

    2008-11-01

    "Dirty-appearing white matter" (DAWM) in multiple sclerosis (MS) is defined as a region(s) with ill-defined borders of intermediate signal intensity between that of normal-appearing white matter (NAWM) and that of plaque on T(2)-weighted and proton density imaging. To delineate the histopathology of DAWM, four formalin-fixed cerebral hemisphere slices of three MS patients with DAWM were scanned with T(2)- weighted and proton density sequences. The myelin water fraction (MWF) was obtained by expressing the short T(2) component as a fraction of the total T(2) distribution. Hemispheric sections were then stained with Luxol fast blue (LFB) for myelin phospholipids, for myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) for myelin; Bielschowsky silver impregnation for axons; and for glial fibrillary acidic protein (GFAP) for astrocytes. Compared to NAWM, DAWM showed reduction in MWF, corresponding to a reduction of LFB staining. DAWM also showed reduced Bielschowsky staining. Quantitatively, the change in MWF in DAWM most consistently correlated with the change in LFB staining. The findings of this preliminary study suggest that DAWM is characterized by loss of myelin phospholipids, detected by the short T(2) component, and axonal reduction. PMID:18821049

  9. Phospholipids in X-linked adrenoleukodystrophy white matter: fatty acid abnormalities before the onset of demyelination.

    PubMed

    Theda, C; Moser, A B; Powers, J M; Moser, H W

    1992-07-01

    Changes in fatty acid composition of complex lipids were analyzed in postmortem white matter from a patient with late onset adrenoleukodystrophy (ALD). The specimen showed three regions with progressive myelin breakdown: morphologically normal white matter; areas with active demyelination and perivascular lymphocyte and macrophage infiltration; and areas with marked gliosis. In the morphologically intact region, cholesterol esters were similar in amount and fatty acid composition to those in control tissue, although marked changes were observed in the actively demyelinating area. Galactolipids in these areas were also similar to those in controls. In contrast, glycerophospholipids were increased in amount and in very long chain fatty acids (VLCFA), which are the hallmark of ALD, at the active edge of the demyelinative lesion and even in the apparently intact sample. Further fractionation of the glycerophospholipids by high performance liquid chromatography showed a significant (up to 39-fold) accumulation of hexacosanoic acid (C26:0) in phosphatidylcholine, but not in other phosphatidyl derivatives. The consistent increases in phosphatidylcholine VLCFA in all samples from the ALD brain, which are postulated to represent progressive stages in the development of the disorder, suggest that phosphatidylcholine may be involved in antigen formation and may underlie an immunological basis for the pathogenesis of ALD. PMID:1506859

  10. White matter alterations differ in primary lateral sclerosis and amyotrophic lateral sclerosis

    PubMed Central

    Iwata, Nobue K.; Kwan, Justin Y.; Danielian, Laura E.; Butman, John A.; Tovar-Moll, Fernanda; Bayat, Elham

    2011-01-01

    Primary lateral sclerosis is a sporadic disorder characterized by slowly progressive corticospinal dysfunction. Primary lateral sclerosis differs from amyotrophic lateral sclerosis by its lack of lower motor neuron signs and long survival. Few pathological studies have been carried out on patients with primary lateral sclerosis, and the relationship between primary lateral sclerosis and amyotrophic lateral sclerosis remains uncertain. To detect in vivo structural differences between the two disorders, diffusion tensor imaging of white matter tracts was carried out in 19 patients with primary lateral sclerosis, 18 patients with amyotrophic lateral sclerosis and 19 age-matched controls. Fibre tracking was used to reconstruct the intracranial portion of the corticospinal tract and three regions of the corpus callosum: the genu, splenium and callosal fibres connecting the motor cortices. Both patient groups had reduced fractional anisotropy, a measure associated with axonal organization, and increased mean diffusivity of the reconstructed corticospinal and callosal motor fibres compared with controls, without changes in the genu or splenium. Voxelwise comparison of the whole brain white matter using tract-based spatial statistics confirmed the differences between patients and controls in the diffusion properties of the corticospinal tracts and motor fibres of the callosum. This analysis further revealed differences in the regional distribution of white matter alterations between the patient groups. In patients with amyotrophic lateral sclerosis, the greatest reduction in fractional anisotropy occurred in the distal portions of the intracranial corticospinal tract, consistent with a distal axonal degeneration. In patients with primary lateral sclerosis, the greatest loss of fractional anisotropy and mean diffusivity occurred in the subcortical white matter underlying the motor cortex, with reduced volume, suggesting tissue loss. Clinical measures of upper motor neuron dysfunction correlated with reductions in fractional anisotropy in the corticospinal tract in patients with amyotrophic lateral sclerosis and increased mean diffusivity and volume loss of the corticospinal tract in patients with primary lateral sclerosis. Changes in the diffusion properties of the motor fibres of the corpus callosum were strongly correlated with changes in corticospinal fibres in patients, but not in controls. These findings indicate that degeneration is not selective for corticospinal neurons, but affects callosal neurons within the motor cortex in motor neuron disorders. PMID:21798965

  11. Atlas-based whole brain white matter analysis using large deformation diffeomorphic metric mapping: application to normal elderly and Alzheimer's disease participants.

    PubMed

    Oishi, Kenichi; Faria, Andreia; Jiang, Hangyi; Li, Xin; Akhter, Kazi; Zhang, Jiangyang; Hsu, John T; Miller, Michael I; van Zijl, Peter C M; Albert, Marilyn; Lyketsos, Constantine G; Woods, Roger; Toga, Arthur W; Pike, G Bruce; Rosa-Neto, Pedro; Evans, Alan; Mazziotta, John; Mori, Susumu

    2009-06-01

    The purpose of this paper is to establish single-participant white matter atlases based on diffusion tensor imaging. As one of the applications of the atlas, automated brain segmentation was performed and the accuracy was measured using Large Deformation Diffeomorphic Metric Mapping (LDDMM). High-quality diffusion tensor imaging (DTI) data from a single-participant were B0-distortion-corrected and transformed to the ICBM-152 atlas or to Talairach coordinates. The deep white matter structures, which have been previously well documented and clearly identified by DTI, were manually segmented. The superficial white matter areas beneath the cortex were defined, based on a population-averaged white matter probability map. The white matter was parcellated into 176 regions based on the anatomical labeling in the ICBM-DTI-81 atlas. The automated parcellation was achieved by warping this parcellation map to normal controls and to Alzheimer's disease patients with severe anatomical atrophy. The parcellation accuracy was measured by a kappa analysis between the automated and manual parcellation at 11 anatomical regions. The kappa values were 0.70 for both normal controls and patients while the inter-rater reproducibility was 0.81 (controls) and 0.82 (patients), suggesting "almost perfect" agreement. A power analysis suggested that the proposed method is suitable for detecting FA and size abnormalities of the white matter in clinical studies. PMID:19385016

  12. The effects of white matter hyperintensities and amyloid deposition on Alzheimer dementia

    PubMed Central

    Gordon, Brian A.; Najmi, Safa; Hsu, Phillip; Roe, Catherine M.; Morris, John C.; Benzinger, Tammie L.S.

    2015-01-01

    Background and purpose Elevated levels of amyloid deposition as well as white matter damage are thought to be risk factors for Alzheimer Disease (AD). Here we examined whether qualitative ratings of white matter damage predicted cognitive impairment beyond measures of amyloid. Materials and methods The study examined 397 cognitively normal, 51 very mildly demented, and 11 mildly demented individuals aged 42–90 (mean 68.5). Participants obtained a T2-weighted scan as well as a positron emission tomography scan using 11[C] Pittsburgh Compound B. Periventricular white matter hyperintensities (PVWMHs) and deep white matter hyperintensities (DWMHs) were measured on each T2 scan using the Fazekas rating scale. The effects of amyloid deposition and white matter damage were assessed using logistic regressions. Results Levels of amyloid deposition (ps < 0.01), as well as ratings of PVWMH (p < 0.01) and DWMH (p < 0.05) discriminated between cognitively normal and demented individuals. Conclusions The amount of amyloid deposition and white matter damage independently predicts cognitive impairment. This suggests a diagnostic utility of qualitative white matter scales in addition to measuring amyloid levels. PMID:26106548

  13. Delay discounting behavior and white matter microstructure abnormalities in youth with a family history of alcoholism

    PubMed Central

    Herting, Megan M.; Schwartz, Daniel; Mitchell, Suzanne H.; Nagel, Bonnie J.

    2011-01-01

    Background Youth with family history of alcohol abuse have a greater risk of developing an alcohol use disorder (AUD). Brain and behavior differences may underlie this increased vulnerability. The current study examined delay discounting behavior and white matter microstructure in youth at high-risk for alcohol abuse, as determined by a family history of alcoholism (FH+), and youth without such family history (FH?). Methods Thirty-three healthy youth (FH+ = 15, FH? = 18), ages 11 to 15 years, completed a delay discounting task and underwent diffusion tensor imaging (DTI). Tract Based Spatial Statistics (Smith et al., 2006), as well as follow-up region-of-interest analyses, were performed in order to compare fractional anisotropy (FA) between FH+ and FH? youth. Results FH+ youth showed a trend toward increased discounting behavior and had significantly slower reaction times on the delay discounting paradigm compared to FH? youth. Group differences in FA were seen in several white matter tracts. Furthermore, lower FA in the left inferior longitudinal fasciculus and the right optic radiation statistically mediated the relationship between FH status and slower reaction times on the delay discounting task. Conclusion Youth with a family history of substance abuse have disrupted white matter microstructure, which likely contributes to less efficient cortical processing, and may act as an intrinsic risk-factor contributing to an increased susceptibility of developing AUD. In addition, FHP youth showed a trend toward greater impulsive decision making, possibly representing an inherent personal characteristic that may facilitate substance use onset and abuse in high-risk youth. PMID:20586754

  14. Altered white matter integrity in individuals with cognitive vulnerability to depression: a tract-based spatial statistics study

    PubMed Central

    Xiao, Jing; He, Yini; McWhinnie, Chad M.; Yao, Shuqiao

    2015-01-01

    The microstructure of white matter in patients with major depressive disorder (MDD) has been demonstrated to be abnormal. However, it remains unclear whether these changes exist prior to the onset of disease. In this study, diffusion tensor imaging was used to evaluate white matter integrity in individuals who exhibited cognitive vulnerability to depression (CVD), MDD, and healthy controls (HC). Compared with the HC, MDD exhibited a lower fractional anisotropy (FA) in ten brain regions: the cerebral peduncle, the anterior and posterior limbs of the internal capsule (ALIC and PLIC), the external capsule, the retrolenticular part of the internal capsule (RLIC), the body and splenium of the corpus callosum, the superior and posterior corona radiata, and the cingulum. Moreover, CVD had significantly lower FA in the ALIC, the PLIC, the external capsule, the RLIC, the cerebral peduncle, and the superior corona radiata than did the HC. However, the white matter integrity was not significantly different between the CVD and MDD. These preliminary results indicate that alterations in the white matter observed in CVD may be a marker of vulnerability to MDD and that these alterations may exist prior to the onset of depression. PMID:25984712

  15. Independent Component Analysis-Based Identification of Covariance Patterns of Microstructural White Matter Damage in Alzheimer’s Disease

    PubMed Central

    Ouyang, Xin; Chen, Kewei; Yao, Li; Wu, Xia; Zhang, Jiacai; Li, Ke; Jin, Zhen; Guo, Xiaojuan

    2015-01-01

    The existing DTI studies have suggested that white matter damage constitutes an important part of the neurodegenerative changes in Alzheimer’s disease (AD). The present study aimed to identify the regional covariance patterns of microstructural white matter changes associated with AD. In this study, we applied a multivariate analysis approach, independent component analysis (ICA), to identify covariance patterns of microstructural white matter damage based on fractional anisotropy (FA) skeletonised images from DTI data in 39 AD patients and 41 healthy controls (HCs) from the Alzheimer’s Disease Neuroimaging Initiative database. The multivariate ICA decomposed the subject-dimension concatenated FA data into a mixing coefficient matrix and a source matrix. Twenty-eight independent components (ICs) were extracted, and a two sample t-test on each column of the corresponding mixing coefficient matrix revealed significant AD/HC differences in ICA weights for 7 ICs. The covariant FA changes primarily involved the bilateral corona radiata, the superior longitudinal fasciculus, the cingulum, the hippocampal commissure, and the corpus callosum in AD patients compared to HCs. Our findings identified covariant white matter damage associated with AD based on DTI in combination with multivariate ICA, potentially expanding our understanding of the neuropathological mechanisms of AD. PMID:25775003

  16. Altered white matter integrity in individuals with cognitive vulnerability to depression: a tract-based spatial statistics study.

    PubMed

    Xiao, Jing; He, Yini; McWhinnie, Chad M; Yao, Shuqiao

    2015-01-01

    The microstructure of white matter in patients with major depressive disorder (MDD) has been demonstrated to be abnormal. However, it remains unclear whether these changes exist prior to the onset of disease. In this study, diffusion tensor imaging was used to evaluate white matter integrity in individuals who exhibited cognitive vulnerability to depression (CVD), MDD, and healthy controls (HC). Compared with the HC, MDD exhibited a lower fractional anisotropy (FA) in ten brain regions: the cerebral peduncle, the anterior and posterior limbs of the internal capsule (ALIC and PLIC), the external capsule, the retrolenticular part of the internal capsule (RLIC), the body and splenium of the corpus callosum, the superior and posterior corona radiata, and the cingulum. Moreover, CVD had significantly lower FA in the ALIC, the PLIC, the external capsule, the RLIC, the cerebral peduncle, and the superior corona radiata than did the HC. However, the white matter integrity was not significantly different between the CVD and MDD. These preliminary results indicate that alterations in the white matter observed in CVD may be a marker of vulnerability to MDD and that these alterations may exist prior to the onset of depression. PMID:25984712

  17. 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?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

  18. Orientation dependence of magnetization transfer parameters in human white matter.

    PubMed

    Pampel, André; Müller, Dirk K; Anwander, Alfred; Marschner, Henrik; Möller, Harald E

    2015-07-01

    Quantification of magnetization-transfer (MT) experiments is typically based on a model comprising a liquid pool "a" of free water and a semisolid pool "b" of motionally restricted macromolecules or membrane compounds. By a comprehensive fitting approach, high quality MT parameter maps of the human brain are obtained. In particular, a distinct correlation between the diffusion-tensor orientation with respect to the B0-magnetic field and the apparent transverse relaxation time, T2(b), of the semisolid pool (i.e., the width of its absorption line) is observed. This orientation dependence is quantitatively explained by a refined dipolar lineshape for pool b that explicitly considers the specific geometrical arrangement of lipid bilayers wrapped around a cylindrical axon. The model inherently reduces the myelin membrane to its lipid constituents, which is motivated by previous studies on efficient interaction sites (e.g., cholesterol or galactocerebrosides) in the myelin membrane and on the origin of ultrashort T2 signals in cerebral white matter. The agreement between MT orientation effects and corresponding forward simulations using empirical diffusion imaging results as input as well as results from fits employing the novel lineshape support previous suggestions that the fiber orientation distribution in a voxel can be modeled as a scaled Bingham distribution. PMID:25862261

  19. Mapping White Matter Integrity in Elderly People with HIV

    PubMed Central

    Nir, Talia M.; Jahanshad, Neda; Busovaca, Edgar; Wendelken, Lauren; Nicolas, Krista; Thompson, Paul M.; Valcour, Victor G.

    2013-01-01

    People with HIV are living longer as combination antiretroviral therapy (cART) becomes more widely available. However, even when plasma viral load is reduced to untraceable levels, chronic HIV infection is associated with neurological deficits and brain atrophy beyond that of normal aging. HIV is often marked by cortical and subcortical atrophy, but the integrity of the brain’s white matter (WM) pathways also progressively declines. Few studies focus on older cohorts where normal aging may be compounded with HIV infection to influence deficit patterns. In this relatively large diffusion tensor imaging (DTI) study, we investigated abnormalities in WM fiber integrity in 56 HIV+ adults with access to cART (mean age: 63.9 ± 3.7 years), compared to 31 matched healthy controls (65.4 ± 2.2 years). Statistical 3D maps revealed the independent effects of HIV diagnosis and age on fractional anisotropy (FA) and diffusivity, but we did not find any evidence for an age by diagnosis interaction in our current sample. Compared to healthy controls, HIV patients showed pervasive FA decreases and diffusivity increases throughout WM. We also assessed neuropsychological (NP) summary z-score associations. In both patients and controls, fiber integrity measures were associated with NP summary scores. The greatest differences were detected in the corpus callosum and in the projection fibers of the corona radiata. These deficits are consistent with published NP deficits and cortical atrophy patterns in elderly people with HIV. PMID:23362139

  20. [Age-related white matter lesions (leukoaraiosis): an update].

    PubMed

    Miki, Yukio; Sakamoto, Shinichi

    2013-07-01

    Leukoaraiosis (age-related white matter hyperintensities) is the most frequently seen lesion on brain magnetic resonance (MR) images. This lesion is a subject of much current interest, because a number of multicenter studies have revealed that it is associated with various disturbances and poor prognoses. Leukoaraiosis corresponds to various pathologies, including demyelination, apoptosis, edema, dilated perivascular spaces, axonal damage, gliosis, and infarcts. Also noted in leukoaraiosis are changes in small vessels, such as fibrohyalinosis and venous collagenosis. The main cause of leukoaraiosis is thought to be chronic ischemia; other causes include edema and breakdown of the blood-brain barrier. Major risk factors for leukoaraiosis are age and hypertension. Disturbances that are related to leukoaraiosis include stroke, dementia, cognitive impairment, gait disturbance, fall, and depression. Leukoaraiosis is also a risk factor for death. Technologies, such as automatic volumetry, tissue segmentation, diffusion tensor imaging, magnetization tensor imaging, diffusion kurtosis imaging, and ultra-high field MR imaging may provide further insights into leukoaraiosis. PMID:23832982

  1. Mapping white matter integrity in elderly people with HIV.

    PubMed

    Nir, Talia M; Jahanshad, Neda; Busovaca, Edgar; Wendelken, Lauren; Nicolas, Krista; Thompson, Paul M; Valcour, Victor G

    2014-03-01

    People with HIV are living longer as combination antiretroviral therapy (cART) becomes more widely available. However, even when plasma viral load is reduced to untraceable levels, chronic HIV infection is associated with neurological deficits and brain atrophy beyond that of normal aging. HIV is often marked by cortical and subcortical atrophy, but the integrity of the brain's white matter (WM) pathways also progressively declines. Few studies focus on older cohorts where normal aging may be compounded with HIV infection to influence deficit patterns. In this relatively large diffusion tensor imaging (DTI) study, we investigated abnormalities in WM fiber integrity in 56 HIV+ adults with access to cART (mean age: 63.9 ± 3.7 years), compared to 31 matched healthy controls (65.4 ± 2.2 years). Statistical 3D maps revealed the independent effects of HIV diagnosis and age on fractional anisotropy (FA) and diffusivity, but we did not find any evidence for an age by diagnosis interaction in our current sample. Compared to healthy controls, HIV patients showed pervasive FA decreases and diffusivity increases throughout WM. We also assessed neuropsychological (NP) summary z-score associations. In both patients and controls, fiber integrity measures were associated with NP summary scores. The greatest differences were detected in the corpus callosum and in the projection fibers of the corona radiata. These deficits are consistent with published NP deficits and cortical atrophy patterns in elderly people with HIV. PMID:23362139

  2. Cognitive Impact of Lacunar Infarcts and White Matter Hyperintensity Volume

    PubMed Central

    Warren, Matthew W.; Weiner, Myron F.; Rossetti, Heidi C.; McColl, Roderick; Peshock, Ron; King, Kevin S.

    2015-01-01

    Background Subcortical lacunar infarcts and white matter hyperintensities (WMH) are common neuroradiological findings, but few studies associate between these insults and cognition in a community-dwelling population. Methods The Dallas Heart Study is a population-based initiative whose assessments included demographic and clinical findings including brain MRI and the Montreal Cognitive Assessment (MoCA). The presence and number of lacunes in subjects aged over 55 years were assessed by study physicians. The WMH volume was measured by an automated method. The association between the presence and number of lacunar infarcts and of WMH volume with the total MoCA score and subdomains was assessed using linear regression with adjustment for age, gender and self-reported ethnicity. Results In 609 subjects with valid data, both the presence and the increasing number of lacunes were associated with lower MoCA scores, even after adjusting for demographic variables. The presence of lacunes was also associated with lower scores in the memory, executive and attention subdomains. The WMH volume was not significantly associated with the MoCA score. Conclusion The presence and increasing number of lacunes in midlife is associated with a lower performance in multiple domains of a cognitive screening measure after adjusting for demographic factors. PMID:26034488

  3. White matter degeneration in schizophrenia: a comparative diffusion tensor analysis

    NASA Astrophysics Data System (ADS)

    Ingalhalikar, Madhura A.; Andreasen, Nancy C.; Kim, Jinsuh; Alexander, Andrew L.; Magnotta, Vincent A.

    2010-03-01

    Schizophrenia is a serious and disabling mental disorder. Diffusion tensor imaging (DTI) studies performed on schizophrenia have demonstrated white matter degeneration either due to loss of myelination or deterioration of fiber tracts although the areas where the changes occur are variable across studies. Most of the population based studies analyze the changes in schizophrenia using scalar indices computed from the diffusion tensor such as fractional anisotropy (FA) and relative anisotropy (RA). The scalar measures may not capture the complete information from the diffusion tensor. In this paper we have applied the RADTI method on a group of 9 controls and 9 patients with schizophrenia. The RADTI method converts the tensors to log-Euclidean space where a linear regression model is applied and hypothesis testing is performed between the control and patient groups. Results show that there is a significant difference in the anisotropy between patients and controls especially in the parts of forceps minor, superior corona radiata, anterior limb of internal capsule and genu of corpus callosum. To check if the tensor analysis gives a better idea of the changes in anisotropy, we compared the results with voxelwise FA analysis as well as voxelwise geodesic anisotropy (GA) analysis.

  4. Robust white matter lesion segmentation in FLAIR MRI.

    PubMed

    Khademi, April; Venetsanopoulos, Anastasios; Moody, Alan R

    2012-03-01

    This paper discusses a white matter lesion (WML) segmentation scheme for fluid attenuation inversion recovery (FLAIR) MRI. The method computes the volume of lesions with subvoxel precision by accounting for the partial volume averaging (PVA) artifact. As WMLs are related to stroke and carotid disease, accurate volume measurements are most important. Manual volume computation is laborious, subjective, time consuming, and error prone. Automated methods are a nice alternative since they quantify WML volumes in an objective, efficient, and reliable manner. PVA is initially modeled with a localized edge strength measure since PVA resides in the boundaries between tissues. This map is computed in 3-D and is transformed to a global representation to increase robustness to noise. Significant edges correspond to PVA voxels, which are used to find the PVA fraction ? (amount of each tissue present in mixture voxels). Results on simulated and real FLAIR images show high WML segmentation performance compared to ground truth (98.9% and 83% overlap, respectively), which outperforms other methods. Lesion load studies are included that automatically analyze WML volumes for each brain hemisphere separately. This technique does not require any distributional assumptions/parameters or training samples and is applied on a single MR modality, which is a major advantage compared to the traditional methods. PMID:22203699

  5. White Matter Consequences of Retinal Receptor and Ganglion Cell Damage

    PubMed Central

    Ogawa, Shumpei; Takemura, Hiromasa; Horiguchi, Hiroshi; Terao, Masahiko; Haji, Tomoki; Pestilli, Franco; Yeatman, Jason D.; Tsuneoka, Hiroshi; Wandell, Brian A.; Masuda, Yoichiro

    2014-01-01

    Purpose. Patients with Leber hereditary optic neuropathy (LHON) and cone-rod dystrophy (CRD) have central vision loss; but CRD damages the retinal photoreceptor layer, and LHON damages the retinal ganglion cell (RGC) layer. Using diffusion MRI, we measured how these two types of retinal damage affect the optic tract (ganglion cell axons) and optic radiation (geniculo-striate axons). Methods. Adult onset CRD (n = 5), LHON (n = 6), and healthy controls (n = 14) participated in the study. We used probabilistic fiber tractography to identify the optic tract and the optic radiation. We compared axial and radial diffusivity at many positions along the optic tract and the optic radiation. Results. In both types of patients, diffusion measures within the optic tract and the optic radiation differ from controls. The optic tract change is principally a decrease in axial diffusivity; the optic radiation change is principally an increase in radial diffusivity. Conclusions. Both photoreceptor layer (CRD) and retinal ganglion cell (LHON) retinal disease causes substantial change in the visual white matter. These changes can be measured using diffusion MRI. The diffusion changes measured in the optic tract and the optic radiation differ, suggesting that they are caused by different biological mechanisms. PMID:25257055

  6. White Matter Compromise in Veterans Exposed to Primary Blast Forces

    PubMed Central

    Taber, Katherine H.; Hurley, Robin A.; Haswell, Courtney C.; Rowland, Jared A.; Hurt, Susan D.; Lamar, Cory D.; Morey, Rajendra A.

    2015-01-01

    Objective Use Diffusion Tensor Imaging (DTI) to investigate white matter alterations associated with blast exposure with or without acute symptoms of traumatic brain injury (TBI). Participants Forty-five veterans of the recent military conflicts included twenty-three exposed to primary blast without TBI symptoms, six having primary blast mild TBI, and sixteen unexposed to blast. Design Cross-sectional case control study. Main Measures Neuropsychological testing and DTI metrics that quantified the number of voxel clusters with altered fractional anisotropy (FA) radial diffusivity (RD), and axial diffusivity (AD), regardless of their spatial location. Results Significantly lower FA and higher RD was observed in veterans exposed to primary blast with and without mild TBI relative to blast unexposed veterans. Voxel clusters of lower FA were spatially dispersed and heterogeneous across affected individuals. Conclusion These results suggest that lack of clear TBI symptoms following primary blast exposure may not accurately reflect the extent of brain injury. If confirmed, our findings would argue for supplementing the established approach of making diagnoses based purely on clinical history and observable acute symptoms with novel neuroimaging-based diagnostic criteria that “look below the surface” for pathology. PMID:24590156

  7. Reconstruction of the human cerebral cortex robust to white matter lesions: method and validation.

    PubMed

    Shiee, Navid; Bazin, Pierre-Louis; Cuzzocreo, Jennifer L; Ye, Chuyang; Kishore, Bhaskar; Carass, Aaron; Calabresi, Peter A; Reich, Daniel S; Prince, Jerry L; Pham, Dzung L

    2014-07-01

    Cortical atrophy has been reported in a number of diseases, such as multiple sclerosis and Alzheimer's disease, that are also associated with white matter (WM) lesions. However, most cortical reconstruction techniques do not account for these pathologies, thereby requiring additional processing to correct for the effect of WM lesions. In this work, we introduce CRUISE(+), an automated process for cortical reconstruction from magnetic resonance brain images with WM lesions. The process extends previously well validated methods to allow for multichannel input images and to accommodate for the presence of WM lesions. We provide new validation data and tools for measuring the accuracy of cortical reconstruction methods on healthy brains as well as brains with multiple sclerosis lesions. Using this data, we validate the accuracy of CRUISE(+) and compare it to another state-of-the-art cortical reconstruction tool. Our results demonstrate that CRUISE(+) has superior performance in the cortical regions near WM lesions, and similar performance in other regions. PMID:24382742

  8. White matter pathway supporting phonological encoding in speech production: a multi-modal imaging study of brain damage patients.

    PubMed

    Han, Zaizhu; Ma, Yujun; Gong, Gaolang; Huang, Ruiwang; Song, Luping; Bi, Yanchao

    2014-10-31

    In speech production, an important step before motor programming is the retrieval and encoding of the phonological elements of target words. It has been proposed that phonological encoding is supported by multiple regions in the left frontal, temporal and parietal regions and their underlying white matter, especially the left arcuate fasciculus (AF) or superior longitudinal fasciculus (SLF). It is unclear, however, whether the effects of AF/SLF are indeed related to phonological encoding for output and whether there are other white matter tracts that also contribute to this process. We comprehensively investigated the anatomical connectivity supporting phonological encoding in production by studying the relationship between the integrity of all major white matter tracts across the entire brain and phonological encoding deficits in a group of 69 patients with brain damage. The integrity of each white matter tract was measured both by the percentage of damaged voxels (structural imaging) and the mean fractional anisotropy value (diffusion tensor imaging). The phonological encoding deficits were assessed by various measures in two oral production tasks that involve phonological encoding: the percentage of nonword (phonological) errors in oral picture naming and the accuracy of word reading aloud with word comprehension ability regressed out. We found that the integrity of the left SLF in both the structural and diffusion tensor imaging measures consistently predicted the severity of phonological encoding impairment in the two phonological production tasks. Such effects of the left SLF on phonological production remained significant when a range of potential confounding factors were considered through partial correlation, including total lesion volume, demographic factors, lesions on phonological-relevant grey matter regions, or effects originating from the phonological perception or semantic processes. Our results therefore conclusively demonstrate the central role of the left SLF in phonological encoding in speech production. PMID:25359657

  9. Volume changes and brain-behavior relationships in white matter and subcortical gray matter in children with prenatal alcohol exposure.

    PubMed

    Gautam, Prapti; Lebel, Catherine; Narr, Katherine L; Mattson, Sarah N; May, Philip A; Adnams, Colleen M; Riley, Edward P; Jones, Kenneth L; Kan, Eric C; Sowell, Elizabeth R

    2015-06-01

    Children with prenatal alcohol exposure (PAE) may have cognitive, behavioral and brain abnormalities. Here, we compare rates of white matter and subcortical gray matter volume change in PAE and control children, and examine relationships between annual volume change and arithmetic ability, behavior, and executive function. Participants (n?=?75 PAE/64 control; age: 7.1-15.9 years) each received two structural magnetic resonance scans, ?2 years apart. Assessments included Wechsler Intelligence Scale for Children (WISC-IV), the Child Behavior Checklist and the Behavior Rating Inventory of Executive Function. Subcortical white and gray volumes were extracted for each hemisphere. Group volume differences were tested using false discovery rate (q?regions for WISC arithmetic scores and in frontal and parietal regions for behavioral measures. Poorer cognitive/ behavioral outcomes were associated with larger volume increases in PAE, while control subjects generally showed no significant correlations. In contrast with previous results demonstrating different trajectories of cortical volume change in PAE, our results show similar rates of subcortical volume growth in subjects with PAE and control subjects. We also demonstrate abnormal brain-behavior relationships in subjects with PAE, suggesting different use of brain resources. Our results are encouraging in that, due to the stable volume differences, there may be an extended window of opportunity for intervention in children with PAE. Hum Brain Mapp 36:2318-2329, 2015. © 2015 Wiley Periodicals, Inc. PMID:25711175

  10. Chondroitin sulfate proteoglycans impede myelination by oligodendrocytes after perinatal white matter injury.

    PubMed

    Deng, Ying-Ping; Sun, Yi; Hu, Lan; Li, Zhi-Hua; Xu, Quan-Mei; Pei, Yi-Ling; Huang, Zhi-Heng; Yang, Zhen-Gang; Chen, Chao

    2015-07-01

    Hypomyelination is the major cause of neurodevelopmental deficits that are associated with perinatal white matter injury. Chondroitin sulfate proteoglycans (CSPGs) are known to exert inhibitory effects on the migration and differentiation of oligodendrocytes (OLs). However, few studies describe the roles of CSPGs in myelination by OLs and the cognitive dysfunction that follows perinatal white matter injury. Here, we examined the alterations in the expression of CSPGs and their functional impact on the maturation of OLs and myelination in a neonatal rat model of hypoxic-ischemic (HI) brain injury. Three-day-old Sprague-Dawley rats underwent a right common carotid artery ligation and were exposed to hypoxia (6% oxygen for 2.5h). Rats were given chondroitinase ABC (cABC) via an intracerebroventricular injection to digest CSPGs. Animals were sacrificed at 7, 14, 28 and 56days after HI injury and the accompanying surgical procedure. We found that the expression of CSPGs was significantly up-regulated in the cortical regions surrounding the white matter after HI injury. cABC successfully degraded CSPGs in the rats that received cABC. Immunostaining showed decreased expression of the pre-oligodendrocyte marker O4 in the cingulum, external capsule and corpus callosum in HI+cABC rats compared to HI rats. However HI+cABC rats exhibited greater maturation of OLs than did HI rats, with increased expression of O1 and myelin basic protein in the white matter. Furthermore, using electron microscopy, we demonstrated that myelin formation was enhanced in HI+cABC rats, which had an increased number of myelinated axons and decreased G-ratios of myelin compared to HI rats. Finally, HI+cABC rats performed better in the Morris water maze task than HI rats, which indicates an improvement in cognitive ability. Our results suggest that CSPGs inhibit both the maturation of OLs and the process of myelination after neonatal HI brain injury. The data also raise the possibility that modifying CSPGs may repair this type of lesion associated with demyelination. PMID:25862289

  11. Neurodevelopmental and Neurodegenerative Models of Schizophrenia: White Matter at the Center Stage

    PubMed Central

    Kochunov, Peter; Hong, L. Elliot

    2014-01-01

    Schizophrenia is a disorder of cerebral disconnectivity whose lifetime course is modeled as both neurodevelopmental and neurodegenerative. The neurodevelopmental models attribute schizophrenia to alterations in the prenatal-to-early adolescent development. The neurodegenerative models identify progressive neurodegeneration as its core attribute. Historically, the physiology, pharmacology, and treatment targets in schizophrenia were conceptualized in terms of neurons, neurotransmitter levels, and synaptic receptors. Much of the evidence for both models was derived from studies of cortical and subcortical gray matter. We argue that the dynamics of the lifetime trajectory of white matter, and the consistency of connectivity deficits in schizophrenia, support white matter integrity as a promising phenotype to evaluate the competing evidence for and against neurodevelopmental and neurodegenerative heuristics. We develop this perspective by reviewing normal lifetime trajectories of white and gray matter changes. We highlighted the overlap between the age of peak of white matter development and the age of onset of schizophrenia and reviewed findings of white matter abnormalities prior to, at the onset, and at chronic stages of schizophrenia. We emphasized the findings of reduced white matter integrity at the onset and findings of accelerated decline in chronic stages, but the developmental trajectory that precedes the onset is largely unknown. We propose 4 probable lifetime white matter trajectory models that can be used as the basis for separation between the neurodevelopmental and neurodegenerative etiologies. We argue that a combination of the cross-sectional and longitudinal studies of white matter integrity in patients may be used to bridge the neurodevelopment and degeneration heuristics to advance schizophrenia research PMID:24870447

  12. Functional Diffusion Tensor Imaging: Measuring Task-Related Fractional Anisotropy Changes in the Human Brain along White Matter Tracts

    PubMed Central

    Mandl, René C. W.; Schnack, Hugo G.; Zwiers, Marcel P.; van der Schaaf, Arjen; Kahn, René S.; Hulshoff Pol, Hilleke E.

    2008-01-01

    Background Functional neural networks in the human brain can be studied from correlations between activated gray matter regions measured with fMRI. However, while providing important information on gray matter activation, no information is gathered on the co-activity along white matter tracts in neural networks. Methodology/Principal Findings We report on a functional diffusion tensor imaging (fDTI) method that measures task-related changes in fractional anisotropy (FA) along white matter tracts. We hypothesize that these fractional anisotropy changes relate to morphological changes of glial cells induced by axonal activity although the exact physiological underpinnings of the measured FA changes remain to be elucidated. As expected, these changes are very small as compared to the physiological noise and a reliable detection of the signal change would require a large number of measurements. However, a substantial increase in signal-to-noise ratio was achieved by pooling the signal over the complete fiber tract. Adopting such a tract-based statistics enabled us to measure the signal within a practically feasible time period. Activation in the sensory thalamocortical tract and optic radiation in eight healthy human subjects was found during tactile and visual stimulation, respectively. Conclusions/Significance The results of our experiments indicate that these FA changes may serve as a functional contrast mechanism for white matter. This noninvasive fDTI method may provide a new approach to study functional neural networks in the human brain. PMID:18982065

  13. Automated Fiber Tracking of Human Brain White Matter Using Diffusion Tensor Imaging

    PubMed Central

    Zhang, Weihong; Olivi, Alessandro; Hertig, Samuel J.; van Zijl, Peter; Mori, Susumu

    2008-01-01

    Reconstruction of white matter tracts based on diffusion tensor imaging (DTI) is currently widely used in clinical research. This reconstruction allows us to identify coordinates of specific white matter tracts and to investigate their anatomy. Fiber reconstruction, however, relies on manual identification of anatomical landmarks of a tract of interest, which is based on subjective judgment and thus a potential source of experimental variability. Here, an automated tract reconstruction approach is introduced. A set of reference regions of interest (rROIs) known to select a tract of interest was marked in our DTI brain atlas. The atlas was then linearly transformed to each subject, and the rROI set was transferred to the subject for tract reconstruction. Agreement between the automated and manual approaches was measured for 11 tracts in 10 healthy volunteers and found to be excellent (kappa > 0.8) and remained high up to 4–5 mm of the linear transformation errors. As a first example, the automated approach was applied to brain tumor patients and strategies to cope with severe anatomical abnormalities are discussed. PMID:18554930

  14. 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 ?4 (ApoE-?4) 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 A?. By making measurements of white matter integrity via diffusion MR and correlating the metrics in a voxel-based statistical analysis with ApoE-?4 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 ?4 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).

  15. Soccer Heading Is Associated with White Matter Microstructural and Cognitive Abnormalities

    PubMed Central

    Kim, Namhee; Zimmerman, Molly E.; Kim, Mimi; Stewart, Walter F.; Branch, Craig A.

    2013-01-01

    Purpose: To investigate the association of soccer heading with subclinical evidence of traumatic brain injury. Materials and Methods: With institutional review board approval and compliance with HIPAA guidelines, 37 amateur soccer players (mean age, 30.9 years; 78% [29] men, 22% [eight] women) gave written informed consent and completed a questionnaire to quantify heading in the prior 12 months and lifetime concussions. Diffusion-tensor magnetic resonance (MR) imaging at 3.0 T was performed (32 directions; b value, 800 sec/mm2; 2 × 2 × 2-mm voxels). Cognitive function was measured by using a computerized battery of tests. Voxelwise linear regression (heading vs fractional anisotropy [FA]) was applied to identify significant regional associations. FA at each location and cognition were tested for a nonlinear relationship to heading by using an inverse logit model that incorporated demographic covariates and history of concussion. Results: Participants had headed 32–5400 times (median, 432 times) over the previous year. Heading was associated with lower FA at three locations in temporo-occipital white matter with a threshold that varied according to location (885–1550 headings per year) (P < .00001). Lower levels of FA were also associated with poorer memory scores (P < .00001), with a threshold of 1800 headings per year. Lifetime concussion history and demographic features were not significantly associated with either FA or cognitive performance. Conclusion: Heading is associated with abnormal white matter microstructure and with poorer neurocognitive performance. This relationship is not explained by a history of concussion. © RSNA, 2013 PMID:23757503

  16. Inferior frontal gyrus white matter abnormalities in obsessive-compulsive disorder.

    PubMed

    Gonçalves, Óscar F; Sousa, Sónia; Maia, Liliana; Carvalho, Sandra; Leite, Jorge; Ganho, Ana; Fernandes-Gonçalves, Ana; Frank, Brandon; Pocinho, Fernando; Carracedo, Angel; Sampaio, Adriana

    2015-06-17

    The aim of the present study is to explore obsessive-compulsive disorder (OCD)-related abnormalities in white matter connectivity in OCD for a core region associated with inhibitory control [i.e. inferior frontal gyrus (IFG)]. Fifteen patients with OCD (11 men) and 15 healthy controls (nine men) underwent diffusion tensor imaging scanning to study four diffusivity indexes of white matter integrity [fractional anisotropy, mean diffusivity (MD), axial diffusivity and radial diffusivity (RD)]. The results showed that persons with OCD manifested significantly lower fractional anisotropy levels in the bilateral IFG as well as its parcellations in the pars opercularis, pars triangularis, and pars orbitalis. Significantly higher levels of MD, RD were evident for the OCD group in the IFG as a whole as well as in the bilateral subregions of the pars triangularis and pars opercularis (for MD and RD), the right side of the pars orbitalis (for RD), and the left side of the pars triangularis and right side pars opercularis (for axial diffusivity). Overall, the results suggest significant alterations in structural connectivity, probably associated with myelination and axonal abnormalities in the IFG of OCD patients. PMID:25945482

  17. Alterations in frontal white matter neurochemistry and microstructure in schizophrenia: implications for neuroinflammation

    PubMed Central

    Chiappelli, J; Hong, L E; Wijtenburg, S A; Du, X; Gaston, F; Kochunov, P; Rowland, L M

    2015-01-01

    We investigated in vivo neurochemical markers reflective of neuronal health and glial activation to determine if these could yield clues regarding the reduced fractional anisotropy (FA) of white matter and accelerated decline of FA with age in schizophrenia. Participants with schizophrenia and healthy controls completed diffusion tensor imaging to assess FA and proton magnetic resonance spectroscopy to assess neurochemical metabolites in the same frontal region. Frontal FA was significantly lower in the schizophrenia and declined more rapidly with age compared with the healthy control group. In both groups, N-acetylaspartate (NAA), a putative marker of neuronal integrity, and glutamate declined with age, and this decline was stronger in patients. Myo-inositol, a marker of glial cells, was negatively related to FA in both groups. The relationship between FA and age remained significant in schizophrenia even when controlling for all metabolites. The relationships of FA, NAA and myo-inositol to age appear to be independent of one another. The relationship between FA and myo-inositol was independently present in both patients and controls, even after controlling for age, indicating a potential general effect of neuroinflammation on white matter microstructure. Further studies are warranted to determine the underlying mechanism driving the accelerated FA decline with age in schizophrenia. PMID:25871973

  18. A Diffusion-Tensor-Based White Matter Atlas for Rhesus Macaques

    PubMed Central

    Zakszewski, Elizabeth; Adluru, Nagesh; Tromp, Do P. M.; Kalin, Ned; Alexander, Andrew L.

    2014-01-01

    Atlases of key white matter (WM) structures in humans are widely available, and are very useful for region of interest (ROI)-based analyses of WM properties. There are histology-based atlases of cortical areas in the rhesus macaque, but none currently of specific WM structures. Since ROI-based analysis of WM pathways is also useful in studies using rhesus diffusion tensor imaging (DTI) data, we have here created an atlas based on a publicly available DTI-based template of young rhesus macaques. The atlas was constructed to mimic the structure of an existing human atlas that is widely used, making results translatable between species. Parcellations were carefully hand-drawn on a principle-direction color-coded fractional anisotropy image of the population template. The resulting atlas can be used as a reference to which registration of individual rhesus data can be performed for the purpose of white-matter parcellation. Alternatively, specific ROIs from the atlas may be warped into individual space to be used in ROI-based group analyses. This atlas will be made publicly available so that it may be used as a resource for DTI studies of rhesus macaques. PMID:25203614

  19. A Preliminary Study of White Matter in Adolescent Depression: Relationships with Illness Severity, Anhedonia, and Irritability

    PubMed Central

    Henderson, Sarah E.; Johnson, Amy R.; Vallejo, Ana I.; Katz, Lev; Wong, Edmund; Gabbay, Vilma

    2013-01-01

    Major depressive disorder (MDD) during adolescence is a common and disabling psychiatric condition; yet, little is known about its neurobiological underpinning. Evidence indicates that MDD in adults involves alterations in white and gray matter; however, sparse research has focused on adolescent MDD. Similarly, little research has accounted for the wide variability of symptom severity among depressed teens. Here, we aimed to investigate white matter (WM) microstructure between 17 adolescents with MDD and 16 matched healthy controls (HC) using diffusion tensor imaging. We further assessed within the MDD group relationships between WM integrity and depression severity, as well as anhedonia and irritability – two core symptoms of adolescent MDD. As expected, adolescents with MDD manifested decreased WM integrity compared to HC in the anterior cingulum and anterior corona radiata. Within the MDD group, greater depression severity was correlated with reduced WM integrity in the genu of corpus callosum, anterior thalamic radiation, anterior cingulum, and sagittal stratum. However, anhedonia and irritability were associated with alterations in distinct WM tracts. Specifically, anhedonia was associated with disturbances in tracts related to reward processing, including the anterior limb of the internal capsule and projection fibers to the orbitofrontal cortex. Irritability was associated with decreased integrity in the sagittal stratum, anterior corona radiata, and tracts leading to prefrontal and temporal cortices. Overall, these preliminary findings provide further support for the hypotheses that there is a disconnect between prefrontal and limbic emotional regions in depression, and that specific clinical symptoms involve distinct alterations in WM tracts. PMID:24324445

  20. White matter tractography by anisotropic wavefront evolution and diffusion tensor imaging

    PubMed Central

    Jackowski, Marcel; Kao, Chiu Yen; Qiu, Maolin; Constable, R. Todd; Staib, Lawrence H.

    2010-01-01

    Determination of axonal pathways provides an invaluable means to study the connectivity of the human brain and its functional network. Diffusion tensor imaging (DTI) is unique in its ability to capture the restricted diffusion of water molecules which can be used to infer the directionality of tissue components. In this paper, we introduce a white matter tractography method based on anisotropic wavefront propagation in diffusion tensor images. A front propagates in the white matter with a speed profile governed by the isocontour of the diffusion tensor ellipsoid. By using the ellipsoid, we avoid possible misclassification of the principal eigenvector in oblate regions. The wavefront evolution is described by an anisotropic version of the static Hamilton–Jacobi equation, which is solved by a sweeping method in order to obtain correct arrival times. Pathways of connection are determined by tracing minimum-cost trajectories using the characteristic vector field of the resulting partial differential equation. A validity index is described to rate the goodness of the resulting pathways with respect to the directionality of the tensor field. Connectivity results using normal human DTI brain images are illustrated and discussed. We also compared our method with a similar level set-based tractography technique, and found that the anisotropic evolution increased the validity index of the obtained pathways by 18%. PMID:16040268

  1. Stereotaxic White Matter Atlas Based on Diffusion Tensor Imaging in an ICBM Template

    PubMed Central

    Mori, Susumu; Oishi, Kenichi; Jiang, Hangyi; Jiang, Li; Li, Xin; Akhter, Kazi; Hua, Kegang; Faria, Andreia V.; Mahmood, Asif; Woods, Roger; Toga, Arthur; Pike, Bruce; Neto, Pedro Rosa; Evans, Alan; Zhang, Jiangyang; Huang, Hao; Miller, Michael I.; Zijl, Peter van; Mazziotta, John

    2008-01-01

    Brain registration to a stereotaxic atlas is an effective way to report anatomic locations of interest and to perform anatomic quantification. However, existing stereotaxic atlases lack comprehensive coordinate information about white matter structures. In this paper, white matter specific atlases in stereotaxic coordinates are introduced. As a reference template, the widely-used ICBM-152 was used. The atlas contains fiber orientation maps and hand-segmented white matter parcellation maps based on diffusion tensor imaging (DTI). Registration accuracy by linear and nonlinear transformation was measured, and automated template-based white matter parcellation was tested. The results showed high correlation between the manual ROI-based and the automated approaches for normal adult populations. The atlases are freely available and believed to be a useful resource as a target template and for automated parcellation methods. PMID:18255316

  2. White matter diffusion alterations in normal women at risk of Alzheimer's disease.

    PubMed

    Smith, Charles D; Chebrolu, Himachandra; Andersen, Anders H; Powell, David A; Lovell, Mark A; Xiong, Shuling; Gold, Brian T

    2010-07-01

    Increased white matter mean diffusivity and decreased fractional anisotropy (FA) has been observed in subjects diagnosed with mild cognitive impairment (MCI) and Alzheimer's disease (AD). We sought to determine whether similar alterations of white matter occur in normal individuals at risk of AD. Diffusion tensor images were acquired in 42 cognitively normal right-handed women with both a family history of dementia and at least one apolipoprotein E4 allele. These were compared with images from 23 normal women without either AD risk factor. Group analyses were performed using tract-based spatial statistics. Reduced FA was observed in the fronto-occipital and inferior temporal fasciculi (particularly posteriorly), the splenium of the corpus callosum, subcallosal white matter and the cingulum bundle. These findings demonstrate that specific white matter pathways are altered in normal women at increased risk of AD years before the expected onset of cognitive symptoms. PMID:18801597

  3. Brain white matter lesions detected by magnetic resosnance imaging are associated with balance and gait speed 

    E-print Network

    Starr, John M; Leaper, S A; Murray, A D; Lemmon, H A; Staff, R T; Deary, Ian J; Whalley, Lawrence J

    2003-01-01

    Objective: To investigate the relations between premorbid and current mental ability, mood, and white matter signal abnormalities detected by T2 weighted brain magnetic resonance imaging (MRI) and impairment of balance and ...

  4. SEMIPARAMETRIC GEOMETRIC METHODS FOR EXTRACTING AND MODELING WHITE MATTER VOLUMETRIC STRUCTURES

    E-print Network

    Dyer, Charles R.

    and Organization of Neural Tissue of the Brain 15 2.3 DiscussionSEMIPARAMETRIC GEOMETRIC METHODS FOR EXTRACTING AND MODELING WHITE MATTER VOLUMETRIC STRUCTURES.1 Semiparametric Models . . . . . . . . . . . . . . . . . . . . . . 6 1.2 Implicit Algebraic Polynomial Functions

  5. J Alzheimers Dis . Author manuscript Caffeine, cognitive functioning, and white matter lesions in the elderly

    E-print Network

    Paris-Sud XI, Université de

    J Alzheimers Dis . Author manuscript Page /1 6 Caffeine, cognitive functioning, and white matter Objective The present study examines the epidemiological evidence for a causal relationship between caffeine examining cognitive functioning, caffeine consumption, magnetic resonance imaging volumetrics and other

  6. Long-Term Intermittent Hypoxia Elevates Cobalt Levels in the Brain and Injures White Matter in Adult Mice

    PubMed Central

    Veasey, Sigrid C.; Lear, Jessica; Zhu, Yan; Grinspan, Judith B.; Hare, Dominic J.; Wang, SiHe; Bunch, Dustin; Doble, Philip A.; Robinson, Stephen R.

    2013-01-01

    Study Objectives: Exposure to the variable oxygenation patterns in obstructive sleep apnea (OSA) causes oxidative stress within the brain. We hypothesized that this stress is associated with increased levels of redox-active metals and white matter injury. Design: Participants were randomly allocated to a control or experimental group (single independent variable). Setting: University animal house. Participants: Adult male C57BL/6J mice. Interventions: To model OSA, mice were exposed to long-term intermittent hypoxia (LTIH) for 10 hours/day for 8 weeks or sham intermittent hypoxia (SIH). Measurements and Results: Laser ablation-inductively coupled plasma-mass spectrometry was used to quantitatively map the distribution of the trace elements cobalt, copper, iron, and zinc in forebrain sections. Control mice contained 62 ± 7 ng cobalt/g wet weight, whereas LTIH mice contained 5600 ± 600 ng cobalt/g wet weight (P < 0.0001). Other elements were unchanged between conditions. Cobalt was concentrated within white matter regions of the brain, including the corpus callosum. Compared to that of control mice, the corpus callosum of LTIH mice had significantly more endoplasmic reticulum stress, fewer myelin-associated proteins, disorganized myelin sheaths, and more degenerated axon profiles. Because cobalt is an essential component of vitamin B12, serum methylmalonic acid (MMA) levels were measured. LTIH mice had low MMA levels (P < 0.0001), indicative of increased B12 activity. Conclusions: Long-term intermittent hypoxia increases brain cobalt, predominantly in the white matter. The increased cobalt is associated with endoplasmic reticulum stress, myelin loss, and axonal injury. Low plasma methylmalonic acid levels are associated with white matter injury in long-term intermittent hypoxia and possibly in obstructive sleep apnea. Citation: Veasey SC; Lear J; Zhu Y; Grinspan JB; Hare DJ; Wang S; Bunch D; Doble PA; Robinson SR. Long-term intermittent hypoxia elevates cobalt levels in the brain and injures white matter in adult mice. SLEEP 2013;36(10):1471-1481. PMID:24082306

  7. One-Year Change in Anterior Cingulate Cortex White Matter Microstructure: Relationship with Late-Life Depression Outcomes

    PubMed Central

    Taylor, Warren D.; MacFall, James R.; Boyd, Brian; Payne, Martha E.; Sheline, Yvette I.; Krishnan, K. Ranga R.; Doraiswamy, P. Murali

    2010-01-01

    Objectives Differences in white matter structure measured with diffusion tensor imaging (DTI) are associated with late-life depression, but results examining how these differences relate to antidepressant remission are mixed. To better describe these relationships, we examined how one-year change in DTI measures are related to one-year course of depression. Design One-year cross-sectional follow-up to a 12-week clinical trial of sertraline. Setting Outpatients at an academic medical center. Participants 29 depressed and 20 never-depressed elderly subjects. Over the one-year period, 16 depressed subjects achieved and maintained remission, while 13 did not. Measurements One-year change in fractional anisotropy (FA) and diffusivity in frontal white matter, as measured by DTI. Results Contrary to our hypotheses, depressed subjects who did not remit over the study interval exhibited significantly less change in anterior cingulate cortex white matter FA than did never-depressed or depressed-remitted subjects. There were no group differences in other frontal or central white matter regions. Moreover, there was a significant positive relationship between change in MADRS and change in anterior cingulate cortex FA, wherein greater interval decline in FA was associated with greater interval decline in MADRS. Conclusions Older depressed individuals who remit exhibit white matter changes comparable to what is observed in never-depressed individuals, while nonremitters exhibit significantly less change in anterior cingulate cortex FA. Such a finding may be related to either antidepressant effects on brain structure or the effects of chronic stress on brain structure. Further work is needed to better understand this relationship. PMID:20808126

  8. Effects of Prenatal Exposure to Air Pollutants (Polycyclic Aromatic Hydrocarbons) on Development of Brain White Matter, Cognition, and Behavior in Later Childhood

    PubMed Central

    Peterson, Bradley S.; Rauh, Virginia A.; Bansal, Ravi; Hao, Xuejun; Toth, Zachary; Nati, Giancarlo; Walsh, Kirwan; Miller, Rachel; Arias, Franchesca; Semanek, David; Perera, Frederica

    2015-01-01

    Importance Polycyclic aromatic hydrocarbons (PAH) are ubiquitous and neurotoxic environmental contaminants. Prenatal PAH exposure is associated with subsequent cognitive and behavioral disturbances in childhood. Objective To identify the effects of prenatal PAH exposure on brain structure, and to assess the cognitive and behavioral correlates of those abnormalities, in school-age children. Design Cross-sectional imaging study in a representative, community-based cohort followed prospectively from the fetal period to 7–9 years of age. Setting Urban community residences and an academic imaging center Participants A community-based sample of 40 minority urban youth born to Latina (Dominican) or African-America women and followed prospectively from gestation to early school age. Main Outcome Measures Morphological measures that index local volumes of the surface of the brain and of the white matter surface after cortical gray matter was removed Results We detected a powerful dose-response relationship between increased prenatal PAH exposure (measured in the 3rd trimester, but thought to index exposure for all of gestation) and reductions of the white matter surface in later childhood that were confined almost exclusively to the left hemisphere of the brain, and that involved nearly its entire surface. Reduced left hemisphere white matter was associated with slower information processing speed during intelligence testing and more severe externalizing behavioral problems, including ADHD symptoms and conduct disorder problems. The magnitude of left hemisphere white matter disturbances mediated the significant association of PAH exposure with slower processing speed. Measures of postnatal PAH exposure correlated with white matter surface measures in dorsal prefrontal regions bilaterally while controlling for prenatal PAH exposure. Conclusions and Relevance Our findings suggest that prenatal exposure to PAH air pollutants contributes to slower processing speed, ADHD symptoms, and externalizing problems in urban youth by disrupting development of left hemisphere white matter, whereas postnatal PAH exposure contributes to additional disturbances in development of white matter in dorsal prefrontal regions. PMID:25807066

  9. White-etching matter in bearing steel Part 2: Distinguishing cause and eect in bearing steel

    E-print Network

    Cambridge, University of

    White-etching matter in bearing steel Part 2: Distinguishing cause and eect in bearing steel of Cambridge, U.K Abstract The premature failure of large bearings of the type used in wind turbines, possibly as reported observations on real bearings. Evidence suggests that the formation mechanism of the white

  10. Etiology of Cortical and White Matter Lesions in Cyclosporin-A and FK-506 Neurotoxicity

    Microsoft Academic Search

    Walter S. Bartynski; Zella Zeigler; Michael P. Spearman; Luke Lin; Richard K. Shadduck; John Lister

    2001-01-01

    BACKGROUND AND PURPOSE: The etiology of the neurotoxicity associated with cyclo- sporin-A (CsA) and FK-506 treatment is not fully understood. At our institution, we noticed a distinct, abrupt change in the imaging characteristics of CsA and FK-506 neurotoxicity, which consisted of a shift in lesion morphology from a white matter abnormality to a mixed cortical and white matter pattern. The

  11. Assessing the effects of age on long white matter tracts using diffusion tensor tractography

    PubMed Central

    Davis, Simon W.; Dennis, Nancy A.; Buchler, Norbou G.; White, Leonard E.; Madden, David J.; Cabeza, Roberto

    2009-01-01

    Aging is associated with significant white matter deterioration and this deterioration is assumed to be at least partly a consequence of myelin degeneration. The present study investigated specific predictions of the myelodegeneration hypothesis using diffusion tensor tractography. This technique has several advantages over other methods of assessing white matter architecture, including the possibility of isolating individual white matter tracts and measuring effects along the whole extent of each tract. The study yielded three main findings. First, age-related white matter deficits increased gradually from posterior to anterior segments within specific fiber tracts traversing frontal and parietal, but not temporal cortex. This pattern inverts the sequence of myelination during childhood and early development observed in previous studies and lends support to a “last-in-first-out” theory of the white matter health across the lifespan. Second, both the effects aging on white matter and their impact on cognitive performance were stronger for radial diffusivity (RD) than for axial diffusivity (AD). Given that RD has previously been shown to be more sensitive to myelin integrity than AD, this second finding is also consistent with the myelodegeneration hypothesis. Finally, the effects of aging on select white matter tracts were associated with age difference in specific cognitive functions. Specifically, FA in anterior tracts was shown to be primarily associated with executive tasks and FA in posterior tracts mainly associated with visual memory tasks. Furthermore, these correlations were mirrored in RD, but not AD, suggesting that RD is more sensitive to age-related changes in cognition. Taken together, the results help to clarify how age-related white matter decline impairs cognitive performance. PMID:19385018

  12. Hypoxia–ischemia preferentially triggers glutamate depletion from oligodendroglia and axons in perinatal cerebral white matter

    Microsoft Academic Search

    Stephen A Back; Andrew Craig; Robert J Kayton; Ning Ling Luo; Charles K Meshul; Natalie Allcock; Robert Fern

    2007-01-01

    Ischemia is implicated in periventricular white matter injury (PWMI), a lesion associated with cerebral palsy. PWMI features selective damage to early cells of the oligodendrocyte lineage, a phenomenon associated with glutamate receptor activation. We have investigated the distribution of glutamate in rat periventricular white matter at post-natal day 7. Immuno-electron microcopy was used to identify O4(+) oligodendroglia in control rats,

  13. Genetic underpinnings of white matter 'connectivity': heritability, risk, and heterogeneity in schizophrenia.

    PubMed

    Voineskos, Aristotle N

    2015-01-01

    Schizophrenia is a highly heritable disorder. Thus, the combination of genetics and brain imaging may be a useful strategy to investigate the effects of risk genes on anatomical connectivity, and for gene discovery, i.e. discovering the genetic correlates of white matter phenotypes. Following a database search, I review evidence for heritability of white matter phenotypes. I also review candidate gene investigations, examining association of putative risk variants with white matter phenotypes, as well as the recent flurry of research exploring relationships of genome-wide significant risk loci with white matter phenotypes. Finally, I review multivariate and polygene approaches, which constitute a new wave of imaging-genetics research, including large collaborative initiatives aiming to discover new genes that may predict aspects of white matter microstructure. The literature supports the heritability of white matter phenotypes. Loci in genes intimately implicated in oligodendrocyte and myelin development, growth and maintenance, and neurotrophic systems are associated with white matter microstructure. GWAS variants have not yet sufficiently been explored using DTI-based evaluation of white matter to draw conclusions, although micro-RNA 137 is promising due to its potential regulation of other GWAS schizophrenia genes. Many imaging-genetic studies only include healthy participants, which, while helping control for certain confounds, cannot address questions related to disease heterogeneity or symptom expression, and thus more studies should include participants with schizophrenia. With sufficiently large sample sizes, the future of this field lies in polygene strategies aimed at risk prediction and heterogeneity dissection of schizophrenia that can translate to personalized interventions. PMID:24893906

  14. White matter hypoperfusion and damage in dementia: post-mortem assessment.

    PubMed

    Love, Seth; Miners, J Scott

    2015-01-01

    Neuroimaging has revealed a range of white matter abnormalities that are common in dementia, some that predict cognitive decline. The abnormalities may result from structural diseases of the cerebral vasculature, such as arteriolosclerosis and amyloid angiopathy, but can also be caused by nonstructural vascular abnormalities (eg, of vascular contractility or permeability), neurovascular instability or extracranial cardiac or vascular disease. Conventional histopathological assessment of the white matter has tended to conflate morphological vascular abnormalities with changes that reflect altered interstitial fluid dynamics or white matter ischemic damage, even though the latter may be of extracranial or nonstructural etiology. However, histopathology is being supplemented by biochemical approaches, including the measurement of proteins involved in the molecular responses to brain ischemia, myelin proteins differentially susceptible to ischemic damage, vessel-associated proteins that allow rapid measurement of microvessel density, markers of blood-brain barrier dysfunction and axonal injury, and mediators of white matter damage. By combining neuroimaging with histopathology and biochemical analysis, we can provide reproducible, quantitative data on the severity of white matter damage, and information on its etiology and pathogenesis. Together these have the potential to inform and improve treatment, particularly in forms of dementia to which white matter hypoperfusion makes a significant contribution. PMID:25521180

  15. Vestibular Loss and Balance Training Cause Similar Changes in Human Cerebral White Matter Fractional Anisotropy

    PubMed Central

    Hummel, Nadine; Hüfner, Katharina; Stephan, Thomas; Linn, Jennifer; Kremmyda, Olympia; Brandt, Thomas; Flanagin, Virginia L.

    2014-01-01

    Patients with bilateral vestibular loss suffer from severe balance deficits during normal everyday movements. Ballet dancers, figure skaters, or slackliners, in contrast, are extraordinarily well trained in maintaining balance for the extreme balance situations that they are exposed to. Both training and disease can lead to changes in the diffusion properties of white matter that are related to skill level or disease progression respectively. In this study, we used diffusion tensor imaging (DTI) to compare white matter diffusivity between these two study groups and their age- and sex-matched controls. We found that vestibular patients and balance-trained subjects show a reduction of fractional anisotropy in similar white matter tracts, due to a relative increase in radial diffusivity (perpendicular to the main diffusion direction). Reduced fractional anisotropy was not only found in sensory and motor areas, but in a widespread network including long-range connections, limbic and association pathways. The reduced fractional anisotropy did not correlate with any cognitive, disease-related or skill-related factors. The similarity in FA between the two study groups, together with the absence of a relationship between skill or disease factors and white matter changes, suggests a common mechanism for these white matter differences. We propose that both study groups must exert increased effort to meet their respective usual balance requirements. Since balance training has been shown to effectively reduce the symptoms of vestibular failure, the changes in white matter shown here may represent a neuronal mechanism for rehabilitation. PMID:24776524

  16. 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. PMID:25669910

  17. Effects of DTI spatial normalization on white matter tract reconstructions

    PubMed Central

    Adluru, Nagesh; Zhang, Hui; Tromp, Do P. M.; Alexander, Andrew L.

    2013-01-01

    Major white matter (WM) pathways in the brain can be reconstructed in vivo using tractography on diffusion tensor imaging (DTI) data. Performing tractography using the native DTI data is often considered to produce more faithful results than performing it using the spatially normalized DTI obtained using highly non-linear transformations. However, tractography in the normalized DTI is playing an increasingly important role in population analyses of the WM. In particular, the emerging tract specific analyses (TSA) can benefit from tractography in the normalized DTI for statistical parametric mapping in specific WM pathways. It is well known that the preservation of tensor orientations at the individual voxel level is enforced in tensor based registrations. However small reorientation errors at individual voxel level can accumulate and could potentially affect the tractography results adversely. To our knowledge, there has been no study investigating the effects of normalization on consistency of tractography that demands non-local preservation of tensor orientations which is not explicitly enforced in typical DTI spatial normalization routines. This study aims to evaluate and compare tract reconstructions obtained using normalized DTI against those obtained using native DTI. Although tractography results have been used to measure and influence the quality of spatial normalization, the presented study addresses a distinct question: whether non-linear spatial normalization preserves even long-range anatomical connections obtained using tractography for accurate reconstructions of pathways. Our results demonstrate that spatial normalization of DTI data does preserve tract reconstructions of major WM pathways and does not alter the variance (individual differences) of their macro and microstructural properties. This suggests one can extract quantitative and shape properties efficiently from the tractography data in the normalized DTI for performing population statistics on major WM pathways. PMID:24163728

  18. Fiber Tractography Reveals Disruption of Temporal Lobe White Matter Tracts in Schizophrenia

    PubMed Central

    Phillips, Owen R.; Nuechterlein, Keith H.; Clark, Kristi A.; Hamilton, Liberty S.; Asarnow, Robert F.; Hageman, Nathan S.; Toga, Arthur W.; Narr, Katherine L.

    2009-01-01

    Diffusion tensor imaging (DTI) studies have demonstrated abnormal anisotropic diffusion in schizophrenia. However, examining data with low spatial resolution and/or a low number of gradient directions and limitations associated with analysis approaches sensitive to registration confounds may have contributed to mixed findings concerning the regional specificity and direction of results. This study examined three major white matter tracts connecting lateral and medial temporal lobe regions with neocortical association regions widely implicated in systems-level functional and structural disturbances in schizophrenia. Using DTIstudio, a previously validated regions of interest tractography method was applied to 30 direction diffusion weighted imaging data collected from demographically similar schizophrenia (n=23) and healthy control subjects (n=22). The diffusion tensor was computed at each voxel after intra-subject registration of diffusion-weighted images. Three-dimensional tract reconstruction was performed using the Fiber Assignment by Continuous Tracking (FACT) algorithm. Tractography results showed reduced fractional anisotropy (FA) of the arcuate fasciculi (AF) and inferior longitudinal fasciculi (ILF) in patients compared to controls. FA changes within the right ILF were negatively correlated with measures of thought disturbance. Reduced volume of the left AF was also observed in patients. These results, which avoid registration issues associated with voxel-based analyses of DTI data, support that fiber pathways connecting lateral and medial temporal lobe regions with neocortical regions are compromised in schizophrenia. Disruptions of connectivity within these pathways may potentially contribute to the disturbances of memory, language, and social cognitive processing that characterize the disorder. PMID:19028423

  19. Numerical investigation of white matter anisotropic conductivity in defining current distribution under tDCS.

    PubMed

    Shahid, Salman; Wen, Peng; Ahfock, Tony

    2013-01-01

    The study investigates the impact of white matter directional conductivity on brain current density under the influence of Transcranial direct current stimulation (tDCS). The study employed different conductivity estimation algorithms to represent conductivity distribution in the white matter (WM) of the brain. Two procedures, one mathematically driven and the second one based on the Diffusion tensor imaging (DTI) are considered. The finite element method has been applied to estimate the current density distribution across the head models. Strengths and weaknesses of these algorithms have been compared by analyzing the variation in current density magnitude and distribution patterns with respect to the isotropic case. Results indicate that anisotropy has a profound influence on the strength of current density (up to ?50% in WM) as it causes current flow to deviate from its isotropically defined path along with diffused distribution patterns across the gray and WM. The extent of this variation is highly correlated with the degree of the anisotropy of the regions. Regions of high anisotropy and models of fixed anisotropic ratio displayed higher and wider degree of variations across the structures (topographic variations up to 48%), respectively. In contrast, models, which are correlated with the magnitude of local diffusion tensor behaved in a less exacerbated manner (?10% topographic changes in WM). Anisotropy increased the current density strength across the cortical gyri under and between the stimulating electrodes, whereas a significant drop has been recorded in deeper regions of the GM (max % difference ?±10). In addition, it has been observed that Equivalent isotropic trace algorithm is more suitable to incorporate directional conductivity under tDCS paradigm, than other considered approaches, as this algorithm is computationally less expensive and insensitive to the limiting factor imposed by the volume constraint. PMID:23040278

  20. Reconstruction of White Matter Tracts via Repeated Deterministic Streamline Tracking – Initial Experience

    PubMed Central

    Bauer, Miriam H. A.; Kuhnt, Daniela; Barbieri, Sebastiano; Klein, Jan; Becker, Andreas; Freisleben, Bernd; Hahn, Horst K.; Nimsky, Christopher

    2013-01-01

    Diffusion Tensor Imaging (DTI) and fiber tractography are established methods to reconstruct major white matter tracts in the human brain in-vivo. Particularly in the context of neurosurgical procedures, reliable information about the course of fiber bundles is important to minimize postoperative deficits while maximizing the tumor resection volume. Since routinely used deterministic streamline tractography approaches often underestimate the spatial extent of white matter tracts, a novel approach to improve fiber segmentation is presented here, considering clinical time constraints. Therefore, fiber tracking visualization is enhanced with statistical information from multiple tracking applications to determine uncertainty in reconstruction based on clinical DTI data. After initial deterministic fiber tracking and centerline calculation, new seed regions are generated along the result’s midline. Tracking is applied to all new seed regions afterwards, varying in number and applied offset. The number of fibers passing each voxel is computed to model different levels of fiber bundle membership. Experimental results using an artificial data set of an anatomical software phantom are presented, using the Dice Similarity Coefficient (DSC) as a measure of segmentation quality. Different parameter combinations were classified to be superior to others providing significantly improved results with DSCs of 81.02%±4.12%, 81.32%±4.22% and 80.99%±3.81% for different levels of added noise in comparison to the deterministic fiber tracking procedure using the two-ROI approach with average DSCs of 65.08%±5.31%, 64.73%±6.02% and 65.91%±6.42%. Whole brain tractography based on the seed volume generated by the calculated seeds delivers average DSCs of 67.12%±0.86%, 75.10%±0.28% and 72.91%±0.15%, original whole brain tractography delivers DSCs of 67.16%, 75.03% and 75.54%, using initial ROIs as combined include regions, which is clearly improved by the repeated fiber tractography method. PMID:23671656

  1. Modality-Spanning Deficits in Attention-Deficit/Hyperactivity Disorder in Functional Networks, Gray Matter, and White Matter

    PubMed Central

    Kessler, Daniel; Angstadt, Michael; Welsh, Robert C.

    2014-01-01

    Previous neuroimaging investigations in attention-deficit/hyperactivity disorder (ADHD) have separately identified distributed structural and functional deficits, but interconnections between these deficits have not been explored. To unite these modalities in a common model, we used joint independent component analysis, a multivariate, multimodal method that identifies cohesive components that span modalities. Based on recent network models of ADHD, we hypothesized that altered relationships between large-scale networks, in particular, default mode network (DMN) and task-positive networks (TPNs), would co-occur with structural abnormalities in cognitive regulation regions. For 756 human participants in the ADHD-200 sample, we produced gray and white matter volume maps with voxel-based morphometry, as well as whole-brain functional connectomes. Joint independent component analysis was performed, and the resulting transmodal components were tested for differential expression in ADHD versus healthy controls. Four components showed greater expression in ADHD. Consistent with our a priori hypothesis, we observed reduced DMN-TPN segregation co-occurring with structural abnormalities in dorsolateral prefrontal cortex and anterior cingulate cortex, two important cognitive control regions. We also observed altered intranetwork connectivity in DMN, dorsal attention network, and visual network, with co-occurring distributed structural deficits. There was strong evidence of spatial correspondence across modalities: For all four components, the impact of the respective component on gray matter at a region strongly predicted the impact on functional connectivity at that region. Overall, our results demonstrate that ADHD involves multiple, cohesive modality spanning deficits, each one of which exhibits strong spatial overlap in the pattern of structural and functional alterations. PMID:25505309

  2. The Paradoxical Relationship between White Matter, Psychopathology and Cognition in Schizophrenia: A Diffusion Tensor and Proton Spectroscopic Imaging Study.

    PubMed

    Caprihan, Arvind; Jones, Thomas; Chen, Hongji; Lemke, Nicholas; Abbott, Christopher; Qualls, Clifford; Canive, Jose; Gasparovic, Charles; Bustillo, Juan R

    2015-08-01

    White matter disruption has been repeatedly documented in schizophrenia consistent with microstructural disorganization (reduced fractional anisotropy (FA)) and axonal dysfunction (reduced N-acetylaspartate NAAc). However, the clinical significance of these abnormalities is poorly understood. Diffusion tensor and proton spectroscopic imaging where used to assess FA, axial diffusivity and radial diffusivity (RD), and supra-ventricular white matter NAAc, respectively, in 64 schizophrenia and 64 healthy subjects. Schizophrenia patients had reduced FA across several regions, with additional regions where FA correlated positively with positive symptoms severity. These regions included genu, body and splenium of corpus callosum, anterior and superior corona radiata, superior longitudinal and inferior fronto-occipital fasciculi, and internal capsule. The FA/symptoms relationships corresponded with opposite correlations between RD and positive symptoms. The schizophrenia group (SP group) had progressively reduced NAAc with age, and NAAc correlated negatively with positive symptoms. Cognition correlated positively with both FA and NAAc in controls, whereas in the SP group it had a negative correlation with NAAc and no significant relationship with FA. Antipsychotic dose did not account for the results. Correlates of psychosis, cognitive and negative symptoms can be found in white matter. The significant correlations between positive symptoms in schizophrenia and diffusion and NAAc measures suggest decreased axonal density with increased glial cells and higher myelination in this subpopulation. A separate set of abnormal relationships between cognition and FA/RD, as well as with NAAc, converge to suggest that in schizophrenia, white matter microstructure supports the two core illness domains: psychosis and cognitive/negative symptoms. PMID:25786581

  3. Quantitative structural changes in white and gray matter 1 year following traumatic brain injury in rats.

    PubMed

    Bramlett, Helen M; Dietrich, W Dalton

    2002-06-01

    There is evidence for chronic atrophy after human head trauma, which may be associated with long-term functional deficits. However, using established models of traumatic brain injury (TBI) only limited data are available for clarifying the extent of progressive gray and white matter atrophy. In the present study, male Sprague-Dawley rats underwent moderate (2.01-2.21 atm) parasagittal fluid percussion brain injury ( n=7) or sham ( n=3) surgery and were killed at 1 year post TBI. Semiserial sections were obtained through the neuraxis and double stained with hematoxylin and eosin to demarcate gray matter structures and Luxol fast blue for white matter visualization. Both ipsilateral and contralateral volume measurements were obtained for the following structures: cerebral cortex, hippocampus, dentate gyrus, thalamus, lateral ventricle, external capsule, internal capsule, cerebral peduncle and corpus callosum. Quantitative assessment of ipsilateral gray matter structures from TBI rats revealed significant reductions in cerebral cortical area measurements posterior from the trauma epicenter compared to sham animals. Importantly, several white matter tracts exhibited dramatic atrophy. A comparison of TBI and sham groups demonstrated a significant ( P<0.05) decrease in the external capsule and cerebral peduncle volumes ( P<0.007). In addition, there was a significant volume expansion (533% of control) of the ipsilateral lateral ventricle ( P<0.03). These novel data emphasize the need to clarify the pathophysiology of progressive white matter damage after TBI and the development of therapeutic strategies to target white matter pathology. PMID:12012093

  4. Tract-based analysis of white matter degeneration in Alzheimer's disease.

    PubMed

    Lee, S-H; Coutu, J-P; Wilkens, P; Yendiki, A; Rosas, H D; Salat, D H

    2015-08-20

    Although much prior work has focused on the known cortical pathology that defines Alzheimer's disease (AD) histologically, recent work has additionally demonstrated substantial damage to the cerebral white matter in this condition. While there is large evidence of diffuse damage to the white matter in AD, it is unclear whether specific white matter tracts exhibit a more accelerated pattern of damage and whether the damage is associated with the classical neurodegenerative changes of AD. In this study, we investigated microstructural differences in the large fascicular bundles of the cerebral white matter of individuals with AD and mild cognitive impairment (MCI), using recently developed automated diffusion tractography procedures in the Alzheimer's disease Neuroimaging Initiative (ADNI) dataset. Eighteen major fiber bundles in a total of 36 individuals with AD, 81 MCI and 60 control participants were examined with the TRActs Constrained by UnderLying Anatomy (TRACULA) procedure available as part of the FreeSurfer image processing software package. For each fiber bundle, the mean fractional anisotropy (FA), and mean, radial and axial diffusivities were calculated. Individuals with AD had increased diffusivities in both left and right cingulum-angular bundles compared to control participants (p<0.001). Individuals with MCI also had increased axial and mean diffusivities and increased FA in both cingulum-angular bundles compared to control participants (p<0.05) and decreased radial diffusivity compared to individuals with AD (p<0.05). We additionally examined how white matter deterioration relates to hippocampal volume, a traditional imaging measure of AD pathology, and found the strongest negative correlations in AD patients between hippocampal volume and the diffusivities of the cingulum-angular and cingulum-cingulate gyrus bundles and of the corticospinal tracts (p<0.05). However, statistically controlling for hippocampal volume did not remove all group differences in white matter measures, suggesting a unique contribution of white matter damage to AD unexplained by this disease biomarker. These results suggest that (1) AD-associated deterioration of white matter fibers is greatest in tracts known to be connected to areas of pathology in AD and (2) lower white matter tract integrity is more diffusely associated with lower hippocampal volume indicating that the pathology in the white matter follows to some degree the neurodegenerative staging and progression of this condition. PMID:26026680

  5. White Matter Integrity Linked To Functional Impairments in Aging and Early Alzheimer’s Disease

    PubMed Central

    Kavcic, Voyko; Ni, Hongyan; Zhu, Tong; Zhong, Jianhui; Duffy, Charles J.

    2008-01-01

    Background Alzheimer’s disease (AD) is associated with changes in cerebral white matter (WM) but the functional significance of such findings is not yet established. We hypothesized that diffusion tensor imaging (DTI) might reveal links between regional WM changes and specific neuropsychologically and psychophysically defined impairments in early AD. Methods Older adult control subjects (OA, n=18) and mildly impaired AD patients (n=14) underwent neuropsychological and visual perceptual testing along with DTI of cerebral WM. DTI yielded factional anisotropy (FA) and mean diffusivity () maps for nine ROIs in three brain regions that were then compared to the performance measures. Results AD patients showed non-significant trends toward lower FAs in the posterior region’s callosal and sub-cortical ROIs. However, posterior callosal FA was significantly correlated with verbal fluency and figural memory impairments, whereas posterior subcortical FA was correlated with delayed verbal memory, figural memory, and optic flow perceptual impairments. Conclusions WM changes in early AD are concentrated in posterior cerebral areas with distributions that correspond to specific functional impairments. DTI can be used to assess regional pathology related to individual’s deficits in early AD. PMID:19012862

  6. White Matter Lesions Are Not Related to ?-Amyloid Deposition in an Autopsy-Based Study

    PubMed Central

    Rutten-Jacobs, Loes C. A.; de Leeuw, Frank-Erik; Geurts-van Bon, Lenny; Gordinou de Gouberville, Marije C.; Schepens-Franke, Annelieke N.; Dederen, P. Jos; Spliet, Wim G. M.; Wesseling, Pieter; Kiliaan, Amanda J.

    2011-01-01

    Population-based studies have investigated the relation between ?-amyloid levels in cerebrospinal fluid or plasma and white matter lesions (WMLs). However, these circulating levels of ?-amyloid in cerebrospinal fluid or plasma may not reliably reflect the actual degree of amyloid present in the brain. Therefore, we investigated the relation between WMLs and ?-amyloid plaques and amyloid angiopathy in brain tissue. WML on MRI or CT were rated in 28 nondemented patients whose neuroimaging was available prior to death. ?-amyloid in plaques and arterioles were immunohistochemically stained and quantified in postmortem brain necropsies. WMLs were present in 43% of the total population. Both cortex and periventricular region showed no differences for ?-amyloid deposition in either plaques or blood vessel walls in patients with WMLs compared to those without WMLs. Thus, our results indicate that there is no relation between the degree of WMLs and ?-amyloid deposition in the brain. PMID:22203842

  7. Last Interglacial marine environments in the White Sea region, northwestern Russia

    E-print Network

    Ingólfsson, Ólafur

    Last Interglacial marine environments in the White Sea region, northwestern Russia KARI GRŘSFJELD., Seidenkrantz, M.-S. & Glaister, C. 2006 (August): Last Interglacial marine environments in the White Sea region passages to the White Sea. Local, low-saline, stratified basins developed and characterized the next five

  8. Depressive symptoms and white matter dysfunction in retired NFL players with concussion history

    PubMed Central

    Strain, Jeremy; Didehbani, Nyaz; Cullum, C. Munro; Mansinghani, Sethesh; Conover, Heather; Kraut, Michael A.; Womack, Kyle B.

    2013-01-01

    Objective: To determine whether correlates of white matter integrity can provide general as well as specific insight into the chronic effects of head injury coupled with depression symptom expression in professional football players. Method: We studied 26 retired National Football League (NFL) athletes who underwent diffusion tensor imaging (DTI) scanning. Depressive symptom severity was measured using the Beck Depression Inventory II (BDI-II) including affective, cognitive, and somatic subfactor scores (Buckley 3-factor model). Fractional anisotropy (FA) maps were processed using tract-based spatial statistics from FSL. Correlations between FA and BDI-II scores were assessed using both voxel-wise and region of interest (ROI) techniques, with ROIs that corresponded to white matter tracts. Tracts demonstrating significant correlations were further evaluated using a receiver operating characteristic curve that utilized the mean FA to distinguish depressed from nondepressed subjects. Results: Voxel-wise analysis identified widely distributed voxels that negatively correlated with total BDI-II and cognitive and somatic subfactors, with voxels correlating with the affective component (p < 0.05 corrected) localized to frontal regions. Four tract ROIs negatively correlated (p < 0.01) with total BDI-II: forceps minor, right frontal aslant tract, right uncinate fasciculus, and left superior longitudinal fasciculus. FA of the forceps minor differentiated depressed from nondepressed athletes with 100% sensitivity and 95% specificity. Conclusion: Depressive symptoms in retired NFL athletes correlate negatively with FA using either an unbiased voxel-wise or an ROI-based, tract-wise approach. DTI is a promising biomarker for depression in this population. PMID:23709590

  9. Morphology of neurons in the white matter of the adult human neocortex.

    PubMed

    Meyer, G; Wahle, P; Castaneyra-Perdomo, A; Ferres-Torres, R

    1992-01-01

    Neurons in the human cerebral cortical white matter below motor, visual, auditory and prefrontal orbital areas have been studied with the Golgi method, immunohistochemistry and diaphorase histochemistry. The majority of white matter neurons are pyramidal cells displaying the typical polarized, spiny dendritic system. The morphological variety includes stellate forms as well as bipolar pyramidal cells, and the expression of a certain morphological phenotype seems to depend on the position of the neuron. Spineless nonpyramidal neurons with multipolar to bitufted dendritic fields constitute less than 10% of the neurons stained for microtubule associated protein (MAP-2). Only 3% of the MAP-2 immunoreactive neurons display nicotine adenine dinucleotide-diaphorase activity. The white matter pyramidal neurons are arranged in radial rows continuous with the columns of layer VI neurons. Neuron density is highest below layer VI, and decreases with increasing distance from the gray matter. White matter neurons are especially abundant below the primary motor cortex, and are least frequent below the visual cortex area 17. In contrast to other mammalian species, the white matter neurons in man are not only present during development, but persist throughout life. PMID:1541357

  10. Altered white matter microstructure is associated with social cognition and psychotic symptoms in 22q11.2 microdeletion syndrome.

    PubMed

    Jalbrzikowski, Maria; Villalon-Reina, Julio E; Karlsgodt, Katherine H; Senturk, Damla; Chow, Carolyn; Thompson, Paul M; Bearden, Carrie E

    2014-01-01

    22q11.2 Microdeletion Syndrome (22q11DS) is a highly penetrant genetic mutation associated with a significantly increased risk for psychosis. Aberrant neurodevelopment may lead to inappropriate neural circuit formation and cerebral dysconnectivity in 22q11DS, which may contribute to symptom development. Here we examined: (1) differences between 22q11DS participants and typically developing controls in diffusion tensor imaging (DTI) measures within white matter tracts; (2) whether there is an altered age-related trajectory of white matter pathways in 22q11DS; and (3) relationships between DTI measures, social cognition task performance, and positive symptoms of psychosis in 22q11DS and typically developing controls. Sixty-four direction diffusion weighted imaging data were acquired on 65 participants (36 22q11DS, 29 controls). We examined differences between 22q11DS vs. controls in measures of fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD), using both a voxel-based and region of interest approach. Social cognition domains assessed were: Theory of Mind and emotion recognition. Positive symptoms were assessed using the Structured Interview for Prodromal Syndromes. Compared to typically developing controls, 22q11DS participants showed significantly lower AD and RD in multiple white matter tracts, with effects of greatest magnitude for AD in the superior longitudinal fasciculus. Additionally, 22q11DS participants failed to show typical age-associated changes in FA and RD in the left inferior longitudinal fasciculus. Higher AD in the left inferior fronto-occipital fasciculus (IFO) and left uncinate fasciculus was associated with better social cognition in 22q11DS and controls. In contrast, greater severity of positive symptoms was associated with lower AD in bilateral regions of the IFO in 22q11DS. White matter microstructure in tracts relevant to social cognition is disrupted in 22q11DS, and may contribute to psychosis risk. PMID:25426042

  11. Gray matter contamination in arterial spin labeling white matter perfusion measurements in patients with dementia?

    PubMed Central

    Mutsaerts, Henri J.M.M.; Richard, Edo; Heijtel, Dennis F.R.; van Osch, Matthias J.P.; Majoie, Charles B.L.M.; Nederveen, Aart J.

    2013-01-01

    Introduction White matter (WM) perfusion measurements with arterial spin labeling can be severely contaminated by gray matter (GM) perfusion signal, especially in the elderly. The current study investigates the spatial extent of GM contamination by comparing perfusion signal measured in the WM with signal measured outside the brain. Material and methods Four minute 3T pseudo-continuous arterial spin labeling scans were performed in 41 elderly subjects with cognitive impairment. Outward and inward geodesic distance maps were created, based on dilations and erosions of GM and WM masks. For all outward and inward geodesic distances, the mean CBF was calculated and compared. Results GM contamination was mainly found in the first 3 subcortical WM voxels and had only minor influence on the deep WM signal (distances 4 to 7 voxels). Perfusion signal in the WM was significantly higher than perfusion signal outside the brain, indicating the presence of WM signal. Conclusion These findings indicate that WM perfusion signal can be measured unaffected by GM contamination in elderly patients with cognitive impairment. GM contamination can be avoided by the erosion of WM masks, removing subcortical WM voxels from the analysis. These results should be taken into account when exploring the use of WM perfusion as micro-vascular biomarker. PMID:24371796

  12. Unique transcriptome patterns of the white and grey matter corroborate structural and functional heterogeneity in the human frontal lobe.

    PubMed

    Mills, James D; Kavanagh, Tomas; Kim, Woojin S; Chen, Bei Jun; Kawahara, Yoshihiro; Halliday, Glenda M; Janitz, Michael

    2013-01-01

    The human frontal lobe has undergone accelerated evolution, leading to the development of unique human features such as language and self-reflection. Cortical grey matter and underlying white matter reflect distinct cellular compositions in the frontal lobe. Surprisingly little is known about the transcriptomal landscape of these distinct regions. Here, for the first time, we report a detailed transcriptomal profile of the frontal grey (GM) and white matter (WM) with resolution to alternatively spliced isoforms obtained using the RNA-Seq approach. We observed more vigorous transcriptome activity in GM compared to WM, presumably because of the presence of cellular bodies of neurons in the GM and RNA associated with the nucleus and perinuclear space. Among the top differentially expressed genes, we also identified a number of long intergenic non-coding RNAs (lincRNAs), specifically expressed in white matter, such as LINC00162. Furthermore, along with confirmation of expression of known markers for neurons and oligodendrocytes, we identified a number of genes and splicing isoforms that are exclusively expressed in GM or WM with examples of GABRB2 and PAK2 transcripts, respectively. Pathway analysis identified distinct physiological and biochemical processes specific to grey and white matter samples with a prevalence of synaptic processes in GM and myelination regulation and axonogenesis in the WM. Our study also revealed that expression of many genes, for example, the GPR123, is characterized by isoform switching, depending in which structure the gene is expressed. Our report clearly shows that GM and WM have perhaps surprisingly divergent transcriptome profiles, reflecting distinct roles in brain physiology. Further, this study provides the first reference data set for a normal human frontal lobe, which will be useful in comparative transcriptome studies of cerebral disorders, in particular, neurodegenerative diseases. PMID:24194939

  13. Catechol-O-Methyltransferase Val158Met Polymorphism on the Relationship between White Matter Hyperintensity and Cognition in Healthy People

    PubMed Central

    Liu, Mu-En; Huang, Chu-Chung; Yang, Albert C.; Tu, Pei-Chi; Yeh, Heng-Liang; Hong, Chen-Jee; Liou, Ying-Jay; Chen, Jin-Fan; Chou, Kun-Hsien; Lin, Ching-Po; Tsai, Shih-Jen

    2014-01-01

    Background White matter lesions can be easily observed on T2-weighted MR images, and are termed white matter hyperintensities (WMH). Their presence may be correlated with cognitive impairment; however, the relationship between regional WMH volume and catechol-O-methyltransferase (COMT) Val158Met polymorphism in healthy populations remains unclear. Methods We recruited 315 ethnic Chinese adults with a mean age of 54.9±21.8 years (range: 21–89 y) to examine the genetic effect of COMT on regional WMH and the manner in which they interact to affect cognitive function in a healthy adult population. Cognitive tests, structural MRI scans, and genotyping of COMT were conducted for each participant. Results Negative correlations between the Digit Span Forward (DSF) score and frontal WMH volumes (r?=??.123, P?=?.032, uncorrected) were noted. For the genetic effect of COMT, no significant difference in cognitive performance was observed among 3 genotypic groups. However, differences in WMH volumes over the subcortical region (P?=?.016, uncorrected), whole brain (P?=?.047, uncorrected), and a trend over the frontal region (P?=?.050, uncorrected) were observed among 3 COMT genotypic groups. Met homozygotes and Met/Val heterozygotes exhibited larger WMH volumes in these brain regions than the Val homozygotes. Furthermore, a correlation between the DSF and regional WMH volume was observed only in Met homozygotes. The effect size (cohen’s f) revealed a small effect. Conclusions The results indicate that COMT might modulate WMH volumes and the effects of WMH on cognition. PMID:24551149

  14. Unraveling the secrets of white matter--bridging the gap between cellular, animal and human imaging studies.

    PubMed

    Walhovd, K B; Johansen-Berg, H; Káradóttir, R T

    2014-09-12

    The CNS white matter makes up about half of the human brain, and with advances in human imaging it is increasingly becoming clear that changes in the white matter play a major role in shaping human behavior and learning. However, the mechanisms underlying these white matter changes remain poorly understood. Within this special issue of Neuroscience on white matter, recent advances in our knowledge of the function of white matter, from the molecular level to human imaging, are reviewed. Collaboration between fields is essential to understand the function of the white matter, but due to differences in methods and field-specific 'language', communication is often hindered. In this review, we try to address this hindrance by introducing the methods and providing a basic background to myelin biology and human imaging as a prelude to the other reviews within this special issue. PMID:25003711

  15. Interactions between white matter asymmetry and language during neurodevelopment.

    PubMed

    O'Muircheartaigh, Jonathan; Dean, Douglas C; Dirks, Holly; Waskiewicz, Nicole; Lehman, Katie; Jerskey, Beth A; Deoni, Sean C L

    2013-10-01

    The human brain is asymmetric in gross structure as well as functional organization. However, the developmental basis and trajectory of this asymmetry is unclear, and its relationship(s) to functional and cognitive development, especially language, remain to be fully elucidated. During infancy and early childhood, in concert with cortical gray matter growth, underlying axonal bundles become progressively myelinated. This myelination is critical for efficient and coherent interneuronal communication and, as revealed in animal studies, the degree of myelination changes in response to environment and neuronal activity. Using a novel quantitative magnetic resonance imaging method to investigate myelin content in vivo in human infants and young children, we investigated gross asymmetry of myelin in a large cohort of 108 typically developing children between 1 and 6 years of age, hypothesizing that asymmetry would predict language abilities in this cohort. While asymmetry of myelin content was evident in multiple cortical and subcortical regions, language ability was predicted only by leftward asymmetry of caudate and frontal cortex myelin content and rightward asymmetry in the extreme capsule. Importantly, the influence of this asymmetry was found to change with age, suggesting an age-specific influence of structure and myelin on language function. The relationship between language ability and asymmetry of myelin stabilized at ?4 years, indicating anatomical evidence for a critical time during development before which environmental influence on cognition may be greatest. PMID:24107949

  16. A fully automated method for quantifying and localizing white matter hyperintensities on MR images.

    PubMed

    Wu, Minjie; Rosano, Caterina; Butters, Meryl; Whyte, Ellen; Nable, Megan; Crooks, Ryan; Meltzer, Carolyn C; Reynolds, Charles F; Aizenstein, Howard J

    2006-12-01

    White matter hyperintensities (WMH), commonly found on T2-weighted FLAIR brain MR images in the elderly, are associated with a number of neuropsychiatric disorders, including vascular dementia, Alzheimer's disease, and late-life depression. Previous MRI studies of WMHs have primarily relied on the subjective and global (i.e., full-brain) ratings of WMH grade. In the current study we implement and validate an automated method for quantifying and localizing WMHs. We adapt a fuzzy-connected algorithm to automate the segmentation of WMHs and use a demons-based image registration to automate the anatomic localization of the WMHs using the Johns Hopkins University White Matter Atlas. The method is validated using the brain MR images acquired from eleven elderly subjects with late-onset late-life depression (LLD) and eight elderly controls. This dataset was chosen because LLD subjects are known to have significant WMH burden. The volumes of WMH identified in our automated method are compared with the accepted gold standard (manual ratings). A significant correlation of the automated method and the manual ratings is found (P<0.0001), thus demonstrating similar WMH quantifications of both methods. As has been shown in other studies (e.g. [Taylor, W.D., MacFall, J.R., Steffens, D.C., Payne, M.E., Provenzale, J.M., Krishnan, K.R., 2003. Localization of age-associated white matter hyperintensities in late-life depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 27 (3), 539-544.]), we found there was a significantly greater WMH burden in the LLD subjects versus the controls for both the manual and automated method. The effect size was greater for the automated method, suggesting that it is a more specific measure. Additionally, we describe the anatomic localization of the WMHs in LLD subjects as well as in the control subjects, and detect the regions of interest (ROIs) specific for the WMH burden of LLD patients. Given the emergence of large NeuroImage databases, techniques, such as that described here, will allow for a better understanding of the relationship between WMHs and neuropsychiatric disorders. PMID:17097277

  17. Coupled Changes in Brain White Matter Microstructure and Fluid Intelligence in Later Life

    PubMed Central

    Bastin, Mark E.; Tucker-Drob, Elliot M.; Maniega, Susana Muńoz; 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.

    2015-01-01

    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. PMID:26041932

  18. 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 Muńoz; 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

    2015-06-01

    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. PMID:26041932

  19. A Schizophrenia Risk Gene, ZNF804A, is Associated with Brain White Matter Microstructure

    PubMed Central

    Ikuta, Toshikazu; Peters, Bart D.; Guha, Saurav; John, Majnu; Karlsgodt, Katherine H.; Lencz, Todd; Szeszko, Philip R.; Malhotra, Anil K.

    2014-01-01

    Genome-wide association studies have provided strong evidence for association of the SNP rs1344706 in the ZNF804A gene with schizophrenia and bipolar disorder. Neuroimaging studies have suggested that variation at rs1344706 may be associated with neural endophenotypes such as white matter volumes and densities. However, analyses of white matter microstructure using diffusion tensor imaging (DTI) have produced conflicting results. We examined the association between rs1344706 and white matter microstructure in 107 healthy individuals using Tract-Based Spatial Statistics (TBSS). TBSS analysis showed significant association between the risk allele and lower fractional anisotropy in the corpus callosum, left forceps minor, and right parietal white matter (p < .05; FWE corrected). Post-hoc analyses indicated that this association was largely driven by alterations in radial diffusivity, consistent with an effect of genotype on myelination. In light of the strong DTI evidence for white matter microstructural abnormalities in schizophrenia, the current results implicate a potential mechanism for schizophrenia risk formation by ZNF804A rs1344706 genotype. PMID:24685285

  20. A schizophrenia risk gene, ZNF804A, is associated with brain white matter microstructure.

    PubMed

    Ikuta, T; Peters, B D; Guha, S; John, M; Karlsgodt, K H; Lencz, T; Szeszko, P R; Malhotra, A K

    2014-05-01

    Genome-wide association studies have provided strong evidence for association of the SNP rs1344706 in the ZNF804A gene with schizophrenia and bipolar disorder. Neuroimaging studies have suggested that variation at rs1344706 may be associated with neural endophenotypes such as white matter volumes and densities. However, analyses of white matter microstructure using diffusion tensor imaging (DTI) have produced conflicting results. We examined the association between rs1344706 and white matter microstructure in 107 healthy individuals using tract-based spatial statistics (TBSS). TBSS analysis showed significant association between the risk allele and lower fractional anisotropy in the corpus callosum, left forceps minor, and right parietal white matter (p<.05; FWE corrected). Post-hoc analyses indicated that this association was largely driven by alterations in radial diffusivity, consistent with an effect of genotype on myelination. In light of the strong DTI evidence for white matter microstructural abnormalities in schizophrenia, the current results implicate a potential mechanism for schizophrenia risk formation by ZNF804A rs1344706 genotype. PMID:24685285

  1. Tract Probability Maps in Stereotaxic Spaces: Analyses of White Matter Anatomy and Tract-Specific Quantification

    PubMed Central

    Hua, Kegang; Zhang, Jiangyang; Wakana, Setsu; Jiang, Hangyi; Li, Xin; Reich, Daniel S.; Calabresi, Peter A.; Pekar, James J.; van Zijl, Peter C. M.; Mori, Susumu

    2009-01-01

    Diffusion tensor imaging (DTI) is an exciting new MRI modality that can reveal detailed anatomy of the white matter. DTI also allows us to approximate the 3D trajectories of major white matter bundles. By combining the identified tract coordinates with various types of MR parameter maps, such as T2 and diffusion properties, we can perform tract-specific analysis of these parameters. Unfortunately, 3D tract reconstruction is marred by noise, partial volume effects, and complicated axonal structures. Furthermore, changes in diffusion anisotropy under pathological conditions could alter the results of 3D tract reconstruction. In this study, we created a white matter parcellation atlas based on probabilistic maps of 11 major white matter tracts derived from the DTI data from 28 normal subjects. Using these probabilistic maps, automated tract-specific quantification of fractional anisotropy and mean diffusivity were performed. Excellent correlation was found between the automated and the individual tractography-based results. This tool allows efficient initial screening of the status of multiple white matter tracts. PMID:17931890

  2. Microstructural changes in white matter associated with freezing of gait in Parkinson's disease.

    PubMed

    Vercruysse, Sarah; Leunissen, Inge; Vervoort, Griet; Vandenberghe, Wim; Swinnen, Stephan; Nieuwboer, Alice

    2015-04-01

    In Parkinson's disease (PD), freezing of gait (FOG) is associated with widespread functional and structural gray matter changes throughout the brain. Previous study of freezing-related white matter changes was restricted to brainstem and cerebellar locomotor tracts. This study was undertaken to determine the spatial distribution of white matter damage associated with FOG by combining whole brain and striatofrontal seed-based diffusion tensor imaging. Diffusion-weighted images were collected in 26 PD patients and 16 age-matched controls. Parkinson's disease groups with (n?=?11) and without freezing of gait (n?=?15) were matched for age and disease severity. We applied tract-based spatial statistics to compare fractional anisotropy and mean diffusivity of white matter structure across the whole brain between groups. Probabilistic tractography was used to evaluate fractional anisotropy and mean diffusivity of key subcortico-cortical tracts. Tract-based spatial statistics revealed decreased fractional anisotropy in PD with FOG in bilateral cerebellar and superior longitudinal fascicle clusters. Increased mean diffusivity values were apparent in the right internal capsule, superior frontal cortex, anterior corona radiata, the left anterior thalamic radiation, and cerebellum. Tractography showed consistent white matter alterations in striatofrontal tracts through the putamen, caudate, pallidum, subthalamic nucleus, and in connections of the cerebellar peduncle with subthalamic nucleus and pedunculopontine nucleus bilaterally. We conclude that FOG is associated with diffuse white matter damage involving major cortico-cortical, corticofugal motor, and several striatofrontal tracts in addition to previously described cerebello-pontine connectivity changes. These distributed white matter abnormalities may contribute to the motor and non-motor correlates of FOG. PMID:25640958

  3. 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

  4. A Japanese girl with an early-infantile onset vanishing white matter disease resembling Cree leukoencephalopathy.

    PubMed

    Takano, Kyoko; Tsuyusaki, Yu; Sato, Mutsumi; Takagi, Mariko; Anzai, Rie; Okuda, Mitsuko; Iai, Mizue; Yamashita, Sumimasa; Okabe, Tetsuhiko; Aida, Noriko; Tsurusaki, Yoshinori; Saitsu, Hirotomo; Matsumoto, Naomichi; Osaka, Hitoshi

    2015-06-01

    Vanishing white matter disease (VWM)/childhood ataxia with central hypomyelination (CACH) is an autosomal recessive leukoencephalopathy caused by mutations in one of five genes, EIF2B1-5, encoding the 5 subunits of eukaryotic translation initiation factor 2B (eIF2B). The classical phenotype is characterized by early childhood onset and chronic progressive neurological deterioration with cerebellar ataxia, spasticity, optic atrophy and epilepsy. However, the onset of disease varies from antenatal period to adulthood. Cree leukoencephalopathy (CLE) is a severe variant of VWM and caused by a homozygous mutation (R195H) in the EIF2B5 gene. The patient reported in this study developed lethargy, vomiting and seizure 3days after an oral poliovirus vaccination at the age of 4months. She presented with rapid neurological deterioration within a month of onset. Brain MRI showed abnormal white matter intensity. Whole-exome sequencing identified two heterozygous mutations in the EIF2B5 gene: a known mutation, c.584G>A (R195H, which is homozygous in CLE), and a novel mutation, c.1223T>C (I408T, which resides in the "I-patch"). Mutations in the "I-patch" encoded region of eIF2B? may be related to an early-infantile onset phenotype. This patient exhibits an early-infantile onset and progressive disease course resembling CLE, suggesting a severe functional disruption of eIF2B? caused by R195H as well as by I408T mutations. PMID:25457085

  5. The structural plasticity of white matter networks following anterior temporal lobe resection

    PubMed Central

    Yogarajah, Mahinda; Focke, Niels K.; Bonelli, Silvia B.; Thompson, Pamela; Vollmar, Christian; McEvoy, Andrew W.; Alexander, Daniel C.; Symms, Mark R.; Koepp, Matthias J.

    2010-01-01

    Anterior temporal lobe resection is an effective treatment for refractory temporal lobe epilepsy. The structural consequences of such surgery in the white matter, and how these relate to language function after surgery remain unknown. We carried out a longitudinal study with diffusion tensor imaging in 26 left and 20 right temporal lobe epilepsy patients before and a mean of 4.5 months after anterior temporal lobe resection. The whole-brain analysis technique tract-based spatial statistics was used to compare pre- and postoperative data in the left and right temporal lobe epilepsy groups separately. We observed widespread, significant, mean 7%, decreases in fractional anisotropy in white matter networks connected to the area of resection, following both left and right temporal lobe resections. However, we also observed a widespread, mean 8%, increase in fractional anisotropy after left anterior temporal lobe resection in the ipsilateral external capsule and posterior limb of the internal capsule, and corona radiata. These findings were confirmed on analysis of the native clusters and hand drawn regions of interest. Postoperative tractography seeded from this area suggests that this cluster is part of the ventro-medial language network. The mean pre- and postoperative fractional anisotropy and parallel diffusivity in this cluster were significantly correlated with postoperative verbal fluency and naming test scores. In addition, the percentage change in parallel diffusivity in this cluster was correlated with the percentage change in verbal fluency after anterior temporal lobe resection, such that the bigger the increase in parallel diffusivity, the smaller the fall in language proficiency after surgery. We suggest that the findings of increased fractional anisotropy in this ventro-medial language network represent structural reorganization in response to the anterior temporal lobe resection, which may damage the more susceptible dorso-lateral language pathway. These findings have important implications for our understanding of brain injury and rehabilitation, and may also prove useful in the prediction and minimization of postoperative language deficits. PMID:20826432

  6. The structural plasticity of white matter networks following anterior temporal lobe resection.

    PubMed

    Yogarajah, Mahinda; Focke, Niels K; Bonelli, Silvia B; Thompson, Pamela; Vollmar, Christian; McEvoy, Andrew W; Alexander, Daniel C; Symms, Mark R; Koepp, Matthias J; Duncan, John S

    2010-08-01

    Anterior temporal lobe resection is an effective treatment for refractory temporal lobe epilepsy. The structural consequences of such surgery in the white matter, and how these relate to language function after surgery remain unknown. We carried out a longitudinal study with diffusion tensor imaging in 26 left and 20 right temporal lobe epilepsy patients before and a mean of 4.5 months after anterior temporal lobe resection. The whole-brain analysis technique tract-based spatial statistics was used to compare pre- and postoperative data in the left and right temporal lobe epilepsy groups separately. We observed widespread, significant, mean 7%, decreases in fractional anisotropy in white matter networks connected to the area of resection, following both left and right temporal lobe resections. However, we also observed a widespread, mean 8%, increase in fractional anisotropy after left anterior temporal lobe resection in the ipsilateral external capsule and posterior limb of the internal capsule, and corona radiata. These findings were confirmed on analysis of the native clusters and hand drawn regions of interest. Postoperative tractography seeded from this area suggests that this cluster is part of the ventro-medial language network. The mean pre- and postoperative fractional anisotropy and parallel diffusivity in this cluster were significantly correlated with postoperative verbal fluency and naming test scores. In addition, the percentage change in parallel diffusivity in this cluster was correlated with the percentage change in verbal fluency after anterior temporal lobe resection, such that the bigger the increase in parallel diffusivity, the smaller the fall in language proficiency after surgery. We suggest that the findings of increased fractional anisotropy in this ventro-medial language network represent structural reorganization in response to the anterior temporal lobe resection, which may damage the more susceptible dorso-lateral language pathway. These findings have important implications for our understanding of brain injury and rehabilitation, and may also prove useful in the prediction and minimization of postoperative language deficits. PMID:20826432

  7. Color discrimination deficits in Parkinson's disease are related to cognitive impairment and white-matter alterations.

    PubMed

    Bertrand, Josie-Anne; Bedetti, Christophe; Postuma, Ronald B; Monchi, Oury; Génier Marchand, Daphné; Jubault, Thomas; Gagnon, Jean-François

    2012-12-01

    Color discrimination deficit is a common nonmotor manifestation of Parkinson's disease (PD). However, the pathophysiology of this dysfunction remains poorly understood. Although retinal structure changes found in PD have been suggested to cause color discrimination deficits, the impact of cognitive impairment and cortical alterations remains to be determined. We investigated the contribution of cognitive impairment to color discrimination deficits in PD and correlated them with cortical anomalies. Sixty-six PD patients without dementia and 20 healthy controls performed the Farnsworth-Munsell 100 hue test and underwent a comprehensive neuropsychological assessment for mild cognitive impairment diagnosis. In a subgroup of 26 PD patients, we also used high-definition neuroanatomical magnetic resonance imaging for cortical thickness and diffusion tensor analysis. PD patients with mild cognitive impairment performed poorly on the Farnsworth-Munsell 100 hue test compared with PD patients without mild cognitive impairment and controls. In PD patients, performance on the Farnsworth-Munsell 100 hue test was correlated with measures of visuospatial abilities and executive functions. Neuroimaging analysis revealed higher mean and radial diffusivity values in right posterior white-matter structures that correlated with poor performance on the Farnsworth-Munsell 100 hue test. No cortical thickness correlation reached significance. This study showed that cognitive impairment makes a major contribution to the color discrimination deficits reported in PD. Thus, performance on the Farnsworth-Munsell 100 hue test may reflect cognitive impairment more than color discrimination deficits in PD. Poor performance on the Farnsworth-Munsell 100 hue test was also associated with white-matter alterations in right posterior brain regions. PMID:23147270

  8. Microstructural abnormalities of the brain white matter in attention-deficit/hyperactivity disorder

    PubMed Central

    Chen, Lizhou; Huang, Xiaoqi; Lei, Du; He, Ning; Hu, Xinyu; Chen, Ying; Li, Yuanyuan; Zhou, Jinbo; Guo, Lanting; Kemp, Graham J.; Gong, Qiyong

    2015-01-01

    Background Attention-deficit/hyperactivity disorder (ADHD) is an early-onset neurodevelopmental disorder with multiple behavioural problems and executive dysfunctions for which neuroimaging studies have reported a variety of abnormalities, with inconsistencies partly owing to confounding by medication and concurrent psychiatric disease. We aimed to investigate the microstructural abnormalities of white matter in unmedicated children and adolescents with pure ADHD and to explore the association between these abnormalities and behavioural symptoms and executive functions. Methods We assessed children and adolescents with ADHD and healthy controls using psychiatric interviews. Behavioural problems were rated using the revised Conners’ Parent Rating Scale, and executive functions were measured using the Stroop Colour-Word Test and the Wisconsin Card Sorting test. We acquired diffusion tensor imaging data using a 3 T MRI system, and we compared diffusion parameters, including fractional anisotropy (FA) and mean, axial and radial diffusivities, between the 2 groups. Results Thirty-three children and adolescents with ADHD and 35 healthy controls were included in our study. In patients compared with controls, FA was increased in the left posterior cingulum bundle as a result of both increased axial diffusivity and decreased radial diffusivity. In addition, the averaged FA of the cluster in this region correlated with behavioural measures as well as executive function in patients with ADHD. Limitations This study was limited by its cross-sectional design and small sample size. The cluster size of the significant result was small. Conclusion Our findings suggest that white matter abnormalities within the limbic network could be part of the neural underpinning of behavioural problems and executive dysfunction in patients with ADHD. PMID:25853285

  9. Spatial HARDI: Improved Visualization of Complex White Matter Architecture with Bayesian Spatial Regularization

    PubMed Central

    Raj, Ashish; Hess, Christopher; Mukherjee, Pratik

    2010-01-01

    Imaging of water diffusion using magnetic resonance imaging has become an important noninvasive method for probing the white matter connectivity of the human brain for scientific and clinical studies. Current methods such as diffusion tensor imaging (DTI), high angular resolution diffusion imaging (HARDI) such as q-ball imaging, and diffusion spectrum imaging (DSI), are limited by low spatial resolution, long scan times, and low signal-to-noise ratio (SNR). These methods fundamentally perform reconstruction on a voxel-by-voxel level, effectively discarding the natural coherence of the data at different points in space. This paper attempts to overcome these tradeoffs by using spatial information to constrain the reconstruction from raw diffusion MRI data, and thereby improve angular resolution and noise tolerance. Spatial constraints are specified in terms of a prior probability distribution, which is then incorporated in a Bayesian reconstruction formulation. By taking the log of the resulting posterior distribution, optimal Bayesian reconstruction is reduced to a cost minimization problem. The minimization is solved using a new iterative algorithm based on successive least squares quadratic descent. Simulation studies and in vivo results are presented which indicate significant gains in terms of higher angular resolution of diffusion orientation distribution functions, better separation of crossing fibers, and improved reconstruction SNR over the same HARDI method, spherical harmonic q-ball imaging, without spatial regularization. Preliminary data also indicate that the proposed method might be better at maintaining accurate ODFs for smaller numbers of diffusion-weighted acquisition directions (hence faster scans) compared to conventional methods. Possible impacts of this work include improved evaluation of white matter microstructural integrity in regions of crossing fibers and higher spatial and angular resolution for more accurate tractography. PMID:20670684

  10. Effects of a Balanced Translocation between Chromosomes 1 and 11 Disrupting the DISC1 Locus on White Matter Integrity

    PubMed Central

    Whalley, Heather C.; Dimitrova, Rali; Sprooten, Emma; Dauvermann, Maria R.; Romaniuk, Liana; Duff, Barbara; Watson, Andrew R.; Moorhead, Bill; Bastin, Mark; Semple, Scott I.; Giles, Stephen; Hall, Jeremy; Thomson, Pippa; Roberts, Neil; Hughes, Zoe A.; Brandon, Nick J.; Dunlop, John; Whitcher, Brandon; Blackwood, Douglas H. R.; McIntosh, Andrew M.; Lawrie, Stephen M.

    2015-01-01

    Objective Individuals carrying rare, but biologically informative genetic variants provide a unique opportunity to model major mental illness and inform understanding of disease mechanisms. The rarity of such variations means that their study involves small group numbers, however they are amongst the strongest known genetic risk factors for major mental illness and are likely to have large neural effects. DISC1 (Disrupted in Schizophrenia 1) is a gene containing one such risk variant, identified in a single Scottish family through its disruption by a balanced translocation of chromosomes 1 and 11; t(1;11) (q42.1;q14.3). Method Within the original pedigree, we examined the effects of the t(1;11) translocation on white matter integrity, measured by fractional anisotropy (FA). This included family members with (n = 7) and without (n = 13) the translocation, along with a clinical control sample of patients with psychosis (n = 34), and a group of healthy controls (n = 33). Results We report decreased white matter integrity in five clusters in the genu of the corpus callosum, the right inferior fronto-occipital fasciculus, acoustic radiation and fornix. Analysis of the mixed psychosis group also demonstrated decreased white matter integrity in the above regions. FA values within the corpus callosum correlated significantly with positive psychotic symptom severity. Conclusions We demonstrate that the t(1;11) translocation is associated with reduced white matter integrity in frontal commissural and association fibre tracts. These findings overlap with those shown in affected patients with psychosis and in DISC1 animal models and highlight the value of rare but biologically informative mutations in modeling psychosis. PMID:26102360

  11. Abnormal hippocampal–thalamic white matter tract development and positive symptom course in individuals at ultra-high risk for psychosis

    PubMed Central

    Bernard, Jessica A; Orr, Joseph M; Mittal, Vijay A

    2015-01-01

    Background/Objectives Abnormal development of the hippocampus has been reported in adolescents at ultra-high risk (UHR) for psychosis and thalamic abnormalities have been found. However, the white matter connections between the hippocampus and the thalamus have not been studied. The connections between these regions are of key importance to our understanding of the pathophysiology of psychosis. Methods Twenty-six UHR and 21 healthy age-matched controls were tested at a baseline assessment and 12 months later. Symptoms were assessed at both the time points and all the participants underwent diffusion tensor imaging scans. We used tractography to trace the white matter connections in each individual between the thalamus and hippocampus and then extracted fractional anisotropy (FA) to assess white matter structural integrity. Results There was a significant group by time interaction indicating that FA decreased in UHR, and increased in controls over 12 months. Across both groups, baseline FA of the thalamic–hippocampal tract was predictive of positive symptoms at 12-month follow-up. Critically, this pattern remained significant in UHR individual group alone. At baseline, those with higher FA, indicative of abnormal white matter development, show higher positive symptoms 1 year later. Conclusions Here, we provide evidence to indicate that there are differences in white matter development in hippocampal–thalamic connections, both of which are important nodes in networks associated with schizophrenia. Furthermore, abnormal developmental patterns in UHR individuals are associated with positive symptom course.

  12. White matter in the older brain is more plastic than in the younger brain

    PubMed Central

    Yotsumoto, Yuko; Chang, Li-Hung; Ni, Rui; Pierce, Russell; Andersen, George J; Watanabe, Takeo; Sasaki, Yuka

    2014-01-01

    Visual perceptual learning (VPL) with younger subjects is associated with changes in functional activation of the early visual cortex. Although overall brain properties decline with age, it is unclear whether these declines are associated with visual perceptual learning. Here we use diffusion tensor imaging to test whether changes in white matter are involved in VPL for older adults. After training on a texture discrimination task for 3 daily sessions, both older and younger subjects show performance improvements. While the older subjects show significant changes in fractional anisotropy (FA) in the white matter beneath the early visual cortex after training, no significant change in FA is observed for younger subjects. These results suggest that the mechanism for VPL in older individuals is considerably different from that in younger individuals and that VPL of older individuals involves re-organization of white matter. PMID:25407566

  13. White Matter Changes in Bipolar Disorder, Alzheimer Disease, and Mild Cognitive Impairment: New Insights from DTI

    PubMed Central

    Xekardaki, Aikaterini; Giannakopoulos, Panteleimon; Haller, Sven

    2011-01-01

    Neuropathological and neuroimaging studies have reported significant changes in white matter in psychiatric and neurodegenerative diseases. Diffusion tensor imaging (DTI), a recently developed technique, enables the detection of microstructural changes in white matter. It is a noninvasive in vivo technique that assesses water molecules' diffusion in brain tissues. The most commonly used parameters are axial and radial diffusivity reflecting diffusion along and perpendicular to the axons, as well as mean diffusivity and fractional anisotropy representing global diffusion. Although the combination of these parameters provides valuable information about the integrity of brain circuits, their physiological meaning still remains controversial. After reviewing the basic principles of DTI, we report on recent contributions that used this technique to explore subtle structural changes in white matter occurring in elderly patients with bipolar disorder and Alzheimer disease. PMID:22187647

  14. Myelin peroxisomes - essential organelles for the maintenance of white matter in the nervous system.

    PubMed

    Kassmann, Celia M

    2014-03-01

    Peroxisomes are cellular compartments primarily associated with lipid metabolism. Most cell types, including nervous system cells, harbor several hundred of these organelles. The importance of peroxisomes for central nervous system white matter is evidenced by a variety of human peroxisomal disorders with neurological impairment frequently involving the white matter. Moreover, the most frequent childhood white matter disease, X-linked adrenoleukodystrophy, is a peroxisomal disorder. During the past decade advances in imaging techniques have enabled the identification of peroxisomes within the myelin sheath, especially close to nodes of Ranvier. Although the function of myelin peroxisomes is not solved yet on molecular level, recently acquired knowledge suggests a central role for these organelles in axo-glial metabolism. This review focuses on the biology of myelin peroxisomes as well as on the pathology of myelin and myelinated axons that is observed as a consequence of partial or complete peroxisomal dysfunction in the brain. PMID:24120688

  15. Automatic clustering and population analysis of white matter tracts using maximum density paths.

    PubMed

    Prasad, Gautam; Joshi, Shantanu H; Jahanshad, Neda; Villalon-Reina, Julio; Aganj, Iman; Lenglet, Christophe; Sapiro, Guillermo; McMahon, Katie L; de Zubicaray, Greig I; Martin, Nicholas G; Wright, Margaret J; Toga, Arthur W; Thompson, Paul M

    2014-08-15

    We introduce a framework for population analysis of white matter tracts based on diffusion-weighted images of the brain. The framework enables extraction of fibers from high angular resolution diffusion images (HARDI); clustering of the fibers based partly on prior knowledge from an atlas; representation of the fiber bundles compactly using a path following points of highest density (maximum density path; MDP); and registration of these paths together using geodesic curve matching to find local correspondences across a population. We demonstrate our method on 4-Tesla HARDI scans from 565 young adults to compute localized statistics across 50 white matter tracts based on fractional anisotropy (FA). Experimental results show increased sensitivity in the determination of genetic influences on principal fiber tracts compared to the tract-based spatial statistics (TBSS) method. Our results show that the MDP representation reveals important parts of the white matter structure and considerably reduces the dimensionality over comparable fiber matching approaches. PMID:24747738

  16. Distribution of axon diameters in cortical white matter: an electron-microscopic study on three human brains and a macaque.

    PubMed

    Liewald, Daniel; Miller, Robert; Logothetis, Nikos; Wagner, Hans-Joachim; Schüz, Almut

    2014-10-01

    The aim of this study was to obtain information on the axonal diameters of cortico-cortical fibres in the human brain, connecting distant regions of the same hemisphere via the white matter. Samples for electron microscopy were taken from the region of the superior longitudinal fascicle and from the transitional white matter between temporal and frontal lobe where the uncinate and inferior occipitofrontal fascicle merge. We measured the inner diameter of cross sections of myelinated axons. For comparison with data from the literature on the human corpus callosum, we also took samples from that region. For comparison with well-fixed material, we also included samples from corresponding regions of a monkey brain (Macaca mulatta). Fibre diameters in human brains ranged from 0.16 to 9 ?m. Distributions of diameters were similar in the three systems of cortico-cortical fibres investigated, both in humans and the monkey, with most of the average values below 1 ?m diameter and a small population of much thicker fibres. Within individual human brains, the averages were larger in the superior longitudinal fascicle than in the transitional zone between temporal and frontal lobe. An asymmetry between left and right could be found in one of the human brains, as well as in the monkey brain. A correlation was also found between the thickness of the myelin sheath and the inner axon diameter for axons whose calibre was greater than about 0.6 ?m. The results are compared to white matter data in other mammals and are discussed with respect to conduction velocity, brain size, cognition, as well as diffusion weighted imaging studies. PMID:25142940

  17. Transcriptome analysis of grey and white matter cortical tissue in multiple system atrophy.

    PubMed

    Mills, James D; Kim, Woojin S; Halliday, Glenda M; Janitz, Michael

    2015-04-01

    Multiple system atrophy (MSA) is a distinct member of a group of neurodegenerative diseases known as ?-synucleinopathies, which are characterized by the presence of aggregated ?-synuclein in the brain. MSA is unique in that the principal site for ?-synuclein deposition is in the oligodendrocytes rather than neurons. The cause of MSA is unknown, and the pathogenesis of MSA is still largely speculative. Brain transcriptome perturbations during the onset and progression of MSA are mostly unknown. Using RNA sequencing, we performed a comparative transcriptome profiling analysis of the grey matter (GM) and white matter (WM) of the frontal cortex of MSA and control brains. The transcriptome sequencing revealed increased expression of the alpha and beta haemoglobin genes in MSA WM, decreased expression of the transthyretin (TTR) gene in MSA GM and numerous region-specific long intervening non-coding RNAs (lincRNAs). In contrast, we observed only moderate changes in the expression patterns of the ?-synuclein (SNCA) gene, which confirmed previous observations by other research groups. Our study suggests that at the transcriptional level, MSA pathology may be related to increased iron levels in WM and perturbations of the non-coding fraction of the transcriptome. PMID:25370810

  18. The Black-White Achievement Gap: Do State Policies Matter?

    ERIC Educational Resources Information Center

    Braun, Henry I.; Wang, Aubrey; Jenkins, Frank; Weinbaum, Elliot

    2006-01-01

    A longstanding issue in American education is the gap in academic achievement between majority and minority students. The goal of this study is to accumulate and evaluate evidence on the relationship between state education policies and changes in the Black-White achievement gap, while addressing some of the methodological issues that have led to…

  19. Abnormal functional connectivity during visuospatial processing is associated with disrupted organisation of white matter in autism

    PubMed Central

    McGrath, Jane; Johnson, Katherine; O'Hanlon, Erik; Garavan, Hugh; Leemans, Alexander; Gallagher, Louise

    2013-01-01

    Disruption of structural and functional neural connectivity has been widely reported in Autism Spectrum Disorder (ASD) but there is a striking lack of research attempting to integrate analysis of functional and structural connectivity in the same study population, an approach that may provide key insights into the specific neurobiological underpinnings of altered functional connectivity in autism. The aims of this study were (1) to determine whether functional connectivity abnormalities were associated with structural abnormalities of white matter (WM) in ASD and (2) to examine the relationships between aberrant neural connectivity and behavior in ASD. Twenty-two individuals with ASD and 22 age, IQ-matched controls completed a high-angular-resolution diffusion MRI scan. Structural connectivity was analysed using constrained spherical deconvolution (CSD) based tractography. Regions for tractography were generated from the results of a previous study, in which 10 pairs of brain regions showed abnormal functional connectivity during visuospatial processing in ASD. WM tracts directly connected 5 of the 10 region pairs that showed abnormal functional connectivity; linking a region in the left occipital lobe (left BA19) and five paired regions: left caudate head, left caudate body, left uncus, left thalamus, and left cuneus. Measures of WM microstructural organization were extracted from these tracts. Fractional anisotropy (FA) reductions in the ASD group relative to controls were significant for WM connecting left BA19 to left caudate head and left BA19 to left thalamus. Using a multimodal imaging approach, this study has revealed aberrant WM microstructure in tracts that directly connect brain regions that are abnormally functionally connected in ASD. These results provide novel evidence to suggest that structural brain pathology may contribute (1) to abnormal functional connectivity and (2) to atypical visuospatial processing in ASD. PMID:24133425

  20. A Stylized Binarization Procedure for Black\\/White Comics Using HSV Region Extension

    Microsoft Academic Search

    Dong-Sung Ryu; Hwan-Gue Cho

    2008-01-01

    Generally most of the black\\/white comics color in human's skin as white, while the dark region is filled with the irregular but regular patterns like hatching. Note that it is not enough for simple threshold method to perform this work. In this paper, we propose a simple and straightforward binarization procedure which can generate black\\/white comics from the video frame

  1. Mineral composition of the suspended particulate matter in the White Sea

    NASA Astrophysics Data System (ADS)

    Kravchishina, M. D.; Dara, O. M.

    2014-05-01

    The mineral composition of the suspended particulate matter (SPM) was studied for the White Sea area. The comparative analysis of the composition of the marine SMP and the SPM of the rivers of the White Sea catchment area was performed, including the Severnaya Dvina River, one of the major sources of the terrigenous suspended matter to the sea. The research of such kind is faced with numerous methodological difficulties, which slows down the study process. Data on the mineral composition of the SPM are scarce. Applying the method of X-ray powder diffractometry, we assessed the bulk mineral composition of the SPM with special regard to its clay fraction.

  2. Developmental white matter microstructure in autism phenotype and corresponding endophenotype during adolescence

    E-print Network

    Lisiecka, D. M.; Holt, R.; Tait, R.; Ford, M.; Lai, M.-C.; Chura, L. R.; Baron-Cohen, S.; Spencer, M. D.; Suckling, J.

    2015-03-17

    OPEN ORIGINAL ARTICLE Developmental white matter microstructure in autism phenotype and corresponding endophenotype during adolescence DM Lisiecka1,2, R Holt3, R Tait2, M Ford4, M-C Lai3,5, LR Chura3, S Baron-Cohen2,3,6, MD Spencer3,7 and J Suckling... 1,2,6 During adolescence, white matter microstructure undergoes an important stage of development. It is hypothesized that the alterations of brain connectivity that have a key role in autism spectrum conditions (ASCs) may interact...

  3. 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.

  4. Cognitive impairment and memory disorders in relapsing-remitting multiple sclerosis: the role of white matter, gray matter and hippocampus.

    PubMed

    Sacco, R; Bisecco, A; Corbo, D; Della Corte, M; d'Ambrosio, A; Docimo, R; Gallo, A; Esposito, F; Esposito, S; Cirillo, M; Lavorgna, L; Tedeschi, G; Bonavita, S

    2015-07-01

    Cognitive disorders occur in up to 65 % of multiple sclerosis (MS) patients; they have been correlated with different MRI measures of brain tissue damage, whole and regional brain atrophy. The hippocampal involvement has been poorly investigated in cognitively impaired (CI) MS patients. The objective of this study is to analyze and compare brain tissue abnormalities, including hippocampal atrophy, in relapsing-remitting MS (RRMS) patients with and without cognitive deficits, and to investigate their role in determining cognitive impairment in MS. Forty-six RRMS patients [20 CI and 26 cognitively preserved (CP)] and 25 age, sex and education-matched healthy controls (HCs) underwent neuropsychological evaluation and 3-Tesla anatomical MRI. T2 lesion load (T2-LL) was computed with a semiautomatic method, gray matter volume and white matter volume were estimated using SIENAX. Hippocampal volume (HV) was obtained by manual segmentation. Brain tissues volumes were compared among groups and correlated with cognitive performances. Compared to HCs, RRMS patients had significant atrophy of WM, GM, left and right Hippocampus (p < 0.001). Compared to CP, CI RRMS patients showed higher T2-LL (p = 0.02) and WM atrophy (p = 0.01). In the whole RRMS group, several cognitive tests correlated with brain tissue abnormalities (T2-LL, WM and GM atrophy); only verbal memory performances correlated with left hippocampal atrophy. Our results emphasize the role of T2-LL and WM atrophy in determining clinically evident cognitive impairment in MS patients and provide evidence that GM and hippocampal atrophy occur in MS patients regardless of cognitive status. PMID:25957638

  5. White matter integrity of the cerebellar peduncles as a mediator of effects of prenatal alcohol exposure on eyeblink conditioning.

    PubMed

    Fan, Jia; Meintjes, Ernesta M; Molteno, Christopher D; Spottiswoode, Bruce S; Dodge, Neil C; Alhamud, Alkathafi A; Stanton, Mark E; Peterson, Bradley S; Jacobson, Joseph L; Jacobson, Sandra W

    2015-07-01

    Fetal alcohol spectrum disorders (FASD) are characterized by a range of neurodevelopmental deficits that result from prenatal exposure to alcohol. These can include cognitive, behavioural, and neurological impairment, as well as structural and functional brain damage. Eyeblink conditioning (EBC) is among the most sensitive endpoints affected in FASD. The cerebellar peduncles, large bundles of myelinated nerve fibers that connect the cerebellum to the brainstem, constitute the principal white matter element of the EBC circuit. Diffusion tensor imaging (DTI) is used to assess white matter integrity in fibre pathways linking brain regions. DTI scans of 54 children with FASD and 23 healthy controls, mean age 10.1?±?1.0 years, from the Cape Town Longitudinal Cohort were processed using voxelwise group comparisons. Prenatal alcohol exposure was related to lower fractional anisotropy (FA) bilaterally in the superior cerebellar peduncles and higher mean diffusivity (MD) in the left middle peduncle, effects that remained significant after controlling for potential confounding variables. Lower FA and higher MD in these regions were associated with poorer EBC performance. Moreover, effects of alcohol exposure on EBC decreased significantly after inclusion of these DTI measures in regression models, suggesting that these white matter deficits partially mediate the relation of prenatal alcohol exposure to EBC. The associations of greater alcohol consumption with these DTI measures are largely attributable to greater radial diffusivity, possibly indicating poorer myelination. Thus, these data suggest that fetal alcohol-related deficits in EBC are attributable, in part, to poorer myelination in key regions of the cerebellar peduncles. Hum Brain Mapp 36:2470-2482, 2015. © 2015 Wiley Periodicals, Inc. PMID:25783559

  6. Cerebral White Matter Abnormalities and Their Associations with Negative but not Positive Symptoms of Schizophrenia

    PubMed Central

    Asami, Takeshi; Lee, Sang Hyuk; Bouix, Sylvain; Rathi, Yogesh; Whitford, Thomas J.; Niznikiewicz, Margaret; Nestor, Paul; McCarley, Robert W.; Shenton, Martha E.; Kubicki, Marek

    2014-01-01

    Although diffusion tensor imaging (DTI) studies have reported fractional anisotropy (FA) abnormalities in multiple white matter (WM) regions in schizophrenia, relationship between abnormal FA and negative symptoms has not been fully explored. DTI data were acquired from twenty-four patients with chronic schizophrenia and twenty-five healthy controls. Regional brain abnormalities were evaluated by conducting FA comparisons in the cerebral and each lobar WMs between groups. Focal abnormalities were also evaluated with a voxel-wise tract specific method. Associations between structural WM changes and negative symptoms were assessed using the Scale for the Assessment of Negative Symptoms (SANS). The patient group showed decreased FA in the cerebrum, especially in the frontal lobe, compared with controls. A voxel-wise analysis showed FA decreases in almost all WM tracts in schizophrenia. Correlation analyses demonstrated negative relationships between FA in the cerebrum, particularly in the left hemisphere, and SANS global and global rating scores (Anhedonia-Asociality, Attention, and Affective-Flattening), and also associations between FA of left frontal lobe and SANS global score, Anhedonia-Asociality, and Attention. This study demonstrates that patients with chronic schizophrenia evince widespread cerebral FA abnormalities and that these abnormalities, especially in the left hemisphere, are associated with negative symptoms. PMID:24650453

  7. Effects of age on white matter integrity and negative symptoms in schizophrenia.

    PubMed

    Bijanki, Kelly Rowe; Hodis, Brendan; Magnotta, Vincent A; Zeien, Eugene; Andreasen, Nancy C

    2015-01-01

    The current study examined the relationship between white matter integrity as indexed by diffusion tensor imaging and negative symptom severity in schizophrenia. The current study included statistical controls for age effects on the relationship of interest, a major weakness of the existing literature on the subject. Participants included 59 chronic schizophrenia patients, and 31 first-episode schizophrenia patients. Diffusion-weighted neuroimaging was used to calculate fractional anisotropy (FA) in each major brain region (frontal, temporal, parietal, and occipital lobes). Negative symptoms were measured using the Scale for the Assessment of Negative Symptoms (SANS) in all schizophrenia patients. Significant bivariate correlations were observed between global SANS scores and global FA, as well as in most brain regions. These relationships appeared to be driven by SANS items measuring facial expressiveness, poor eye contact, affective flattening, inappropriate affect, poverty of speech, poverty of speech content, alogia, and avolition. However, upon addition of age as a covariate, the observed relationships became non-significant. Further analysis revealed very strong age effects on both FA and SANS scores in the current sample. The findings of this study refute previous reports of significant relationships between DTI variables and negative symptoms in schizophrenia, and they suggest an important confounding variable to be considered in future studies in this population. PMID:24957354

  8. Cerebral white matter abnormalities and their associations with negative but not positive symptoms of schizophrenia.

    PubMed

    Asami, Takeshi; Hyuk Lee, Sang; Bouix, Sylvain; Rathi, Yogesh; Whitford, Thomas J; Niznikiewicz, Margaret; Nestor, Paul; McCarley, Robert W; Shenton, Martha E; Kubicki, Marek

    2014-04-30

    Although diffusion tensor imaging (DTI) studies have reported fractional anisotropy (FA) abnormalities in multiple white matter (WM) regions in schizophrenia, relationship between abnormal FA and negative symptoms has not been fully explored. DTI data were acquired from twenty-four patients with chronic schizophrenia and twenty-five healthy controls. Regional brain abnormalities were evaluated by conducting FA comparisons in the cerebral and each lobar WMs between groups. Focal abnormalities were also evaluated with a voxel-wise tract specific method. Associations between structural WM changes and negative symptoms were assessed using the Scale for the Assessment of Negative Symptoms (SANS). The patient group showed decreased FA in the cerebrum, especially in the frontal lobe, compared with controls. A voxel-wise analysis showed FA decreases in almost all WM tracts in schizophrenia. Correlation analyses demonstrated negative relationships between FA in the cerebrum, particularly in the left hemisphere, and SANS global and global rating scores (Anhedonia-Asociality, Attention, and Affective-Flattening), and also associations between FA of left frontal lobe and SANS global score, Anhedonia-Asociality, and Attention. This study demonstrates that patients with chronic schizophrenia evince widespread cerebral FA abnormalities and that these abnormalities, especially in the left hemisphere, are associated with negative symptoms. PMID:24650453

  9. Structural Network Topology Revealed by White Matter Tractography in Cannabis Users: A Graph Theoretical Analysis

    PubMed Central

    Kim, Dae-Jin; Skosnik, Patrick D.; Cheng, Hu; Pruce, Ben J.; Brumbaugh, Margaret S.; Vollmer, Jennifer M.; Hetrick, William P.; O'Donnell, Brian F.; Sporns, Olaf; Puce, Aina

    2011-01-01

    Abstract Endocannabinoid receptors modulate synaptic plasticity in the brain and may therefore impact cortical connectivity not only during development but also in response to substance abuse in later life. Such alterations may not be evident in volumetric measures utilized in brain imaging, but could affect the local and global organization of brain networks. To test this hypothesis, we used a novel computational approach to estimate network measures of structural brain connectivity derived from diffusion tensor imaging (DTI) and white matter tractography. Twelve adult cannabis (CB) users and 13 healthy subjects were evaluated using a graph theoretic analysis of both global and local brain network properties. Structural brain networks in both CB subjects and controls exhibited robust small-world network attributes in both groups. However, CB subjects showed significantly decreased global network efficiency and significantly increased clustering coefficients (degree to which nodes tend to cluster around individual nodes). CB subjects also exhibited altered patterns of local network organization in the cingulate region. Among all subjects, schizotypal and impulsive personality characteristics correlated with global efficiency but not with the clustering coefficient. Our data indicate that structural brain networks in CB subjects are less efficiently integrated and exhibit altered regional connectivity. These differences in network properties may reflect physiological processes secondary to substance abuse-induced synaptic plasticity, or differences in brain organization that increase vulnerability to substance use. PMID:22432904

  10. Reduced frontal cortex efficiency is associated with lower white matter integrity in aging.

    PubMed

    Zhu, Zude; Johnson, Nathan F; Kim, Chobok; Gold, Brian T

    2015-01-01

    Increased frontal cortex activation during cognitive task performance is common in aging but remains poorly understood. Here we explored patterns of age-related frontal brain activations under multiple task performance conditions and their relationship to white matter (WM) microstructure. Groups of younger (N = 28) and older (N = 33) participants completed a task-switching paradigm while functional magnetic resonance imaging (fMRI) was performed, and rested while diffusion tensor imaging was performed. Results from fMRI analyses indicated age-related increases in frontal brain activations under conditions of poorer performance in the older group (the nonswitch and switch conditions) and for a contrast in which behavioral performance was equated (older group nonswitch condition vs. younger group switch condition). Within the older adult group, higher frontal activation was associated with poorer behavioral performance under all task conditions. In 2 regions in right frontal cortex, blood oxygen level-dependent (BOLD) magnitudes were negatively correlated with WM integrity in tracts connecting these structures with other task-relevant frontoparietal and striatal regions. Our results link age-related declines in the efficiency of frontal cortex functioning with lower WM integrity in aging. PMID:23960206

  11. Reconstruction of the Human Cerebral Cortex Robust to White Matter Lesions: Method and Validation

    PubMed Central

    Shiee, Navid; Bazin, Pierre-Louis; Cuzzocreo, Jennifer L.; Ye, Chuyang; Kishore, Bhaskar; Carass, Aaron; Calabresi, Peter A.; Reich, Daniel S.; Prince, Jerry L.; Pham, Dzung L.

    2014-01-01

    Cortical atrophy has been reported in a number of diseases, such as multiple sclerosis and Alzheimer’s disease, that are also associated with white matter (WM) lesions. However, most cortical reconstruction techniques do not account for these pathologies, thereby requiring additional processing to correct for the effect of WM lesions. In this work we introduce CRUISE+, an automated process for cortical reconstruction from magnetic resonance brain images with WM lesions. The process extends previously well validated methods to allow for multichannel input images and to accommodate for the presence of WM lesions. We provide new validation data and tools for measuring the accuracy of cortical reconstruction methods on healthy brains as well as brains with multiple sclerosis lesions. Using this data, we validate the accuracy of CRUISE+ and compare it to another state-of-the-art cortical reconstruction tool. Our results demonstrate that CRUISE+ has superior performance in the cortical regions near WM lesions, and similar performance in other regions. PMID:24382742

  12. 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…

  13. Gender differences in the rate of white matter microstructural development during late childhood and adolescence J. D. Clayden1

    E-print Network

    Clayden, Jonathan D.

    Gender differences in the rate of white matter microstructural development during late childhood There is evidence for various changes in white matter microstructure during development. Particular pathways gender differences in dMRI parameters such as mean diffusivity (MD) and fractional anisotropy (FA) have

  14. Loss of connectivity in Alzheimer's disease: an evaluation of white matter tract integrity with colour coded MR diffusion tensor imaging

    Microsoft Academic Search

    Stephen E Rose; Fang Chen; Jonathan B Chalk; Fernando O Zelaya; Wendy E Strugnell; Mark Benson; James Semple; David M Doddrell

    2000-01-01

    A NOVEL MRI METHODdiffusion tensor imaging—was used to compare the integrity of several white matter fibre tracts in patients with probable Alzheimer's disease. Relative to normal controls, patients with probable Alzheimer's disease showed a highly significant reduction in the integrity of the association white matter fibre tracts, such as the splenium of the corpus callosum, superior longitudinal fasciculus, and cingulum.

  15. Increase in periventricular white matter hyperintensities parallels decline in mental processing speed in a non demented elderly population

    Microsoft Academic Search

    DMJ van den Heuvel; J Jolles; HM Murray; MA van Buchem; E L E M Bollen; G J Blauw; R G J Westendorp; M A van Buchem

    2005-01-01

    Objective: To investigate the influence of deep white matter hyperintensities (DWMH) and periventricular white matter hyperintensities (PVWMH) on progression of cognitive decline in non-demented elderly people. Methods: All data come from the nested MRI sub-study of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). We performed a 3 year follow up study on 554 subjects of the

  16. Systematic network lesioning reveals the core white matter scaffold of the human brain

    PubMed Central

    Irimia, Andrei; Van Horn, John D.

    2013-01-01

    Brain connectivity loss due to traumatic brain injury, stroke or multiple sclerosis can have serious consequences on life quality and a measurable impact upon neural and cognitive function. Though brain network properties are known to be affected disproportionately by injuries to certain gray matter regions, the manner in which white matter (WM) insults affect such properties remains poorly understood. Here, network-theoretic analysis allows us to identify the existence of a macroscopic neural connectivity core in the adult human brain which is particularly sensitive to network lesioning. The systematic lesion analysis of brain connectivity matrices from diffusion neuroimaging over a large sample (N = 110) reveals that the global vulnerability of brain networks can be predicated upon the extent to which injuries disrupt this connectivity core, which is found to be quite distinct from the set of connections between rich club nodes in the brain. Thus, in addition to connectivity within the rich club, the brain as a network also contains a distinct core scaffold of network edges consisting of WM connections whose damage dramatically lowers the integrative properties of brain networks. This pattern of core WM fasciculi whose injury results in major alterations to overall network integrity presents new avenues for clinical outcome prediction following brain injury by relating lesion locations to connectivity core disruption and implications for recovery. The findings of this study contribute substantially to current understanding of the human WM connectome, its sensitivity to injury, and clarify a long-standing debate regarding the relative prominence of gray vs. WM regions in the context of brain structure and connectomic architecture. PMID:24574993

  17. Does white matter matter? Spatio-temporal dynamics of task switching in aging.

    PubMed

    Gratton, Gabriele; Wee, Emily; Rykhlevskaia, Elena I; Leaver, Echo E; Fabiani, Monica

    2009-07-01

    Older adults often encounter difficulties in switching between tasks, perhaps because of age-related decreases in executive function. Executive function may largely depend on connections between brain areas-connections that may become structurally and functionally weaker in aging. Here we investigated functional and structural age-related changes in switching between a spatial and a verbal task. These tasks were chosen because they are expected to differentially use the two hemispheres. Brain measures included anatomical information about anterior corpus callosum size (CC; the major commissure linking the left and right hemisphere), and the event-related optical signal (EROS). Behavioral results indicated that older adults had greater task-switching difficulties, which, however, were largely restricted to switching to the spatial task and to individuals with smaller anterior CCs. The EROS data showed both general switching-related activity in the left middle frontal gyrus (with approximately 300-msec latency) and task-specific activity in the inferior frontal gyrus, lateralized to the left for the switch-to-verbal condition and to the right for the switch-to-spatial condition. This lateralization was most evident in younger adults. In older adults, activity in the switch-to-spatial condition was lateralized to the right hemisphere in individuals with large CC, and to the left in individuals with small CC. These data suggest that (a) task switching may involve both task-general and task-specific processes; and (b) white matter changes may underlie some of the age-related problems in switching. These effects are discussed in terms of the hypothesis that aging involves some degree of cortical disconnection, both functional and anatomical. PMID:18752402

  18. NON EXPLOSIVE COLLAPSE OF A WHITE DWARF Abstract.-Matter accretion on a white dwarf has been proposed to explain the novae

    E-print Network

    Boyer, Edmond

    NON EXPLOSIVE COLLAPSE OF A WHITE DWARF Abstract.- Matter accretion on a white dwarf has been proposed to explain the novae and type I supernovae explosions. Accretion followed by a non explosive Meudon Résumé.- L'accrétion de matičre sur une naine blanche a été proposée comme origine des explosions

  19. White-matter astrocytes, axonal energy metabolism, and axonal degeneration in multiple sclerosis

    PubMed Central

    Cambron, Melissa; D'Haeseleer, Miguel; Laureys, Guy; Clinckers, Ralph; Debruyne, Jan; De Keyser, Jacques

    2012-01-01

    In patients with multiple sclerosis (MS), a diffuse axonal degeneration occurring throughout the white matter of the central nervous system causes progressive neurologic disability. The underlying mechanism is unclear. This review describes a number of pathways by which dysfunctional astrocytes in MS might lead to axonal degeneration. White-matter astrocytes in MS show a reduced metabolism of adenosine triphosphate-generating phosphocreatine, which may impair the astrocytic sodium potassium pump and lead to a reduced sodium-dependent glutamate uptake. Astrocytes in MS white matter appear to be deficient in ?2 adrenergic receptors, which are involved in stimulating glycogenolysis and suppressing inducible nitric oxide synthase (NOS2). Glutamate toxicity, reduced astrocytic glycogenolysis leading to reduced lactate and glutamine production, and enhanced nitric oxide (NO) levels may all impair axonal mitochondrial metabolism, leading to axonal degeneration. In addition, glutamate-mediated oligodendrocyte damage and impaired myelination caused by a decreased production of N-acetylaspartate by axonal mitochondria might also contribute to axonal loss. White-matter astrocytes may be considered as a potential target for neuroprotective MS therapies. PMID:22214904

  20. A Quantitative Tractography Approach for Exploring Associations Between White Matter Pathways and Cognitive Functions

    E-print Network

    Laidlaw, David

    functional subdivisions of white matter pathways may help refine our current results. Results generally. Acknowledgement DWI DATA Tensor Fitting [1] DTI DATA Fiber Tracking [2] Diffusivity Scalars QT Metrics however support speculations that relate the SLF to motor control, processing speed, and working memory

  1. Research Report Gray and white matter reduction in hyposmic subjects --A

    E-print Network

    Gaser, Christian

    of the gray and white matter in a group of subjects with an impaired but not complete loss of olfaction.V. All rights reserved. Keywords: Human Olfaction Structural plasticity Laterality Volumetry Magnetic resonance imaging 1. Introduction Several studies indicated that an impaired sense of olfaction leads

  2. White(etching!matter!in!bearing!steel! Part1:!Controlled(cracking!of!52100!steel!

    E-print Network

    Cambridge, University of

    ! 1! White(etching!matter!in!bearing!steel! Part1:!Controlled(cracking!of!52100!steel! ! W!the!research!performed!in!bearing!steel!metallurgy!aims!to!prevent! crack!nucleation!and!propagation! quenched! and! untempered! steel! normally! used! in! the! manufacture! of! bearings.!The!varieties

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  4. The mechanisms of acute ischemic injury in the cell processes of developing white matter astrocytes

    Microsoft Academic Search

    Michael G Salter; Robert Fern

    2008-01-01

    Astrocytes are fundamentally important to the maintenance and proper functioning of the central nervous system. During the period of development when myelination is occurring, white matter astrocytes are particularly sensitive to ischemic injury and their failure to regulate glutamate during ischemic conditions may be an important factor in excitotoxic injury. Here, we have identified key mechanisms of injury that operate

  5. White Matter Microstructure Changes in the Thalamus in Parkinson Disease with Depression

    E-print Network

    Tian, Jie

    with Depression: A Diffusion Tensor MR Imaging Study W. Li J. Liu F. Skidmore Y. Liu J. Tian K. Li BACKGROUND AND PURPOSE: Depression occurs frequently in PD; however the neural basis of depression in PD remains unclear. The aim of this study was to characterize possible depression- related white matter microstructural

  6. Does Framingham stroke risk profile predict white-matter changes in late-life depression?

    E-print Network

    Paris-Sud XI, Université de

    1 Does Framingham stroke risk profile predict white-matter changes in late-life depression? Dr: Cardiovascular risk factors and diseases are important aetiological factors in depression, particularly late-life depression. Brain changes associated with vascular disease and depression can be detected using magnetic

  7. The white matter of the human cerebrum: Part I The occipital lobe by Heinrich Sachs

    PubMed Central

    Forkel, Stephanie J.; Mahmood, Sajedha; Vergani, Francesco; Catani, Marco

    2015-01-01

    This is the first complete translation of Heinrich Sachs' outstanding white matter atlas dedicated to the occipital lobe. This work is accompanied by a prologue by Prof Carl Wernicke who for many years was Sachs' mentor in Breslau and enthusiastically supported his work. PMID:25527430

  8. Why So Impulsive? White Matter Alterations Are Associated With Impulsivity in Chronic Marijuana Smokers

    Microsoft Academic Search

    Staci A. Gruber; Marisa M. Silveri; Mary Kathryn Dahlgren; Deborah Yurgelun-Todd

    2011-01-01

    Difficulty monitoring and inhibiting impulsive behaviors has been reported in marijuana (MJ) smokers; neuroimaging studies, which examined frontal systems in chronic MJ smokers, have reported alterations during inhibitory tasks. Diffusion tensor imaging (DTI) provides a quantitative estimate of white matter integrity at the microstructural level. We applied DTI, clinical ratings, and impulsivity measures to explore the hypotheses that chronic, heavy

  9. White Matter Bundle Registration and Population Analysis Based on Gaussian Processes

    E-print Network

    is in fact an inner product, to drive a diffeomorphic registration algorithm between two sets of homologous estimate a dense deformation of the underlying white matter using the bundles as anatomical landmarks the resulting deformation field obtained from this registration process. These methods use scalar images like

  10. Registration, Atlas Estimation and Variability Analysis of White Matter Fiber Bundles Modeled as Currents

    E-print Network

    Utah, University of

    anatomical differences between fiber bundles, seen as global homologous structures across subjects. It avoids to drive the registration between two sets of homologous fiber bundles of two different subjects. A dense deformation of the underlying white matter is estimated, which is constrained by the bundles seen as global

  11. Accrual of MRI white matter abnormalities in elderly with normal and impaired mobility

    Microsoft Academic Search

    Leslie Wolfson; Xingchang Wei; Charles B. Hall; Victoria Panzer; Dorothy Wakefield; Randall R. Benson; Julia A. Schmidt; Simon K. Warfield; Charles R. G. Guttmann

    2005-01-01

    White matter signal abnormality (WMSA) is often present in the MRIs of older persons with mobility impairment. We examined the relationship between impaired mobility and the progressive accrual of WMSA. Mobility was assessed with the Short Physical Performance Battery (SPPB) and quantitative measures of gait and balance. Fourteen subjects had baseline and follow-up MRI scans performed 20 months apart. WMSA

  12. Quantitative analysis of MRI signal abnormalities of brain white matter with high reproducibility and accuracy

    Microsoft Academic Search

    Xingchang Wei; Simon K. Warfield; Kelly H. Zou; Ying Wu; Xiaoming Li; Alexandre Guimond; John P. Mugler; Randall R. Benson; Leslie Wolfson; Howard L. Weiner; Charles R. G. Guttmann

    2002-01-01

    Purpose: To assess the reproducibility and accuracy com- pared to radiologists of three automated segmentation pipe- lines for quantitative magnetic resonance imaging (MRI) mea- surement of brain white matter signal abnormalities (WMSA). Materials and Methods: WMSA segmentation was per- formed on pairs of whole brain scans from 20 patients with multiple sclerosis (MS) and 10 older subjects who were positioned

  13. Slowly progressive familial dementia with recurrent strokes and white matter hypodensities on CT scan

    Microsoft Academic Search

    F. Salvi; R. Michelucci; R. Plasmati; L. Parmeggiani; P. Zonari; M. Mascalchi; C. A. Tassinari

    1992-01-01

    We describe 2 normotensive sisters presenting slowly progressive dementia associated with acute or subacute focal neurological symptoms, unilateral or bilateral motor signs, and dysarthria. Their father, who died in the seventh decade, had a similar clinical picture. Computerized axial tomography (CT) scan of the head showed symmetrical hypodensities in the periventricular white matter and mild to moderate hydrocephalus. In these

  14. Decreased plasma tryptophan associated with deep white matter lesions in elderly subjects

    Microsoft Academic Search

    H Yao; T Yuzuriha; H Koga; K Fukuda; K Endo; T Matsumoto; A Kato; A Uchino; T Ezaki; S Ibayashi; H Uchimura; M Fujishima

    1999-01-01

    The aim was to identify potentially treatable risk factors for cerebral white matter lesions often found on MRI in elderly persons. findings were assessed on 1.0 T MRI of 178 subjects living in the community and aged 60 years or older. Participants underwent standardised evaluations including standard questionnaires, a physical and neurological examination, cognitive function tests, electrocardiogram, a complete blood

  15. Clinical prediction of fall risk and white matter abnormalities: a diffusion tensor imaging study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Tinetti scale is a simple clinical tool designed to predict risk of falling by focusing on gait and stance impairment in elderly persons. Gait impairment is also associated with white matter (WM) abnormalities. Objective: To test the hypothesis that elderly subjects at risk for falling, as deter...

  16. White matter changes in mild cognitive impairment and AD: A diffusion tensor imaging study

    Microsoft Academic Search

    David Medina; Leyla deToledo-Morrell; Fabio Urresta; John D. E. Gabrieli; Michael Moseley; Debra Fleischman; David A. Bennett; Sue Leurgans; David A. Turner; Glenn T. Stebbins

    2006-01-01

    Diffusion tensor imaging (DTI) can detect, in vivo, the directionality of molecular diffusion and estimate the microstructural integrity of white matter (WM) tracts. In this study, we examined WM changes in patients with Alzheimer's disease (AD) and in subjects with amnestic mild cognitive impairment (MCI) who are at greater risk for developing AD. A DTI index of WM integrity, fractional

  17. Neonatal White Matter Abnormalities Predict Global Executive Function Impairment in Children Born Very Preterm

    Microsoft Academic Search

    Lianne J. Woodward; Caron A. C. Clark; Verena E. Pritchard; Peter J. Anderson; Terrie E. Inder

    2011-01-01

    Using prospective longitudinal data from 110 very preterm and 113 full term children, this article describes the executive functioning abilities of very preterm children at age 4, and examines relations between the extent of white matter abnormality on neonatal magnetic resonance imaging (MRI) and later executive function outcomes. Very preterm children performed less well than full term children on measures

  18. Neurological Signs in Relation to White Matter Hyperintensity Volumes in Memory Clinic Patients

    Microsoft Academic Search

    S. S. Staekenborg; H. de Waal; F. Admiraal-Behloul; F. Barkhof; J. H. C. Reiber; P. Scheltens; Y. A. L. Pijnenburg; H. Vrenken; W. M. van der Flier

    2010-01-01

    Purpose: To determine the frequency of neurological signs in a memory clinic population and to explore their associations with white matter hyperintensity (WMH). Methods: We included patients with Alzheimer disease (AD; n = 210), vascular dementia (VaD; n = 34), mild cognitive impairment (MCI; n = 86) and subjective complaints (n = 153). The presence of extrapyramidal and unilateral signs

  19. Proton MR spectroscopy features of normal appearing white matter in neurofibromatosis type 1.

    PubMed

    Alkan, Alpay; Sarac, Kaya; Kutlu, Ramazan; Yakinci, Cengiz; Sigirci, Ahmet; Aslan, Mehmet; Ozcan, Hamdi; Yologlu, Saim

    2003-11-01

    To determine whether differences exist between neurofibromatosis type 1 (NF1) patients with or without focal lesions and healthy normal volunteers in the metabolite ratios of normal appearing white matter, 27 patients with NF1 (with parenchymal lesion, MR positive, n: 17; without parenchymal lesions, MR negative, n: 10) and 20 healthy volunteers underwent MRI and short TE (31 ms) proton MR spectroscopy (MRS). In 17 patients with parenchymal lesions, 61 focal lesions were detected by MRI. MRS was performed from normal appearing frontal and posterior parietal white matter (FWM and PWM) in NF1 and from control groups. NAA/Cr, Cho/Cr and MI/Cr ratios were calculated. Significant increase in Cho/Cr and MI/Cr ratios were found in FWM and PWM in MR negative and positive groups when compared to control group. NAA/Cr ratio in MR positive group was significantly decreased in FWM compared to control group. There were no significant differences between FWM and PWM in all metabolite ratios of MR negative group. MI/Cr ratio in MR positive group was significantly elevated in PWM compared to FWM. Metabolite changes detected by MRS could indicate demyelination and gliosis in normal appearing white matter in all NF1 patients, and additionally neuroaxonal damage in the FWM of NF1 patients with focal lesions. For that reason, in the clinical evaluation and follow-up of these patients MRS features of normal appearing white matter should be considered in addition to focal lesions. PMID:14684211

  20. Sex differences in the IQ-white matter microstructure relationship: a DTI study.

    PubMed

    Dunst, Beate; Benedek, Mathias; Koschutnig, Karl; Jauk, Emanuel; Neubauer, Aljoscha C

    2014-11-01

    Sex differences in the relationship between general intelligence and brain structure are a topic of increasing research interest. Early studies focused mainly on gray and white matter differences using voxel-based morphometry, while more recent studies investigated neural fiber tracts using diffusion tensor imaging (DTI) to analyze the white matter microstructure. In this study we used tract-based spatial statistics (TBSS) on DTI to test how intelligence is associated with brain diffusion indices and to see whether this relationship differs between men and women. 63 Men and women divided into groups of lower and higher intelligence were selected. Whole-brain DTI scans were analyzed using TBSS calculating maps of fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). The results reveal that the white matter microstructure differs between individuals as a function of intelligence and sex. In men, higher intelligence was related to higher FA and lower RD in the corpus callosum. In women, in contrast, intelligence was not related to the white matter microstructure. The higher values of FA and lower values of RD suggest that intelligence is associated with higher myelination and/or a higher number of axons particularly in men. This microstructural difference in the corpus callosum may increase cognitive functioning by reducing inter-hemispheric transfer time and thus account for more efficient brain functioning in men. PMID:25238623

  1. Prolonged focal application of polyethylene glycol induces conduction block in guinea pig spinal cord white matter

    E-print Network

    Shi, Riyi

    of Polyethylene Glycol (PEG) to injured mammalian spinal cords can offer significant yet limited res- toration injuries. In this study, isolated spinal cord white matter strips from adult guinea pigs were subjected spinal cord victims. Ó 2004 Elsevier Ltd. All rights reserved. Keywords: Axon; Membrane fusion; Neuronal

  2. Differences in the right inferior longitudinal fasciculus but no general disruption of white matter tracts in

    E-print Network

    Kanwisher, Nancy

    , and worse in the ASD group, with some scans unusable because of head motion artifacts. When we follow is reduced "integrity" of long-range white matter tracts, a claim based primarily on diffusion imaging standard data analysis practices (i.e., without matching head motion between groups), we replicate

  3. White Matter and Development in Children with an Autism Spectrum Disorder

    ERIC Educational Resources Information Center

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

    2013-01-01

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

  4. Diffusion tensor imaging of white matter tracts in the dog brain.

    PubMed

    Jacqmot, Olivier; Van Thielen, Bert; Fierens, Yves; Hammond, Martha; Willekens, Inneke; Van Schuerbeek, Peter; Verhelle, Filip; Goossens, Peter; De Ridder, Filip; Clarys, Jan Pieter; Vanbinst, Anne; De Mey, Johan

    2013-02-01

    Diffusion weighted imaging sequences are now widely available on Magnetic Resonance Imaging (MRI) scanners. Diffusion Tensor Imaging (DTI) of the brain is able to show white matter tracts and is now commonly used in human medicine to study brain anatomy, tumors, structural pathways,… The purpose of this study was to show the interest of DTI to reveal the white matter fibers in the dogs' brain. DTI MR Images for this study were obtained with a 3 T system of 4 dogs euthanized for other reasons than neurological disorders. Combined fractional anisotropic (FA) and directional maps were obtained in the first 2 hours after death. The heads were amputated immediately after scanning and stored in 10% formalin until preparation for dissection. An experienced anatomist tracked white matter tracts with clinical relevance using the scanner software. The selected tracts were REFVIDume rendered and correlated with gross dissection. Using DTI we were able to track relevant neurological connections, such as the corticospinal tract, the optic and the cerebellar tract. The three dimensional anatomy is better presented using modern visualization techniques. DTI seems to be a valuable tool in order to present clinically relevant white matter tracts to neurological clinicians and researchers. PMID:23355519

  5. Penalized functional regression analysis of white-matter tract profiles in multiple sclerosis

    Microsoft Academic Search

    Jeff Goldsmith; Ciprian M. Crainiceanu; Brian S. Caffo; Daniel S. Reich

    2011-01-01

    Diffusion tensor imaging (DTI) enables noninvasive parcellation of cerebral white matter into its component fiber bundles or tracts. These tracts often subserve specific functions, and damage to the tracts can therefore result in characteristic forms of disability. Attempts to quantify the extent of tract-specific damage have been limited in part by substantial spatial variation of imaging properties from one end

  6. Abnormalities of White Matter Microstructure in Unmedicated Obsessive-Compulsive Disorder and

    E-print Network

    Abnormalities of White Matter Microstructure in Unmedicated Obsessive-Compulsive Disorder of myelin integrity have been reported in obsessive-compulsive disorder (OCD) using multi- parameter maps Obsessive-Compulsive Disorder and Changes after Medication. PLoS ONE 7(4): e35889. doi:10.1371/journal

  7. Principal eigenvector field segmentation for reproducible diffusion tensor tractography of white matter structures

    Microsoft Academic Search

    Ram K. S. Rathore; Rakesh K. Gupta; Shruti Agarwal; Richa Trivedi; Rajendra P. Tripathi; Rishi Awasthi

    2011-01-01

    The study was aimed to test the feasibility of utilizing an algorithmically determinable stable fiber mass (SFM) map obtained by an unsupervised principal eigenvector field segmentation (PEVFS) for automatic delineation of 18 white matter (WM) tracts: (1) corpus callosum (CC), (2) tapetum (TP), (3) inferior longitudinal fasciculus (ILF), (4) uncinate fasciculus (UNC), (5) inferior fronto-occipital fasciculus (IFO), (6) optic pathways

  8. Late Oligodendrocyte Progenitors Coincide with the Developmental Window of Vulnerability for Human Perinatal White Matter Injury

    Microsoft Academic Search

    Stephen A. Back; Ning Ling Luo; Natalya S. Borenstein; Joel M. Levine; Joseph J. Volpe; Hannah C. Kinney

    2001-01-01

    Hypoxic-ischemic injury to the periventricular cerebral white matter (periventricular leukomalacia (PVL)) results in cerebral palsy and is the leading cause of brain injury in premature infants. The principal feature of PVL is a chronic disturbance of myelination and suggests that oligodendrocyte (OL) lineage progression is disrupted by ischemic injury. We determined the OL lineage stages at risk for injury during

  9. Assessing white matter ischemic damage in dementia patients by measurement of myelin proteins

    PubMed Central

    Barker, Rachel; Wellington, Dannielle; Esiri, Margaret M; Love, Seth

    2013-01-01

    White matter ischemia is difficult to quantify histologically. Myelin-associated glycoprotein (MAG) is highly susceptible to ischemia, being expressed only adaxonally, far from the oligodendrocyte cell body. Myelin-basic protein (MBP) and proteolipid protein (PLP) are expressed throughout the myelin sheath. We compared MAG, MBP, and PLP levels in parietal white matter homogenates from 17 vascular dementia (VaD), 49 Alzheimer's disease (AD), and 33 control brains, after assessing the post-mortem stability of these proteins. Small vessel disease (SVD) and cerebral amyloid angiopathy (CAA) severity had been assessed in paraffin sections. The concentration of MAG remained stable post-mortem, declined with increasing SVD, and was significantly lower in VaD than controls. The concentration of MBP fell progressively post-mortem, limiting its diagnostic utility in this context. Proteolipid protein was stable post-mortem and increased significantly with SVD severity. The MAG/PLP ratio declined significantly with SVD and CAA severity. The MAG and PLP levels and MAG/PLP did not differ significantly between AD and control brains. We validated the utility of MAG and MAG/PLP measurements on analysis of 74 frontal white matter samples from an Oxford cohort in which SVD had previously been scored. MAG concentration and the MAG/PLP ratio are useful post-mortem measures of ante-mortem white matter ischemia. PMID:23532085

  10. Erythropoietin Attenuates Lipopolysaccharide-Induced White Matter Injury in the Neonatal Rat Brain

    Microsoft Academic Search

    Abdullah Kumral; Huseyin Baskin; Didem Cemile Yesilirmak; Bekir Ugur Ergur; Simge Aykan; Sermin Genc; Kursad Genc; Osman Yilmaz; Kazim Tugyan; Ozlem Giray; Nuray Duman; Hasan Ozkan

    2007-01-01

    Periventricular leukomalacia (PVL), a common neonatal brain white matter (WM) lesion, is frequently associated with cerebral palsy. Growing evidence has indicated that in addition to ischemia\\/reperfusion injury, cytokine-induced brain injury associated with maternal or fetal infection may also play an important role in the pathogenesis of PVL. Recent studies have shown that administration of lipopolysaccharide (LPS) to pregnant rats causes

  11. Detection of crossing white matter fibers with high-order tensors and rank-k decompositions

    E-print Network

    Utah, University of

    Detection of crossing white matter fibers with high-order tensors and rank-k decompositions Fangxiang Jiao , Yaniv Gur , Chris R. Johnson and Sarang Joshi SCI Institute, University of Utah, Salt Lake City, UT 84112, USA {fjiao, yanivg, crj, sjoshi}@sci.utah.edu Abstract. Fundamental to high angular

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

    E-print Network

    Clayden, Jonathan D.

    development; from conception to birth, in infancy, and onwards through childhood and adolescence. SeveralNormative development of white matter tracts: Similarities and differences in relation to age of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK; 2 School of Medicine

  13. Syntactic comprehension deficits are associated with MRI white matter alterations in dementia

    Microsoft Academic Search

    TANIA GIOVANNETTI; MARY W. HOPKINS; JACLYN CRAWFORD; BRIANNE MAGOUIRK BETTCHER; KARA S. SCHMIDT; DAVID J. LIBON

    2008-01-01

    Comprehension difficulties associated with periventricular and deep white matter alterations (WMA) in mild dementia were investigated using portions of the Boston Diagnostic Aphasia Examination (BDAE) Complex Ideation subtest and Syntax subtests. Mild dementia participants were grouped according to the extent of their WMA as observed on magnetic resonance imaging (mild WMA n 5 45 vs. moderate to severe WMA n

  14. A geometry-based particle filtering approach to white matter tractography

    E-print Network

    A geometry-based particle filtering approach to white matter tractography Peter Savadjiev1 for a robust inference of local tract geometry, which, in the context of the causal filter estima- tion, guides.g. [2], or particle filters, e.g. [1, 7]. In this paper, we propose a novel tractography approach which

  15. Neurobiology of Disease Relationship of a Variant in the NTRK1 Gene to White Matter

    E-print Network

    Thompson, Paul

    in Young Adults Meredith N. Braskie,1 Neda Jahanshad,1,2 Jason L. Stein,1 Marina Barysheva,1 Kori Johnson,4 implicated in neurological function via links between the T allele at rs6336 (NTRK1-T) and schizophrenia risk. A variant in the neurotrophin gene, BDNF, was previously associated with white matter integrity in young

  16. 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

  17. White matter integrity in the vicinity of Broca's area predicts grammar learning success

    Microsoft Academic Search

    Agnes Flöel; Meinou H. de Vries; Jan Scholz; Caterina Breitenstein; Heidi Johansen-Berg

    2009-01-01

    Humans differ substantially in their ability to implicitly extract structural regularities from experience, as required for learning the grammar of a language. The mechanisms underlying this fundamental inter-individual difference, which may determine initial success in language learning, are incompletely understood. Here, we use diffusion tensor magnetic resonance imaging (DTI) to determine white matter integrity around Broca's area, which is crucially

  18. Early White-Matter Abnormalities of the Ventral Frontostriatal Pathway in Fragile X Syndrome

    ERIC Educational Resources Information Center

    Haas, Brian W.; Barnea-Goraly, Naama; Lightbody, Amy A.; Patnaik, Swetapadma S.; Hoeft, Fumiko; Hazlett, Heather; Piven, Joseph; Reiss, Allan L.

    2009-01-01

    Aim: Fragile X syndrome is associated with cognitive deficits in inhibitory control and with abnormal neuronal morphology and development. Method: In this study, we used a diffusion tensor imaging (DTI) tractography approach to reconstruct white-matter fibers in the ventral frontostriatal pathway in young males with fragile X syndrome (n = 17;…

  19. Genome-wide association studies of cerebral white matter lesion burden

    Microsoft Academic Search

    M. Fornage; S. Debette; J. C. Bis; R. Schmidt; M. A. Ikram; C. Dufouil; S. Sigurdsson; T. Lumley; A. L. DeStefano; F. Fazekas; H. A. Vrooman; D. K. Shibata; P. Maillard; A. P. Zijdenbos; A. V. Smith; H. Gudnason; Boer de R; M. Cushman; B. Mazoyer; G. Heiss; M. W. Vernooij; C. Enzinger; N. L. Glazer; A. Beiser; D. S. Knopman; M. Cavalieri; W. J. Niessen; T. B. Harris; K. Petrovic; O. L. Lopez; R. Au; J. C. Lambert; A. Hofman; R. F. Gottesman; M. Garcia; S. R. Heckbert; L. D. Atwood; D. J. Catellier; A. G. Uitterlinden; Q. Yang; T. Aspelund; J. R. Romero; K. Rice; K. D. Taylor; M. A. Nalls; J. I. Rotter; R. Sharrett; P. Tikka-Kleemola; P. Amouyel; P. A. Wolf; Lugt van der A; E. Boerwinkle; B. M. Psaty; S. Seshadri; C. Tzourio; M. M. B. Breteler; T. H. Mosley; W. T. Longstreth; C. DeCarli; L. J. Launer

    2011-01-01

    Objective: White matter hyperintensities (WMHs) detectable by magnetic resonance imaging are part of the spectrum of vascular injury associated with aging of the brain and are thought to reflect ischemic damage to the small deep cerebral vessels. WMHs are associated with an increased risk of cognitive and motor dysfunction, dementia, depression, and stroke. Despite a significant heritability, few genetic loci

  20. Inter-Parietal White Matter Development Predicts Numerical Performance in Young Children

    ERIC Educational Resources Information Center

    Cantlon, Jessica F.; Davis, Simon W.; Libertus, Melissa E.; Kahane, Jill; Brannon, Elizabeth M.; Pelphrey, Kevin A.

    2011-01-01

    In an effort to understand the role of interhemispheric transfer in numerical development, we investigated the relationship between children's developing knowledge of numbers and the integrity of their white matter connections between the cerebral hemispheres (the corpus callosum). We used diffusion tensor imaging (DTI) tractography analyses to…

  1. White Matter Abnormalities in Major Depression: A Tract-Based Spatial Statistics and Rumination Study

    Microsoft Academic Search

    Nianming Zuo; Jiliang Fang; Xueyu Lv; Yuan Zhou; Yang Hong; Tao Li; Haibing Tong; Xiaoling Wang; Weidong Wang; Tianzi Jiang

    2012-01-01

    Increasing evidence indicates that major depressive disorder (MDD) is usually accompanied by altered white matter in the prefrontal cortex, the parietal lobe and the limbic system. As a behavioral abnormity of MDD, rumination has been believed to be a substantial indicator of the mental state of the depressive state. So far, however, no report that we are aware of has

  2. Risk Factors for Silent Cerebral Infarcts in Subcortical White Matter and Basal Ganglia

    Microsoft Academic Search

    Toshiyuki Uehara; Masayasu Tabuchi; Etsuro Mori

    Background and Purpose—The purpose of this study was to clarify whether the relevant risk factors for silent cerebral infarcts (SCIs) in subcortical white matter (WM) are different from those in the basal ganglia (BG). Methods—Subjects of this study were 219 adults without a history of stroke or transient ischemic attack and without any abnormality on a neurological examination who consecutively

  3. Imaging axonal damage of normal-appearing white matter in multiple sclerosis

    Microsoft Academic Search

    L. Fu; P. M. Matthews; N. De Stefano; K. J. Worsley; S. Narayanan; G. S. Francis; J. P. Antel; C. Wolfson; D. L. Arnold

    1998-01-01

    Summary The current study was designed to determine the relative distribution of decreases of N-acetylaspartate (NAA), a marker of axonal damage, between lesions and normal- appearing white matter of patients with established multiple sclerosis and to test for associations between changes in the ratio of NAA to creatine\\/phosphocreatine (NAA : Cr) in those compartments and changes in disability. Data were

  4. SILENT MRI WHITE MATTER LESIONS IN PATIENTS WITH CIS SUGGESTIVE OF MULTIPLE SCLEROSIS

    E-print Network

    Lichtarge, Olivier

    SILENT MRI WHITE MATTER LESIONS IN PATIENTS WITH CIS SUGGESTIVE OF MULTIPLE SCLEROSIS 0 1 2 3 4 5 6 7 8 9 OCB SC TOTAL ABNL Brain MRI ABNL SC MRI Suarez-Zambrano GA, Ramirez J , Avila M, Brandt D clear abnormalities on the brain MRI suggestive of demyelination. We found abnormalities in the cord

  5. Test-retest reliability of white matter structural brain networks: a multiband diffusion MRI study

    PubMed Central

    Zhao, Tengda; Duan, Fei; Liao, Xuhong; Dai, Zhengjia; Cao, Miao; He, Yong; Shu, Ni

    2015-01-01

    The multiband EPI sequence has been developed for the human connectome project to accelerate MRI data acquisition. However, no study has yet investigated the test-retest (TRT) reliability of the graph metrics of white matter (WM) structural brain networks constructed from this new sequence. Here, we employed a multiband diffusion MRI (dMRI) dataset with repeated scanning sessions and constructed both low- and high-resolution WM networks by volume- and surface-based parcellation methods. The reproducibility of network metrics and its dependence on type of construction procedures was assessed by the intra-class correlation coefficient (ICC). We observed conserved topological architecture of WM structural networks constructed from the multiband dMRI data as previous findings from conventional dMRI. For the global network properties, the first order metrics were more reliable than second order metrics. Between two parcellation methods, networks with volume-based parcellation showed better reliability than surface-based parcellation, especially for the global metrics. Between different resolutions, the high-resolution network exhibited higher TRT performance than the low-resolution in terms of the global metrics with a large effect size, whereas the low-resolution performs better in terms of local (region and connection) properties with a relatively low effect size. Moreover, we identified that the association and primary cortices showed higher reproducibility than the paralimbic/limbic regions. The important hub regions and rich-club connections are more reliable than the non-hub regions and connections. Finally, we found WM networks from the multiband dMRI showed higher reproducibility compared with those from the conventional dMRI. Together, our results demonstrated the fair to good reliability of the WM structural brain networks from the multiband EPI sequence, suggesting its potential utility for exploring individual differences and for clinical applications. PMID:25741265

  6. Surface-based reconstruction and diffusion MRI in the assessment of gray and white matter damage in multiple sclerosis

    NASA Astrophysics Data System (ADS)

    Caffini, Matteo; Bergsland, Niels; LaganĂ, Marcella; Tavazzi, Eleonora; Tortorella, Paola; Rovaris, Marco; Baselli, Giuseppe

    2014-03-01

    Despite advances in the application of nonconventional MRI techniques in furthering the understanding of multiple sclerosis pathogenic mechanisms, there are still many unanswered questions, such as the relationship between gray and white matter damage. We applied a combination of advanced surface-based reconstruction and diffusion tensor imaging techniques to address this issue. We found significant relationships between white matter tract integrity indices and corresponding cortical structures. Our results suggest a direct link between damage in white and gray matter and contribute to the notion of gray matter loss relating to clinical disability.

  7. Associations between white matter hyperintensities and ? amyloid on integrity of projection, association, and limbic fiber tracts measured with diffusion tensor MRI.

    PubMed

    Chao, Linda L; Decarli, Charles; Kriger, Stephen; Truran, Diana; Zhang, Yu; Laxamana, Joel; Villeneuve, Sylvia; Jagust, William J; Sanossian, Nerses; Mack, Wendy J; Chui, Helena C; Weiner, Michael W

    2013-01-01

    The goal of this study was to assess the relationship between A? deposition and white matter pathology (i.e., white matter hyperintensities, WMH) on microstructural integrity of the white matter. Fifty-seven participants (mean age: 78±7 years) from an ongoing multi-site research program who spanned the spectrum of normal to mild cognitive impairment (Clinical dementia rating 0-0.5) and low to high risk factors for arteriosclerosis and WMH pathology (defined as WMH volume >0.5% total intracranial volume) were assessed with positron emission tomography (PET) with Pittsburg compound B (PiB) and magnetic resonance and diffusion tensor imaging (DTI). Multivariate analysis of covariance were used to investigate the relationship between A? deposition and WMH pathology on fractional anisotropy (FA) from 9 tracts of interest (i.e., corona radiata, internal capsule, cingulum, parahippocampal white matter, corpus callosum, superior longitudinal, superior and inferior front-occipital fasciculi, and fornix). WMH pathology was associated with reduced FA in projection (i.e., internal capsule and corona radiate) and association (i.e., superior longitudinal, superior and inferior fronto-occipital fasciculi) fiber tracts. A? deposition (i.e., PiB positivity) was associated with reduced FA in the fornix and splenium of the corpus callosum. There were interactions between PiB and WMH pathology in the internal capsule and parahippocampal white matter, where A? deposition reduced FA more among subjects with WMH pathology than those without. However, accounting for apoE ?4 genotype rendered these interactions insignificant. Although this finding suggests that apoE4 may increase amyloid deposition, both in the parenchyma (resulting in PiB positivity) and in blood vessels (resulting in amyloid angiopathy and WMH pathology), and that these two factors together may be associated with compromised white matter microstructural integrity in multiple brain regions, additional studies with a longitudinal design will be necessary to resolve this issue. PMID:23762308

  8. White matter microstructure in late middle-age: Effects of apolipoprotein E4 and parental family history of Alzheimer's disease

    PubMed Central

    Adluru, Nagesh; Destiche, Daniel J.; Lu, Sharon Yuan-Fu; Doran, Samuel T.; Birdsill, Alex C.; Melah, Kelsey E.; Okonkwo, Ozioma C.; Alexander, Andrew L.; Dowling, N. Maritza; Johnson, Sterling C.; Sager, Mark A.; Bendlin, Barbara B.

    2014-01-01

    Introduction Little is still known about the effects of risk factors for Alzheimer's disease (AD) on white matter microstructure in cognitively healthy adults. The purpose of this cross-sectional study was to assess the effect of two well-known risk factors for AD, parental family history and APOE4 genotype. Methods This study included 343 participants from the Wisconsin Registry for Alzheimer's Prevention, who underwent diffusion tensor imaging (DTI). A region of interest analysis was performed on fractional anisotropy maps, in addition to mean, radial, and axial diffusivity maps, aligned to a common template space using a diffeomorphic, tensor-based registration method. The analysis focused on brain regions known to be affected in AD including the corpus callosum, superior longitudinal fasciculus, fornix, cingulum, and uncinate fasciculus. Analyses assessed the impact of APOE4, parental family history of AD, age, and sex on white matter microstructure in late middle-aged participants (aged 47–76 years). Results Both APOE4 and parental family history were associated with microstructural white matter differences. Participants with parental family history of AD had higher FA in the genu of the corpus callosum and the superior longitudinal fasciculus. We observed an interaction between family history and APOE4, where participants who were family history positive but APOE4 negative had lower axial diffusivity in the uncinate fasciculus, and participants who were both family history positive and APOE4 positive had higher axial diffusivity in this region. We also observed an interaction between APOE4 and age, whereby older participants (=65 years of age) who were APOE4 carriers, had higher MD in the superior longitudinal fasciculus and in the portion of the cingulum bundle running adjacent to the cingulate cortex, compared to non-carriers. Older participants who were APOE4 carriers also showed higher radial diffusivity in the genu compared to non-carriers. Across all participants, age had an effect on FA, MD, and axial and radial diffusivities. Sex differences were observed in FA and radial diffusivity. Conclusion APOE4 genotype, parental family history of AD, age, and sex are all associated with microstructural white matter differences in late middle-aged adults. In participants at risk for AD, alterations in diffusion characteristics—both expected and unexpected—may represent cellular changes occurring at the earliest disease stages, but further work is needed. Higher mean, radial, and axial diffusivities were observed in participants who are more likely to be experiencing later stage preclinical pathology, including participants who were both older and carried APOE4, or who were positive for both APOE4 and parental family history of AD. PMID:24936424

  9. The Relationship between Intelligence and Anxiety: An Association with Subcortical White Matter Metabolism.

    PubMed

    Coplan, Jeremy D; Hodulik, Sarah; Mathew, Sanjay J; Mao, Xiangling; Hof, Patrick R; Gorman, Jack M; Shungu, Dikoma C

    2011-01-01

    We have demonstrated in a previous study that a high degree of worry in patients with generalized anxiety disorder (GAD) correlates positively with intelligence and that a low degree of worry in healthy subjects correlates positively with intelligence. We have also shown that both worry and intelligence exhibit an inverse correlation with certain metabolites in the subcortical white matter. Here we re-examine the relationships among generalized anxiety, worry, intelligence, and subcortical white matter metabolism in an extended sample. Results from the original study were combined with results from a second study to create a sample comprised of 26 patients with GAD and 18 healthy volunteers. Subjects were evaluated using the Penn State Worry Questionnaire, the Wechsler Brief intelligence quotient (IQ) assessment, and proton magnetic resonance spectroscopic imaging ((1)H-MRSI) to measure subcortical white matter metabolism of choline and related compounds (CHO). Patients with GAD exhibited higher IQ's and lower metabolite concentrations of CHO in the subcortical white matter in comparison to healthy volunteers. When data from GAD patients and healthy controls were combined, relatively low CHO predicted both relatively higher IQ and worry scores. Relatively high anxiety in patients with GAD predicted high IQ whereas relatively low anxiety in controls also predicted high IQ. That is, the relationship between anxiety and intelligence was positive in GAD patients but inverse in healthy volunteers. The collective data suggest that both worry and intelligence are characterized by depletion of metabolic substrate in the subcortical white matter and that intelligence may have co-evolved with worry in humans. PMID:22347183

  10. Genetic schizophrenia risk variants jointly modulate total brain and white matter volume

    PubMed Central

    Terwisscha van Scheltinga, AF; Bakker, Steven C.; van Haren, Neeltje E.M.; Derks, Eske M.; Buizer-Voskamp, Jacobine E.; Boos, Heleen B.M.; Cahn, Wiepke; Hulshoff Pol, HE; Ripke, Stephan; Ophoff, Roel A.; Kahn, RS

    2012-01-01

    Background Thousands of common single nucleotide polymorphisms (SNPs) are weakly associated with schizophrenia. It is likely that subsets of disease-associated SNPs are associated with distinct heritable disease-associated phenotypes. Therefore, we examined the shared genetic susceptibility modulating schizophrenia and brain volume. Methods Odds ratios for genome-wide SNP data were calculated in the sample collected by the Psychiatric GWAS Consortium (8,690 schizophrenia patients and 11,831 controls, excluding subjects from the present study). These were used to calculate individual polygenic schizophrenia (“risk”) scores (PSSs) in an independent sample of 152 schizophrenia patients and 142 healthy controls with available structural MRI scans. Results In the entire group, the PSS was significantly associated with total brain volume (R2=0.048, p=1.6×10?4) and white matter volume (R2=0.051, p=8.6×10?5) equally in patients and controls. The number of (independent) SNPs that substantially influenced both disease risk and white matter (n=2,020) was much smaller than the entire set of SNPs that modulated disease status (n=14,751). From the set of 2,020 SNPs, a group of 186 SNPs showed most evidence for association with white matter volume and an explorative functional analysis showed that these SNPs were located in genes with neuronal functions. Conclusions These results indicate that a relatively small subset of schizophrenia genetic risk variants is related to the (normal) development of white matter. This in turn suggests that disruptions in white matter growth increase the susceptibility to develop schizophrenia. PMID:23039932

  11. Improved longitudinal [(18)F]-AV45 amyloid PET by white matter reference and VOI-based partial volume effect correction.

    PubMed

    Brendel, Matthias; Högenauer, Marcus; Delker, Andreas; Sauerbeck, Julia; Bartenstein, Peter; Seibyl, John; Rominger, Axel

    2015-03-01

    Amyloid positron-emission-tomography (PET) offers an important research and diagnostic tool for investigating Alzheimer's disease (AD). The majority of amyloid PET studies have used the cerebellum as a reference region, and clinical studies have not accounted for atrophy-based partial volume effects (PVE). Longitudinal studies using cerebellum as reference tissue have revealed only small mean increases and high inter-subject variability in amyloid binding. We aimed to test the effects of different reference regions and PVE-correction (PVEC) on the discriminatory power and longitudinal performance of amyloid PET. We analyzed [(18)F]-AV45 PET and T1-weighted MRI data of 962 subjects at baseline and two-year follow-up data of 258 subjects. Cortical composite volume-of-interest (VOI) values (COMP) for tracer uptake were generated using either full brain atlas VOIs, gray matter segmented VOIs or gray matter segmented VOIs after VOI-based PVEC. Standard-uptake-value ratios (SUVR) were calculated by scaling the COMP values to uptake in cerebellum (SUVRCBL), brainstem (SUVRBST) or white matter (SUVRWM). Mean SUV, SUVR, and changes after PVEC were compared at baseline between diagnostic groups of healthy controls (HC; N=316), mild cognitive impairment (MCI; N=483) and AD (N=163). Receiver operating characteristics (ROC) were calculated for the discriminations between HC, MCI and AD, and expressed as area under the curve (AUC). Finally, the longitudinal [(18)F]-AV45-PET data were used to analyze the impact of quantitation procedures on apparent changes in amyloid load over time. Reference region SUV was most constant between diagnosis groups for the white matter. PVEC led to decreases of COMP-SUV in HC (-18%) and MCI (-10%), but increases in AD (+7%). Highest AUCs were found when using PVEC with white matter scaling for the contrast between HC/AD (0.907) or with brainstem scaling for the contrast between HC/MCI (0.658). Longitudinal increases were greatest in all diagnosis groups with application of PVEC, and inter-subject variability was lowest for the white matter reference. Thus, discriminatory power of [(18)F]-AV45-PET was improved by use of a VOI-based PVEC and white matter or brainstem rather than cerebellum reference region. Detection of longitudinal amyloid increases was optimized with PVEC and white matter reference tissue. PMID:25482269

  12. Addressing the Path-Length-Dependency Confound in White Matter Tract Segmentation

    PubMed Central

    Liptrot, Matthew G.; Sidaros, Karam; Dyrby, Tim B.

    2014-01-01

    We derive the Iterative Confidence Enhancement of Tractography (ICE-T) framework to address the problem of path-length dependency (PLD), the streamline dispersivity confound inherent to probabilistic tractography methods. We show that PLD can arise as a non-linear effect, compounded by tissue complexity, and therefore cannot be handled using linear correction methods. ICE-T is an easy-to-implement framework that acts as a wrapper around most probabilistic streamline tractography methods, iteratively growing the tractography seed regions. Tract networks segmented with ICE-T can subsequently be delineated with a global threshold, even from a single-voxel seed. We investigated ICE-T performance using ex vivo pig-brain datasets where true positives were known via in vivo tracers, and applied the derived ICE-T parameters to a human in vivo dataset. We examined the parameter space of ICE-T: the number of streamlines emitted per voxel, and a threshold applied at each iteration. As few as 20 streamlines per seed-voxel, and a robust range of ICE-T thresholds, were shown to sufficiently segment the desired tract network. Outside this range, the tract network either approximated the complete white-matter compartment (too low threshold) or failed to propagate through complex regions (too high threshold). The parameters were shown to be generalizable across seed regions. With ICE-T, the degree of both near-seed flare due to false positives, and of distal false negatives, are decreased when compared with thresholded probabilistic tractography without ICE-T. Since ICE-T only addresses PLD, the degree of remaining false-positives and false-negatives will consequently be mainly attributable to the particular tractography method employed. Given the benefits offered by ICE-T, we would suggest that future studies consider this or a similar approach when using tractography to provide tract segmentations for tract based analysis, or for brain network analysis. PMID:24797510

  13. Hyperintense White Matter Lesions in 50 High-Altitude Pilots With Neurologic Decompression Sickness

    PubMed Central

    McGuire, Stephen A.; Sherman, Paul M.; Brown, Anthony C.; Robinson, Andrew Y.; Tate, David F.; Fox, Peter T.; Kochunov, Peter V.

    2013-01-01

    Introduction Neurologic decompression sickness (NDCS) can affect high-altitude pilots, causing variable central nervous system symptoms. Five recent severe episodes prompted further investigation. Methods We report the hyperintense white matter (HWM) lesion imaging findings in 50 U-2 pilot volunteers, and compare 12 U-2 pilots who experienced clinical NDCS to 38 U-2 pilots who did not. The imaging data were collected using a 3T magnetic resonance imaging scanner and high-resolution (1-mm isotropic) three-dimensional fluid-attenuated inversion recovery sequence. Whole-brain and regional lesion volume and number were compared between groups. Results The NDCS group had significantly increased whole brain and insular volumes of HWM lesions. The intergroup difference in lesion numbers was not significant. Conclusion A clinical episode of NDCS was associated with a significant increase in HWM lesion volume, especially in the insula. We postulate this to be due to hypobaric exposure rather than hypoxia since all pilots were maintained on 100% oxygen throughout the flight. Further studies will be necessary to better understand the pathophysiology underlying these lesions. PMID:23316539

  14. Abnormal white matter integrity and impairment of cognitive abilities in adolescent inhalant abusers.

    PubMed

    Yuncu, Zeki; Zorlu, Nabi; Saatcioglu, Hozan; Basay, Burge; Basay, Omer; Zorlu, Pelin Kurtgoz; Kitis, Omer; Gelal, Fazil

    2015-01-01

    Inhalant abuse represents a major health problem especially among adolescents and young adults. However, less is known about white matter (WM) microstructure in adolescent inhalant abusers. In the present study, we used diffusion tensor imaging (DTI) to study WM changes in adolescent inhalant abusers compared with healthy controls. We also tested whether there was any relationship between WM integrity and neuropsychological measures in adolescent inhalant abusers. The study included 19 adolescent inhalant abusers and 19 healthy control subjects. Whole brain analysis of WM microstructure was performed using tract-based spatial statistics (TBSS) to detect abnormal WM regions between groups. Wisconsin card sorting test (WCST) and Stroop test were used to measure neuropsychological performance. We found that adolescent inhalant abuser group had significantly higher axial diffusivity (AD) values in left parietal, occipital and temporal WM than in healthy control group. Inhalant abuser and control groups did not differ significantly on fractional anisotropy (FA) and radial diffusivity (RD) values. Adolescent inhalant abusers showed worse performance when compared with control group in WCST and Stroop test. There was no significant correlation of AD values in significant clusters with neuropsychological test performances within the two groups. We only found discrete impairments in neuropsychological test performance and WM integrity in adolescent inhalant abusers compared with healthy control subjects and we were not able to demonstrate a direct correlation between WM alterations and neurocognitive performance. Future work is required to longitudinally evaluate brain abnormalities through methods assessing brain structure, function and connectivity. PMID:25479538

  15. Physical Activity and Cardiorespiratory Fitness Are Beneficial for White Matter in Low-Fit Older Adults

    PubMed Central

    Burzynska, Agnieszka Zofia; Chaddock-Heyman, Laura; Voss, Michelle W.; Wong, Chelsea N.; Gothe, Neha P.; Olson, Erin A.; Knecht, Anya; Lewis, Andrew; Monti, Jim M.; Cooke, Gillian E.; Wojcicki, Thomas R.; Fanning, Jason; Chung, Hyondo David; Awick, Elisabeth; McAuley, Edward; Kramer, Arthur F.

    2014-01-01

    Physical activity (PA) and cardiorespiratory fitness (CRF) are associated with better cognitive function in late life, but the neural correlates for these relationships are unclear. To study these correlates, we examined the association of both PA and CRF with measures of white matter (WM) integrity in 88 healthy low-fit adults (age 60–78). Using accelerometry, we objectively measured sedentary behavior, light PA, and moderate to vigorous PA (MV-PA) over a week. We showed that greater MV-PA was related to lower volume of WM lesions. The association between PA and WM microstructural integrity (measured with diffusion tensor imaging) was region-specific: light PA was related to temporal WM, while sedentary behavior was associated with lower integrity in the parahippocampal WM. Our findings highlight that engaging in PA of various intensity in parallel with avoiding sedentariness are important in maintaining WM health in older age, supporting public health recommendations that emphasize the importance of active lifestyle. PMID:25229455

  16. White matter anisotropy in the ventral language pathway predicts sound-to-word learning success.

    PubMed

    Wong, Francis C K; Chandrasekaran, Bharath; Garibaldi, Kyla; Wong, Patrick C M

    2011-06-15

    According to the dual stream model of auditory language processing, the dorsal stream is responsible for mapping sound to articulation and the ventral stream plays the role of mapping sound to meaning. Most researchers agree that the arcuate fasciculus (AF) is the neuroanatomical correlate of the dorsal steam; however, less is known about what constitutes the ventral one. Nevertheless, two hypotheses exist: one suggests that the segment of the AF that terminates in middle temporal gyrus corresponds to the ventral stream, and the other suggests that it is the extreme capsule that underlies this sound-to-meaning pathway. The goal of this study was to evaluate these two competing hypotheses. We trained participants with a sound-to-word learning paradigm in which they learned to use a foreign phonetic contrast for signaling word meaning. Using diffusion tensor imaging, a brain-imaging tool to investigate white matter connectivity in humans, we found that fractional anisotropy in the left parietal-temporal region positively correlated with the performance in sound-to-word learning. In addition, fiber tracking revealed a ventral pathway, composed of the extreme capsule and the inferior longitudinal fasciculus, that mediated auditory comprehension. Our findings provide converging evidence supporting the importance of the ventral steam, an extreme capsule system, in the frontal-temporal language network. Implications for current models of speech processing are also discussed. PMID:21677162

  17. Widespread white matter tract aberrations in youth with familial risk for bipolar disorder.

    PubMed

    Roybal, Donna J; Barnea-Goraly, Naama; Kelley, Ryan; Bararpour, Layla; Howe, Meghan E; Reiss, Allan L; Chang, Kiki D

    2015-05-30

    Few studies have examined multiple measures of white matter (WM) differences in youth with familial risk for bipolar disorder (FR-BD). To investigate WM in the FR-BD group, we used three measures of WM structure and two methods of analysis. We used fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) to analyze diffusion tensor imaging (DTI) findings in 25 youth with familial risk for bipolar disorder, defined as having both a parent with BD and mood dysregulation, and 16 sex-, age-, and IQ-matched healthy controls. We conducted a whole brain voxelwise analysis using tract based spatial statistics (TBSS). Subsequently, we conducted a complementary atlas-based, region-of-interest analysis using Diffeomap to confirm results seen in TBSS. When TBSS was used, significant widespread between-group differences were found showing increased FA, increased AD, and decreased RD in the FR-BD group in the bilateral uncinate fasciculus, cingulum, cingulate, superior fronto-occipital fasciculus (SFOF), superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus, and corpus callosum. Atlas-based analysis confirmed significant between-group differences, with increased FA and decreased RD in the FR-BD group in the SLF, cingulum, and SFOF. We found significant widespread WM tract aberrations in youth with familial risk for BD using two complementary methods of DTI analysis. PMID:25779034

  18. Accurate Identification of MCI Patients via Enriched White-Matter Connectivity Network

    NASA Astrophysics Data System (ADS)

    Wee, Chong-Yaw; Yap, Pew-Thian; Brownyke, Jeffery N.; Potter, Guy G.; Steffens, David C.; Welsh-Bohmer, Kathleen; Wang, Lihong; Shen, Dinggang

    Mild cognitive impairment (MCI), often a prodromal phase of Alzheimer's disease (AD), is frequently considered to be a good target for early diagnosis and therapeutic interventions of AD. Recent emergence of reliable network characterization techniques have made understanding neurological disorders at a whole brain connectivity level possible. Accordingly, we propose a network-based multivariate classification algorithm, using a collection of measures derived from white-matter (WM) connectivity networks, to accurately identify MCI patients from normal controls. An enriched description of WM connections, utilizing six physiological parameters, i.e., fiber penetration count, fractional anisotropy (FA), mean diffusivity (MD), and principal diffusivities (? 1, ? 2, ? 3), results in six connectivity networks for each subject to account for the connection topology and the biophysical properties of the connections. Upon parcellating the brain into 90 regions-of-interest (ROIs), the average statistics of each ROI in relation to the remaining ROIs are extracted as features for classification. These features are then sieved to select the most discriminant subset of features for building an MCI classifier via support vector machines (SVMs). Cross-validation results indicate better diagnostic power of the proposed enriched WM connection description than simple description with any single physiological parameter.

  19. Frontal white matter integrity in adults with Down syndrome with and without dementia

    PubMed Central

    Powell, David; Caban-Holt, Allison; Jicha, Gregory; Robertson, William; Davis, Roberta; Gold, Brian T.; Schmitt, Frederick A.; Head, Elizabeth

    2014-01-01

    Adults with Down syndrome (DS) are at high risk for developing Alzheimer’s disease after the age of 40 years. To detect white matter (WM) changes in the brain linked to dementia, fractional anisotropy (FA) from diffusion tensor imaging was used. We hypothesized that adults with DS without dementia (DS n = 10), DS with dementia (DSAD n = 10) and age matched non-DS subjects (CTL n = 10) would show differential levels of FA and an association with scores from the Brief Praxis Test and the Severe Impairment Battery. WM integrity differences in DS compared with CTL were found predominantly in the frontal lobes. Across all DS adults, poorer Brief Praxis Test performance correlated with reduced FA in the corpus callosum as well as several association tracts, primarily within frontoparietal regions. Our results demonstrate significantly lower WM integrity in DS compared with controls, particularly in the frontal tracts. DS-related WM integrity reductions in a number of tracts were associated with poorer cognition. These preliminary results suggest that late myelinating frontal pathways may be vulnerable to aging in DS. PMID:24582640

  20. Diffusion Tensor Imaging Study of White Matter Damage in Chronic Meningitis

    PubMed Central

    Lin, Wei-Che; Chen, Pei-Chin; Wang, Hung-Chen; Tsai, Nai-Wen; Chou, Kun-Hsien; Chen, Hsiu-Ling; Su, Yu-Jih; Lin, Ching-Po; Li, Shau-Hsuan; Chang, Wen-Neng; Lu, Cheng-Hsien

    2014-01-01

    Tuberculous meningitis (TBM) and cryptococcal meningitis (CM) are two of the most common types of chronic meningitis. This study aimed to assess whether chronic neuro-psychological sequelae are associated with micro-structure white matter (WM) damage in HIV-negative chronic meningitis. Nineteen HIV-negative TBM patients, 13 HIV-negative CM patients, and 32 sex- and age-matched healthy volunteers were evaluated and compared. The clinical relevance of WM integrity was studied using voxel-based diffusion tensor imaging (DTI) magnetic resonance imaging. All of the participants underwent complete medical and neurologic examinations, and neuro-psychological testing. Differences in DTI indices correlated with the presence of neuro-psychological rating scores and cerebrospinal fluid (CSF) analysis during the initial hospitalization. Patients with CM had more severe cognitive deficits than healthy subjects, especially in TBM. There were changes in WM integrity in several limbic regions, including the para-hippocampal gyrus and cingulate gyrus, and in the WM close to the globus pallidus. A decline in WM integrity close to the globus pallidus and anterior cingulate gyrus was associated with worse CSF analysis profiles. Poorer DTI parameters directly correlated with worse cognitive performance on follow-up. These correlations suggest that WM alterations may be involved in the psychopathology and pathophysiology of co-morbidities. Abnormalities in the limbic system and globus pallidus, with their close relationship to the CSF space, may be specific biomarkers for disease evaluation. PMID:24892826

  1. Longitudinal grey and white matter changes in frontotemporal dementia and Alzheimer's disease.

    PubMed

    Frings, Lars; Yew, Belinda; Flanagan, Emma; Lam, Bonnie Y K; Hüll, Michael; Huppertz, Hans-Jürgen; Hodges, John R; Hornberger, Michael

    2014-01-01

    Behavioural variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) dementia are characterised by progressive brain atrophy. Longitudinal MRI volumetry may help to characterise ongoing structural degeneration and support the differential diagnosis of dementia subtypes. Automated, observer-independent atlas-based MRI volumetry was applied to analyse 102 MRI data sets from 15 bvFTD, 14 AD, and 10 healthy elderly control participants with consecutive scans over at least 12 months. Anatomically defined targets were chosen a priori as brain structures of interest. Groups were compared regarding volumes at clinic presentation and annual change rates. Baseline volumes, especially of grey matter compartments, were significantly reduced in bvFTD and AD patients. Grey matter volumes of the caudate and the gyrus rectus were significantly smaller in bvFTD than AD. The bvFTD group could be separated from AD on the basis of caudate volume with high accuracy (79% cases correct). Annual volume decline was markedly larger in bvFTD and AD than controls, predominantly in white matter of temporal structures. Decline in grey matter volume of the lateral orbitofrontal gyrus separated bvFTD from AD and controls. Automated longitudinal MRI volumetry discriminates bvFTD from AD. In particular, greater reduction of orbitofrontal grey matter and temporal white matter structures after 12 months is indicative of bvFTD. PMID:24595028

  2. Quantitative Magnetic Susceptibility of the Developing Mouse Brain Reveals Microstructural Changes in the White Matter

    PubMed Central

    Argyridis, Ioannis; Li, Wei; Johnson, G. Allan; Liu, Chunlei

    2014-01-01

    Cerebral development involves a complex cascade of events which are difficult to visualize and quantify in vivo. In this study we combine information from Diffusion Tensor Imaging (DTI) and Quantitative Susceptibility Mapping (QSM) to analyze developing mouse brains at five stages up to 56 days postnatal. Susceptibility maps were calculated using frequency shifts in gradient echo MR images acquired at 9.4 T. Mean apparent magnetic susceptibility and magnetic susceptibility anisotropy of major white matter tracts were evaluated as a function of age. During the first two weeks, susceptibility of white matter appeared paramagnetic relative to surrounding gray matter; it then gradually became more diamagnetic. While diffusion anisotropy was already apparent and high at postnatal day 2, susceptibility anisotropy only became significant during the third week. This mismatch indicated different microstructural underpinnings for diffusion anisotropy and susceptibility anisotropy. Histological exams were also performed to evaluate myelin and iron content. It is confirmed that the main source of susceptibility contrast in WM is the myelin content. The ability to quantify the magnetic properties of white matter will provide valuable information on the architecture of the brain during development and potentially a more specific indicator for myelin degenerative diseases. PMID:24269576

  3. Polygenic determinants of white matter volume derived from GWAS lack reproducibility in a replicate sample

    PubMed Central

    Papiol, S; Mitjans, M; Assogna, F; Piras, F; Hammer, C; Caltagirone, C; Arias, B; Ehrenreich, H; Spalletta, G

    2014-01-01

    A recent publication reported an exciting polygenic effect of schizophrenia (SCZ) risk variants, identified by a large genome-wide association study (GWAS), on total brain and white matter volumes in schizophrenic patients and, even more prominently, in healthy subjects. The aim of the present work was to replicate and then potentially extend these findings. According to the original publication, polygenic risk scores—using single nucleotide polymorphism (SNP) information of SCZ GWAS—(polygenic SCZ risk scores; PSS) were calculated in 122 healthy subjects, enrolled in a structural magnetic resonance imaging (MRI) study. These scores were computed based on P-values and odds ratios available through the Psychiatric GWAS Consortium. In addition, polygenic white matter scores (PWM) were calculated, using the respective SNP subset in the original publication. None of the polygenic scores, either PSS or PWM, were found to be associated with total brain, white matter or gray matter volume in our replicate sample. Minor differences between the original and the present study that might have contributed to lack of reproducibility (but unlikely explain it fully), are number of subjects, ethnicity, age distribution, array technology, SNP imputation quality and MRI scanner type. In contrast to the original publication, our results do not reveal the slightest signal of association of the described sets of GWAS-identified SCZ risk variants with brain volumes in adults. Caution is indicated in interpreting studies building on polygenic risk scores without replication sample. PMID:24548877

  4. Parameter comparison of white matter diffusion tensor imaging (DTI) in rhesus macaques (Macaca mulatta).

    PubMed

    Mo, Yin; Chao, Fang; Song, Ming; Liu, Ci-Rong; Liu, Hui-Lang; Qian, Xi-Ying; Zhao, Xu-Dong

    2014-05-01

    In this study, we analyzed diffusion tensor imaging (DTI) results of brain white matter in rhesus macaques (Macaca mulatta) with four different parameter settings and found that the sequence A (b=1 000 s/mm(2), spatial resolution=1.25 mm×1.25 mm× 1.25 mm, numbers of direction=33, NSA=3) and B (b=800 s/mm(2), spatial resolution=1.25 mm×1.25 mm×1.25 mm, numbers of direction=33, NSA=3) could accurately track coarse fibers. The fractional anisotropy (FA) derived from sequence C (b=1 000s/mm(2), spatial resolution=0.55 mm×0.55 mm×2.5 mm, direction number=33, NSA=3) was too fuzzy to be used in tracking white matter fibers. By comparison, the high resolution and the FA with high contrast of gray matter and white matter derived from sequence D (b=800 s/mm(2), spatial resolution=1.0 mm×1.0 mm ×1.0 mm, numbers of direction=33, NSA=3) qualified in its application in tracking both thick and thin fibers, making it an optimal DTI setting for rhesus macaques. PMID:24866488

  5. Whole-brain white matter disruption in semantic and nonfluent variants of primary progressive aphasia.

    PubMed

    Schwindt, Graeme C; Graham, Naida L; Rochon, Elizabeth; Tang-Wai, David F; Lobaugh, Nancy J; Chow, Tiffany W; Black, Sandra E

    2013-04-01

    Semantic (svPPA) and nonfluent (nfPPA) variants of primary progressive aphasia are associated with distinct patterns of cortical atrophy and underlying pathology. Little is known, however, about their contrasting spread of white matter disruption and how this relates to grey matter (GM) loss. We undertook a structural MRI study to investigate this relationship. We used diffusion tensor imaging, tract-based spatial statistics, and voxel-based morphometry to examine fractional anisotropy (FA) and directional diffusivities in nine patients with svPPA and nine patients with nfPPA, and compared them to 16 matched controls after accounting for global GM atrophy. Significant differences in topography of white matter changes were found, with more ventral involvement in svPPA patients and more widespread frontal involvement in nfPPA individuals. However, each group had both ventral and dorsal tract changes, and both showed spread of diffusion abnormalities beyond sites of local atrophy. There was a clear dissociation in sensitivity of diffusion tensor imaging measures between groups. SvPPA patients showed widespread changes in FA and radial diffusivity, whereas changes in axial diffusivity were more restricted and proximal to sites of GM atrophy. NfPPA patients showed isolated changes in FA, but widespread axial and radial diffusivity changes. These findings reveal the extent of white matter disruption in these variants of PPA after accounting for GM loss. Further, they suggest that differences in the relative sensitivity of diffusion metrics may reflect differences in the nature of underlying white matter pathology in these two subtypes. PMID:22109837

  6. White Matter Fractional Anisotropy Correlates With Speed of Processing and Motor Speed in Young Childhood Cancer Survivors

    SciTech Connect

    Aukema, Eline J. [Pediatric Psychosocial Department, Emma Children's Hospital/Academic Medical Center, Amsterdam (Netherlands)], E-mail: e.j.aukema@amc.uva.nl; Caan, Matthan W.A. [Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Delft University of Technology, Delft (Netherlands); Oudhuis, Nienke [Pediatric Psychosocial Department, Emma Children's Hospital/Academic Medical Center, Amsterdam (Netherlands); Majoie, Charles [Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Vos, Frans M. [Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Delft University of Technology, Delft (Netherlands); Reneman, Liesbeth [Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Last, Bob F. [Pediatric Psychosocial Department, Emma Children's Hospital/Academic Medical Center, Amsterdam (Netherlands); Department of Developmental Psychology, Free University of Amsterdam, Amsterdam (Netherlands); Grootenhuis, Martha A. [Pediatric Psychosocial Department, Emma Children's Hospital/Academic Medical Center, Amsterdam (Netherlands); Schouten-van Meeteren, Antoinette Y.N. [Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam (Netherlands)

    2009-07-01

    Purpose: To determine whether childhood medulloblastoma and acute lymphoblastic leukemia (ALL) survivors have decreased white matter fractional anisotropy (WMFA) and whether WMFA is related to the speed of processing and motor speed. Methods and Materials: For this study, 17 patients (6 medulloblastoma, 5 ALL treated with high-dose methotrexate (MTX) (4 x 5 g/m{sup 2}) and 6 with low-dose MTX (3 x 2 g/m{sup 2})) and 17 age-matched controls participated. On a 3.0-T magnetic resonance imaging (MRI) scanner, diffusion tensor imaging (DTI) was performed, and WMFA values were calculated, including specific regions of interest (ROIs), and correlated with the speed of processing and motor speed. Results: Mean WMFA in the patient group, mean age 14 years (range 8.9 - 16.9), was decreased compared with the control group (p = 0.01), as well as WMFA in the right inferior fronto-occipital fasciliculus (IFO) (p = 0.03) and in the genu of the corpus callosum (gCC) (p = 0.01). Based on neurocognitive results, significant positive correlations were present between processing speed and WMFA in the splenium (sCC) (r = 0.53, p = 0.03) and the body of the corpus callosum (bCC) (r = 0.52, p = 0.03), whereas the right IFO WMFA was related to motor speed (r = 0.49, p < 0.05). Conclusions: White matter tracts, using a 3.0-T MRI scanner, show impairment in childhood cancer survivors, medulloblastoma survivors, and also those treated with high doses of MTX. In particular, white matter tracts in the sCC, bCC and right IFO are positively correlated with speed of processing and motor speed.

  7. Cerebral white matter injuries following a hypoxic/ischemic insult during the perinatal period: pathophysiology, prognostic factors, and future strategy of treatment approach. A minireview.

    PubMed

    Zammit, Christian; Muscat, Richard; Sani, Gabriele; Pomara, Cristoforo; Valentino, Mario

    2015-01-01

    Recent advances in medical care have significantly improved the survival rate of neonates who suffer a hypoxic/ ischemic event, before, during, or after birth. These infants are extremely vulnerable to brain injury and are at high risk of developing motor and cognitive abnormalities later on in life. The regional distribution of perinatal brain injury varies, and depends primarily on; the severity, pattern and type of insult, the metabolic status, and on the gestational age. The principal neuropathological substrate that is affected in the premature infant is cerebral white matter. The aim of this article is to re-examine the current knowledge on the ischemic pathophysiology of all cellular components that comprise the white matter, pred ict the consequences of the long-term neurological outcome, and analyze possible therapeutic strategies. Although oligodendrocytes have long been regarded as the hallmark of perinatal white matter injury, axons, astrocytes and microglia, all contribute to the complex pattern of brain injury that occurs in this cohort of individuals. It is hoped that a better understanding of the pathophysiology of white matter injury and its underlying prognostic factors, may lead to the development of new therapeutic strategies for such a complex and debilitating condition. PMID:25564391

  8. Impaired functional but preserved structural connectivity in limbic white matter tracts in youth with conduct disorder or oppositional defiant disorder plus psychopathic traits.

    PubMed

    Finger, Elizabeth Carrie; Marsh, Abigail; Blair, Karina Simone; Majestic, Catherine; Evangelou, Iordanis; Gupta, Karan; Schneider, Marguerite Reid; Sims, Courtney; Pope, Kayla; Fowler, Katherine; Sinclair, Stephen; Tovar-Moll, Fernanda; Pine, Daniel; Blair, Robert James

    2012-06-30

    Youths with conduct disorder or oppositional defiant disorder and psychopathic traits (CD/ODD+PT) are at high risk of adult antisocial behavior and psychopathy. Neuroimaging studies demonstrate functional abnormalities in orbitofrontal cortex and the amygdala in both youths and adults with psychopathic traits. Diffusion tensor imaging in psychopathic adults demonstrates disrupted structural connectivity between these regions (uncinate fasiculus). The current study examined whether functional neural abnormalities present in youths with CD/ODD+PT are associated with similar white matter abnormalities. Youths with CD/ODD+PT and comparison participants completed 3.0 T diffusion tensor scans and functional magnetic resonance imaging scans. Diffusion tensor imaging did not reveal disruption in structural connections within the uncinate fasiculus or other white matter tracts in youths with CD/ODD+PT, despite the demonstration of disrupted amygdala-prefrontal functional connectivity in these youths. These results suggest that disrupted amygdala-frontal white matter connectivity as measured by fractional anisotropy is less sensitive than imaging measurements of functional perturbations in youths with psychopathic traits. If white matter tracts are intact in youths with this disorder, childhood may provide a critical window for intervention and treatment, before significant structural brain abnormalities solidify. PMID:22819939

  9. Graph theoretical analysis of developmental patterns of the white matter network

    PubMed Central

    Chen, Zhang; Liu, Min; Gross, Donald W.; Beaulieu, Christian

    2013-01-01

    Understanding the development of human brain organization is critical for gaining insight into how the enhancement of cognitive processes is related to the fine-tuning of the brain network. However, the developmental trajectory of the large-scale white matter (WM) network is not fully understood. Here, using graph theory, we examine developmental changes in the organization of WM networks in 180 typically-developing participants. WM networks were constructed using whole brain tractography and 78 cortical regions of interest were extracted from each participant. The subjects were first divided into 5 equal sample size (n = 36) groups (early childhood: 6.0–9.7 years; late childhood: 9.8–12.7 years; adolescence: 12.9–17.5 years; young adult: 17.6–21.8 years; adult: 21.9–29.6 years). Most prominent changes in the topological properties of developing brain networks occur at late childhood and adolescence. During late childhood period, the structural brain network showed significant increase in the global efficiency but decrease in modularity, suggesting a shift of topological organization toward a more randomized configuration. However, while preserving most topological features, there was a significant increase in the local efficiency at adolescence, suggesting the dynamic process of rewiring and rebalancing brain connections at different growth stages. In addition, several pivotal hubs were identified that are vital for the global coordination of information flow over the whole brain network across all age groups. Significant increases of nodal efficiency were present in several regions such as precuneus at late childhood. Finally, a stable and functionally/anatomically related modular organization was identified throughout the development of the WM network. This study used network analysis to elucidate the topological changes in brain maturation, paving the way for developing novel methods for analyzing disrupted brain connectivity in neurodevelopmental disorders. PMID:24198774

  10. Liquid metal feeding through dendritic region in Ni-Hard white iron

    SciTech Connect

    Oryshchyn, Danylo B.; Dogan, Omer N.

    2005-01-01

    Liquid permeability in the dendritic regions is one of the factors that determine porosity formation and macro segregation in castings. Permeability in the dendritic structure of Ni-Hard white iron was measured as a function of temperature. Effect of microstructural coarsening on the permeability was also investigated. Permeability increased with coarsening dendritic structure in Ni-Hard white iron.

  11. Pharmacological Effects of Erythropoietin and its Derivative Carbamyl erythropoietin in Cerebral White Matter Injury

    NASA Astrophysics Data System (ADS)

    Liu, Wei

    Periventricular leukomalacia (PVL) is the predominant form of brain injury in the premature infant and the most common cause of cerebral palsy, yet no therapy currently exists for this serious human disorder. As PVL often occurs in preterm infants suffering from cerebral hypoxia/ischemia with or without prior exposure to maternal-fetal infection/inflammation, we used hypoxia/ischemia with or without lipopolysaccharide (LPS) injection, to produce clinically relevant PVL-like lesions in the white matter in postnatal day six (P6) mice. We studied the white matter pathology under different conditions, such as different durations of hypoxia and different doses of LPS, to evaluate the effects of those etiological factors on neonatal white matter injury. Distinct related pathological events were investigated at different time points during the progression of PVL. We used immunohistochemistry, histological analysis, and electron microscopy (EM) to study demylination that occurs in the white matter area, which is consistent with the pathology of human PVL. Previous studies have shown that erythropoietin (EPO) and its derivative carbamylated EPO (CEPO) are neuroprotective in various experimental models of brain injury. However, none of these studies investigated their efficacy against white matter injury using appropriate animal models of PVL. We produced unilateral or bilateral white matter injury in P6 mice using unilateral carotid ligation (UCL) followed by hypoxia (6% oxygen, 35 min) or by UCL/hypoxia plus LPS injection, respectively. We administered a single intraperitoneal (i.p.) dose of EPO or CEPO (5000 IU/kg) immediately after the insult, and found both drugs to provide significant protection against white matter injury in PVL mice compared to vehicle-treated groups. In addition, EPO and CEPO treatments attenuated neurobehavioral dysfunctions in an acute manner after PVL injury. EPO and CEPO have relatively few adverse effects, and thus may be a therapeutic agent with translational potential for PVL, which is the primary injury underlying cerebral palsy. After confirming the neuroprotective effects of EPO and CEPO on PVL mice, we continued to study the mechanisms relating to their functions. As we learned from our lab's previous study, microglia play an important role in the pathogenesis of PVL, linking multiple effectors downstream of hypoxia-ischemia and inflammation. We found that EPO and CEPO inhibit microglial activation and reduced the severity of injury. Furthermore, we found that EPO and CEPO decreased the activity of poly (ADP-ribose) polymerase-1 (PARP-1) in activated microglia. PARP-1 activity increases in response to many insults, such as infection, ischemia and toxicity. Therefore, we hypothesized that EPO and CEPO decrease microglial activation by inhibiting PARP-1 activity, and thus leading to protection against inflammation and cell death. Besides pharmacological studies of EPO and CEPO on PVL, we also investigated other endogenous factors that may affect neonatal white matter injury. Heat shock proteins (HSPs) are important chaperones that facilitate appropriate protein folding and modification. HSP60, a chaperonin located in the mitochondria, is one of these important molecules that promote appropriate protein folding. HSP60 expression levels increased significantly in the brains of PVL mice compared with control animals. In microglial cell culture, we found that after LPS treatment, HSP60 expression levels increased both inside microglial cells and in the extracellular medium. In addition, we noted enhanced HSP60 immunoreactivity in the brains of PVL mice, which localized inside activated microglial cells and extracellularly. The rise in HSP60 activity after hypoxia-ischemia and LPS administration implies that it potentially functions as one of the triggers of microglial activation and central nervous system inflammation.

  12. White matter in temporal lobe epilepsy: clinico-pathological correlates of water diffusion abnormalities

    PubMed Central

    Rodríguez-Cruces, Raúl

    2015-01-01

    Using magnetic resonance imaging, it is possible to measure the behavior of diffusing water molecules, and the metrics derived can be used as indirect markers of tissue micro-architectural properties. Numerous reports have demonstrated that patients with temporal lobe epilepsy (TLE) have water diffusion abnormalities in several white matter structures located within and beyond the epileptogenic temporal lobe, showing that TLE is not a focal disorder, but rather a brain network disease. Differences in severity and spatial extent between patients with or without mesial temporal sclerosis (MTS), as well as differences related to hemispheric seizure onset, are suggestive of different pathophysiological mechanisms behind different forms of TLE, which in turn result in specific cognitive disabilities. The biological interpretation of diffusion abnormalities is based on a wealth of information from animal models of white matter damage, and is supported by recent reports that directly correlate diffusion metrics with histological characteristics of surgical specimens of TLE patients. Thus, there is now more evidence showing that the increased mean diffusivity (MD) and concomitant reductions of diffusion anisotropy that are frequently observed in several white matter bundles in TLE patients reflect reduced axonal density (increased extra-axonal space) due to smaller-caliber axons, and abnormalities in the myelin sheaths of the remaining axons. Whether these histological and diffusion features are a predisposing factor for epilepsy or secondary to seizures is still uncertain; some reports suggest the latter. This article summarizes recent findings in this field and provides a synopsis of the histological features seen most frequently in post-surgical specimens of TLE patients in an effort to aid the interpretation of white matter diffusion abnormalities. PMID:25853084

  13. White matter integrity in alcohol-naive youth with a family history of alcohol use disorders

    PubMed Central

    Squeglia, L. M.; Jacobus, J.; Brumback, T.; Meloy, M. J.; Tapert, S. F.

    2014-01-01

    Background Understanding pre-existing neural vulnerabilities found in youth who are family history positive (FHP) for alcohol use disorders could help inform preventative interventions created to delay initiation age and escalation of heavy drinking. The goal of this study was to compare indices of white matter integrity using diffusion tensor imaging (DTI) between FHP and family history negative (FHN) youth using a sample of 94 alcohol-naive adolescents and to examine if differences were associated with global and domain-specific cognitive functioning. Method Participants were 48 FHP and 46 FHN demographically matched, healthy, substance-naive 12- to 14-year-olds (54% female) recruited from local middle schools. Participants completed a neuropsychological test battery and magnetic resonance imaging session, including DTI. Results FHP youth had higher fractional anisotropy and axial diffusivity, and lower radial and mean diffusivity, than FHN youth in 19 clusters spanning projection, association and interhemispheric white matter tracts. Findings were replicated after controlling for age, gender, socio-economic status, grade and pubertal development. Groups did not differ significantly on global or domain-specific neuropsychological test scores. Conclusions FHP teens showed higher white matter integrity, but similar cognitive functioning, to FHN youth. More mature neural features could be related to more precocious behaviors, such as substance use initiation, in FHP youth. Future research exploring white matter maturation before and after substance use initiation will help elucidate the neuro-developmental trajectories in youth at risk for substance use disorders, to inform preventive efforts and better understand the sequelae of adolescent alcohol and drug use. PMID:25066702

  14. Evidence of Nitrosative Damage in the Brain White Matter of Patients with Multiple Sclerosis

    Microsoft Academic Search

    Oscar A. Bizzozero; Gisela DeJesus; Heather A. Bixler; Andrzej Pastuszyn

    2005-01-01

    Nitric oxide (NO) has been implicated in the pathophysiology of both experimental autoimmune encephalomyelitis and multiple sclerosis (MS). NO-mediated protein damage in MS appears to be confined to large plaques where 3-nitrotyrosine has been detected. To determine whether nitrosative damage takes place beyond visible MS plaques, the occurrence of various NO-triggered protein modifications in normal-appearing white matter (NAWM) of eight

  15. White Matter Medullary Infarcts: Acute Subcortical Infarction in the Centrum ovale

    Microsoft Academic Search

    Stephen J. Read; Louise Pettigrew; Laetitia Schimmel; Christopher R. Levi; Christopher F. Bladin; Brian R. Chambers; Geoffrey A. Donnan

    1998-01-01

    Acute infarction confined to the territory of the white matter medullary arteries is a poorly characterised acute stroke subtype. 22 patients with infarction confined to this vascular territory on CT and\\/or MRI were identified from a series of 1,800 consecutive admissions to our stroke unit (1.2%) between August 1993 and March 1997. 19 patients had small infarcts (<1.5 cm maximum

  16. Randomized clinical trial of dialysate cooling and effects on brain white matter.

    PubMed

    Eldehni, Mohamed T; Odudu, Aghogho; McIntyre, Christopher W

    2015-04-01

    Hemodialysis is associated with significant circulatory stress that could produce recurrent and cumulative ischemic insults to multiple organs, such as the brain. We aimed to characterize hemodialysis-induced brain injury by longitudinally studying the effects of hemodialysis on brain white matter microstructure and further examine if the use of cooled dialysate could provide protection against hemodialysis-associated brain injury. In total, 73 patients on incident hemodialysis starting within 6 months were randomized to dialyze with a dialysate temperature of either 37°C or 0.5°C below the core body temperature and followed up for 1 year. Brain white matter microstructure was studied by diffusion tensor magnetic resonance imaging at baseline and follow-up (38 patients available for paired analysis). Intradialytic hemodynamic stress was quantified using the extrema points analysis model. Patients on hemodialysis exhibited a pattern of ischemic brain injury (increased fractional anisotropy and reduced radial diffusivity). Cooled dialysate improved hemodynamic tolerability, and changes in brain white matter were associated with hemodynamic instability (higher mean arterial pressure extrema points frequencies were associated with higher fractional anisotropy [peak r=0.443, P<0.03] and lower radial diffusivity [peak r=-0.439, P<0.02]). Patients who dialyzed at 0.5°C below core body temperature exhibited complete protection against white matter changes at 1 year. Our data suggest that hemodialysis results in significant brain injury and that improvement in hemodynamic tolerability achieved by using cooled dialysate is effective at abrogating these effects. This intervention can be delivered without additional cost and is universally applicable. PMID:25234925

  17. Depression in small-vessel disease relates to white matter ultrastructural damage, not disability

    PubMed Central

    Herbert, Vanessa; Lawrence, Andrew J.; Morris, Robin G.; Markus, Hugh S.

    2014-01-01

    Objective: To determine whether cerebral small-vessel disease (SVD) is a specific risk factor for depression, whether any association is mediated via white matter damage, and to study the role of depressive symptoms and disability on quality of life (QoL) in this patient group. Methods: Using path analyses in cross-sectional data, we modeled the relationships among depression, disability, and QoL in patients with SVD presenting with radiologically confirmed lacunar stroke (n = 100), and replicated results in a second SVD cohort (n = 100). We then compared the same model in a non-SVD stroke cohort (n = 50) and healthy older adults (n = 203). In a further study, to determine the role of white matter damage in mediating the association with depression, a subgroup of patients with SVD (n = 101) underwent diffusion tensor imaging (DTI). Results: Reduced QoL was associated with depression in patients with SVD, but this association was not mediated by disability or cognition; very similar results were found in the replication SVD cohort. In contrast, the non-SVD stroke group and the healthy older adult group showed a direct relationship between disability and depression. The DTI study showed that fractional anisotropy, a marker of white matter damage, was related to depressive symptoms in patients with SVD. Conclusion: These results suggest that in stroke patients without SVD, disability is an important causal factor for depression, whereas in SVD stroke, other factors specific to this stroke subtype have a causal role. White matter damage detected on DTI is one factor that mediates the association between SVD and depression. PMID:25230999

  18. Multiple sclerosis and amyloid deposits in the white matter of the brain

    Microsoft Academic Search

    Inger Nennesmo; Nenad Bogdanovic; Anna-Lena Petrén; Sten Fredrikson

    1997-01-01

    We present the neuropathological findings in a female patient with clinically definite multiple sclerosis (MS), who at autopsy\\u000a had multifocal amyloid deposits in the white matter of the brain without other signs of amyloidosis. The patient had relapsing\\/remitting\\u000a MS between the ages of 26 and 45, and during her last 14 years she had a secondary chronic progressive form of

  19. Reading Performance Correlates with White-Matter Properties in Preterm and Term Children

    ERIC Educational Resources Information Center

    Andrews, James S.; Ben-Shachar, Michal; Yeatman, Jason D.; Flom, Lynda L.; Luna, Beatriz; Feldman, Heidi M.

    2010-01-01

    Aim: We used diffusion tensor imaging to investigate the association between white-matter integrity and reading ability in a cohort of 28 children. Nineteen preterm children (14 males, five females; mean age 11y 11mo [SD 1y 10mo], mean gestational age 30.5wks (SD 3.2), mean birthweight was 1455g [SD 625]); and nine term children (five males, four…

  20. Enhancement of the white matter following prophylactic therapy of the central nervous system for leukemia

    SciTech Connect

    Shalen, P.R.; Ostrow; P.T.; Glass, P.J.

    1981-08-01

    A case of fatal necrotizing leukoencephalopathy following prophylactic therapy of the central nervous system for acute lymphoblastic leukemia is reported. The clinical, CT, and neuropathological findings are described. The CT scan demonstrated symmetrical white-matter enhancement. Histological analysis was consistent with the effects of irradiation and methotrexate. The differential diagnosis of the clinical and CT findings is discussed. Brain biopsy is the diagnostic procedure of choice.

  1. Bral1: "Superglue" for the extracellular matrix in the brain white matter.

    PubMed

    Cicanic, Michal; Sykova, Eva; Vargova, Lydia

    2012-04-01

    Bral1 is a link protein that stabilizes the binding between lecticans and hyaluronic acid and thus maintains the extracellular matrix assembly in the CNS. Bral1 is specifically located in the white matter around the nodes of Ranvier. Recent studies suggest its function in promoting saltatory neural conduction. This article reviews the current knowledge about the structure, expression and function of this link protein. PMID:22300985

  2. Longitudinal Brain White Matter Alterations in Minimal Hepatic Encephalopathy before and after Liver Transplantation

    PubMed Central

    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. PMID:25166619

  3. White matter lesions and cognitive performance: the role of cognitively complex leisure activity

    Microsoft Academic Search

    Jane S. Saczynski; Maria K. Jonsdottir; Sigurdur Sigurdsson; Gudny Eiriksdottir; Palmi V. Jonsson; Melissa E. Garcia; Olafur Kjartansson; Mark A. van Buchem; Vilmundur Gudnason; Lenore J. Launer

    2008-01-01

    BACKGROUND: Among persons with white matter lesions (WMLs), there is a range of cognitive function. We examine whether participation in leisure activities modifies the effect of WML load on cognitive function.\\u000aMETHODS: Data are from 2300 men and women (aged 66-92 years) participating in the population-based Age Gene\\/Environment Susceptibility-Reykjavik Study. Subcortical WML load was calculated as a weighted sum, based

  4. White Matter Correlates of Cognitive Capacity Studied With Diffusion Tensor Imaging: Implications for Cognitive Reserve

    Microsoft Academic Search

    Marc W. Haut; Maria T. Moran; Melissa A. Lancaster; Hiroto Kuwabara; Michael W. Parsons; Aina Puce

    2007-01-01

    Cognitive reserve (CR) is a theoretical concept used to explain and study individual differences in cognitive symptom expression\\u000a in neurological disease. In the absence of neurologic injury or demands on processing, compensatory and protective factors\\u000a may be considered to represent cognitive capacity (CC), rather than cognitive reserve, per se. We studied the white matter\\u000a structural correlates of CC in 51

  5. White Matter Volume as a Major Predictor of Cognitive Function in Sturge-Weber Syndrome

    Microsoft Academic Search

    Csaba Juhasz; Christopher Lai; Michael E. Behen; Otto Muzik; Emily J. Helder; Diane C. Chugani; Harry T. Chugani

    2007-01-01

    Objective: To assess the role of gray and white matter volume loss vs seizures in cognitive impairment of chil- dren with Sturge-Weber syndrome with unilateral in- volvement. Design: Patients were enrolled in this prospective co- hort during a period of 3 years. Setting: Pediatric neurology clinic with national refer- ral through the Sturge-Weber Foundation. Participants: Twenty-one children (age range, 1

  6. Normal Appearing and Diffusely Abnormal White Matter in Patients with Multiple Sclerosis Assessed with Quantitative MR

    PubMed Central

    West, Janne; Aalto, Anne; Tisell, Anders; Leinhard, Olof Dahlqvist; Landtblom, Anne-Marie; Smedby, Örjan; Lundberg, Peter

    2014-01-01

    Introduction: Magnetic Resonance Imaging is a sensitive technique for detecting white matter (WM) MS lesions, but the relation with clinical disability is low. Because of this, changes in both ‘normal appearing white matter’ (NAWM) and ‘diffusely abnormal white matter’ (DAWM) have been of interest in recent years. MR techniques, including quantitative magnetic resonance imaging (qMRI) and quantitative magnetic resonance spectroscopy (qMRS), have been developed in order to detect and quantify such changes. In this study, qMRI and qMRS were used to investigate NAWM and DAWM in typical MS patients and in MS patients with low number of WM lesions. Patient data were compared to ‘normal white matter’ (NWM) in healthy controls. Methods: QMRI and qMRS measurements were performed on a 1.5 T Philips MR-scanner. 35 patients with clinically definite MS and 20 healthy controls were included. Twenty of the patients fulfilled the ‘Barkhof-Tintoré criteria’ for MS, (‘MRIpos’), whereas 15 showed radiologically atypical findings with few WM lesions (‘MRIneg’). QMRI properties were determined in ROIs of NAWM, DAWM and lesions in the MS groups and of NWM in controls. Descriptive statistical analysis and comparisons were performed. Correlations were calculated between qMRI measurements and (1) clinical parameters and (2) WM metabolite concentrations. Regression analyses were performed with brain parenchyma fraction and MSSS. Results: NAWM in the MRIneg group was significantly different from NAWM in the MRIpos group and NWM. In addition, R1 and R2 of NAWM in the MRIpos group correlated negatively with EDSS and MSSS. DAWM was significantly different from NWM, but similar in the MS groups. N-acetyl aspartate correlated negatively with R1 and R2 in MRIneg. R2 of DAWM was associated with BPF. Conclusions: Changes in NAWM and DAWM are independent pathological entities in the disease. The correlation between qMRI and clinical status may shed new light on the clinicoradiological paradox. PMID:24747946

  7. Lasting pure-motor deficits after focal posterior internal capsule white-matter infarcts in rats.

    PubMed

    Blasi, Francesco; Whalen, Michael J; Ayata, Cenk

    2015-06-01

    Small white-matter infarcts of the internal capsule are clinically prevalent but underrepresented among currently available animal models of ischemic stroke. In particular, the assessment of long-term outcome, a primary end point in clinical practice, has been challenging due to mild deficits and the rapid and often complete recovery in most experimental models. We, therefore, sought to develop a focal white-matter infarction model that can mimic the lasting neurologic deficits commonly observed in stroke patients. The potent vasoconstrictor endothelin-1 (n=24) or vehicle (n=9) was stereotactically injected into the internal capsule at one of three antero-posterior levels (1, 2, or 3?mm posterior to bregma) in male Sprague-Dawley rats. Endothelin-injected animals showed highly focal (~1?mm(3)) and reproducible ischemic infarcts, with severe axonal and myelin loss accompanied by cellular infiltration when examined 2 and 4 weeks after injection. Only those rats injected with endothelin-1 at the most posterior location developed robust and pure-motor deficits in adhesive removal, cylinder and foot-fault tests that persisted at 1 month, without detectable sensory impairments. In summary, we present an internal capsule stroke model optimized to produce lasting pure-motor deficits in rats that may be suitable to study neurologic recovery and rehabilitation after white-matter injury. PMID:25649992

  8. Developmental white matter microstructure in autism phenotype and corresponding endophenotype during adolescence

    PubMed Central

    Lisiecka, D M; Holt, R; Tait, R; Ford, M; Lai, M-C; Chura, L R; Baron-Cohen, S; Spencer, M D; Suckling, J

    2015-01-01

    During adolescence, white matter microstructure undergoes an important stage of development. It is hypothesized that the alterations of brain connectivity that have a key role in autism spectrum conditions (ASCs) may interact with the development of white matter microstructure. This interaction may be present beyond the phenotype of autism in siblings of individuals with ASC, who are 10 to 20 times more likely to develop certain forms of ASC. We use diffusion tensor imaging to examine how white matter microstructure measurements correlate with age in typically developing individuals, and how this correlation differs in n=43 adolescents with ASC and their n=38 siblings. Correlations observed in n=40 typically developing individuals match developmental changes noted in previous longitudinal studies. In comparison, individuals with ASC display weaker negative correlation between age and mean diffusivity in a broad area centred in the right superior longitudinal fasciculus. These differences may be caused either by increased heterogeneity in ASC or by temporal alterations in the group's developmental pattern. Siblings of individuals with ASC also show diminished negative correlation between age and one component of mean diffusivity—second diffusion eigenvalue—in the right superior longitudinal fasciculus. As the observed differences match for location and correlation directionality in our comparison of typically developing individuals to those with ASC and their siblings, we propose that these alterations constitute a part of the endophenotype of autism. PMID:25781228

  9. Microdysgenesis in temporal lobe epilepsy. A quantitative and immunohistochemical study of white matter neurones.

    PubMed

    Thom, M; Sisodiya, S; Harkness, W; Scaravilli, F

    2001-11-01

    Microdysgenesis is a microscopic cortical malformation considered to act as a substrate for seizures in some patients with generalized epilepsy. It is also recognized to involve the temporal lobe in a proportion of patients with intractable temporal lobe epilepsy, but the incidence of this abnormality, its relationship to mesial temporal lobe sclerosis and relevance to epileptogenesis remain unknown. This is partly due to a lack of well-defined quantitative pathological diagnostic criteria. To begin to address these issues, we have carried out a rigorous quantitative analysis, using three-dimensional cell counting methods, of several components of microdysgenesis in temporal lobectomy specimens. White matter, cortical and layer I neuronal densities (NDs) were measured using immunohistochemistry for the neuronal markers neuronal nuclear antigen and calbindin D-28-K. Patients with a seizure-free outcome (Class I) showed significantly more microdysgenetic features including higher white matter ND (P < 0.05), particularly of small (<10 microm diameter) neurones (P < 0.01), higher layer I ND (P < 0.05) and increased numbers of Cajal-Retzius-like calbindin-positive neurones (P < 0.05). We also demonstrated that white matter ND was independent of the degree of temporal lobe gliosis as assessed by quantitation of glial fibrillary acidic protein-immunoreactive cells. These findings suggest that microdysgenesis may be a significant lesion in temporal lobe epilepsy in terms of post-surgical prognosis. PMID:11673330

  10. White matter bundle registration and population analysis based on Gaussian processes.

    PubMed

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

    2011-01-01

    This paper proposes a method for the registration of white matter tract bundles traced from diffusion images and its extension to atlas generation, Our framework is based on a Gaussian process representation of tract density maps. Such a representation avoids the need for point-to-point correspondences, is robust to tract interruptions and reconnections and seamlessly handles the comparison and combination of white matter tract bundles. Moreover, being a parametric model, this approach has the potential to be defined in the Gaussian processes' parameter space, without the need for resampling the fiber bundles during the registration process. We use the similarity measure of our Gaussian process framework, which is in fact an inner product, to drive a diffeomorphic registration algorithm between two sets of homologous bundles which is not biased by point-to-point correspondences or the parametrization of the tracts. We estimate a dense deformation of the underlying white matter using the bundles as anatomical landmarks and obtain a population atlas of those fiber bundles. Finally we test our results in several different bundles obtained from in-vivo data. PMID:21761667

  11. White Matter Injury Due to Experimental Chronic Cerebral Hypoperfusion Is Associated with C5 Deposition

    PubMed Central

    Liu, Qinghai; He, Shuhan; Groysman, Leonid; Shaked, David; Russin, Jonathan; Cen, Steven; Mack, William J.

    2013-01-01

    The C5 complement protein is a potent inflammatory mediator that has been implicated in the pathogenesis of both stroke and neurodegenerative disease. Microvascular failure is proposed as a potential mechanism of injury. Along these lines, this investigation examines the role of C5 in the setting of chronic cerebral hypoperfusion. Following experimental bilateral carotid artery stenosis, C5 protein deposition increases in the corpus callosum over thirty days (p<0.05). The time course is temporally consistent with the appearance of white matter injury. Concurrently, systemic serum C5 levels do not appear to differ between bilateral carotid artery stenosis and sham-operated mice, implicating a local cerebral process. Following bilateral carotid artery stenosis, C5 deficient mice demonstrate decreased white matter ischemia in the corpus callosum when compared to C5 sufficient controls (p<0.05). Further, the C5 deficient mice exhibit fewer reactive astrocytes and microglia (p<0.01). This study reveals that the C5 complement protein may play a critical role in mediating white matter injury through inflammation in the setting of chronic cerebral hypoperfusion. PMID:24386419

  12. SOX2+ Cell Population from Normal Human Brain White Matter Is Able to Generate Mature Oligodendrocytes

    PubMed Central

    Oliver-De La Cruz, Jorge; Carrión-Navarro, Josefa; García-Romero, Noemí; Gutiérrez-Martín, Antonio; Lázaro-Ibáńez, Elisa; Escobedo-Lucea, Carmen; Perona, Rosario; Belda-Iniesta, Cristobal; Ayuso-Sacido, Angel

    2014-01-01

    Objectives A number of neurodegenerative diseases progress with a loss of myelin, which makes them candidate diseases for the development of cell-replacement therapies based on mobilisation or isolation of the endogenous neural/glial progenitor cells, in vitro expansion, and further implantation. Cells expressing A2B5 or PDGFRA/CNP have been isolated within the pool of glial progenitor cells in the subcortical white matter of the normal adult human brain, all of which demonstrate glial progenitor features. However, the heterogeneity and differentiation potential of this pool of cells is not yet well established. Methods We used diffusion tensor images, histopathology, and immunostaining analysis to demonstrate normal cytoarchitecture and the absence of abnormalities in human temporal lobe samples from patients with mesial temporal sclerosis. These samples were used to isolate and enrich glial progenitor cells in vitro, and later to detect such cells in vivo. Results We have identified a subpopulation of SOX2+ cells, most of them co-localising with OLIG2, in the white matter of the normal adult human brain in vivo. These cells can be isolated and enriched in vitro, where they proliferate and generate immature (O4+) and mature (MBP+) oligodendrocytes and, to a lesser extent, astrocytes (GFAP+). Conclusion Our results demonstrate the existence of a new glial progenitor cell subpopulation that expresses SOX2 in the white matter of the normal adult human brain. These cells might be of use for tissue regeneration procedures. PMID:24901457

  13. Melatonin Promotes Oligodendroglial Maturation of Injured White Matter in Neonatal Rats

    PubMed Central

    Olivier, Paul; Fontaine, Romain H.; Loron, Gauthier; Van Steenwinckel, Juliette; Biran, Valérie; Massonneau, Véronique; Kaindl, Angela; Dalous, Jeremie; Charriaut-Marlangue, Christiane; Aigrot, Marie-Stéphane; Pansiot, Julien; Verney, Catherine; Gressens, Pierre; Baud, Olivier

    2009-01-01

    Objective To investigate the effects of melatonin treatment in a rat model of white matter damage (WMD) in the developing brain. Additionally, we aim to delineate the cellular mechanisms of melatonin effect on the oligodendroglial cell lineage. Methods A unilateral ligation of the uterine artery in pregnant rat at the embryonic day 17 induces fetal hypoxia and subsequent growth restriction (GR) in neonatal pups. GR and control pups received a daily intra-peritoneal injection of melatonin from birth to post-natal day (P) 3. Results Melatonin administration was associated with a dramatic decrease in microglial activation and astroglial reaction compared to untreated GR pups. At P14, melatonin prevented white matter myelination defects with an increased number of mature oligodendrocytes (APC-immunoreactive) in treated GR pups. Conversely, melatonin was not found to be associated with an increased density of total oligodendrocytes (Olig2-immunoreactive), suggesting that melatonin is able to promote oligodendrocyte maturation but not proliferation. These effects appear to be melatonin-receptor dependent and were reproduced in vitro. Interpretation These data suggest that melatonin has a strong protective effect on developing damaged white matter through decreased microglial activation and oligodendroglial maturation leading to a normalization of the myelination process. Consequently, melatonin should be a considered as an effective neuroprotective candidate not only in perinatal brain damage but also in inflammatory and demyelinating diseases observed in adults. PMID:19771167

  14. Glutathione deficit impairs myelin maturation: relevance for white matter integrity in schizophrenia patients.

    PubMed

    Monin, A; Baumann, P S; Griffa, A; Xin, L; Mekle, R; Fournier, M; Butticaz, C; Klaey, M; Cabungcal, J H; Steullet, P; Ferrari, C; Cuenod, M; Gruetter, R; Thiran, J P; Hagmann, P; Conus, P; Do, K Q

    2015-07-01

    Schizophrenia pathophysiology implies both abnormal redox control and dysconnectivity of the prefrontal cortex, partly related to oligodendrocyte and myelin impairments. As oligodendrocytes are highly vulnerable to altered redox state, we investigated the interplay between glutathione and myelin. In control subjects, multimodal brain imaging revealed a positive association between medial prefrontal glutathione levels and both white matter integrity and resting-state functional connectivity along the cingulum bundle. In early psychosis patients, only white matter integrity was correlated with glutathione levels. On the other side, in the prefrontal cortex of peripubertal mice with genetically impaired glutathione synthesis, mature oligodendrocyte numbers, as well as myelin markers, were decreased. At the molecular levels, under glutathione-deficit conditions induced by short hairpin RNA targeting the key glutathione synthesis enzyme, oligodendrocyte progenitors showed a decreased proliferation mediated by an upregulation of Fyn kinase activity, reversed by either the antioxidant N-acetylcysteine or Fyn kinase inhibitors. In addition, oligodendrocyte maturation was impaired. Interestingly, the regulation of Fyn mRNA and protein expression was also impaired in fibroblasts of patients deficient in glutathione synthesis. Thus, glutathione and redox regulation have a critical role in myelination processes and white matter maturation in the prefrontal cortex of rodent and human, a mechanism potentially disrupted in schizophrenia. PMID:25155877

  15. Robust and efficient linear registration of white-matter fascicles in the space of streamlines.

    PubMed

    Garyfallidis, Eleftherios; Ocegueda, Omar; Wassermann, Demian; Descoteaux, Maxime

    2015-08-15

    The neuroscientific community today is very much interested in analyzing specific white matter bundles like the arcuate fasciculus, the corticospinal tract, or the recently discovered Aslant tract to study sex differences, lateralization and many other connectivity applications. For this reason, experts spend time manually segmenting these fascicles and bundles using streamlines obtained from diffusion MRI tractography. However, to date, there are very few computational tools available to register these fascicles directly so that they can be analyzed and their differences quantified across populations. In this paper, we introduce a novel, robust and efficient framework to align bundles of streamlines directly in the space of streamlines. We call this framework Streamline-based Linear Registration. We first show that this method can be used successfully to align individual bundles as well as whole brain streamlines. Additionally, if used as a piecewise linear registration across many bundles, we show that our novel method systematically provides higher overlap (Jaccard indices) than state-of-the-art nonlinear image-based registration in the white matter. We also show how our novel method can be used to create bundle-specific atlases in a straightforward manner and we give an example of a probabilistic atlas construction of the optic radiation. In summary, Streamline-based Linear Registration provides a solid registration framework for creating new methods to study the white matter and perform group-level tractometry analysis. PMID:25987367

  16. Directional volume growing for the extraction of white matter tracts from diffusion tensor data

    NASA Astrophysics Data System (ADS)

    Merhof, D.; Hastreiter, P.; Nimsky, C.; Fahlbusch, R.; Greiner, G.

    2005-04-01

    Diffusion tensor imaging measures diffusion of water in tissue. Within structured tissue, such as neural fiber tracts of the human brain, anisotropic diffusion is observed since the cell membranes of the long cylindric nerves restrict diffusion. Diffusion tensor imaging thus provides information about neural fiber tracts within the human brain which is of major interest for neurosurgery. However, the visualization is a challenging task due to noise and limited resolution of the data. A common visualization strategy of white matter is fiber tracking which utilizes techniques known from flow visualization. The resulting streamlines provide a good impression of the spatial relation of fibers and anatomy. Therefore, they are a valuable supplement for neurosurgical planning. As a drawback, fibers may diverge from the exact path due to numerical inaccuracies during streamline propagation even if higher order integration is used. To overcome this problem, a novel strategy for directional volume growing is presented which enables the extraction of separate tract systems and thus allows to compare and estimate the quality of fiber tracking algorithms. Furthermore, the presented approach is suited to get a more precise representation of the volume encompassing white matter tracts. Thereby, the entire volume potentially containing fibers is provided in contrast to fiber tracking which only shows a more restricted representation of the actual volume of interest. This is of major importance in brain tumor cases where white matter tracts are in the close vicinity of brain tumors. Overall, the presented strategy contributes to make surgical planning safer and more reliable.

  17. Differential diagnosis of white matter diseases in the tropics: An overview

    PubMed Central

    Pandit, Lekha

    2009-01-01

    In hospitals in the tropics, the availability of magnetic resonance imaging (MRI) facilities in urban areas and especially in teaching institutions have resulted in white matter diseases being frequently reported in a variety of clinical settings. Unlike the west where multiple sclerosis (MS) is the commonest white matter disease encountered, in the tropics, there are myriad causes for the same. Infectious and post infectious disorders probably account for the vast majority of these diseases. Human immunodeficiency virus (HIV) infection tops the list of infective conditions. Central nervous system (CNS) tuberculosis occasionally presents with patchy parenchymal lesions unaccompanied by meningeal involvement. Human T cell leukemia virus (HTLV) infection and cystic inflammatory lesions such as neurocysticercosis are important causes to be considered in the differential diagnosis. Diagnosing post infectious demyelinating disorders is equally challenging since more than a third of cases seen in the tropics do not present with history of past infection or vaccinations. Metabolic and deficiency disorders such as Wernicke's encephalopathy, osmotic demyelinating syndrome associated with extra pontine lesions and Vitamin B12 deficiency states can occassionaly cause confusion in diagnosis. This review considers a few important disorders which manifest with white matter changes on MRI and create diagnostic difficulties in a population in the tropics. PMID:20151003

  18. Linking White and Grey Matter in Schizophrenia: Oligodendrocyte and Neuron Pathology in the Prefrontal Cortex

    PubMed Central

    Höistad, Malin; Segal, Devorah; Takahashi, Nagahide; Sakurai, Takeshi; Buxbaum, Joseph D.; Hof, Patrick R.

    2009-01-01

    Neuronal circuitry relies to a large extent on the presence of functional myelin produced in the brain by oligodendrocytes. Schizophrenia has been proposed to arise partly from altered brain connectivity. Brain imaging and neuropathologic studies have revealed changes in white matter and reduction in myelin content in patients with schizophrenia. In particular, alterations in the directionality and alignment of axons have been documented in schizophrenia. Moreover, the expression levels of several myelin-related genes are decreased in postmortem brains obtained from patients with schizophrenia. These findings have led to the formulation of the oligodendrocyte/myelin dysfunction hypothesis of schizophrenia. In this review, we present a brief overview of the neuropathologic findings obtained on white matter and oligodendrocyte status observed in schizophrenia patients, and relate these changes to the processes of brain maturation and myelination. We also review recent data on oligodendrocyte/myelin genes, and present some recent mouse models of myelin deficiencies. The use of transgenic and mutant animal models offers a unique opportunity to analyze oligodendrocyte and neuronal changes that may have a clinical impact. Lastly, we present some recent morphological findings supporting possible causal involvement of white and grey matter abnormalities, in the aim of determining the morphologic characteristics of the circuits whose alteration leads to the cortical dysfunction that possibly underlies the pathogenesis of schizophrenia. PMID:19636386

  19. Differentiating therapy-induced leukoencephalopathy from unmyelinated white matter in children treated for acute lymphoblastic leukemia (ALL)

    NASA Astrophysics Data System (ADS)

    Reddick, Wilburn E.; Glass, John O.; Pui, Ching-Hon

    2003-05-01

    Reliably detecting subtle therapy-induced leukoencephalopathy in children treated for cancer is a challenging task due to its nearly identical MR properties and location with unmyelinated white matter. T1, T2, PD, and FLAIR images were collected for 44 children aged 1.7-18.7 (median 5.9) years near the start of therapy for ALL. The ICBM atlas and corresponding apriori maps were spatially normalized to each patient and resliced using SPM99 software. A combined imaging set consisting of MR images and WM, GM and CSF apriori maps were then analyzed with a Kohonen Self-Organizing Map. Vectors from hyperintense regions were compared to normal appearing genu vectors from the same patient. Analysis of the distributions of the differences, calculated on T2 and FLAIR images, revealed two distinct groups. The first large group, assumed normal unmyelinated white matter, consisted of 37 patients with changes in FLAIR ranging from 80 to 147 (mean 117-/+17) and T2 ranging from 92 to 217 (mean 144-/+28). The second group, assumed leukoencephalopathy, consisted of seven patients with changes in FLAIR ranging from 154 to 196 (mean 171-/+19) and T2 ranging from 190 to 287 (mean 216-/+33). A threshold was established for both FLAIR (change > 150) and T2 (change > 180).

  20. Absence of white matter changes on magnetic resonance imaging in children treated with CNS prophylaxis therapy for leukemia

    SciTech Connect

    Kramer, J.H.; Norman, D.; Brant-Zawadzki, M.; Ablin, A.; Moore, I.M.

    1988-03-01

    Previous studies have shown that magnetic resonance imaging (MRI) is sensitive to white matter changes in children receiving cranial radiation of 3000 cGy or greater. The current study used MRI to investigate the integrity of white matter in children receiving 1800 to 2400 cGy of cranial radiation. Ten survivors of acute lymphoblastic leukemia (ALL) who received intrathecal methotrexate (MTX) and either 1800 or 2400 cGy of cranial radiation were studied with MRI and neuropsychologic testing. Magnetic resonance (MR) scans were normal in nine of ten patients. One patient had prominent and asymmetrical lateral ventricles and mildly enlarged cortical sulci. White matter tracts were normal in appearance. However, seven of nine children had below average intellectual functioning. Results indicate that children receiving less than 2500 cGy of cranial radiation fail to show white matter changes on MRI, despite evidence of cognitive impairment.

  1. Vulnerability of white matter structure and function to chronic cerebral hypoperfusion and the effects of pharmacological modulation 

    E-print Network

    McQueen, Jamie

    2014-06-28

    The structural integrity of the white matter is required for neuronal communication within the brain which is essential for normal cognitive function. Post-mortem and clinical imaging studies of elderly individuals have ...

  2. HDAC inhibition prevents white matter injury by modulating microglia/macrophage polarization through the GSK3?/PTEN/Akt axis.

    PubMed

    Wang, Guohua; Shi, Yejie; Jiang, Xiaoyan; Leak, Rehana K; Hu, Xiaoming; Wu, Yun; Pu, Hongjian; Li, Wei-Wei; Tang, Bo; Wang, Yun; Gao, Yanqin; Zheng, Ping; Bennett, Michael V L; Chen, Jun

    2015-03-01

    Severe traumatic brain injury (TBI) elicits destruction of both gray and white matter, which is exacerbated by secondary proinflammatory responses. Although white matter injury (WMI) is strongly correlated with poor neurological status, the maintenance of white matter integrity is poorly understood, and no current therapies protect both gray and white matter. One candidate approach that may fulfill this role is inhibition of class I/II histone deacetylases (HDACs). Here we demonstrate that the HDAC inhibitor Scriptaid protects white matter up to 35 d after TBI, as shown by reductions in abnormally dephosphorylated neurofilament protein, increases in myelin basic protein, anatomic preservation of myelinated axons, and improved nerve conduction. Furthermore, Scriptaid shifted microglia/macrophage polarization toward the protective M2 phenotype and mitigated inflammation. In primary cocultures of microglia and oligodendrocytes, Scriptaid increased expression of microglial glycogen synthase kinase 3 beta (GSK3?), which phosphorylated and inactivated phosphatase and tensin homologue (PTEN), thereby enhancing phosphatidylinositide 3-kinases (PI3K)/Akt signaling and polarizing microglia toward M2. The increase in GSK3? in microglia and their phenotypic switch to M2 was associated with increased preservation of neighboring oligodendrocytes. These findings are consistent with recent findings that microglial phenotypic switching modulates white matter repair and axonal remyelination and highlight a previously unexplored role for HDAC activity in this process. Furthermore, the functions of GSK3? may be more subtle than previously thought, in that GSK3? can modulate microglial functions via the PTEN/PI3K/Akt signaling pathway and preserve white matter homeostasis. Thus, inhibition of HDACs in microglia is a potential future therapy in TBI and other neurological conditions with white matter destruction. PMID:25691750

  3. White Matter Integrity in Veterans With Mild Traumatic Brain Injury: Associations With Executive Function and Loss of Consciousness

    PubMed Central

    Sorg, Scott F.; Delano-Wood, Lisa; Luc, Norman; Schiehser, Dawn M.; Hanson, Karen L.; Nation, Daniel A.; Lanni, Elisa; Jak, Amy J.; Lu, Kun; Meloy, M. J.; Frank, Lawrence R.; Lohr, James B.; Bondi, Mark W.

    2014-01-01

    Objective We investigated using diffusion tensor imaging (DTI) and the association between white matter integrity and executive function (EF) performance in postacute mild traumatic brain injury (mTBI). In addition, we examined whether injury severity, as measured by loss of consciousness (LOC) versus alterations in consciousness (AOC), is related to white matter microstructural alterations and neuropsychological outcome. Participants Thirty Iraq and Afghanistan War era veterans with a history of mTBI and 15 healthy veteran control participants. Results There were no significant overall group differences between control and mTBI participants on DTI measures. However, a subgroup of mTBI participants with EF decrements (n = 13) demonstrated significantly decreased fractional anisotropy of prefrontal white matter, corpus callosum, and cingulum bundle structures compared with mTBI participants without EF decrements (n = 17) and control participants. Participants having mTBI with LOC were more likely to evidence reduced EF performances and disrupted ventral prefrontal white matter integrity when compared with either mTBI participants without LOC or control participants. Conclusions Findings suggest that altered white matter integrity contributes to reduced EF in subgroups of veterans with a history of mTBI and that LOC may be a risk factor for reduced EF as well as associated changes to ventral prefrontal white matter. PMID:23640539

  4. Maximum Principal Strain and Strain Rate Associated with Concussion Diagnosis Correlates with Changes in Corpus Callosum White Matter Indices

    PubMed Central

    MCALLISTER, THOMAS W.; FORD, JAMES C.; JI, SONGBAI; BECKWITH, JONATHAN G.; FLASHMAN, LAURA A.; PAULSEN, KEITH; GREENWALD, RICHARD M.

    2014-01-01

    On-field monitoring of head impacts, combined with finite element (FE) biomechanical simulation, allow for predictions of regional strain associated with a diagnosed concussion. However, attempts to correlate these predictions with in vivo measures of brain injury have not been published. This article reports an approach to and preliminary results from the correlation of subject-specific FE model-predicted regions of high strain associated with diagnosed concussion and diffusion tensor imaging to assess changes in white matter integrity in the corpus callosum (CC). Ten football and ice hockey players who wore instrumented helmets to record head impacts sustained during play completed high field magnetic resonance imaging preseason and within 10 days of a diagnosed concussion. The Dartmouth Subject-Specific FE Head model was used to generate regional predictions of strain and strain rate following each impact associated with concussion. Maps of change in fractional anisotropy (FA) and median diffusivity (MD) were generated for the CC of each athlete to correlate strain with change in FA and MD. Mean and maximum strain rate correlated with change in FA (Spearman ? = 0.77, p = 0.01; 0.70, p = 0.031), and there was a similar trend for mean and maximum strain (0.56, p = 0.10; 0.6, p = 0.07), as well as for maximum strain with change in MD (?0.63, p = 0.07). Change in MD correlated with injury-to-imaging interval (? = ?0.80, p = 0.006) but change in FA did not (? = 0.18, p = 0.62). These results provide preliminary confirmation that model-predicted strain and strain rate in the CC correlate with changes in indices of white matter integrity. PMID:21994062

  5. Maximum principal strain and strain rate associated with concussion diagnosis correlates with changes in corpus callosum white matter indices.

    PubMed

    McAllister, Thomas W; Ford, James C; Ji, Songbai; Beckwith, Jonathan G; Flashman, Laura A; Paulsen, Keith; Greenwald, Richard M

    2012-01-01

    On-field monitoring of head impacts, combined with finite element (FE) biomechanical simulation, allow for predictions of regional strain associated with a diagnosed concussion. However, attempts to correlate these predictions with in vivo measures of brain injury have not been published. This article reports an approach to and preliminary results from the correlation of subject-specific FE model-predicted regions of high strain associated with diagnosed concussion and diffusion tensor imaging to assess changes in white matter integrity in the corpus callosum (CC). Ten football and ice hockey players who wore instrumented helmets to record head impacts sustained during play completed high field magnetic resonance imaging preseason and within 10 days of a diagnosed concussion. The Dartmouth Subject-Specific FE Head model was used to generate regional predictions of strain and strain rate following each impact associated with concussion. Maps of change in fractional anisotropy (FA) and median diffusivity (MD) were generated for the CC of each athlete to correlate strain with change in FA and MD. Mean and maximum strain rate correlated with change in FA (Spearman ? = 0.77, p = 0.01; 0.70, p = 0.031), and there was a similar trend for mean and maximum strain (0.56, p = 0.10; 0.6, p = 0.07), as well as for maximum strain with change in MD (-0.63, p = 0.07). Change in MD correlated with injury-to-imaging interval (? = -0.80, p = 0.006) but change in FA did not (? = 0.18, p = 0.62). These results provide preliminary confirmation that model-predicted strain and strain rate in the CC correlate with changes in indices of white matter integrity. PMID:21994062

  6. White matter lesion segmentation using machine learning and weakly labeled MR images

    NASA Astrophysics Data System (ADS)

    Xie, Yuchen; Tao, Xiaodong

    2011-03-01

    We propose a fast, learning-based algorithm for segmenting white matter (WM) lesions for magnetic resonance (MR) brain images. The inputs to the algorithm are T1, T2, and FLAIR images. Unlike most of the previously reported learning-based algorithms, which treat expert labeled lesion map as ground truth in the training step, the proposed algorithm only requires the user to provide a few regions of interest (ROI's) containing lesions. An unsupervised clustering algorithm is applied to segment these ROI's into areas. Based on the assumption that lesion voxels have higher intensity on FLAIR image, areas corresponding to lesions are identified and their probability distributions in T1, T2, and FLAIR images are computed. The lesion segmentation in 3D is done by using the probability distributions to generate a confidence map of lesion and applying a graph based segmentation algorithm to label lesion voxels. The initial lesion label is used to further refine the probability distribution estimation for the final lesion segmentation. The advantages of the proposed algorithm are: 1. By using the weak labels, we reduced the dependency of the segmentation performance on the expert discrimination of lesion voxels in the training samples; 2. The training can be done using labels generated by users with only general knowledge of brain anatomy and image characteristics of WM lesion, instead of these carefully labeled by experienced radiologists; 3. The algorithm is fast enough to make interactive segmentation possible. We test the algorithm on nine ACCORD-MIND MRI datasets. Experimental results show that our algorithm agrees well with expert labels and outperforms a support vector machine based WM lesion segmentation algorithm.

  7. White Matter Hyperintensity in Ischemic Stroke Patients: It May Regress Over Time

    PubMed Central

    Kim, Hyeong-Ryul; Kim, Woojun; Yang, Dong Won

    2015-01-01

    Background and Purpose White matter hyperintensities (WMH) are frequently observed on MRI in ischemic stroke patients as well as in normal elderly individuals. Besides the progression of WMH, the regression of WMH has been rarely reported. Thus, we aimed to investigate how WMH change over time in patients with ischemic stroke, particularly focusing on regression. Methods We enrolled ischemic stroke patients who underwent brain MRI more than twice with at least a 6 month time-interval. Based on T2-weighted or FLAIR MRI, WMH were visually assessed, followed by semiautomatic volume measurement. Progression or regression of WMH change was defined when 0.25 cc increase or decrease was observed and it was also combined with visible change. A statistical analysis was performed on the pattern of WMH change over time and factors associated with change. Results A total of 100 patients were enrolled. Their age (mean±SD) was 67.5±11.8 years and 63 were male. The imaging time-interval (mean) was 28.0 months. WMH progressed in 27, regressed in 9 and progressed in distinctive regions and regressed in others in 5 patients. A multiple logistic regression model showed that age (odds ratio[OR] 2.51, 90% confidence interval[CI] 1.056-5.958), male gender (OR 2.957, 95% CI 1.051-9.037), large vessel disease (OR 1.955, 95% CI 1.171-3.366), and renal dysfunction (OR 2.900, 90% CI 1.045-8.046) were associated with progression. Regarding regression, no significant factor was found in the multivariate analysis. Conclusions In 21.5% of ischemic stroke patients, regression of WMH was observed. WMH progression was observed in a third of ischemic stroke patients. PMID:25692108

  8. Proposal of a new tractographic feature for analysis of white matter in Alzheimer diffusion mr images.

    PubMed

    Ranjan, Piyush; Ramakrishnan, S

    2014-01-01

    Alzheimer's disease (AD) is a leading cause of dementia in elderly adults. In this, the white matter (WM) tracts in brain are disintegrated leading to loss of important cognitive functionality. Recent analysis have shown that early diagnosis of AD is still a challenging task. Although several reports are available, tractography remains the most promising and clinically relevant method for in-vivo study of WM tracts. In tractography, continuous WM pathways are reconstructed from voxel based models of discrete fiber orientation generated using diffusion tensor images. In this work an attempt has been made to classify AD using average length of tracts, a significant feature extracted from tractographic brain maps. The diffusion weighted images for AD and matched controls were obtained from ADNI, an international open access repository for Alzheimer's study. Data from equal number of AD and controls were used for this study. Fiber tracking was performed for the whole brain using tract based spatial statistics algorithm. ICBM Mori Labels 1 atlas provided in the Network Analysis option of ExploreDTI was used to divide the WM into 48 anatomical regions. Classification was performed using random forest, random tree and decision stumps, and their performance indices were compared. The results show that all the classifiers are able to classify AD and controls using the extracted feature. An accuracy of 78.4% is obtained using decision stumps. Random forest and random tree provide an increased accuracy of 96% and 97% respectively. The precision and recall is also found to be higher for random forest and random tree as compared to decision stumps. These results suggest that random forest and random tree are suitable for classification of AD and controls using average tract length as a feature. In this paper, the introduction, objectives, materials and methods, results and discussions and conclusions are presented in detail. PMID:25405440

  9. Electroconvulsive therapy mediates neuroplasticity of white matter microstructure in major depression

    PubMed Central

    Lyden, H; Espinoza, R T; Pirnia, T; Clark, K; Joshi, S H; Leaver, A M; Woods, R P; Narr, K L

    2014-01-01

    Whether plasticity of white matter (WM) microstructure relates to therapeutic response in major depressive disorder (MDD) remains uncertain. We examined diffusion tensor imaging (DTI) correlates of WM structural connectivity in patients receiving electroconvulsive therapy (ECT), a rapidly acting treatment for severe MDD. Tract-Based Spatial Statistics (TBSS) applied to DTI data (61 directions, 2.5?mm3 voxel size) targeted voxel-level changes in fractional anisotropy (FA), and radial (RD), axial (AD) and mean diffusivity (MD) in major WM pathways in MDD patients (n=20, mean age: 41.15 years, 10.32 s.d.) scanned before ECT, after their second ECT and at transition to maintenance therapy. Comparisons made at baseline with demographically similar controls (n=28, mean age: 39.42 years, 12.20 s.d.) established effects of diagnosis. Controls were imaged twice to estimate scanning-related variance. Patients showed significant increases of FA in dorsal fronto-limbic circuits encompassing the anterior cingulum, forceps minor and left superior longitudinal fasciculus between baseline and transition to maintenance therapy (P<0.05, corrected). Decreases in RD and MD were observed in overlapping regions and the anterior thalamic radiation (P<0.05, corrected). Changes in DTI metrics associated with therapeutic response in tracts showing significant ECT effects differed between patients and controls. All measures remained stable across time in controls. Altered WM microstructure in pathways connecting frontal and limbic areas occur in MDD, are modulated by ECT and relate to therapeutic response. Increased FA together with decreased MD and RD, which trend towards normative values with treatment, suggest increased fiber integrity in dorsal fronto-limbic pathways involved in mood regulation. PMID:24713861

  10. Electroconvulsive therapy mediates neuroplasticity of white matter microstructure in major depression.

    PubMed

    Lyden, H; Espinoza, R T; Pirnia, T; Clark, K; Joshi, S H; Leaver, A M; Woods, R P; Narr, K L

    2014-01-01

    Whether plasticity of white matter (WM) microstructure relates to therapeutic response in major depressive disorder (MDD) remains uncertain. We examined diffusion tensor imaging (DTI) correlates of WM structural connectivity in patients receiving electroconvulsive therapy (ECT), a rapidly acting treatment for severe MDD. Tract-Based Spatial Statistics (TBSS) applied to DTI data (61 directions, 2.5 mm(3) voxel size) targeted voxel-level changes in fractional anisotropy (FA), and radial (RD), axial (AD) and mean diffusivity (MD) in major WM pathways in MDD patients (n=20, mean age: 41.15 years, 10.32 s.d.) scanned before ECT, after their second ECT and at transition to maintenance therapy. Comparisons made at baseline with demographically similar controls (n=28, mean age: 39.42 years, 12.20 s.d.) established effects of diagnosis. Controls were imaged twice to estimate scanning-related variance. Patients showed significant increases of FA in dorsal fronto-limbic circuits encompassing the anterior cingulum, forceps minor and left superior longitudinal fasciculus between baseline and transition to maintenance therapy (P<0.05, corrected). Decreases in RD and MD were observed in overlapping regions and the anterior thalamic radiation (P<0.05, corrected). Changes in DTI metrics associated with therapeutic response in tracts showing significant ECT effects differed between patients and controls. All measures remained stable across time in controls. Altered WM microstructure in pathways connecting frontal and limbic areas occur in MDD, are modulated by ECT and relate to therapeutic response. Increased FA together with decreased MD and RD, which trend towards normative values with treatment, suggest increased fiber integrity in dorsal fronto-limbic pathways involved in mood regulation. PMID:24713861

  11. An Analytical Model for Estimating Water Exchange Rate in White Matter Using Diffusion MRI

    PubMed Central

    Davoodi-Bojd, Esmaeil; Chopp, Michael; Soltanian-Zadeh, Hamid; Wang, Shiyang; Ding, Guangliang; Jiang, Quan

    2014-01-01

    Substantial effort is being expended on using micro-structural modeling of the white matter, with the goal of relating diffusion weighted magnetic resonance imaging (DWMRI) to the underlying structure of the tissue, such as axonal density. However, one of the important parameters affecting diffusion is the water exchange rate between the intra- and extra-axonal space, which has not been fully investigated and is a crucial marker of brain injury such as multiple sclerosis (MS), stroke, and traumatic brain injury (TBI). To our knowledge, there is no diffusion analytical model which includes the Water eXchange Rate (WXR) without the requirement of short gradient pulse (SGP) approximation. We therefore propose a new analytical model by deriving the diffusion signal for a permeable cylinder, assuming a clinically feasible pulse gradient spin echo (PGSE) sequence. Simulations based on Markov Random Walk confirm that the exchange parameter included in our model has a linear correlation (R2>0.88) with the actual WXR. Moreover, increasing WXR causes the estimated values of diameter and volume fraction of the cylinders to increase and decrease, respectively, which is consistent with our findings from histology measurements in tissues near TBI regions. This model was also applied to the diffusion signal acquired from ex vivo brains of 14 male (10 TBI and 4 normal) rats using hybrid diffusion imaging. The estimated values of axon diameter and axonal volume fraction are in agreement with their corresponding histological measurements in normal brains, with 0.96 intra-class correlation coefficient value resulting from consistency analysis. Moreover, a significant increase (p?=?0.001) in WXR and diameter and decrease in axonal volume fraction in the TBI boundary were detected in the TBI rats compared with the normal rats. PMID:24836290

  12. Simultaneous changes in gray matter volume and white matter fractional anisotropy in Alzheimer's disease revealed by multimodal CCA and joint ICA.

    PubMed

    Ouyang, X; Chen, K; Yao, L; Hu, B; Wu, X; Ye, Q; Guo, X

    2015-08-20

    The prominent morphometric alterations of Alzheimer's disease (AD) occur both in gray matter and in white matter. Multimodal fusion can examine joint information by combining multiple neuroimaging datasets to identify the covariant morphometric alterations in AD in greater detail. In the current study, we conducted a multimodal canonical correlation analysis and joint independent component analysis to identify the covariance patterns of the gray and white matter by fusing structural magnetic resonance imaging and diffusion tensor imaging data of 39 AD patients (23 males and 16 females, mean age: 74.91±8.13years) and 41 normal controls (NCs) (20 males and 21 females, mean age: 73.97±6.34years) derived from the Alzheimer's Disease Neuroimaging Initiative database. The results revealed 25 joint independent components (ICs), of which three joint ICs exhibited strong links between the gray matter volume and the white matter fractional anisotropy (FA) and significant differences between the AD and NC group. The joint IC maps revealed that the simultaneous changes in the gray matter and FA values primarily involved the following areas: (1) the temporal lobe/hippocampus-cingulum, (2) the frontal/cingulate gyrus-corpus callosum, and (3) the temporal/occipital/parietal lobe-corpus callosum/corona radiata. Our findings suggest that gray matter atrophy is associated with reduced white matter fiber integrity in AD and possibly expand the understanding of the neuropathological mechanisms in AD. PMID:26116521

  13. Combined analysis of grey matter voxel-based morphometry and white matter tract-based spatial statistics in late-life bipolar disorder

    PubMed Central

    Haller, Sven; Xekardaki, Aikaterini; Delaloye, Christophe; Canuto, Alessandra; Lövblad, Karl Olof; Gold, Gabriel; Giannakopoulos, Panteleimon

    2011-01-01

    Background Previous magnetic resonance imaging (MRI) studies in young patients with bipolar disorder indicated the presence of grey matter concentration changes as well as microstructural alterations in white matter in various neocortical areas and the corpus callosum. Whether these structural changes are also present in elderly patients with bipolar disorder with long-lasting clinical evolution remains unclear. Methods We performed a prospective MRI study of consecutive elderly, euthymic patients with bipolar disorder and healthy, elderly controls. We conducted a voxel-based morphometry (VBM) analysis and a tract-based spatial statistics (TBSS) analysis to assess fractional anisotropy and longitudinal, radial and mean diffusivity derived by diffusion tensor imaging (DTI). Results We included 19 patients with bipolar disorder and 47 controls in our study. Fractional anisotropy was the most sensitive DTI marker and decreased significantly in the ventral part of the corpus callosum in patients with bipolar disorder. Longitudinal, radial and mean diffusivity showed no significant between-group differences. Grey matter concentration was reduced in patients with bipolar disorder in the right anterior insula, head of the caudate nucleus, nucleus accumbens, ventral putamen and frontal orbital cortex. Conversely, there was no grey matter concentration or fractional anisotropy increase in any brain region in patients with bipolar disorder compared with controls. Limitations The major limitation of our study is the small number of patients with bipolar disorder. Conclusion Our data document the concomitant presence of grey matter concentration decreases in the anterior limbic areas and the reduced fibre tract coherence in the corpus callosum of elderly patients with long-lasting bipolar disorder. PMID:21284917

  14. Different Patterns of White Matter Disruption among Amnestic Mild Cognitive Impairment Subtypes: Relationship with Neuropsychological Performance

    PubMed Central

    Li, He; Liang, Ying; Chen, Kewei; Li, Xin; Shu, Ni; Zhang, Zhanjun; Wang, Yongyan

    2014-01-01

    Amnestic mild cognitive impairment (aMCI) is recognized as the prodromal phase of Alzheimer’s disease (AD). Evidence showed that patients with multiple-domain (MD) aMCI were at higher risk of converting to dementia and exhibited more severe gray matter atrophy than single-domain (SD) aMCI. The investigation of the microstructural abnormalities of white matter (WM) among different subtypes of aMCI and their relations with cognitive performances can help to understand the variations among aMCI subtypes and to construct potential imaging based biomarkers to monitor the progression of aMCI. Diffusion-weighted MRI data were acquired from 40 patients with aMCI (aMCI-SD: n = 19; aMCI-MD: n= 21) and 37 healthy controls (HC). Voxel-wise and atlas-based analyses of whole-brain WM were performed among three groups. The correlations between the altered diffusion metrics of the WM tracts and the neuropsychological scores in each subtype of aMCI were assessed. The aMCI-MD patients showed disrupted integrity in multiple WM tracts across the whole-brain when compared with HCs or with aMCI-SD. In contrast, only few WM regions with diffusion changes were found in aMCI-SD as compared to HCs and with less significance. For neuropsychological correlations, only aMCI-MD patients exhibited significant associations between disrupted WM connectivity (in the body of the corpus callosum and the right anterior internal capsules) and cognitive impairments (MMSE and Digit Symb-Coding scores), whereas no such correlations were found in aMCI-SD. These findings indicate that the degeneration extensively exists in WM tracts in aMCI-MD that precedes the development of AD, whereas underlying WM pathology in aMCI-SD is imperceptible. The results are consistent with the view that aMCI is not a uniform disease entity and presents heterogeneity in the clinical progression. PMID:23603396

  15. Do brain T2/FLAIR white matter hyperintensities correspond to myelin loss in normal aging? A radiologic-neuropathologic correlation study

    PubMed Central

    2013-01-01

    Background White matter hyperintensities (WMH) lesions on T2/FLAIR brain MRI are frequently seen in healthy elderly people. Whether these radiological lesions correspond to irreversible histological changes is still a matter of debate. We report the radiologic-histopathologic concordance between T2/FLAIR WMHs and neuropathologically confirmed demyelination in the periventricular, perivascular and deep white matter (WM) areas. Results Inter-rater reliability was substantial-almost perfect between neuropathologists (kappa 0.71 - 0.79) and fair-moderate between radiologists (kappa 0.34 - 0.42). Discriminating low versus high lesion scores, radiologic compared to neuropathologic evaluation had sensitivity / specificity of 0.83 / 0.47 for periventricular and 0.44 / 0.88 for deep white matter lesions. T2/FLAIR WMHs overestimate neuropathologically confirmed demyelination in the periventricular (p?regions due to increasing blood–brain-barrier permeability and plasma leakage in brain aging may evoke T2/FLAIR WMH despite relatively mild demyelination. PMID:24252608

  16. Alterations in the cerebral white matter of genetic high risk offspring of patients with schizophrenia spectrum disorder.

    PubMed

    Francis, Alan N; Bhojraj, Tejas S; Prasad, Konasale M; Montrose, Debra; Eack, Shaun M; Rajarethinam, Rajaprabhakaran; van Elst, Ludger T; Keshavan, Matcheri S

    2013-01-10

    Alterations in white matter (WM) may be seen in young relatives at risk and may underlie vulnerability to schizophrenia. We were interested in exploring which of the WM regions were altered in adolescent offspring at familial risk for schizophrenia. We examined structural alterations in the offspring of subjects with schizophrenia or schizoaffective disorder (HR; n=65; 36 males) and healthy controls (HC; n=80: 37 males) matched for age and education. MRI images were collected using a GE 1.5 T scanner at the University of Pittsburgh Medical Center. Image processing was done using FreeSurfer (MGH) by an experienced rater blind to clinical data. We used multivariate analysis of covariance, with intracranial volume (p>0.05) and age as covariates. High Risk offspring had significant reductions in total WM, hemispheric WM and WM within left parietal and left cingulate cortices. Male offspring had more pronounced right hemisphere WM reductions than females. PMID:22910323

  17. Visualization of the Interaction of Multiple Sclerosis Lesions with Adjacent White Matter Fibers Using Streamtubes and Streamsurfaces

    E-print Network

    Laidlaw, David

    Visualization of the Interaction of Multiple Sclerosis Lesions with Adjacent White Matter Fibers of Multiple Sclerosis. N Engl J Med, 338:278­285, 1998. [4] Ferguson et al. Axonal damage in acute. Brain, 120 matter lesion volume and distribution in multiple sclerosis. Brain, 123(9):1845­9, September 2000. [6

  18. White and Grey Matter Changes in the Language Network during Healthy Aging

    PubMed Central

    Howell, Peter; Wang, Xianling; Li, Kuncheng; Lu, Chunming

    2014-01-01

    Neural structures change with age but there is no consensus on the exact processes involved. This study tested the hypothesis that white and grey matter in the language network changes during aging according to a “last in, first out” process. The fractional anisotropy (FA) of white matter and cortical thickness of grey matter were measured in 36 participants whose ages ranged from 55 to 79 years. Within the language network, the dorsal pathway connecting the mid-to-posterior superior temporal cortex (STC) and the inferior frontal cortex (IFC) was affected more by aging in both FA and thickness than the other dorsal pathway connecting the STC with the premotor cortex and the ventral pathway connecting the mid-to-anterior STC with the ventral IFC. These results were independently validated in a second group of 20 participants whose ages ranged from 50 to 73 years. The pathway that is most affected during aging matures later than the other two pathways (which are present at birth). The results are interpreted as showing that the neural structures which mature later are affected more than those that mature earlier, supporting the “last in, first out” theory. PMID:25251441

  19. Oligodendrocyte morphometry and expression of myelin - Related mRNA in ventral prefrontal white matter in major depressive disorder.

    PubMed

    Rajkowska, Grazyna; Mahajan, Gouri; Maciag, Dorota; Sathyanesan, Monica; Iyo, Abiye H; Moulana, Mohadetheh; Kyle, Patrick B; Woolverton, William L; Miguel-Hidalgo, Jose Javier; Stockmeier, Craig A; Newton, Samuel S

    2015-06-01

    White matter disturbance in the ventral prefrontal cortex (vPFC) in major depressive disorder (MDD) has been noted with diffusion tensor imaging (DTI). However, the cellular and molecular pathology of prefrontal white matter in MDD and potential influence of antidepressant medications is not fully understood. Oligodendrocyte morphometry and myelin-related mRNA and protein expression was examined in the white matter of the vPFC in MDD. Sections of deep and gyral white matter from the vPFC were collected from 20 subjects with MDD and 16 control subjects. Density and size of CNPase-immunoreactive (-IR) oligodendrocytes were estimated using 3-dimensional cell counting. While neither density nor soma size of oligodendrocytes was significantly affected in deep white matter, soma size was significantly decreased in the gyral white matter in MDD. In rhesus monkeys treated chronically with fluoxetine there was no significant effect on oligodendrocyte morphometry. Using quantitative RT-PCR to measure oligodendrocyte-related mRNA for CNPase, PLP1, MBP, MOG, MOBP, Olig1 and Olig2, in MDD there was a significantly reduced expression of PLP1 mRNA (which positively correlated with smaller sizes) and increased expression of mRNA for CNPase, OLIG1 and MOG. The expression of CNPase protein was significantly decreased in MDD. Altered expression of four myelin genes and CNPase protein suggests a mechanism for the degeneration of cortical axons and dysfunctional maturation of oligodendrocytes in MDD. The change in oligodendrocyte morphology in gyral white matter may parallel altered axonal integrity as revealed by DTI. PMID:25930075

  20. Genetic markers of white matter integrity in schizophrenia revealed by parallel ICA

    PubMed Central

    Gupta, Cota Navin; Chen, Jiayu; Liu, Jingyu; Damaraju, Eswar; Wright, Carrie; Perrone-Bizzozero, Nora I.; Pearlson, Godfrey; Luo, Li; Michael, Andrew M.; Turner, Jessica A.; Calhoun, Vince D.

    2015-01-01

    It is becoming a consensus that white matter integrity is compromised in schizophrenia (SZ), however the underlying genetics remains elusive. Evidence suggests a polygenic basis of the disorder, which involves various genetic variants with modest individual effect sizes. In this work, we used a multivariate approach, parallel independent component analysis (P-ICA), to explore the genetic underpinnings of white matter abnormalities in SZ. A pre-filtering step was first applied to locate 6527 single nucleotide polymorphisms (SNPs) discriminating patients from controls with a nominal uncorrected p-value of 0.01. These potential susceptibility loci were then investigated for associations with fractional anisotropy (FA) images in a cohort consisting of 73 SZ patients and 87 healthy controls (HC). A significant correlation (r = ?0.37, p = 1.25 × 10?6) was identified between one genetic factor and one FA component after controlling for scanning site, ethnicity, age, and sex. The identified FA-SNP association remained stable in a 10-fold validation. A 5000-run permutation test yielded a p-value of 2.00 × 10?4. The FA component reflected decreased white matter integrity in the forceps major for SZ patients. The SNP component was overrepresented in genes whose products are involved in corpus callosum morphology (e.g., CNTNAP2, NPAS3, and NFIB) as well as canonical pathways of synaptic long term depression and protein kinase A signaling. Taken together, our finding delineates a part of genetic architecture underlying SZ-related FA reduction, emphasizing the important role of genetic variants involved in neural development. PMID:25784871

  1. Characterizing the white matter hyperintensity penumbra with cerebral blood flow measures

    PubMed Central

    Promjunyakul, N.; Lahna, D.; Kaye, J.A.; Dodge, H.H.; Erten-Lyons, D.; Rooney, W.D.; Silbert, L.C.

    2015-01-01

    Objective White matter hyperintensities (WMHs) are common with age, grow over time, and are associated with cognitive and motor impairments. Mechanisms underlying WMH growth are unclear. We aimed to determine the presence and extent of decreased normal appearing white matter (NAWM) cerebral blood flow (CBF) surrounding WMHs to identify ‘WM at risk’, or the WMH CBF penumbra. We aimed to further validate cross-sectional finding by determining whether the baseline WMH penumbra CBF predicts the development of new WMHs at follow-up. Methods Sixty-one cognitively intact elderly subjects received 3 T MPRAGE, FLAIR, and pulsed arterial spin labeling (PASL). Twenty-four subjects returned for follow-up MRI. The inter-scan interval was 18 months. A NAWM layer mask, comprised of fifteen layers, 1 mm thick each surrounding WMHs, was generated for periventricular (PVWMH) and deep (DWMH) WMHs. Mean CBF for each layer was computed. New WMH and persistent NAWM voxels for each penumbra layer were defined from follow-up MRI. Results CBF in the area surrounding WMHs was significantly lower than the total brain NAWM, extending approximately 12 mm from both the established PVWMH and DWMH. Voxels with new WMH at follow-up had significantly lower baseline CBF than voxels that maintained NAWM, suggesting that baseline CBF can predict the development of new WMHs over time. Conclusions A CBF penumbra exists surrounding WMHs, which is associated with future WMH expansion. ASL MRI can be used to monitor interventions to increase white matter blood flow for the prevention of further WM damage and its cognitive and motor consequences.

  2. White matter microstructure in transsexuals and controls investigated by diffusion tensor imaging.

    PubMed

    Kranz, Georg S; Hahn, Andreas; Kaufmann, Ulrike; Küblböck, Martin; Hummer, Allan; Ganger, Sebastian; Seiger, Rene; Winkler, Dietmar; Swaab, Dick F; Windischberger, Christian; Kasper, Siegfried; Lanzenberger, Rupert

    2014-11-12

    Biological causes underpinning the well known gender dimorphisms in human behavior, cognition, and emotion have received increased attention in recent years. The advent of diffusion-weighted magnetic resonance imaging has permitted the investigation of the white matter microstructure in unprecedented detail. Here, we aimed to study the potential influences of biological sex, gender identity, sex hormones, and sexual orientation on white matter microstructure by investigating transsexuals and healthy controls using diffusion tensor imaging (DTI). Twenty-three female-to-male (FtM) and 21 male-to-female (MtF) transsexuals, as well as 23 female (FC) and 22 male (MC) controls underwent DTI at 3 tesla. Fractional anisotropy, axial, radial, and mean diffusivity were calculated using tract-based spatial statistics (TBSS) and fiber tractography. Results showed widespread significant differences in mean diffusivity between groups in almost all white matter tracts. FCs had highest mean diffusivities, followed by FtM transsexuals with lower values, MtF transsexuals with further reduced values, and MCs with lowest values. Investigating axial and radial diffusivities showed that a transition in axial diffusivity accounted for mean diffusivity results. No significant differences in fractional anisotropy maps were found between groups. Plasma testosterone levels were strongly correlated with mean, axial, and radial diffusivities. However, controlling for individual estradiol, testosterone, or progesterone plasma levels or for subjects' sexual orientation did not change group differences. Our data harmonize with the hypothesis that fiber tract development is influenced by the hormonal environment during late prenatal and early postnatal brain development. PMID:25392513

  3. Widespread Changes in White Matter Microstructure after a Day of Waking and Sleep Deprivation

    PubMed Central

    Elvsĺshagen, Torbjřrn; Norbom, Linn B.; Pedersen, Per Ř.; Quraishi, Sophia H.; Bjřrnerud, Atle; Malt, Ulrik F.; Groote, Inge R.; Westlye, Lars T.

    2015-01-01

    Background Elucidating the neurobiological effects of sleep and waking remains an important goal of the neurosciences. Recently, animal studies indicated that sleep is important for cell membrane and myelin maintenance in the brain and that these structures are particularly susceptible to insufficient sleep. Here, we tested the hypothesis that a day of waking and sleep deprivation would be associated with changes in diffusion tensor imaging (DTI) indices of white matter microstructure sensitive to axonal membrane and myelin alterations. Methods Twenty-one healthy adult males underwent DTI in the morning [7:30AM; time point (TP)1], after 14 hours of waking (TP2), and then after another 9 hours of waking (TP3). Whole brain voxel-wise analysis was performed with tract based spatial statistics. Results A day of waking was associated with widespread increases in white matter fractional anisotropy, which were mainly driven by radial diffusivity reductions, and sleep deprivation was associated with widespread fractional anisotropy decreases, which were mainly explained by reductions in axial diffusivity. In addition, larger decreases in axial diffusivity after sleep deprivation were associated with greater sleepiness. All DTI changes remained significant after adjusting for hydration measures. Conclusions This is the first DTI study of sleep deprivation in humans. Although previous studies have observed localized changes in DTI indices of cerebral microstructure over the course of a few hours, further studies are needed to confirm widespread DTI changes within hours of waking and to clarify whether such changes in white matter microstructure serve as neurobiological substrates of sleepiness. PMID:26020651

  4. Inflammasome induction in Rasmussen’s encephalitis: cortical and associated white matter pathogenesis

    PubMed Central

    2013-01-01

    Background Rasmussen’s encephalitis (RE) is an inflammatory encephalopathy of unknown cause defined by seizures with progressive neurological disabilities. Herein, the pathogenesis of RE was investigated focusing on inflammasome activation in the brain. Methods Patients with RE at the University of Alberta, Edmonton, AB, Canada, were identified and analyzed by neuroimaging, neuropsychological, molecular, and pathological tools. Primary human microglia, astrocytes, and neurons were examined using RT-PCR, enzyme-linked immunosorbent assay (ELISA), and western blotting. Results Four patients with RE were identified at the University of Alberta. Magnetic resonance imaging (MRI) disclosed increased signal intensities in cerebral white matter adjacent to cortical lesions of RE patients, accompanied by a decline in neurocognitive processing speed (P <0.05). CD3?, HLA-DRA, and TNF? together with several inflammasome-associated genes (IL-1?, IL-18, NLRP1, NLRP3, and CASP1) showed increased transcript levels in RE brains compared to non-RE controls (n?=?6; P <0.05). Cultured human microglia displayed expression of inflammasome-associated genes and responded to inflammasome activators by releasing IL-1?, which was inhibited by the caspase inhibitor, zVAD-fmk. Major histocompatibility complex (MHC) class II, IL-1?, caspase-1, and alanine/serine/cysteine (ASC) immunoreactivity were increased in RE brain tissues, especially in white matter myeloid cells, in conjunction with mononuclear cell infiltration and gliosis. Neuroinflammation in RE brains was present in both white matter and adjacent cortex with associated induction of inflammasome components, which was correlated with neuroimaging and neuropsychological deficits. Conclusion Inflammasome activation likely contributes to the disease process underlying RE and offers a mechanistic target for future therapeutic interventions. PMID:24330827

  5. Polygenic risk and white matter integrity in individuals at high risk of mood disorder

    PubMed Central

    Whalley, Heather C; Sprooten, Emma; Hackett, Suzanna; Hall, Lynsey; Blackwood, Douglas H; Glahn, David C; Bastin, Mark; Hall, Jeremy; Lawrie, Stephen M; Sussmann, Jessika E; McIntosh, Andrew M

    2014-01-01

    Background Bipolar disorder (BD) and major depressive disorder (MDD) are highly heritable and genetically overlapping conditions characterised by episodic elevation and/or depression of mood. Both demonstrate abnormalities in white matter integrity, measured using diffusion tensor magnetic resonance imaging (MRI), that are also heritable. However it is unclear how these abnormalities relate to the underlying genetic architecture of each disorder. Genome-wide association studies (GWAS) have demonstrated a significant polygenic contribution to BD and MDD, where risk is attributed to the summation of many alleles of small effect. Determining the effects of an overall polygenic risk profile score on neuroimaging abnormalities may help to identify proxy measures of genetic susceptibility and thereby inform models of risk prediction. Methods In the current study we determined the extent to which common genetic variation underlying risk to mood disorders (BD and MDD) was related to fractional anisotropy, an index of white matter integrity. This was conducted in unaffected individuals at familial risk of mood disorder (n=70) and comparison subjects (n=62). Polygenic risk scores were calculated separately for BD and MDD based on GWAS data from the Psychiatric Genome Consortia. Results We report that a higher polygenic risk allele load for MDD was significantly associated with decreased white matter integrity across both groups in a large cluster with a peak in the right-sided superior longitudinal fasciculus. Conclusions These findings suggest that the polygenic approach to examining brain imaging data may be a useful means of identifying traits linked to the genetic risk of mood disorders. PMID:23453289

  6. Visualizing white matter pathways in the living human brain: diffusion tensor imaging and beyond.

    PubMed

    Hess, Christopher P; Mukherjee, Pratik

    2007-11-01

    Biologic connectionism holds as its central tenet that the cognitive, behavioral, and motor functions of the brain are derived from the complex interconnections of simple neural processing units. Much can be learned about the human mind through the study of the brain's connections in normal and diseased states. This article summarizes the essential features of the tensor model of diffusion, outlines newer approaches to overcoming the limitations of the tensor, and provides normal and clinical examples of white matter anatomy derived using diffusion tensor imaging and more sophisticated high angular resolution diffusion imaging methods. Diffusion MR imaging is a powerful adjunct to techniques for studying brain function. PMID:17983960

  7. Pathology Case Study: Two Patients with Putamen and White Matter Necrosis and Hemorrhage

    NSDL National Science Digital Library

    This is a case study presented by the University of Pittsburgh Department of Pathology, which compares the clinical history and autopsy results (microscopic and macroscopic) of two patients â??with putamen and white matter necrosis and hemorrhageâ?ť. In the â??Final Diagnosisâ?ť section the pathology of the two cases are described in detail, and the final diagnosis is also explained. This is an excellent resource for students in the health sciences to familiarize themselves with using patient history and laboratory results to diagnose patientâ??s conditions. It is also a helpful site for educators to use to introduce or test student knowledge of neuropathology.

  8. White matter abnormalities: Insights into the pathophysiology of major affective disorders

    PubMed Central

    Serafini, Gianluca; Gonda, Xenia; Rihmer, Zoltan; Girardi, Paolo; Amore, Mario

    2014-01-01

    The presence of white matter hyperintensities (WMHs) has been commonly associated with poor outcome in subjects with major affective disorders. Unfortunately, WMHs may be frequently confounded by the use of psychoactive medications and duration of illness. Although findings from the current literature are quite conflicting, we proposed that subjects with WMHs may be at higher suicidal risk when compared to other subgroups without. Based on the Fazekas modified scale, the severity of WMHs may serve as a trait marker of disease. Interestingly, the presence of WMHs may represent a neurobiological marker between the underlying vulnerability and clinical presentation of major affective disorders. PMID:24976925

  9. PERSPECTIVE: Snow matters in the polar regions

    NASA Astrophysics Data System (ADS)

    Sodeau, John

    2010-03-01

    Antarctica is not quite as chemically pristine as might sometimes be thought (Jones et al 2008). For example, as elsewhere, reduced sulfur species such as dimethylsulfide (DMS) are emitted from biogenic marine sources at the poles (Read et al 2008). Somewhat less well known is that inland (as opposed to coastal) field campaigns have also detected, within the Antarctic boundary layer (ABL), emissions containing unexpectedly high levels of diverse, oxidizing chemicals such as NOx, nitrate ions, formaldehyde, ozone and hydrogen peroxide (Honrath et al 1999, Hutterli et al 2004, Sumner and Shepson 1999). And then there are the halogen-containing compounds (Simpson et al 2007). The transformation of DMS to sulfate aerosols capable of acting as cloud condensation nuclei often proceeds via one main oxidized product of DMS, namely methanesulfonic acid (MSA). Two specific reactions have been well studied to date in this regard, namely DMS plus either OH or NO3 radicals. Corresponding reactions with halogen radicals, which also contribute to the oxidizing capacity of our atmosphere, have generally been considered to be of less importance. The reason for this view is that even though the reactivity of bromine- and iodine-containing radicals is much greater than that of OH, the halogens were thought to be relatively scarce in the polar atmosphere. However both BrO (and IO) have been detected in the Antarctic CHABLIS campaign, as discussed in depth in the Atmospheric Chemistry and Physics special issue of 2008, see Jones et al (2008). It was subsequently shown that calculated MSA production from the DMS/BrO reaction may be about an order of magnitude greater than when the OH radical was the oxidizing reactant. The recent analytical measurements by Antony et al (2010) of MSA, Br and NO3 found in snow along the Ingrid Christensen Coast of East Antarctica are important in the above field context. Hence it would appear that the concentrations of these ions in ice-cap sites are up to 30 times greater than those found in ice-free areas. The main question to ask is: how might the bromine have become released to the atmosphere? Many ideas have, in fact, been put forward over the last few years as to how such polar ocean-troposphere exchanges can take place. Much of the interest was driven by the so-called 'sudden' ozone depletion episodes first detected in Arctic air during the 1990s alongside simultaneous bromine 'explosions' which were monitored by ground-based instrumentation and satellite (as the radical BrO) over sea-ice covered by snowpack (Hausmann and Platt 1994, Schonhardt et al 2008). The likely precursors suggested, to date, have been sea-salt, frost-flowers and anthropogenic contents rather than organo- bromine matter (Simpson et al 2007). Associated processing routes including the formation of HOBr, the need for acidity, the involvement of trihalide ions and the potential role of freezing processes and the quasi-liquid layer have all been discussed in this context (Abbatt 1994, Neshyba et al 2009, O'Driscoll et al 2006). Computational work has also led to suggestions that preferential surface dispersion of the more highly polarizable halides (iodide and bromide ions) may lead to their direct interfacial reaction with atmospheric ozone leading to BrO or IO formation (Jungwirth and Winter 2008). The involvement of snow micro-algae in the production of halo-compounds such as CHBr3 and CH2Br2 in Antarctica cannot, of course, be ignored following the measurement of these compounds by Sturges and co-workers over 15 years ago (Sturges et al 1993). And the measurement of high levels of nutrient discussed in the recent work by Antony et al (2010) in the ice-cap areas do provide a basis for understanding why micro- algae growth in snow might be promoted. However the question still comes back to: how are these halo-compounds processed to produce 'active' species like BrO radicals, HOBr, Br atoms, Br2 gas or interhalogens such as BrCl? The relatively long history of this topic was surveyed extensively in 2007 and the answer is probably not

  10. A mathematical formula for prediction of gray and white matter volume recovery in abstinent alcohol dependent individuals

    PubMed Central

    Mon, Anderson; Delucchi, Kevin; Durazzo, Timothy C.; Gazdzinski, Stefan; Meyerhoff, Dieter J.

    2011-01-01

    We propose a mathematical formula that predicts the trajectory of the recovery from lobar gray and white matter volume deficits in individuals with sustained abstinence from alcohol. The formula was validated by using MRI-measured volumetric data from 16 alcohol dependent individuals who had brain scans at three time points during abstinence from alcohol. Using the measured volumetric data of each individual from the first two time points, we estimated the individual’s gray and white matter volume of the frontal, parietal and temporal lobes for the third time point using the formula. Similarly, using the measured data for the second and third time points, we estimated the first time point data for each individual. The data predicted from the formula were very similar to the experimentally measured data for all lobes and for both gray and white matter. The intra-class correlation coefficients between the measured data and the data estimated from the formula were > 0.95 for each tissue type. The formula may also be applicable in other neuroimaging studies of tissue volume changes such as white matter myelination during brain development and white matter demyelination or brain volume loss in neurodegenerative diseases, such as Alzheimer’s disease. PMID:21903361

  11. Age-Associated Alterations in Corpus Callosum White Matter Integrity in Bipolar Disorder Assessed Using Probabilistic Tractography

    PubMed Central

    Toteja, Nitin; Cokol, Perihan Guvenek; Ikuta, Toshikazu; Kafantaris, Vivian; Peters, Bart D.; Burdick, Katherine E.; John, Majnu; Malhotra, Anil K.; Szeszko, Philip R.

    2014-01-01

    Objectives Atypical age-associated changes in white matter integrity may play a role in the neurobiology of bipolar disorder, but no studies have examined the major white matter tracts using nonlinear statistical modeling across a wide age range in this disorder. The goal of this study was to identify possible deviations in the typical pattern of age-associated changes in white matter integrity in patients with bipolar disorder across the age range of 9 to 62 years. Methods Diffusion tensor imaging was performed in 57 (20M/37F) patients with a diagnosis of bipolar disorder and 57 (20M/37F) age- and sex-matched healthy volunteers. Mean diffusivity and fractional anisotropy were computed for the genu and splenium of the corpus callosum, two projection tracts, and five association tracts using probabilistic tractography. Results Overall, patients had lower fractional anisotropy and higher mean diffusivity compared to healthy volunteers across all tracts (while controlling for the effects of age and age2). In addition, there were greater age-associated increases in mean diffusivity in patients compared to healthy volunteers within the genu and splenium of the corpus callosum beginning in the second and third decades of life. Conclusions Our findings provide evidence for alterations in the typical pattern of white matter development in patients with bipolar disorder compared to healthy volunteers. Changes in white matter development within the corpus callosum may lead to altered inter-hemispheric communication that is considered integral to the neurobiology of the disorder. PMID:25532972

  12. White matter characterization of adolescent binge drinking with and without co-occurring marijuana use: a 3-year investigation.

    PubMed

    Jacobus, Joanna; Squeglia, Lindsay M; Bava, Sunita; Tapert, Susan F

    2013-12-30

    The aims of this study were to investigate the consequences of prolonged patterns of alcohol and marijuana use on white matter integrity and neurocognitive functioning in late adolescence, and examine neurodevelopmental trajectories over three years of regular follow-up visits. Three groups of demographically similar teens received assessments every 1.5 years (controls with consistently minimal substance use, n=16; teens who gradually increase their heavy episodic drinking n=17, and continuous binge drinkers with heavy marijuana use, n=21), including comprehensive neuropsychological evaluations, diffusion tensor imaging, and detailed substance use interviews. One-way ANOVA identified fifteen white matter clusters that significantly differed between groups at 3-year follow-up, ages 19-22; controls consistently demonstrated higher values of tissue integrity across fiber tracts. Repeated measures ANOVA revealed significant declines in white matter integrity from baseline to 3-year follow-up in the subsample of substance users, along with poorer global neurocognitive performance in alcohol users with heavy marijuana use by the 18-month follow-up. Findings suggest healthier brain white matter microstructure and better neurocognitive performance for teens free from heavy alcohol and marijuana use. Long-term engagement in these substances may adversely influence white matter and increase vulnerability for development of neuropathology purported to underlie future risk-taking and addictive behaviors. PMID:24139957

  13. White matter lesional predictors of chronic visual neglect: a longitudinal study.

    PubMed

    Lunven, Marine; Thiebaut De Schotten, Michel; Bourlon, Clémence; Duret, Christophe; Migliaccio, Raffaella; Rode, Gilles; Bartolomeo, Paolo

    2015-03-01

    Chronic visual neglect prevents brain-damaged patients from returning to an independent and active life. Detecting predictors of persistent neglect as early as possible after the stroke is therefore crucial to plan the relevant interventions. Neglect signs do not only depend on focal brain lesions, but also on dysfunction of large-scale brain networks connected by white matter bundles. We explored the relationship between markers of axonal degeneration occurring after the stroke and visual neglect chronicity. A group of 45 patients with unilateral strokes in the right hemisphere underwent cognitive testing for neglect twice, first at the subacute phase (<3 months after onset) and then at the chronic phase (>1 year). For each patient, magnetic resonance imaging including diffusion sequences was performed at least 4 months after the stroke. After masking each patient's lesion, we used tract-based spatial statistics to obtain a voxel-wise statistical analysis of the fractional anisotropy data. Twenty-seven patients had signs of visual neglect at initial testing. Only 10 of these patients had recovered from neglect at follow-up. When compared with patients without neglect, the group including all subacute neglect patients had decreased fractional anisotropy in the second (II) and third (III) branches of the right superior longitudinal fasciculus, as well as in the splenium of the corpus callosum. The subgroup of chronic patients showed reduced fractional anisotropy in a portion the splenium, the forceps major, which provides interhemispheric communication between regions of the occipital lobe and of the superior parietal lobules. The severity of neglect correlated with fractional anisotropy values in superior longitudinal fasciculus II/III for subacute patients and in its caudal portion for chronic patients. Our results confirm a key role of fronto-parietal disconnection in the emergence and chronic persistence of neglect, and demonstrate an implication of caudal interhemispheric disconnection in chronic neglect. Splenial disconnection may prevent fronto-parietal networks in the left hemisphere from resolving the activity imbalance with their right hemisphere counterparts, thus leading to persistent neglect. PMID:25609686

  14. Traumatic white matter injury and glial activation: from basic science to clinics.

    PubMed

    Kou, Zhifeng; VandeVord, Pamela J

    2014-11-01

    An improved understanding and characterization of glial activation and its relationship with white matter injury will likely serve as a novel treatment target to curb post injury inflammation and promote axonal remyelination after brain trauma. Traumatic brain injury (TBI) is a significant public healthcare burden and a leading cause of death and disability in the United States. Particularly, traumatic white matter (WM) injury or traumatic axonal injury has been reported as being associated with patients' poor outcomes. However, there is very limited data reporting the importance of glial activation after TBI and its interaction with WM injury. This article presents a systematic review of traumatic WM injury and the associated glial activation, from basic science to clinical diagnosis and prognosis, from advanced neuroimaging perspective. It concludes that there is a disconnection between WM injury research and the essential role of glia which serve to restore a healthy environment for axonal regeneration following WM injury. Particularly, there is a significant lack of non-invasive means to characterize the complex pathophysiology of WM injury and glial activation in both animal models and in humans. An improved understanding and characterization of the relationship between glia and WM injury will likely serve as a novel treatment target to curb post injury inflammation and promote axonal remyelination. PMID:24807544

  15. Cerebellar white matter pathways are associated with reading skills in children and adolescents.

    PubMed

    Travis, Katherine E; Leitner, Yael; Feldman, Heidi M; Ben-Shachar, Michal

    2015-04-01

    Reading is a critical life skill in the modern world. The neural basis of reading incorporates a distributed network of cortical areas and their white matter connections. The cerebellum has also been implicated in reading and reading disabilities. However, little is known about the contribution of cerebellar white matter pathways to major component skills of reading. We used diffusion magnetic resonance imaging (dMRI) with tractography to identify the cerebellar peduncles in a group of 9- to 17-year-old children and adolescents born full term (FT, n?=?19) or preterm (PT, n?=?26). In this cohort, no significant differences were found between fractional anisotropy (FA) measures of the peduncles in the PT and FT groups. FA of the cerebellar peduncles correlated significantly with measures of decoding and reading comprehension in the combined sample of FT and PT subjects. Correlations were negative in the superior and inferior cerebellar peduncles and positive in the middle cerebellar peduncle. Additional analyses revealed that FT and PT groups demonstrated similar patterns of reading associations within the left superior cerebellar peduncle, middle cerebellar peduncle, and left inferior cerebellar peduncle. Partial correlation analyses showed that distinct sub-skills of reading were associated with FA in segments of different cerebellar peduncles. Overall, the present findings are the first to document associations of microstructure of the cerebellar peduncles and the component skills of reading. PMID:25504986

  16. Automatic clustering of white matter fibers in brain diffusion MRI with an application to genetics.

    PubMed

    Jin, Yan; Shi, Yonggang; Zhan, Liang; Gutman, Boris A; de Zubicaray, Greig I; McMahon, Katie L; Wright, Margaret J; Toga, Arthur W; Thompson, Paul M

    2014-10-15

    To understand factors that affect brain connectivity and integrity, it is beneficial to automatically cluster white matter (WM) fibers into anatomically recognizable tracts. Whole brain tractography, based on diffusion-weighted MRI, generates vast sets of fibers throughout the brain; clustering them into consistent and recognizable bundles can be difficult as there are wide individual variations in the trajectory and shape of WM pathways. Here we introduce a novel automated tract clustering algorithm based on label fusion--a concept from traditional intensity-based segmentation. Streamline tractography generates many incorrect fibers, so our top-down approach extracts tracts consistent with known anatomy, by mapping multiple hand-labeled atlases into a new dataset. We fuse clustering results from different atlases, using a mean distance fusion scheme. We reliably extracted the major tracts from 105-gradient high angular resolution diffusion images (HARDI) of 198 young normal twins. To compute population statistics, we use a pointwise correspondence method to match, compare, and average WM tracts across subjects. We illustrate our method in a genetic study of white matter tract heritability in twins. PMID:24821529

  17. White Matter Abnormalities and Cognitive Impairment in Early-Onset Schizophrenia-Spectrum Disorders

    PubMed Central

    Epstein, Katherine A.; Cullen, Kathryn; Mueller, Bryon; Lee, Susanne; Kumra, Sanjiv

    2014-01-01

    OBJECTIVE To characterize white matter abnormalities in adolescents with early onset schizophrenia (EOS) relative to three comparison groups (adolescents at clinical high risk for developing schizophrenia [CHR], adolescents with cannabis use disorder [CUD], and healthy controls [HC]), and to identify neurocognitive correlates of white matter abnormalities in EOS. METHOD We used diffusion tensor imaging and tractography methods to examine fractional anisotropy (FA) of the cingulum bundle, superior longitudinal fasciculus, corticospinal tract (CST), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), and uncinate fasciculus in adolescents with EOS (n=55), CHR (n=21), CUD (n=31), and HC (n=55). FA in tracts that were significantly altered in EOS was correlated with neurocognitive performance. RESULTS EOS and CHR groups had significantly lower FA than HC in four tracts: bilateral CST, left ILF, and left IFOF. CUD had lower FA than HC in left IFOF. Lower FA in left IFOF and left ILF predicted worse neurocognitive performance in EOS. CONCLUSIONS This study identified left ILF and left IFOF as possible biomarkers of vulnerability for developing schizophrenia. Lower FA in these tracts may disrupt functioning of ventral visual and language streams, producing domain-specific neurocognitive deficits that interfere with higher order cognitive abilities. PMID:24565363

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

    PubMed Central

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

    2013-01-01

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

  19. Caffeine, cognitive functioning, and white matter lesions in the elderly: establishing causality from epidemiological evidence

    PubMed Central

    Ritchie, Karen; Artero, Sylvaine; Portet, Florence; Brickman, Adam; Muraskin, Jordan; Beaino, Ephrem; Ancelin, Marie-Laure; Carričre, Isabelle

    2010-01-01

    Objective The present study examines the epidemiological evidence for a causal relationship between caffeine consumption and cognitive deterioration in the elderly. Methods A population study of 641 elderly persons examining cognitive functioning, caffeine consumption, magnetic resonance imaging volumetrics and other factors known to affect cognitive performance. Results Our findings demonstrate that the association between caffeine consumption and lower cognitive change over time to be statistically significant for women only, taking into account multiple confounders, to be dose-dependent and temporarily related (caffeine consumption precedes cognitive change). Mean log transformed white matter lesion/cranial volume ratios were found to be significantly lower in women consuming more than 3 units of caffeine per day after adjustment for age (?1.23 SD=0.06) than women consuming 2–3 units (?1.04 SD=0.04) or one unit or less (?1.04 SD=0.07, ?35% in cm3 compared to low drinkers). This observation is coherent with biological assumptions that caffeine through adenosine is linked to amyloid accumulation and subsequently white matter lesion formation. Conclusions The significant relationship observed between caffeine intake in women and lower cognitive decline is highly likely to be a true causal relationship and not a spurious association. PMID:20164564

  20. GABAergic regulation of cerebellar NG2 cell development is altered in perinatal white matter injury.

    PubMed

    Zonouzi, Marzieh; Scafidi, Joseph; Li, Peijun; McEllin, Brian; Edwards, Jorge; Dupree, Jeffrey L; Harvey, Lloyd; Sun, Dandan; Hübner, Christian A; Cull-Candy, Stuart G; Farrant, Mark; Gallo, Vittorio

    2015-05-01

    Diffuse white matter injury (DWMI), a leading cause of neurodevelopmental disabilities in preterm infants, is characterized by reduced oligodendrocyte formation. NG2-expressing oligodendrocyte precursor cells (NG2 cells) are exposed to various extrinsic regulatory signals, including the neurotransmitter GABA. We investigated GABAergic signaling to cerebellar white matter NG2 cells in a mouse model of DWMI (chronic neonatal hypoxia). We found that hypoxia caused a loss of GABAA receptor-mediated synaptic input to NG2 cells, extensive proliferation of these cells and delayed oligodendrocyte maturation, leading to dysmyelination. Treatment of control mice with a GABAA receptor antagonist or deletion of the chloride-accumulating transporter NKCC1 mimicked the effects of hypoxia. Conversely, blockade of GABA catabolism or GABA uptake reduced NG2 cell numbers and increased the formation of mature oligodendrocytes both in control and hypoxic mice. Our results indicate that GABAergic signaling regulates NG2 cell differentiation and proliferation in vivo, and suggest that its perturbation is a key factor in DWMI. PMID:25821912

  1. Delineating White Matter Structure in Diffusion Tensor MRI with Anisotropy Creases

    PubMed Central

    Kindlmann, Gordon; Tricoche, Xavier; Westin, Carl-Fredrik

    2008-01-01

    Geometric models of white matter architecture play an increasing role in neuroscientific applications of diffusion tensor imaging, and the most popular method for building them is fiber tractography. For some analysis tasks, however, a compelling alternative may be found in the first and second derivatives of diffusion anisotropy. We extend to tensor fields the notion from classical computer vision of ridges and valleys, and define anisotropy creases as features of locally extremal values of tensor anisotropy. Mathematically, these are the loci where the gradient of anisotropy is orthogonal to one or more eigenvectors of its Hessian. We propose that anisotropy creases provide a basis for extracting a skeleton of the major white matter pathways, in that ridges of anisotropy coincide with interiors of fiber tracts, and valleys of anisotropy coincide with the interfaces between adjacent but distinctly oriented tracts. The crease extraction algorithm we present generates high-quality polygonal models of crease surfaces, which are further simplified by connected-component analysis. We demonstrate anisotropy creases on measured diffusion MRI data, and visualize them in combination with tractography to confirm their anatomic