WorldWideScience

Sample records for brain white matter

  1. Glutamatergic signaling in the brain's white matter.

    Science.gov (United States)

    Bakiri, Y; Burzomato, V; Frugier, G; Hamilton, N B; Káradóttir, R; Attwell, D

    2009-01-12

    Glutamatergic signaling has been exceptionally well characterized in the brain's gray matter, where it underlies fast information processing, learning and memory, and also generates the neuronal damage that occurs in pathological conditions such as stroke. The role of glutamatergic signaling in the white matter, an area until recently thought to be devoid of synapses, is less well understood. Here we review what is known, and highlight what is not known, of glutamatergic signaling in the white matter. We focus on how glutamate is released, the location and properties of the receptors it acts on, the interacting molecules that may regulate trafficking or signaling of the receptors, the possible functional roles of glutamate in the white matter, and its pathological effects including the possibility of treating white matter disorders with glutamate receptor blockers.

  2. Tracking White Matter Fiber in Human Brain

    Institute of Scientific and Technical Information of China (English)

    KANGNing; ZHANGJun; EricSCarlson

    2004-01-01

    A new approach for noninvasively tracing brain white matter fiber tracts is presented using diffusion tensor magnetic resonance imaging (DT-MRI) data. This technique is based on successive anisotropic diffusion simulations over the human brain, which are utilized to construct three dimensional diffusion fronts. The fiber pathways are determined by evaluating the distance and orientation from fronts to their corresponding diffusion seeds. Real DT-MRI data are used to demonstrate the tracking scheme. It is shown that several major white matter fiber pathways can be reproduced noninvasively, with the tract branching being allowed. Since the diffusion simulation,which is a truly physical phenomenon reflecting the underlying architecture of cerebral tissues, makes full use of the entire diffusion tensor data, the proposed approach is expected to enhance robustness and reliability of the DT-MRI based fiber tracking techniques in white matter fiber reconstruction.

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

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    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…

  4. Relationship between progression of brain white matter changes and late-life depression

    DEFF Research Database (Denmark)

    Firbank, Michael J; Teodorczuk, Andrew; van der Flier, Wiesje M;

    2012-01-01

    Brain white matter changes (WMC) and depressive symptoms are linked, but the directionality of this association remains unclear.......Brain white matter changes (WMC) and depressive symptoms are linked, but the directionality of this association remains unclear....

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

    Science.gov (United States)

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

    2015-02-01

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

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

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    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.

  7. Asymmetry of White Matter Pathways in Developing Human Brains.

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    Song, Jae W; Mitchell, Paul D; Kolasinski, James; Ellen Grant, P; Galaburda, Albert M; Takahashi, Emi

    2015-09-01

    Little is known about the emergence of structural asymmetry of white matter tracts during early brain development. We examined whether and when asymmetry in diffusion parameters of limbic and association white matter pathways emerged in humans in 23 brains ranging from 15 gestational weeks (GW) up to 3 years of age (11 ex vivo and 12 in vivo cases) using high-angular resolution diffusion imaging tractography. Age-related development of laterality was not observed in a limbic connectional pathway (cingulum bundle or fornix). Among the studied cortico-cortical association pathways (inferior longitudinal fasciculus [ILF], inferior fronto-occipital fasciculus, and arcuate fasciculus), only the ILF showed development of age-related laterality emerging as early as the second trimester. Comparisons of ages older and younger than 40 GW revealed a leftward asymmetry in the cingulum bundle volume and a rightward asymmetry in apparent diffusion coefficient and leftward asymmetry in fractional anisotropy in the ILF in ages older than 40 GW. These results suggest that morphometric asymmetry in cortical areas precedes the emergence of white matter pathway asymmetry. Future correlative studies will investigate whether such asymmetry is anatomically/genetically driven or associated with functional stimulation.

  8. Brain asymmetry in the white matter making and globularity

    Directory of Open Access Journals (Sweden)

    Constantina eTheofanopoulou

    2015-09-01

    Full Text Available Recent studies from the field of language genetics and evolutionary anthropology have put forward the hypothesis that the emergence of our species-specific brain is to be understood not in terms of size, but in light of developmental changes that gave rise to a more globular braincase configuration after the split from Neanderthals-Denisovans. On the grounds that (i white matter myelination is delayed relative to other brain structures and in humans is protracted compared with other primates and (ii neural connectivity is linked genetically to our brain/skull morphology and language-ready brain, I take it that one significant evolutionary change in Homo sapiens’ lineage is the interhemispheric connectivity mediated by the Corpus Callosum. The size, myelination and fiber caliber of the Corpus Callosum presents an anterior-to-posterior increase, in a way that inter-hemispheric connectivity is more prominent in the sensory motor areas, whereas high- order areas are more intra-hemispherically connected. Building on evidence from language-processing studies that account for this asymmetry (‘lateralization’ in terms of brain rhythms, I present an evo-devo hypothesis according to which the myelination of the Corpus Callosum, Brain Asymmetry and Globularity are conjectured to make up the angles of a co-evolutionary triangle that gave rise to our language-ready brain.

  9. Brain asymmetry in the white matter making and globularity.

    Science.gov (United States)

    Theofanopoulou, Constantina

    2015-01-01

    Recent studies from the field of language genetics and evolutionary anthropology have put forward the hypothesis that the emergence of our species-specific brain is to be understood not in terms of size, but in light of developmental changes that gave rise to a more globular braincase configuration after the split from Neanderthals-Denisovans. On the grounds that (i) white matter myelination is delayed relative to other brain structures and, in humans, is protracted compared with other primates and that (ii) neural connectivity is linked genetically to our brain/skull morphology and language-ready brain, I argue that one significant evolutionary change in Homo sapiens' lineage is the interhemispheric connectivity mediated by the Corpus Callosum. The size, myelination and fiber caliber of the Corpus Callosum present an anterior-to-posterior increase, in a way that inter-hemispheric connectivity is more prominent in the sensory motor areas, whereas "high- order" areas are more intra-hemispherically connected. Building on evidence from language-processing studies that account for this asymmetry ('lateralization') in terms of brain rhythms, I present an evo-devo hypothesis according to which the myelination of the Corpus Callosum, Brain Asymmetry, and Globularity are conjectured to make up the angles of a co-evolutionary triangle that gave rise to our language-ready brain.

  10. Brain microvascular endothelial cell transplantation ameliorates ischemic white matter damage.

    Science.gov (United States)

    Puentes, Sandra; Kurachi, Masashi; Shibasaki, Koji; Naruse, Masae; Yoshimoto, Yuhei; Mikuni, Masahiko; Imai, Hideaki; Ishizaki, Yasuki

    2012-08-21

    Ischemic insults affecting the internal capsule result in sensory-motor disabilities which adversely affect the patient's life. Cerebral endothelial cells have been reported to exert a protective effect against brain damage, so the transplantation of healthy endothelial cells might have a beneficial effect on the outcome of ischemic brain damage. In this study, endothelin-1 (ET-1) was injected into the rat internal capsule to induce lacunar infarction. Seven days after ET-1 injection, microvascular endothelial cells (MVECs) were transplanted into the internal capsule. Meningeal cells or 0.2% bovine serum albumin-Hank's balanced salt solution were injected as controls. Two weeks later, the footprint test and histochemical analysis were performed. We found that MVEC transplantation improved the behavioral outcome based on recovery of hind-limb rotation angle (P<0.01) and induced remyelination (P<0.01) compared with the control groups. Also the inflammatory response was repressed by MVEC transplantation, judging from fewer ED-1-positive activated microglial cells in the MVEC-transplanted group than in the other groups. Elucidation of the mechanisms by which MVECs ameliorate ischemic damage of the white matter may provide important information for the development of effective therapies for white matter ischemia.

  11. An Optimized Clustering Approach for Automated Detection of White Matter Lesions in MRI Brain Images

    OpenAIRE

    Anitha, M.; P. Tamije Selvy

    2012-01-01

    Settings White Matter lesions (WMLs) are small areas of dead cells found in parts of the brain. In general, it is difficult for medical experts to accurately quantify the WMLs due to decreased contrast between White Matter (WM) and Grey Matter (GM). The aim of this paper is to
    automatically detect the White Matter Lesions which is present in the brains of elderly people. WML detection process includes the following stages: 1. Image preprocessing, 2. Clustering (Fuzzy c-means cluste...

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

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

    2016-04-01

    White matter hyperintensities are associated with increased risk of dementia and cognitive decline. The current study investigates the relationship between white matter hyperintensities burden and patterns of brain atrophy associated with brain ageing and Alzheimer's disease in a large populatison-based sample (n = 2367) encompassing a wide age range (20-90 years), from the Study of Health in Pomerania. We quantified white matter hyperintensities using automated segmentation and summarized atrophy patterns using machine learning methods resulting in two indices: the SPARE-BA index (capturing age-related brain atrophy), and the SPARE-AD index (previously developed to capture patterns of atrophy found in patients with Alzheimer's disease). A characteristic pattern of age-related accumulation of white matter hyperintensities in both periventricular and deep white matter areas was found. Individuals with high white matter hyperintensities burden showed significantly (P brain regions typically affected by ageing and Alzheimer's disease dementia. To investigate a possibly causal role of white matter hyperintensities, structural equation modelling was used to quantify the effect of Framingham cardiovascular disease risk score and white matter hyperintensities burden on SPARE-BA, revealing a statistically significant (P brain atrophy found in beyond-normal brain ageing in the general population. White matter hyperintensities also contribute to brain atrophy patterns in regions related to Alzheimer's disease dementia, in agreement with their known additive role to the likelihood of dementia. Preventive strategies reducing the odds to develop cardiovascular disease and white matter hyperintensities could decrease the incidence or delay the onset of dementia.

  13. Initial study of magnetic resonance diffusion tensor imaging in brain white matter of early AIDS patients

    Institute of Scientific and Technical Information of China (English)

    XUAN Ang; WANG Guang-bin; SHI Da-peng; XU Jun-ling; LI Yong-li

    2013-01-01

    Background HIV is a neurotropic virus which can cause brain white matter demyelination,gliosis,and other pathological changes that appear as H IV encephalitis or AIDS dementia.The purpose of this study was to investigate the change of the diffused condition of water molecules in brain white matter in early acquired immune deficiency syndrome (AIDS) patients using MR diffusion tensor imaging (DTI).Methods DTI examinations were performed on a Siemens 3.0T MR scanner in 23 AIDS patients with normal brain appearance by conventional MRI and 20 healthy volunteers as the control group.Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were measured in nine regions; corpus callosum (CC) knee,CC body,CC splenium,periventricular white matter,frontal lobe white matter,parietal lobe white matter,occipital lobe white matter,and the anterior and posterior limbs of the internal capsule.The mean FA and ADC values from each region were compared in three groups:the symptomatic,asymptomatic and the control.Results The mean FA values were significantly lower and the mean ADC values were significantly higher in all nine regions in patients in the symptomatic group than in the asymptomatic and control group patients.In the asymptomatic group,the mean FA values were significantly lower and the mean ADC values were significantly higher at the CC knee,CC body,CC splenium,periventricular white matter,frontal lobe white matter and parietal lobe white matter,than in the control group.There were no significant differences at other regions between the two groups.Conclusions The diffused changes of water molecules in brain white matter in AIDS patients are related to brain white matter regions.DTI examination can detect the brain white matter lesions early in AIDS patients.

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

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    Paus, Tomas

    2010-01-01

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

  15. Whole-brain voxel-based morphometry of white matter in medial temporal lobe epilepsy

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    Yu Aihong [Department of Radiology, Xuanwu Hospital, Capital University of Medical Sciences, Beijing 100053 (China); Li Kuncheng [Department of Radiology, Xuanwu Hospital, Capital University of Medical Sciences, Beijing 100053 (China)], E-mail: Likuncheng@vip.sina.com; Li Lin; Shan Baoci [Institute of High Energy Physics, Chinese Academy of Sciences (China); Wang Yuping; Xue Sufang [Department of Neurology, Xuanwu Hospital, Capital University of Medical Sciences (China)

    2008-01-15

    Purpose: The purpose of this study was to analyze whole-brain white matter changes in medial temporal lobe epilepsy (MTLE). Materials and methods: We studied 23 patients with MTLE and 13 age- and sex-matched healthy control subjects using voxel-based morphometry (VBM) on T1-weighted 3D datasets. The seizure focus was right sided in 11 patients and left sided in 12. The data were collected on a 1.5 T MR system and analyzed by SPM 99 to generate white matter density maps. Results: Voxel-based morphometry revealed diffusively reduced white matter in MTLE prominently including bilateral frontal lobes, bilateral temporal lobes and corpus callosum. White matter reduction was also found in the bilateral cerebellar hemispheres in the left MTLE group. Conclusion: VBM is a simple and automated approach that is able to identify diffuse whole-brain white matter reduction in MTLE.

  16. Frontal white matter volume is associated with brain enlargement and higher structural connectivity in anthropoid primates.

    Directory of Open Access Journals (Sweden)

    Jeroen Bert Smaers

    Full Text Available Previous research has indicated the importance of the frontal lobe and its 'executive' connections to other brain structures as crucial in explaining primate neocortical adaptations. However, a representative sample of volumetric measurements of frontal connective tissue (white matter has not been available. In this study, we present new volumetric measurements of white and grey matter in the frontal and non-frontal neocortical lobes from 18 anthropoid species. We analyze this data in the context of existing theories of neocortex, frontal lobe and white versus grey matter hyperscaling. Results indicate that the 'universal scaling law' of neocortical white to grey matter applies separately for frontal and non-frontal lobes; that hyperscaling of both neocortex and frontal lobe to rest of brain is mainly due to frontal white matter; and that changes in frontal (but not non-frontal white matter volume are associated with changes in rest of brain and basal ganglia, a group of subcortical nuclei functionally linked to 'executive control'. Results suggest a central role for frontal white matter in explaining neocortex and frontal lobe hyperscaling, brain size variation and higher neural structural connectivity in anthropoids.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    While brain gray matter is primarily associated with sensorimotor processing and cognition, white matter modulates the distribution of action potentials, coordinates communication between different brain regions, and acts as a relay for input/output signals. Previous studies have described......, and microglia) in the cerebral white matter of 9 infants aged 0-33 months, using design-based stereological methods to obtain quantitative data about brain development. There were linear increases with age in the numbers of oligodendrocytes (7-28 billion) and astrocytes (1.5-6.7 billion) during the first 3...

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

    Science.gov (United States)

    Minnerop, Martina; 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

    2011-12-01

    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 (T(1)/T(2)/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 (P(corrected) brain changes with clinical and neuropsychological data. White matter lesions rated visually were more prevalent and severe in myotonic dystrophy type 1 compared with controls, with frontal white matter most prominently affected in both disorders, and temporal lesions restricted to myotonic dystrophy type 1. Voxel-based morphometry analyses demonstrated extensive white matter involvement in all cerebral lobes, brainstem and corpus callosum in myotonic dystrophy types 1 and 2, while grey matter decrease (cortical areas, thalamus, putamen) was restricted to myotonic dystrophy type 1. Accordingly, we found more prominent white matter affection in myotonic dystrophy type 1 than myotonic dystrophy type 2 by diffusion tensor imaging. Association fibres throughout the whole brain, limbic system fibre tracts, the callosal body and projection fibres (e.g. internal/external capsules) were affected in myotonic dystrophy types 1 and 2. Central motor pathways were exclusively impaired in myotonic dystrophy type 1. We found mild executive and attentional deficits in our patients when neuropsychological tests were corrected for manual motor dysfunctioning. Regression analyses revealed associations of white matter affection with several clinical parameters in both disease entities, but not with neuropsychological performance. We showed that depressed mood and fatigue were more prominent in patients with myotonic dystrophy type 1

  19. Whole brain white matter changes revealed by multiple diffusion metrics in multiple sclerosis: A TBSS study

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    Liu, Yaou, E-mail: asiaeurope80@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Duan, Yunyun, E-mail: xiaoyun81.love@163.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); He, Yong, E-mail: yong.h.he@gmail.com [State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875 (China); Yu, Chunshui, E-mail: csyuster@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Wang, Jun, E-mail: jun_wang@bnu.edu.cn [State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875 (China); Huang, Jing, E-mail: sainthj@126.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Ye, Jing, E-mail: jingye.2007@yahoo.com.cn [Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Parizel, Paul M., E-mail: paul.parizel@ua.ac.be [Department of Radiology, Antwerp University Hospital and University of Antwerp, Wilrijkstraat 10, 2650 Edegem, 8 Belgium (Belgium); Li, Kuncheng, E-mail: kunchengli55@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Shu, Ni, E-mail: nshu55@gmail.com [State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875 (China)

    2012-10-15

    Objective: To investigate whole brain white matter changes in multiple sclerosis (MS) by multiple diffusion indices, we examined patients with diffusion tensor imaging and utilized tract-based spatial statistics (TBSS) method to analyze the data. Methods: Forty-one relapsing-remitting multiple sclerosis (RRMS) patients and 41 age- and gender-matched normal controls were included in this study. Diffusion weighted images were acquired by employing a single-shot echo planar imaging sequence on a 1.5 T MR scanner. Voxel-wise analyses of multiple diffusion metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were performed with TBSS. Results: The MS patients had significantly decreased FA (9.11%), increased MD (8.26%), AD (3.48%) and RD (13.17%) in their white matter skeletons compared with the controls. Through TBSS analyses, we found abnormal diffusion changes in widespread white matter regions in MS patients. Specifically, decreased FA, increased MD and increased RD were involved in whole-brain white matter, while several regions exhibited increased AD. Furthermore, white matter regions with significant correlations between the diffusion metrics and the clinical variables (the EDSS scores, disease durations and white matter lesion loads) in MS patients were identified. Conclusion: Widespread white matter abnormalities were observed in MS patients revealed by multiple diffusion metrics. The diffusion changes and correlations with clinical variables were mainly attributed to increased RD, implying the predominant role of RD in reflecting the subtle pathological changes in MS.

  20. Neuroblast Distribution After Cortical Impact is Influenced by White Matter Injury in the Immature Gyrencephalic Brain.

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    Sabrina Taylor

    2016-08-01

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

  1. Segregation of the brain into gray and white matter: a design minimizing conduction delays.

    Directory of Open Access Journals (Sweden)

    2005-12-01

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

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

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

    2016-07-01

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

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

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

    2015-12-01

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

  4. Brain gray and white matter differences in healthy normal weight and obese children

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    To compare brain gray and white matter development in healthy normal weight and obese children. Twenty-four healthy 8- to 10-year-old children whose body mass index was either 95th percentile (obese) completed an MRI examination which included T1-weighted three-d...

  5. Serum L-arginine and dimethylarginine levels in migraine patients with brain white matter lesions

    DEFF Research Database (Denmark)

    Erdélyi-Bótor, Szilvia; Komáromy, Hedvig; Kamson, David Olayinka;

    2017-01-01

    BACKGROUND/AIM: Migraine is a risk factor for the formation of silent brain white matter lesions (WMLs) that are possibly ischemic in nature. Although dysfunction of the L-arginine/nitric oxide (NO) pathway has been associated with oxidative stress and endothelial dysfunction in migraine, its rol...

  6. Microstructure and Cerebral Blood Flow within White Matter of the Human Brain: A TBSS Analysis.

    Directory of Open Access Journals (Sweden)

    Stéphanie Giezendanner

    Full Text Available White matter (WM fibers connect different brain regions and are critical for proper brain function. However, little is known about the cerebral blood flow in WM and its relation to WM microstructure. Recent improvements in measuring cerebral blood flow (CBF by means of arterial spin labeling (ASL suggest that the signal in white matter may be detected. Its implications for physiology needs to be extensively explored. For this purpose, CBF and its relation to anisotropic diffusion was analyzed across subjects on a voxel-wise basis with tract-based spatial statistics (TBSS and also across white matter tracts within subjects.Diffusion tensor imaging and ASL were acquired in 43 healthy subjects (mean age = 26.3 years.CBF in WM was observed to correlate positively with fractional anisotropy across subjects in parts of the splenium of corpus callosum, the right posterior thalamic radiation (including the optic radiation, the forceps major, the right inferior fronto-occipital fasciculus, the right inferior longitudinal fasciculus and the right superior longitudinal fasciculus. Furthermore, radial diffusivity correlated negatively with CBF across subjects in similar regions. Moreover, CBF and FA correlated positively across white matter tracts within subjects.The currently observed findings on a macroscopic level might reflect the metabolic demand of white matter on a microscopic level involving myelination processes or axonal function. However, the exact underlying physiological mechanism of this relationship needs further evaluation.

  7. An Optimized Clustering Approach for Automated Detection of White Matter Lesions in MRI Brain Images

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    M. Anitha

    2012-04-01

    Full Text Available Settings White Matter lesions (WMLs are small areas of dead cells found in parts of the brain. In general, it is difficult for medical experts to accurately quantify the WMLs due to decreased contrast between White Matter (WM and Grey Matter (GM. The aim of this paper is to
    automatically detect the White Matter Lesions which is present in the brains of elderly people. WML detection process includes the following stages: 1. Image preprocessing, 2. Clustering (Fuzzy c-means clustering, Geostatistical Possibilistic clustering and Geostatistical Fuzzy clustering and 3.Optimization using Particle Swarm Optimization (PSO. The proposed system is tested on a database of 208 MRI images. GFCM yields high sensitivity of 89%, specificity of 94% and overall accuracy of 93% over FCM and GPC. The clustered brain images are then subjected to Particle Swarm Optimization (PSO. The optimized result obtained from GFCM-PSO provides sensitivity of 90%, specificity of 94% and accuracy of 95%. The detection results reveals that GFCM and GFCMPSO better localizes the large regions of lesions and gives less false positive rate when compared to GPC and GPC-PSO which captures the largest loads of WMLs only in the upper ventral horns of the brain.

  8. Coordinated brain development: exploring the synchrony between changes in grey and white matter during childhood maturation.

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    Moura, L M; Crossley, N A; Zugman, A; Pan, P M; Gadelha, A; Del Aquilla, M A G; Picon, F A; Anés, M; Amaro, E; de Jesus Mari, J; Miguel, E C; Rohde, L A; Bressan, R A; McGuire, P; Sato, J R; Jackowski, A P

    2016-05-12

    Brain development during childhood and early adolescence is characterized by global changes in brain architecture. Neuroimaging studies have revealed overall decreases in cortical thickness (CT) and increases in fractional anisotropy (FA). Furthermore, previous studies have shown that certain cortical regions display coordinated growth during development. However, there is significant heterogeneity in the timing and speed of these developmental transformations, and it is still unclear whether white and grey matter changes are co-localized. In this multimodal neuroimaging study, we investigated the relationship between grey and white matter developmental changes and asynchronous maturation within brain regions in 249 normally developing children between the ages 7-14. We used structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to analyze CT and FA, respectively, as well as their covariance across development. Consistent with previous studies, we observed overall cortical thinning with age, which was accompanied by increased FA. We then compared the coordinated development of grey and white matter as indexed by covariance measures. Covariance between grey matter regions and the microstructure of white matter tracts connecting those regions were highly similar, suggesting that coordinated changes in the cortex were mirrored by coordinated changes in their respective tracts. Examining within-brain divergent trajectories, we found significant structural decoupling (decreased covariance) between several brain regions and tracts in the 9- to 11-year-old group, particularly involving the forceps minor and the regions that it connects to. We argue that this decoupling could reflect a developmental pattern within the prefrontal region in 9- and 11-year-old children, possibly related to the significant changes in cognitive control observed at this age.

  9. White matter and behavioral neurology.

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    Filley, Christopher M

    2005-12-01

    Although the study of higher brain function has traditionally focused on the cortical gray matter, recent years have witnessed the recognition that white matter also makes an important contribution to cognition and emotion. White matter comprises nearly half the brain volume and plays a key role in development, aging, and many neurologic and psychiatric disorders across the life span. More than 100 disorders exist in which white matter neuropathology is the primary or a prominent feature. A variety of neurobehavioral syndromes may result from these disorders; the concept of white matter dementia has been introduced as characteristic of many patients with white matter involvement, and a wide range of focal neurobehavioral syndromes and psychiatric disorders can also be related to dysfunction of myelinated tracts. Understanding the neurobehavioral aspects of white matter disorders is important for clinical diagnosis, treatment, prognosis, and research on brain-behavior relationships. Central to these investigations is the use of modern neuroimaging techniques, which have already provided substantial information on the characterization of white matter and its disorders, and which promise to advance our knowledge further with continued innovation. Diffusion tensor imaging is an exciting method that will assist with the identification of critical white matter tracts in the brain, and the localization of specific lesions that can be correlated with neurobehavioral syndromes. A behavioral neurology of white matter is thus emerging in which clinical observation combined with sophisticated neuroimaging will enable elucidation of the role of white matter connectivity in the distributed neural networks subserving higher brain function.

  10. Cerebral white matter injury and damage to myelin sheath following whole-brain ischemia.

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    Chen, Yingzhu; Yi, Qiong; Liu, Gang; Shen, Xue; Xuan, Lihui; Tian, Ye

    2013-02-01

    Myelin sheath, either in white matter or in other regions of brain, is vulnerable to ischemia. The specific events involved in the progression of ischemia in white matter have not yet been elucidated. The aim of this study was to determine histopathological alterations in cerebral white matter and levels of myelin basic protein (MBP) in ischemia-injured brain tissue during the acute and subacute phases of central nervous injury following whole-brain ischemia. The whole cerebral ischemia model (four-vessel occlusion (4-VO)) was established in adult Sprague-Dawley rats and MBP gene expression and protein levels in the brain tissue were measured using reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) at 2 days, 4 days, 7 days, 14 days, and 28 days following ischemia. Demyelination was determined by Luxol fast blue myelin staining, routine histopathological staining, and electron microscopy in injured brain tissue. Results showed that edema, vascular dilation, focal necrosis, demyelination, adjacent reactive gliosis and inflammation occurred 7 days after ischemia in HE staining and recovered to control levels at 28 days. The absence of Luxol fast blue staining and vacuolation was clearly visible at 7 days, 14 days, and 28 days. Semiquantitative analysis showed that the transparency of myelin had decreased significantly by 7 days, 14 days, and 28 days. Demyelination and ultrastructual changes were detected 7 days after ischemia. The relative levels of MBP mRNA decreased 2 days after ischemia and this trend continued throughout the remaining four points in time. The MBP levels measured using ELISA also decreased significantly at 2 days and 4 days, but they recovered by 7 days and returned to control levels by 14 days. These results suggest that the impact of ischemia on cerebral white matter is time-sensitive and that different effects may follow different courses over time.

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

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    Jasmeet P. Hayes

    2015-01-01

    Full Text Available 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

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

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    Yi Shin Chang

    Full Text Available 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

  13. Genetic basis of neurocognitive decline and reduced white-matter integrity in normal human brain aging.

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    Glahn, David C; Kent, Jack W; Sprooten, Emma; Diego, Vincent P; Winkler, Anderson M; Curran, Joanne E; McKay, D Reese; Knowles, Emma E; Carless, Melanie A; Göring, Harald H H; Dyer, Thomas D; Olvera, Rene L; Fox, Peter T; Almasy, Laura; Charlesworth, Jac; Kochunov, Peter; Duggirala, Ravi; Blangero, John

    2013-11-19

    Identification of genes associated with brain aging should markedly improve our understanding of the biological processes that govern normal age-related decline. However, challenges to identifying genes that facilitate successful brain aging are considerable, including a lack of established phenotypes and difficulties in modeling the effects of aging per se, rather than genes that influence the underlying trait. In a large cohort of randomly selected pedigrees (n = 1,129 subjects), we documented profound aging effects from young adulthood to old age (18-83 y) on neurocognitive ability and diffusion-based white-matter measures. Despite significant phenotypic correlation between white-matter integrity and tests of processing speed, working memory, declarative memory, and intelligence, no evidence for pleiotropy between these classes of phenotypes was observed. Applying an advanced quantitative gene-by-environment interaction analysis where age is treated as an environmental factor, we demonstrate a heritable basis for neurocognitive deterioration as a function of age. Furthermore, by decomposing gene-by-aging (G × A) interactions, we infer that different genes influence some neurocognitive traits as a function of age, whereas other neurocognitive traits are influenced by the same genes, but to differential levels, from young adulthood to old age. In contrast, increasing white-matter incoherence with age appears to be nongenetic. These results clearly demonstrate that traits sensitive to the genetic influences on brain aging can be identified, a critical first step in delineating the biological mechanisms of successful aging.

  14. SOX2+ cell population from normal human brain white matter is able to generate mature oligodendrocytes.

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    Jorge Oliver-De La Cruz

    Full Text Available 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.

  15. 7.0 tesla MRI brain white matter atlas. 2. ed.

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    Cho, Zang-Hee (ed.) [Gachon Univ., Incheon (Korea, Republic of). Neuroscience Research Institute

    2015-04-01

    Depicts the visualization of brain white matter with the latest 7.0 T MRI and TDI techniques. Represents a useful addition to brain research and clinical settings, such as the Human Connectome Project. Contains a wealth of exquisitely detailed color images. The introduction of techniques that permit visualization of the human nervous system is one of the foremost advances in neuroscience and brain-related research. Among the most recent significant developments in this respect are ultra-high field MRI and the image post-processing technique known as track density imaging (TDI). It is these techniques (including super-resolution TDI) which represent the two major components of 7.0 Tesla MRI - Brain White Matter Atlas. This second edition of the atlas has been revised and updated to fully reflect current application of these technological advancements in order to visualize the nervous system and the brain with the finest resolution and sensitivity. Exquisitely detailed color images offer neuroscientists, neurologists, and neurosurgeons a superb resource that will be of value both for the purpose of research and for the treatment of common brain diseases such as Alzheimer's disease and multiple sclerosis.

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

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

    2011-02-01

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

  17. Brain white matter structure and COMT gene are linked to second-language learning in adults.

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    Mamiya, Ping C; Richards, Todd L; Coe, Bradley P; Eichler, Evan E; Kuhl, Patricia K

    2016-06-28

    Adult human brains retain the capacity to undergo tissue reorganization during second-language learning. Brain-imaging studies show a relationship between neuroanatomical properties and learning for adults exposed to a second language. However, the role of genetic factors in this relationship has not been investigated. The goal of the current study was twofold: (i) to characterize the relationship between brain white matter fiber-tract properties and second-language immersion using diffusion tensor imaging, and (ii) to determine whether polymorphisms in the catechol-O-methyltransferase (COMT) gene affect the relationship. We recruited incoming Chinese students enrolled in the University of Washington and scanned their brains one time. We measured the diffusion properties of the white matter fiber tracts and correlated them with the number of days each student had been in the immersion program at the time of the brain scan. We found that higher numbers of days in the English immersion program correlated with higher fractional anisotropy and lower radial diffusivity in the right superior longitudinal fasciculus. We show that fractional anisotropy declined once the subjects finished the immersion program. The relationship between brain white matter fiber-tract properties and immersion varied in subjects with different COMT genotypes. Subjects with the Methionine (Met)/Valine (Val) and Val/Val genotypes showed higher fractional anisotropy and lower radial diffusivity during immersion, which reversed immediately after immersion ended, whereas those with the Met/Met genotype did not show these relationships. Statistical modeling revealed that subjects' grades in the language immersion program were best predicted by fractional anisotropy and COMT genotype.

  18. Developmental Changes in Topological Asymmetry Between Hemispheric Brain White Matter Networks from Adolescence to Young Adulthood.

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    Zhong, Suyu; He, Yong; Shu, Hua; Gong, Gaolang

    2016-04-24

    Human brain asymmetries have been well described. Intriguingly, a number of asymmetries in brain phenotypes have been shown to change throughout the lifespan. Recent studies have revealed topological asymmetries between hemispheric white matter networks in the human brain. However, it remains unknown whether and how these topological asymmetries evolve from adolescence to young adulthood, a critical period that constitutes the second peak of human brain and cognitive development. To address this question, the present study included a large cohort of healthy adolescents and young adults. Diffusion and structural magnetic resonance imaging were acquired to construct hemispheric white matter networks, and graph-theory was applied to quantify topological parameters of the hemispheric networks. In both adolescents and young adults, rightward asymmetry in both global and local network efficiencies was consistently observed between the 2 hemispheres, but the degree of the asymmetry was significantly decreased in young adults. At the nodal level, the young adults exhibited less rightward asymmetry of nodal efficiency mainly around the parasylvian area, posterior tempo-parietal cortex, and fusiform gyrus. These developmental patterns of network asymmetry provide novel insight into the human brain structural development from adolescence to young adulthood and also likely relate to the maturation of language and social cognition that takes place during this period.

  19. Regional brain gray and white matter changes in perinatally HIV-infected adolescents

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    Manoj K. Sarma

    2014-01-01

    Full Text Available Despite the success of antiretroviral therapy (ART, perinatally infected HIV remains a major health problem worldwide. Although advance neuroimaging studies have investigated structural brain changes in HIV-infected adults, regional gray matter (GM and white matter (WM volume changes have not been reported in perinatally HIV-infected adolescents and young adults. In this cross-sectional study, we investigated regional GM and WM changes in 16 HIV-infected youths receiving ART (age 17.0 ± 2.9 years compared with age-matched 14 healthy controls (age 16.3 ± 2.3 years using magnetic resonance imaging (MRI-based high-resolution T1-weighted images with voxel based morphometry (VBM analyses. White matter atrophy appeared in perinatally HIV-infected youths in brain areas including the bilateral posterior corpus callosum (CC, bilateral external capsule, bilateral ventral temporal WM, mid cerebral peduncles, and basal pons over controls. Gray matter volume increase was observed in HIV-infected youths for several regions including the left superior frontal gyrus, inferior occipital gyrus, gyrus rectus, right mid cingulum, parahippocampal gyrus, bilateral inferior temporal gyrus, and middle temporal gyrus compared with controls. Global WM and GM volumes did not differ significantly between groups. These results indicate WM injury in perinatally HIV-infected youths, but the interpretation of the GM results, which appeared as increased regional volumes, is not clear. Further longitudinal studies are needed to clarify if our results represent active ongoing brain infection or toxicity from HIV treatment resulting in neuronal cell swelling and regional increased GM volume. Our findings suggest that assessment of regional GM and WM volume changes, based on VBM procedures, may be an additional measure to assess brain integrity in HIV-infected youths and to evaluate success of current ART therapy for efficacy in the brain.

  20. The impact of image dynamic range on texture classification of brain white matter

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    de Certaines Jacques D

    2008-12-01

    Full Text Available Abstract Background The Greylevel Cooccurrence Matrix method (COM is one of the most promising methods used in Texture Analysis of Magnetic Resonance Images. This method provides statistical information about the spatial distribution of greylevels in the image which can be used for classification of different tissue regions. Optimizing the size and complexity of the COM has the potential to enhance the reliability of Texture Analysis results. In this paper we investigate the effect of matrix size and calculation approach on the ability of COM to discriminate between peritumoral white matter and other white matter regions. Method MR images were obtained from patients with histologically confirmed brain glioblastoma using MRI at 3-T giving isotropic resolution of 1 mm3. Three Regions of Interest (ROI were outlined in visually normal white matter on three image slices based on relative distance from the tumor: one peritumoral white matter region and two distant white matter regions on both hemispheres. Volumes of Interest (VOI were composed from the three slices. Two different calculation approaches for COM were used: i Classical approach (CCOM on each individual ROI, and ii Three Dimensional approach (3DCOM calculated on VOIs. For, each calculation approach five dynamic ranges (number of greylevels N were investigated (N = 16, 32, 64, 128, and 256. Results Classification showed that peritumoral white matter always represents a homogenous class, separate from other white matter, regardless of the value of N or the calculation approach used. The best test measures (sensitivity and specificity for average CCOM were obtained for N = 128. These measures were also optimal for 3DCOM with N = 128, which additionally showed a balanced tradeoff between the measures. Conclusion We conclude that the dynamic range used for COM calculation significantly influences the classification results for identical samples. In order to obtain more reliable classification

  1. Impact of breast milk on intelligence quotient, brain size, and white matter development.

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    Isaacs, Elizabeth B; Fischl, Bruce R; Quinn, Brian T; Chong, Wui K; Gadian, David G; Lucas, Alan

    2010-04-01

    Although observational findings linking breast milk to higher scores on cognitive tests may be confounded by factors associated with mothers' choice to breastfeed, it has been suggested that one or more constituents of breast milk facilitate cognitive development, particularly in preterms. Because cognitive scores are related to head size, we hypothesized that breast milk mediates cognitive effects by affecting brain growth. We used detailed data from a randomized feeding trial to calculate percentage of expressed maternal breast milk (%EBM) in the infant diet of 50 adolescents. MRI scans were obtained (mean age=15 y 9 mo), allowing volumes of total brain (TBV) and white and gray matter (WMV, GMV) to be calculated. In the total group, %EBM correlated significantly with verbal intelligence quotient (VIQ); in boys, with all IQ scores, TBV and WMV. VIQ was, in turn, correlated with WMV and, in boys only, additionally with TBV. No significant relationships were seen in girls or with gray matter. These data support the hypothesis that breast milk promotes brain development, particularly white matter growth. The selective effect in males accords with animal and human evidence regarding gender effects of early diet. Our data have important neurobiological and public health implications and identify areas for future mechanistic study.

  2. Tissue tears in the white matter after lateral fluid percussion brain injury in the rat: relevance to human brain injury.

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    Graham, D I; Raghupathi, R; Saatman, K E; Meaney, D; McIntosh, T K

    2000-02-01

    A characteristic feature of severe diffuse axonal injury in man is radiological evidence of the "shearing injury triad" represented by lesions, sometimes haemorrhagic, in the corpus callosum, deep white matter and the rostral brain stem. With the exception of studies carried out on the non-human primate, such lesions have not been replicated to date in the multiple and diverse rodent laboratory models of traumatic brain injury. The present report describes tissue tears in the white matter, particularly in the fimbria of Sprague-Dawley rats killed 12, 24, and 48 h and 7 days after lateral fluid percussion brain injury of moderate severity (2.1-2.4 atm). The lesions were most easily seen at 24 h when they appeared as foci of tissue rarefaction in which there were a few polymorphonuclear leucocytes. At the margins of these lesions, large amounts of accumulated amyloid precursor protein (APP) were found in axonal swellings and bulbs. By 1 week post-injury, there was macrophage infiltration with marked astrocytosis and early scar formation. This lesion is considered to be due to severe deformation of white matter and this is the first time that it has been identified reproducibly in a rodent model of head injury under controlled conditions.

  3. Elevated levels of a glycoprotein antigen (P-80) in gray and white matter of brain from victims of multiple sclerosis.

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    Cruz, T F; Quackenbush, E J; Letarte, M; Moscarello, M A

    1986-06-01

    The levels of a glycoprotein reactive with monoclonal antibody (MAb) 44D10 in white and gray matter from brains of victims of several neurological diseases, including Multiple Sclerosis, Alzheimer's, Parkinson's and Huntington's diseases, were compared to that of normal individuals. The concentration of antigen reactive with MAb 44D10 was elevated in both gray and white matter of all MS brains examined, but not in brains with other neurological diseases. The increase in the concentration of antigen varied amongst the MS brains, such that the levels of antigen were only slightly increased in 2 of the 6 MS brains whereas 2 to 4 fold higher levels were found in the other 4 brains. Increased levels of antigen were detected in gray matter of MS brains, whereas this antigen was either not detected or present in very low levels in gray matter homogenates prepared from age-matched normal brains. MAb Leu 1, which reacts with T lymphocytes, was not absorbed by normal and MS brain tissue suggesting the increase in antigen reactive with MAb 44D10 in MS brain homogenates was not associated with non-specific infiltration by T lymphocytes. Comparison of the purified antigen from MS gray matter and normal white matter by gel electrophoresis demonstrated that MAb 44D10 was reacting with a similar protein in both tissues with an apparent molecular weight of 80K. We have named this molecule P-80 glycoprotein.

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

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

    2013-01-01

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

  5. Astrocyte Sodium Signalling and Panglial Spread of Sodium Signals in Brain White Matter.

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    Moshrefi-Ravasdjani, Behrouz; Hammel, Evelyn L; Kafitz, Karl W; Rose, Christine R

    2017-02-18

    In brain grey matter, excitatory synaptic transmission activates glutamate uptake into astrocytes, inducing sodium signals which propagate into neighboring astrocytes through gap junctions. These sodium signals have been suggested to serve an important role in neuro-metabolic coupling. So far, it is unknown if astrocytes in white matter-that is in brain regions devoid of synapses-are also able to undergo such intra- and intercellular sodium signalling. In the present study, we have addressed this question by performing quantitative sodium imaging in acute tissue slices of mouse corpus callosum. Focal application of glutamate induced sodium transients in SR101-positive astrocytes. These were largely unaltered in the presence of ionotropic glutamate receptors blockers, but strongly dampened upon pharmacological inhibition of glutamate uptake. Sodium signals induced in individual astrocytes readily spread into neighboring SR101-positive cells with peak amplitudes decaying monoexponentially with distance from the stimulated cell. In addition, spread of sodium was largely unaltered during pharmacological inhibition of purinergic and glutamate receptors, indicating gap junction-mediated, passive diffusion of sodium between astrocytes. Using cell-type-specific, transgenic reporter mice, we found that sodium signals also propagated, albeit less effectively, from astrocytes to neighboring oligodendrocytes and NG2 cells. Again, panglial spread was unaltered with purinergic and glutamate receptors blocked. Taken together, our results demonstrate that activation of sodium-dependent glutamate transporters induces sodium signals in white matter astrocytes, which spread within the astrocyte syncytium. In addition, we found a panglial passage of sodium signals from astrocytes to NG2 cells and oligodendrocytes, indicating functional coupling between these macroglial cells in white matter.

  6. The subventricular zone in the immature piglet brain: anatomy and exodus of neuroblasts into white matter after traumatic brain injury.

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    Costine, Beth A; Missios, Symeon; Taylor, Sabrina R; McGuone, Declan; Smith, Colin M; Dodge, Carter P; Harris, Brent T; Duhaime, Ann-Christine

    2015-01-01

    Stimulation of postnatal neurogenesis in the subventricular zone (SVZ) and robust migration of neuroblasts to the lesion site in response to traumatic brain injury (TBI) is well established in rodent species; however, it is not yet known whether postnatal neurogenesis plays a role in repair after TBI in gyrencephalic species. Here we describe the anatomy of the SVZ in the piglet for the first time and initiate an investigation into the effect of TBI on the SVZ architecture and the number of neuroblasts in the white matter. Among all ages of immaturity examined the SVZ contained a dense mesh network of neurogenic precursor cells (doublecortin+) positioned directly adjacent to the ependymal cells (ventricular SVZ, Vsvz) and neuroblasts organized into chains that were distinct from the Vsvz (abventricular SVZ, Asvz). Though the architecture of the SVZ was similar among ages, the areas of Vsvz and Asvz neuroblast chains declined with age. At postnatal day (PND) 14 the white matter tracts have a tremendous number of individual neuroblasts. In our scaled cortical impact model, lesion size increased with age. Similarly, the response of the SVZ to injury was also age dependent. The younger age groups that sustained the proportionately smallest lesions had the largest SVZ areas, which further increased in response to injury. In piglets that were injured at 4 months of age and had the largest lesions, the SVZ did not increase in response to injury. Similar to humans, swine have abundant gyri and gyral white matter, providing a unique platform to study neuroblasts potentially migrating from the SVZ to the lesioned cortex along these white matter tracts. In piglets injured at PND 7, TBI did not increase the total number of neuroblasts in the white matter compared to uninjured piglets, but redistribution occurred with a greater number of neuroblasts in the white matter of the hemisphere ipsilateral to the injury compared to the contralateral hemisphere. At 7 days after injury

  7. Brain size and white matter content of cerebrospinal tracts determine the upper cervical cord area: evidence from structural brain MRI

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    Engl, Christina; Arsic, Milan; Boucard, Christine C.; Biberacher, Viola; Nunnemann, Sabine; Muehlau, Mark [Technische Universitaet Muenchen, Department of Neurology, Klinikum rechts der Isar, Munich (Germany); Technische Universitaet Muenchen, TUM-Neuroimaging Center, Klinikum rechts der Isar, Munich (Germany); Schmidt, Paul [Technische Universitaet Muenchen, Department of Neurology, Klinikum rechts der Isar, Munich (Germany); Ludwig-Maximilians-University Muenchen, Department of Statistics, Munich (Germany); Roettinger, Michael [Technische Universitaet Muenchen, Department of Radiology, Klinikum rechts der Isar, Munich (Germany); Muenchner Institut fuer Neuroradiologie, Munich (Germany); Etgen, Thorleif [Technische Universitaet Muenchen, Department of Neurology, Klinikum rechts der Isar, Munich (Germany); Klinikum Traunstein, Department of Neurology, Traunstein (Germany); Koutsouleris, Nikolaos; Meisenzahl, Eva M. [Ludwig-Maximilians-Universitaet Muenchen, Department of Psychiatry and Psychotherapy, Munich (Germany); Reiser, Maximilian [Ludwig-Maximilians-Universitaet, Department of Radiology, Munich (Germany)

    2013-08-15

    Measurement of the upper cervical cord area (UCCA) from brain MRI may be an effective way to quantify spinal cord involvement in neurological disorders such as multiple sclerosis. However, knowledge on the determinants of UCCA in healthy controls (HCs) is limited. In two cohorts of 133 and 285 HCs, we studied the influence of different demographic, body-related, and brain-related parameters on UCCA by simple and partial correlation analyses as well as by voxel-based morphometry (VBM) across both cerebral gray matter (GM) and white matter (WM). First, we confirmed the known but moderate effect of age on UCCA in the older cohort. Second, we studied the correlation of UCCA with sex, body height, and total intracranial volume (TIV). TIV was the only variable that correlated significantly with UCCA after correction for the other variables. Third, we studied the correlation of UCCA with brain-related parameters. Brain volume correlated stronger with UCCA than TIV. Both volumes of the brain tissue compartments GM and WM correlated with UCCA significantly. WM volume explained variance of UCCA after correction for GM volume, whilst the opposite was not observed. Correspondingly, VBM did not yield any brain region, whose GM content correlated significantly with UCCA, whilst cerebral WM content of cerebrospinal tracts strongly correlated with UCCA. This latter effect increased along a craniocaudal gradient. UCCA is mainly determined by brain volume as well as by WM content of cerebrospinal tracts. (orig.)

  8. A neural network that links brain function, white-matter structure and risky behavior.

    Science.gov (United States)

    Kohno, Milky; Morales, Angelica M; Guttman, Zoe; London, Edythe D

    2017-04-01

    The ability to evaluate the balance between risk and reward and to adjust behavior accordingly is fundamental to adaptive decision-making. Although brain-imaging studies consistently have shown involvement of the dorsolateral prefrontal cortex, anterior insula and striatum during risky decision-making, activation in a neural network formed by these regions has not been linked to structural connectivity. Therefore, in this study, white-matter connectivity was measured with diffusion-weighted imaging in 40 healthy research participants who performed the Balloon Analogue Risk Task, a test of risky decision-making, during fMRI. Fractional anisotropy within a network that includes white-matter pathways connecting four regions (the prefrontal cortex, insula and midbrain to the striatum) was positively correlated with the number of risky choices and total amount earned on the task, and with the parametric modulation of activation in regions within the network to the level of risk during choice selection. Furthermore, analysis using a mixed model demonstrated how relationships of the parametric modulation of activation in each of the four aforementioned regions are related to risk probabilities, and how previous trial outcomes and task progression influence the choice to take risk. The present findings provide the first direct evidence that white-matter integrity is linked to function within previously identified components of a network that is activated during risky decision-making, and demonstrate that the integrity of white-matter tracts is critical in consolidating and processing signals between cortical and striatal circuits during the decision-making process.

  9. White Matter Brain Lesions in Midlife Familial Hypercholesterolemic Patients at 3-Tesla Magnetic Resonance Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, S.A.; O' Regan, D.P.; Fitzpatrick, J.; Neuwirth, C.; Potter, E.; Tosi, I.; Hajnal, J.V.; Naoumova, R.P. (Imaging Sciences Dept. and Clinical Research Facility, MRC Clinical Sciences Centre, London (GB))

    2008-03-15

    Background: Patients with hypercholesterolemia of 60 years and older have an increased risk for white matter brain lesions and dementia. Purpose: To investigate whether patients with familial hypercholesterolemia (FH) develop white matter lesions at 3-Tesla (T) MRI as early as in midlife. Material and Methods: Non-diabetic, non-smoking, and non-hypertensive heterozygous FH patients on treatment with maximally tolerated dose of a statin for more than 5 years (n = 14) and matched controls (n = 22) aged 25 to 60 years of age were studied. Imaging was performed at 3T with a fluid-attenuated T2-weighted MR pulse sequence and a T1-weighted spin-echo pulse sequence following 10 ml of i.v. gadopentetate dimeglumine. Images were evaluated by two independent readers. Fasting blood samples were taken. Student's t test was employed at P<0.05. Results: Three volunteers and one FH patient had white matter lesions (P<0.53). No other evidence of past ischemic stroke was observed. Mean total serum cholesterol and low-density lipoprotein (LDL) cholesterol were significantly higher in the FH group (6.0+-1.1 vs. 5.1+-0.9 mmol/l, P<0.02 and 4.1+-0.9 vs. 3.1+-0.8 mmol/l, P<0.004, respectively). Conclusion: Heterozygous FH patients on statin treatment in the age range of 25 to 60 years are not at increased risk of white matter lesions at 3T MRI

  10. Smoking and the Developing Brain : Altered White Matter Microstructure in Attention-Deficit/Hyperactivity Disorder and Healthy Controls

    NARCIS (Netherlands)

    van Ewijk, Hanneke; Groenman, Annabeth P.; Zwiers, Marcel P.; Heslenfeld, Dirk J.; Faraone, Stephen V.; Hartman, Catharina A.; Luman, Marjolein; Greven, Corina U.; Hoekstra, Pieter J.; Franke, Barbara; Buitelaar, Jan; Oosterlaan, Jaap

    2015-01-01

    Brain white matter (WM) tracts, playing a vital role in the communication between brain regions, undergo important maturational changes during adolescence and young adulthood, a critical period for the development of nicotine dependence. Attention-deficit/hyperactivity disorder (ADHD) is associated

  11. Smoking and the developing brain: Altered white matter microstructure in attention-deficit/hyperactivity disorder and healthy controls

    NARCIS (Netherlands)

    Ewijk, H. van; Groenman, A.P.; Zwiers, M.P.; Heslenfeld, D.J.; Faraone, S.V; Hartman, C.A.; Luman, M.; Greven, C.U.; Hoekstra, P.J.; Franke, B.; Buitelaar, J.; Oosterlaan, J.

    2015-01-01

    Brain white matter (WM) tracts, playing a vital role in the communication between brain regions, undergo important maturational changes during adolescence and young adulthood, a critical period for the development of nicotine dependence. Attention-deficit/hyperactivity disorder (ADHD) is associated

  12. Individual differences in true and false memory retrieval are related to white matter brain microstructure.

    Science.gov (United States)

    Fuentemilla, Lluís; Càmara, Estela; Münte, Thomas F; Krämer, Ulrike M; Cunillera, Toni; Marco-Pallarés, Josep; Tempelmann, Claus; Rodriguez-Fornells, Antoni

    2009-07-08

    We sometimes vividly remember things that did not happen, a phenomenon with general relevance, not only in the courtroom. It is unclear to what extent individual differences in false memories are driven by anatomical differences in memory-relevant brain regions. Here we show in humans that microstructural properties of different white matter tracts as quantified using diffusion tensor imaging are strongly correlated with true and false memory retrieval. To investigate these hypotheses, we tested a large group of participants in a version of the Deese-Roediger-McDermott paradigm (recall and recognition) and subsequently obtained diffusion tensor images. A voxel-based whole-brain level linear regression analysis was performed to relate fractional anisotropy to indices of true and false memory recall and recognition. True memory was correlated to diffusion anisotropy in the inferior longitudinal fascicle, the major connective pathway of the medial temporal lobe, whereas a greater proneness to retrieve false items was related to the superior longitudinal fascicle connecting frontoparietal structures. Our results show that individual differences in white matter microstructure underlie true and false memory performance.

  13. A prospective pilot investigation of brain volume, white matter hyperintensities and haemorrhagic lesions after mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Michael eJarrett

    2016-02-01

    Full Text Available Traumatic brain injury (TBI is among the most common neurological disorders. Haemorrhagic lesions and white matter hyperintensities (WMH are radiological features associated with moderate and severe traumatic brain injury TBI. Brain volume reductions have also been observed during the months following injury. In concussion, no signs of injury are observed on conventional MRI, which may be a true feature of concussion or merely due to the limited sensitivity of imaging techniques used so far. Moreover, it is not known whether volume reductions are due to the resolution of trauma related edema or a true volume loss. Forty five collegiate level ice hockey players (20 female and 15 controls (9 female 40 players underwent 3T MRI for haemorrhages (multi echo susceptibility weighted imaging (SWI, WMH (three dimensional FLAIR and brain volume at the beginning and the end of the hockey season. Concussed athletes underwent additional imaging and neuropsychological testing atthree days, two weeks, and two months after injury. At the end of the hockey season, brain volume was reduced compared to controls by 0.32% (p<0.034 in the whole cohort and by 0.26% (p<0.09 in the concussed athletes. Two weeks and two months after concussion, brain volume was reduced by -0.08% (p=0.027 and -0.23% (p=0.035, respectively. In athletes, the WMH were significantly closer to the interface between grey matter and white matter compared to controls. No significant changes in thenumber of WMH over the duration of the study were found in athletes. No microhaemorrhages were detected as a result of concussion or playing a season of ice hockey. We conclude that mild TBI does not lead to transient increases in brain volume and no new microbleeds or WMH are detectable after concussion. Brain volume reductions appear by two weeks after concussion and persist until at least two months after concussion. Brain volume is reduced between the beginning and the end of the icehockey season.

  14. The Plasticity of Brain Gray Matter and White Matter following Lower Limb Amputation

    Directory of Open Access Journals (Sweden)

    Guangyao Jiang

    2015-01-01

    Full Text Available Accumulating evidence has indicated that amputation induces functional reorganization in the sensory and motor cortices. However, the extent of structural changes after lower limb amputation in patients without phantom pain remains uncertain. We studied 17 adult patients with right lower limb amputation and 18 healthy control subjects using T1-weighted magnetic resonance imaging and diffusion tensor imaging. Cortical thickness and fractional anisotropy (FA of white matter (WM were investigated. In amputees, a thinning trend was seen in the left premotor cortex (PMC. Smaller clusters were also noted in the visual-to-motor regions. In addition, the amputees also exhibited a decreased FA in the right superior corona radiata and WM regions underlying the right temporal lobe and left PMC. Fiber tractography from these WM regions showed microstructural changes in the commissural fibers connecting the bilateral premotor cortices, compatible with the hypothesis that amputation can lead to a change in interhemispheric interactions. Finally, the lower limb amputees also displayed significant FA reduction in the right inferior frontooccipital fasciculus, which is negatively correlated with the time since amputation. In conclusion, our findings indicate that the amputation of lower limb could induce changes in the cortical representation of the missing limb and the underlying WM connections.

  15. HTLV-I associated myelopathy with multiple spotty areas in cerebral white matter and brain stem by MRI

    Energy Technology Data Exchange (ETDEWEB)

    Hara, Yasuo; Takahashi, Mitsuo; Yoshikawa, Hiroo; Yorifuji, Shirou; Tarui, Seiichiro

    1988-01-01

    A 48-year-old woman was admitted with complaints of urinary incontinence and gait disturbance, both of which had progressed slowly without any sign of remission. Family history was not contributory. Neurologically, extreme spasticity was recoginized in the lower limbs. Babinski sign was positive bilaterally. Flower-like atypical lymphocytes were seen in blood. Positive anti-HTLV-I antibody was confirmed in serum and spinal fluid by western blot. She was diagnosed as having HTLV-I associated myelopathy (HAM). CT reveald calcification in bilateral globus pallidus, and MRI revealed multiple spotty areas in cerebral white matter and brain stem, but no spinal cord lesion was detectable. Electrophysiologically, brain stem auditory evoked potential (BAEP) suggested the presence of bilateral brain stem lesions. Neither median nor posterior tibial nerve somatosensory evoked potentials were evoked, a finding suggesting the existence of spinal cord lesion. In this case, the lesion was not confined to spinal cord, it was also observed in brain stem and cerebral white matter. Such distinct lesions in cerebral white matter and brain stem have not been reported in patients with HAM. It is suggested that HTLV-I is probably associated with cerebral white matter and brain stem.

  16. Decoupling of structural and functional brain connectivity in older adults with white matter hyperintensities

    NARCIS (Netherlands)

    Reijmer, Y. D.; Schultz, A. P.; Leemans, A.; O'Sullivan, M. J.; Gurol, M. E.; Sperling, R.; Greenberg, S. M.; Viswanathan, A.; Hedden, T.

    2015-01-01

    Age-related impairments in the default network (DN) have been related to disruptions in connecting white matter tracts. We hypothesized that the local correlation between DN structural and functional connectivity is negatively affected in the presence of global white matter injury. In 125 clinically

  17. Association between Peripheral Oxidative Stress and White Matter Damage in Acute Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Wei-Ming Lin

    2014-01-01

    Full Text Available The oxidative stress is believed to be one of the mechanisms involved in the neuronal damage after acute traumatic brain injury (TBI. However, the disease severity correlation between oxidative stress biomarker level and deep brain microstructural changes in acute TBI remains unknown. In present study, twenty-four patients with acute TBI and 24 healthy volunteers underwent DTI. The peripheral blood oxidative biomarkers, like serum thiol and thiobarbituric acid-reactive substances (TBARS concentrations, were also obtained. The DTI metrics of the deep brain regions, as well as the fractional anisotropy (FA and apparent diffusion coefficient, were measured and correlated with disease severity, serum thiol, and TBARS levels. We found that patients with TBI displayed lower FAs in deep brain regions with abundant WMs and further correlated with increased serum TBARS level. Our study has shown a level of anatomic detail to the relationship between white matter (WM damage and increased systemic oxidative stress in TBI which suggests common inflammatory processes that covary in both the peripheral and central reactions after TBI.

  18. Chronic cocaine administration causes extensive white matter damage in brain: diffusion tensor imaging and immunohistochemistry studies.

    Science.gov (United States)

    Narayana, Ponnada A; Herrera, Juan J; Bockhorst, Kurt H; Esparza-Coss, Emilio; Xia, Ying; Steinberg, Joel L; Moeller, F Gerard

    2014-03-30

    The effect of chronic cocaine exposure on multiple white matter structures in rodent brain was examined using diffusion tensor imaging (DTI), locomotor behavior, and end point histology. The animals received either cocaine at a dose of 100mg/kg (N=19), or saline (N=17) for 28 days through an implanted osmotic minipump. The animals underwent serial DTI scans, locomotor assessment, and end point histology for determining the expressions of myelin basic protein (MBP), neurofilament-heavy protein (NF-H), proteolipid protein (PLP), Nogo-A, aquaporin-4 (AQP-4), and growth associated protein-43 (GAP-43). Differences in the DTI measures were observed in the splenium (scc) and genu (gcc) of the corpus callosum (cc), fimbria (fi), and the internal capsule (ic). A significant increase in the activity in the fine motor movements and a significant decrease in the number of rearing events were observed in the cocaine-treated animals. Reduced MBP and Nogo-A and increased GAP-43 expressions were most consistently observed in these structures. A decrease in the NF-H expression was observed in fi and ic. The reduced expression of Nogo-A and the increased expression of GAP-43 may suggest destabilization of axonal connectivity and increased neurite growth with aberrant connections. Increased GAP-43 suggests drug-induced plasticity or a possible repair mechanism response. The findings indicated that multiple white matter tracts are affected following chronic cocaine exposure.

  19. Enhanced brain-derived neurotrophic factor delivery by ultrasound and microbubbles promotes white matter repair after stroke.

    Science.gov (United States)

    Rodríguez-Frutos, Berta; Otero-Ortega, Laura; Ramos-Cejudo, Jaime; Martínez-Sánchez, Patricia; Barahona-Sanz, Inés; Navarro-Hernanz, Teresa; Gómez-de Frutos, María Del Carmen; Díez-Tejedor, Exuperio; Gutiérrez-Fernández, María

    2016-09-01

    Ultrasound-targeted microbubble destruction (UTMD) has been shown to be a promising tool to deliver proteins to select body areas. This study aimed to analyze whether UTMD was able to deliver brain-derived neurotrophic factor (BDNF) to the brain, enhancing functional recovery and white matter repair, in an animal model of subcortical stroke induced by endothelin (ET)-1. UTMD was used to deliver BDNF to the brain 24 h after stroke. This technique was shown to be safe, given there were no cases of hemorrhagic transformation or blood brain barrier (BBB) leakage. UTMD treatment was associated with increased brain BDNF levels at 4 h after administration. Targeted ultrasound delivery of BDNF improved functional recovery associated with fiber tract connectivity restoration, increasing oligodendrocyte markers and remyelination compared to BDNF alone administration in an experimental animal model of white matter injury.

  20. Effects of long-term mindfulness meditation on brain's white matter microstructure and its aging.

    Directory of Open Access Journals (Sweden)

    Davide eLaneri

    2016-01-01

    Full Text Available Although research on the effects of mindfulness meditation (MM is increasing, still very little has been done to address its influence on the white matter (WM of the brain. We hypothesized that the practice of MM might affect the WM microstructure adjacent to five brain regions of interest associated with mindfulness. Diffusion tensor imaging was employed on samples of meditators and non-meditators (n=64 in order to investigate the effects of MM on group difference and aging. Tract-Based Spatial Statistics was used to estimate the fractional anisotrophy of the WM connected to the thalamus, insula, amygdala, hippocampus and anterior cingulate cortex. The subsequent generalized linear model analysis revealed group differences and a group-by-age interaction in all five selected regions. These data provide preliminary indications that the practice of MM might result in WM matter connectivity change and might provide evidence on its ability to help diminish age-related WM degeneration in key regions which participate in processes of mindfulness.

  1. Frontal White Matter Damage Impairs Response Inhibition in Children Following Traumatic Brain Injury

    Science.gov (United States)

    Lipszyc, Jonathan; Levin, Harvey; Hanten, Gerri; Hunter, Jill; Dennis, Maureen; Schachar, Russell

    2014-01-01

    Inhibition, the ability to suppress inappropriate cognitions or behaviors, can be measured using computer tasks and questionnaires. Inhibition depends on the frontal cortex, but the role of the underlying white matter (WM) is unclear. We assessed the specific impact of frontal WM damage on inhibition in 29 children with moderate-to-severe traumatic brain injury (15 with and 14 without frontal WM damage), 21 children with orthopedic injury, and 29 population controls. We used the Stop Signal Task to measure response inhibition, the Behavior Rating Inventory of Executive Function to assess everyday inhibition, and T2 fluid-attenuated inversion recovery magnetic resonance imaging to identify lesions. Children with frontal WM damage had impaired response inhibition compared with all other groups and poorer everyday inhibition than the orthopedic injury group. Frontal WM lesions most often affected the superior frontal gyrus. These results provide evidence for the critical role of frontal WM in inhibition. PMID:24618405

  2. Age dependent white matter lesions and brain volume changes in healthy volunteers

    DEFF Research Database (Denmark)

    Christiansen, P; Larsson, H B; Thomsen, C

    1994-01-01

    The brain of 142 healthy volunteers aged 21 to 80 years were investigated using MR imaging. The number and size of the white matter hyperintensity lesions (WMHL) in the cerebral hemispheres were determined. Furthermore, the volume of the cerebral hemispheres and of the lateral ventricles...... was measured. An almost linear increase in the number of volunteers with WMHL was seen with aging for males and females. With aging a significant decrease in the volume of the cerebral hemispheres was found for males, and a significant increase in the volume of the lateral ventricles was seen for both males...... and females. Our results suggest that with aging central atrophy increases more (relatively) than cortical atrophy. No correlation was found between the decreasing volume of the cerebral hemispheres and the increasing number and size of WMHL, nor between the increasing volume of the lateral ventricles...

  3. Migraine with aura and risk of silent brain infarcts and white matter hyperintensities

    DEFF Research Database (Denmark)

    Gaist, David; Garde, Ellen; Blaabjerg, Morten

    2016-01-01

    A small number of population-based studies reported an association between migraine with aura and risk of silent brain infarcts and white matter hyperintensities in females. We investigated these relations in a population-based sample of female twins. We contacted female twins ages 30-60 years...... identified through the population-based Danish Twin Registry. Based on questionnaire responses, twins were invited to participate in a telephone-based interview conducted by physicians. Headache diagnoses were established according to the International Headache Society criteria. Cases with migraine with aura......% confidence interval): 0.17 (-0.08 to 0.41) cm(3)] and a similar difference was present in analyses restricted to twin pairs discordant for migraine with aura [adjusted mean difference 0.21 (-0.20 to 0.63)], but these differences did not reach statistical significance. We found no evidence of an association...

  4. The effects of bilingualism on the white matter structure of the brain.

    Science.gov (United States)

    Pliatsikas, Christos; Moschopoulou, Elisavet; Saddy, James Douglas

    2015-02-03

    Recent studies suggest that learning and using a second language (L2) can affect brain structure, including the structure of white matter (WM) tracts. This observation comes from research looking at early and older bilingual individuals who have been using both their first and second languages on an everyday basis for many years. This study investigated whether young, highly immersed late bilinguals would also show structural effects in the WM that can be attributed to everyday L2 use, irrespective of critical periods or the length of L2 learning. Our Tract-Based Spatial Statistics analysis revealed higher fractional anisotropy values for bilinguals vs. monolinguals in several WM tracts that have been linked to language processing and in a pattern closely resembling the results reported for older and early bilinguals. We propose that learning and actively using an L2 after childhood can have rapid dynamic effects on WM structure, which in turn may assist in preserving WM integrity in older age.

  5. Statistical machine learning to identify traumatic brain injury (TBI) from structural disconnections of white matter networks.

    Science.gov (United States)

    Mitra, Jhimli; Shen, Kai-kai; Ghose, Soumya; Bourgeat, Pierrick; Fripp, Jurgen; Salvado, Olivier; Pannek, Kerstin; Taylor, D Jamie; Mathias, Jane L; Rose, Stephen

    2016-04-01

    Identifying diffuse axonal injury (DAI) in patients with traumatic brain injury (TBI) presenting with normal appearing radiological MRI presents a significant challenge. Neuroimaging methods such as diffusion MRI and probabilistic tractography, which probe the connectivity of neural networks, show significant promise. We present a machine learning approach to classify TBI participants primarily with mild traumatic brain injury (mTBI) based on altered structural connectivity patterns derived through the network based statistical analysis of structural connectomes generated from TBI and age-matched control groups. In this approach, higher order diffusion models were used to map white matter connections between 116 cortical and subcortical regions. Tracts between these regions were generated using probabilistic tracking and mean fractional anisotropy (FA) measures along these connections were encoded in the connectivity matrices. Network-based statistical analysis of the connectivity matrices was performed to identify the network differences between a representative subset of the two groups. The affected network connections provided the feature vectors for principal component analysis and subsequent classification by random forest. The validity of the approach was tested using data acquired from a total of 179 TBI patients and 146 controls participants. The analysis revealed altered connectivity within a number of intra- and inter-hemispheric white matter pathways associated with DAI, in consensus with existing literature. A mean classification accuracy of 68.16%±1.81% and mean sensitivity of 80.0%±2.36% were achieved in correctly classifying the TBI patients evaluated on the subset of the participants that was not used for the statistical analysis, in a 10-fold cross-validation framework. These results highlight the potential for statistical machine learning approaches applied to structural connectomes to identify patients with diffusive axonal injury.

  6. A Whole-Brain Investigation of White Matter Microstructure in Adolescents with Conduct Disorder

    Science.gov (United States)

    Sarkar, Sagari; Dell’Acqua, Flavio; Froudist Walsh, Seán; Blackwood, Nigel; Scott, Stephen; Craig, Michael C.

    2016-01-01

    Background The biological basis of severe antisocial behaviour in adolescents is poorly understood. We recently reported that adolescents with conduct disorder (CD) have significantly increased fractional anisotropy (FA) of the uncinate fasciculus (a white matter (WM) tract that connects the amygdala to the frontal lobe) compared to their non-CD peers. However, the extent of WM abnormality in other brain regions is currently unclear. Methods We used tract-based spatial statistics to investigate whole brain WM microstructural organisation in 27 adolescent males with CD, and 21 non-CD controls. We also examined relationships between FA and behavioural measures. Groups did not differ significantly in age, ethnicity, or substance use history. Results The CD group, compared to controls, had clusters of significantly greater FA in 7 brain regions corresponding to: 1) the bilateral inferior and superior cerebellar peduncles, corticopontocerebellar tract, posterior limb of internal capsule, and corticospinal tract; 2) right superior longitudinal fasciculus; and 3) left cerebellar WM. Severity of antisocial behavior and callous-unemotional symptoms were significantly correlated with FA in several of these regions across the total sample, but not in the CD or control groups alone. Conclusions Adolescents with CD have significantly greater FA than controls in WM regions corresponding predominantly to the fronto-cerebellar circuit. There is preliminary evidence that variation in WM microstructure may be dimensionally related to behaviour problems in youngsters. These findings are consistent with the hypothesis that antisocial behaviour in some young people is associated with abnormalities in WM ‘connectivity’. PMID:27271503

  7. White matter changes in comatose survivors of anoxic ischemic encephalopathy and traumatic brain injury: comparative diffusion-tensor imaging study.

    NARCIS (Netherlands)

    Eerden, A.W.A.; Khalilzadeh, O.; Perlbarg, V.; Dinkel, J.; Sanchez, P.; Vos, P.E.; Luyt, C.E.; Stevens, R.D.; Menjot de Champfleur, N.; Delmaire, C.; Tollard, E.; Gupta, R; Dormont, D.; Laureys, S.; Benali, H.; Vanhaudenhuyse, A.; Galanaud, D.; Puybasset, L.

    2014-01-01

    PURPOSE: To analyze white matter pathologic abnormalities by using diffusion-tensor (DT) imaging in a multicenter prospective cohort of comatose patients following cardiac arrest or traumatic brain injury (TBI). MATERIALS AND METHODS: Institutional review board approval and informed consent from pro

  8. Sequential relationships between grey matter and white matter atrophy and brain metabolic abnormalities in early Alzheimer's disease.

    Science.gov (United States)

    Villain, Nicolas; Fouquet, Marine; Baron, Jean-Claude; Mézenge, Florence; Landeau, Brigitte; de La Sayette, Vincent; Viader, Fausto; Eustache, Francis; Desgranges, Béatrice; Chételat, Gaël

    2010-11-01

    Hippocampal atrophy, posterior cingulate and frontal glucose hypometabolism, and white-matter tract disruption are well described early macroscopic events in Alzheimer's disease. The relationships between these three types of alterations have been documented in previous studies, but their chronology still remains to be established. The present study used multi-modal fluorodeoxyglucose-positron emission tomography and magnetic resonance imaging longitudinal data to address this question in patients with amnestic mild cognitive impairment. We found unidirectional, specific sequential relationships between: (i) baseline hippocampal atrophy and both cingulum bundle (r = 0.70; P = 3 × 10⁻³) and uncinate fasciculus (r = 0.75; P = 7 × 10⁻⁴) rate of atrophy; (ii) baseline cingulum bundle atrophy and rate of decline of posterior (r = 0.72; P = 2 × 10⁻³); and anterior (r = 0.74; P = 1 × 10⁻³) cingulate metabolism; and (iii) baseline uncinate white matter atrophy and subgenual metabolism rate of change (r = 0.65; P = 6 × 10⁻³). Baseline local grey matter atrophy was not found to contribute to hypometabolism progression within the posterior and anterior cingulate as well as subgenual cortices. These findings suggest that hippocampal atrophy progressively leads to disruption of the cingulum bundle and uncinate fasciculus, which in turn leads to glucose hypometabolism of the cingulate and subgenual cortices, respectively. This study reinforces the relevance of remote mechanisms above local interactions to account for the pattern of metabolic brain alteration observed in amnestic mild cognitive impairment, and provides new avenues to assess the sequence of events in complex diseases characterized by multiple manifestations.

  9. Magnetic resonance imaging assessment of brain maturation in preterm neonates with punctate white matter lesions

    Energy Technology Data Exchange (ETDEWEB)

    Ramenghi, Luca A.; Fumagalli, Monica; Bassi, Laura; Groppo, Michela; Mosca, Fabio [University of Milan, Neonatal Intensive Care Unit - Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, IRCCS, Milan (Italy); Righini, Andrea; Parazzini, Cecilia; Bianchini, Elena; Triulzi, Fabio [Ospedale Pediatrico ' ' Buzzi' ' -ICP, Department of Radiology and Neuroradiology, Milan (Italy)

    2007-02-15

    Early white matter (WM) injury affects brain maturation in preterm infants as revealed by diffusion tensor imaging and volumetric magnetic resonance (MR) imaging at term postmenstrual age (PMA). The aim of the study was to assess quantitatively brain maturation in preterm infants with and without milder forms of WM damage (punctate WM lesions, PWML) using conventional MRI. Brain development was quantitatively assessed using a previously validated scoring system (total maturation score, TMS) which utilizes four parameters (progressive myelination and cortical infolding, progressive involution of glial cell migration bands and germinal matrix tissue). PWML were defined as foci of increased signal on T1-weighted images and decreased signal on T2-weighted images with no evidence of cystic degeneration. A group of 22 preterm infants with PWML at term PMA (PWML group) were compared with 22 matched controls with a normal MR appearance. The two groups were comparable concerning gestational age, birth weight and PMA. TMS was significantly lower in the PWML group than in the control group (mean TMS 12.44 {+-} 2.31 vs 14.00 {+-} 1.44; P = 0.011). Myelination (mean 2.76 {+-} 0.42 PWML group vs 3.32 {+-} 0.55 control group, P = 0.003) and cortical folding (3.64 {+-} 0.79 vs 4.09 {+-} 0.43, P = 0.027) appeared to be significantly delayed in babies with PWML. Conventional MRI appears able to quantify morphological changes in brain maturation of preterm babies with PWML; delayed myelination and reduced cortical infolding seem to be the most significant aspects. (orig.)

  10. Supervised novelty detection in brain tissue classification with an application to white matter hyperintensities

    Science.gov (United States)

    Kuijf, Hugo J.; Moeskops, Pim; de Vos, Bob D.; Bouvy, Willem H.; de Bresser, Jeroen; Biessels, Geert Jan; Viergever, Max A.; Vincken, Koen L.

    2016-03-01

    Novelty detection is concerned with identifying test data that differs from the training data of a classifier. In the case of brain MR images, pathology or imaging artefacts are examples of untrained data. In this proof-of-principle study, we measure the behaviour of a classifier during the classification of trained labels (i.e. normal brain tissue). Next, we devise a measure that distinguishes normal classifier behaviour from abnormal behavior that occurs in the case of a novelty. This will be evaluated by training a kNN classifier on normal brain tissue, applying it to images with an untrained pathology (white matter hyperintensities (WMH)), and determine if our measure is able to identify abnormal classifier behaviour at WMH locations. For our kNN classifier, behaviour is modelled as the mean, median, or q1 distance to the k nearest points. Healthy tissue was trained on 15 images; classifier behaviour was trained/tested on 5 images with leave-one-out cross-validation. For each trained class, we measure the distribution of mean/median/q1 distances to the k nearest point. Next, for each test voxel, we compute its Z-score with respect to the measured distribution of its predicted label. We consider a Z-score >=4 abnormal behaviour of the classifier, having a probability due to chance of 0.000032. Our measure identified >90% of WMH volume and also highlighted other non-trained findings. The latter being predominantly vessels, cerebral falx, brain mask errors, choroid plexus. This measure is generalizable to other classifiers and might help in detecting unexpected findings or novelties by measuring classifier behaviour.

  11. Loss of Consciousness Is Related to White Matter Injury in Mild Traumatic Brain Injury.

    Science.gov (United States)

    Wilde, Elisabeth A; Li, Xiaoqi; Hunter, Jill V; Narayana, Ponnada A; Hasan, Khader; Biekman, Brian; Swank, Paul; Robertson, Claudia; Miller, Emmy; McCauley, Stephen R; Chu, Zili David; Faber, Jessica; McCarthy, James; Levin, Harvey S

    2016-11-15

    To study the relation of loss of consciousness (LOC) to white matter integrity after mild traumatic brain injury (mTBI), we acquired diffusion tensor imaging (DTI) at 3 Tesla in 79 participants with mTBI and normal computed tomography (age 18 to 50 years) whom we imaged after a mean post-injury interval of 25.9 h (standard deviation = 12.3) and at 3 months. For comparison, 64 participants with orthopedic injury (OI) underwent DTI at similar intervals. Quantitative tractography was used to measure fractional anisotropy (FA) and mean diffusivity (MD) in the left and right uncinate fasciculus (UF), left and right inferior frontal occipital fasciculus (IFOF), and the genu of the corpus callosum. Generalized estimating equation models assessed the association between LOC and both MD and FA across time after mTBI and compared their DTI metrics with the OI group. LOC was significantly related to MD in UF and IFOF (p values ranged from p < 0.0001 to 0.0270) and to FA in left UF (p = 0.0104) and right UF (p = 0.0404). Between-group differences in MD were significant for left UF, left and right IFOF, and the genu of the corpus callosum on initial DTI, but not at 3 months post-injury, and these differences were specific to the mTBI subgroup with LOC. Groups did not differ in FA at either occasion. Early DTI may provide a biomarker for mTBI with LOC, even in patients whose consciousness recovers by arrival in the emergency department. MD better differentiates mTBI from OI than FA on early DTI, but this is specific to mTBI with LOC. DTI findings support a continuum of white matter injury in early mTBI.

  12. Sirt1 regulates glial progenitor proliferation and regeneration in white matter after neonatal brain injury

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    Jablonska, Beata; Gierdalski, Marcin; Chew, Li-Jin; Hawley, Teresa; Catron, Mackenzie; Lichauco, Arturo; Cabrera-Luque, Juan; Yuen, Tracy; Rowitch, David; Gallo, Vittorio

    2016-01-01

    Regenerative processes in brain pathologies require the production of distinct neural cell populations from endogenous progenitor cells. We have previously demonstrated that oligodendrocyte progenitor cell (OPC) proliferation is crucial for oligodendrocyte (OL) regeneration in a mouse model of neonatal hypoxia (HX) that reproduces diffuse white matter injury (DWMI) of premature infants. Here we identify the histone deacetylase Sirt1 as a Cdk2 regulator in OPC proliferation and response to HX. HX enhances Sirt1 and Sirt1/Cdk2 complex formation through HIF1α activation. Sirt1 deacetylates retinoblastoma (Rb) in the Rb/E2F1 complex, leading to dissociation of E2F1 and enhanced OPC proliferation. Sirt1 knockdown in culture and its targeted ablation in vivo suppresses basal and HX-induced OPC proliferation. Inhibition of Sirt1 also promotes OPC differentiation after HX. Our results indicate that Sirt1 is an essential regulator of OPC proliferation and OL regeneration after neonatal brain injury. Therefore, enhancing Sirt1 activity may promote OL recovery after DWMI. PMID:27991597

  13. A white matter lesion-filling approach to improve brain tissue volume measurements

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    Sergi Valverde

    2014-01-01

    Full Text Available Multiple sclerosis white matter (WM lesions can affect brain tissue volume measurements of voxel-wise segmentation methods if these lesions are included in the segmentation process. Several authors have presented different techniques to improve brain tissue volume estimations by filling WM lesions before segmentation with intensities similar to those of WM. Here, we propose a new method to refill WM lesions, where contrary to similar approaches, lesion voxel intensities are replaced by random values of a normal distribution generated from the mean WM signal intensity of each two-dimensional slice. We test the performance of our method by estimating the deviation in tissue volume between a set of 30 T1-w 1.5 T and 30 T1-w 3 T images of healthy subjects and the same images where: WM lesions have been previously registered and afterwards replaced their voxel intensities to those between gray matter (GM and WM tissue. Tissue volume is computed independently using FAST and SPM8. When compared with the state-of-the-art methods, on 1.5 T data our method yields the lowest deviation in WM between original and filled images, independently of the segmentation method used. It also performs the lowest differences in GM when FAST is used and equals to the best method when SPM8 is employed. On 3 T data, our method also outperforms the state-of-the-art methods when FAST is used while performs similar to the best method when SPM8 is used. The proposed technique is currently available to researchers as a stand-alone program and as an SPM extension.

  14. Regional variation in brain white matter diffusion index changes following chemoradiotherapy: a prospective study using tract-based spatial statistics.

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    Christopher H Chapman

    Full Text Available There is little known about how brain white matter structures differ in their response to radiation, which may have implications for radiation-induced neurocognitive impairment. We used diffusion tensor imaging (DTI to examine regional variation in white matter changes following chemoradiotherapy.Fourteen patients receiving two or three weeks of whole-brain radiation therapy (RT ± chemotherapy underwent DTI pre-RT, at end-RT, and one month post-RT. Three diffusion indices were measured: fractional anisotropy (FA, radial diffusivity (RD, and axial diffusivity (AD. We determined significant individual voxel changes of diffusion indices using tract-based spatial statistics, and mean changes of the indices within fourteen white matter structures of interest.Voxels of significant FA decreases and RD increases were seen in all structures (p<0.05, with the largest changes (20-50% in the fornix, cingula, and corpus callosum. There were highly significant between-structure differences in pre-RT to end-RT mean FA changes (p<0.001. The inferior cingula had a mean FA decrease from pre-RT to end-RT significantly greater than 11 of the 13 other structures (p<0.00385.Brain white matter structures varied greatly in their response to chemoradiotherapy as measured by DTI changes. Changes in FA and RD related to white matter demyelination were prominent in the cingula and fornix, structures relevant to radiation-induced neurocognitive impairment. Future research should evaluate DTI as a predictive biomarker of brain chemoradiotherapy adverse effects.

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

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    Carissa Nadia Kuswanto

    2013-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    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

  17. JNK signaling is the shared pathway linking neuroinflammation, blood–brain barrier disruption, and oligodendroglial apoptosis in the white matter injury of the immature brain

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    Wang Lan-Wan

    2012-07-01

    Full Text Available Abstract Background White matter injury is the major form of brain damage in very preterm infants. Selective white matter injury in the immature brain can be induced by lipopolysaccharide (LPS-sensitized hypoxic-ischemia (HI in the postpartum (P day 2 rat pups whose brain maturation status is equivalent to that in preterm infants less than 30 weeks of gestation. Neuroinflammation, blood–brain barrier (BBB damage and oligodendrocyte progenitor apoptosis may affect the susceptibility of LPS-sensitized HI in white matter injury. c-Jun N-terminal kinases (JNK are important stress-responsive kinases in various forms of insults. We hypothesized that LPS-sensitized HI causes white matter injury through JNK activation-mediated neuroinflammation, BBB leakage and oligodendroglial apoptosis in the white matter of P2 rat pups. Methods P2 pups received LPS (0.05 mg/kg or normal saline injection followed by 90-min HI. Immunohistochemistry and immunoblotting were used to determine microglia activation, TNF-α, BBB damage, cleaved caspase-3, JNK and phospho-JNK (p-JNK, myelin basic protein (MBP, and glial fibrillary acidic protein (GFAP expression. Immunofluorescence was performed to determine the cellular distribution of p-JNK. Pharmacological and genetic approaches were used to inhibit JNK activity. Results P2 pups had selective white matter injury associated with upregulation of activated microglia, TNF-α, IgG extravasation and oligodendroglial progenitor apoptosis after LPS-sensitized HI. Immunohistochemical analyses showed early and sustained JNK activation in the white matter at 6 and 24 h post-insult. Immunofluorescence demonstrated upregulation of p-JNK in activated microglia, vascular endothelial cells and oligodendrocyte progenitors, and also showed perivascular aggregation of p-JNK-positive cells around the vessels 24 h post-insult. JNK inhibition by AS601245 or by antisense oligodeoxynucleotides (ODN significantly reduced microglial

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

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    Chiara Chiapponi

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

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

    Science.gov (United States)

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

    2013-01-01

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

  20. A common NTRK2 variant is associated with emotional arousal and brain white-matter integrity in healthy young subjects

    Science.gov (United States)

    Spalek, K; Coynel, D; Freytag, V; Hartmann, F; Heck, A; Milnik, A; de Quervain, D; Papassotiropoulos, A

    2016-01-01

    Dysregulation of emotional arousal is observed in many psychiatric diseases such as schizophrenia, mood and anxiety disorders. The neurotrophic tyrosine kinase receptor type 2 gene (NTRK2) has been associated with these disorders. Here we investigated the relation between genetic variability of NTRK2 and emotional arousal in healthy young subjects in two independent samples (n1=1171; n2=707). In addition, diffusion tensor imaging (DTI) data in a subgroup of 342 participants were used to identify NTRK2-related white-matter structure differences. After correction for multiple testing, we identified a NTRK2 single nucleotide polymorphism associated with emotional arousal in both samples (n1: Pnominal=0.0003, Pcorrected=0.048; n2: Pnominal=0.0141, Pcorrected=0.036). DTI revealed significant, whole-brain corrected correlations between emotional arousal and brain white-matter mean diffusivity (MD), as well as significant, whole-brain corrected NTRK2 genotype-related differences in MD (PFWE<0.05). Our study demonstrates that genetic variability of NTRK2, a susceptibility gene for psychiatric disorders, is related to emotional arousal and—independently—to brain white-matter properties in healthy individuals. PMID:26978740

  1. Intra- and interhemispheric variations of diffusivity in subcortical white matter in normal human brain

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    Yoshiura, Takashi; Noguchi, Tomoyuki; Hiwatashi, Akio; Togao, Osamu; Yamashita, Koji; Nagao, Eiki; Kamano, Hironori; Honda, Hiroshi [Kyushu University, Department of Clinical Radiology, Graduate School of Medical Sciences, Fukuoka (Japan)

    2010-01-15

    Our purpose was to reveal potential regional variations in water molecular diffusivity within each cerebral hemisphere and across the right and left hemispheres. Diffusion-weighted images of 44 healthy right-handed adult male subjects were obtained using a diffusion tensor imaging sequence. Mean diffusivity (MD) values in subcortical white matter (WM) within 39 regions in each hemisphere were measured using an automated method. Intrahemispheric comparisons of MDs in subcortical WM were performed among six brain regions (frontal, parietal, occipital and temporal lobes and pre- and postcentral gyri). Interhemispheric comparisons of MDs were performed between the right and left counterparts of the 39 regions. In both hemispheres, diffusivity in the precentral gyrus was lower than those in other regions, while diffusivity in the parietal lobe was higher than others. MD asymmetry in which the left was lower than the right was found in the parietal lobe, middle occipital gyrus, and medial and orbital aspects of the frontal lobe. The converse asymmetry was revealed in the frontal operculum, supplementary motor cortex, temporal lobe, limbic cortices, precuneus and cuneus. Our results revealed significant intra- and interhemispheric regional variations in MD in subcortical WM, which may be related to different densities of axons and myelin sheaths. (orig.)

  2. Adaptive modulation of adult brain gray and white matter to high altitude: structural MRI studies.

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    Jiaxing Zhang

    Full Text Available The aim of this study was to investigate brain structural alterations in adult immigrants who adapted to high altitude (HA. Voxel-based morphometry analysis of gray matter (GM volumes, surface-based analysis of cortical thickness, and Tract-Based Spatial Statistics analysis of white matter fractional anisotropy (FA based on MRI images were conducted on 16 adults (20-22 years who immigrated to the Qinghai-Tibet Plateau (2300-4400 m for 2 years. They had no chronic mountain sickness. Control group consisted of 16 matched sea level subjects. A battery of neuropsychological tests was also conducted. HA immigrants showed significantly decreased GM volumes in the right postcentral gyrus and right superior frontal gyrus, and increased GM volumes in the right middle frontal gyrus, right parahippocampal gyrus, right inferior and middle temporal gyri, bilateral inferior ventral pons, and right cerebellum crus1. While there was some divergence in the left hemisphere, surface-based patterns of GM changes in the right hemisphere resembled those seen for VBM analysis. FA changes were observed in multiple WM tracts. HA immigrants showed significant impairment in pulmonary function, increase in reaction time, and deficit in mental rotation. Parahippocampal and middle frontal GM volumes correlated with vital capacity. Superior frontal GM volume correlated with mental rotation and postcentral GM correlated with reaction time. Paracentral lobule and frontal FA correlated with mental rotation reaction time. There might be structural modifications occurred in the adult immigrants during adaptation to HA. The changes in GM may be related to impaired respiratory function and psychological deficits.

  3. Test-retest reliability of white matter structural brain networks: A multiband diffusion MRI study

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    Tengda eZhao

    2015-02-01

    Full Text Available 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

  4. Test-retest reliability of white matter structural brain networks: a multiband diffusion MRI study.

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    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.

  5. White matter disruption in moderate/severe pediatric traumatic brain injury: Advanced tract-based analyses

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    Emily L. Dennis

    2015-01-01

    Full Text Available Traumatic brain injury (TBI is the leading cause of death and disability in children and can lead to a wide range of impairments. Brain imaging methods such as DTI (diffusion tensor imaging are uniquely sensitive to the white matter (WM damage that is common in TBI. However, higher-level analyses using tractography are complicated by the damage and decreased FA (fractional anisotropy characteristic of TBI, which can result in premature tract endings. We used the newly developed autoMATE (automated multi-atlas tract extraction method to identify differences in WM integrity. 63 pediatric patients aged 8–19 years with moderate/severe TBI were examined with cross sectional scanning at one or two time points after injury: a post-acute assessment 1–5 months post-injury and a chronic assessment 13–19 months post-injury. A battery of cognitive function tests was performed in the same time periods. 56 children were examined in the first phase, 28 TBI patients and 28 healthy controls. In the second phase 34 children were studied, 17 TBI patients and 17 controls (27 participants completed both post-acute and chronic phases. We did not find any significant group differences in the post-acute phase. Chronically, we found extensive group differences, mainly for mean and radial diffusivity (MD and RD. In the chronic phase, we found higher MD and RD across a wide range of WM. Additionally, we found correlations between these WM integrity measures and cognitive deficits. This suggests a distributed pattern of WM disruption that continues over the first year following a TBI in children.

  6. Regional characterization of longitudinal DT-MRI to study white matter maturation of the early developing brain.

    Science.gov (United States)

    Sadeghi, Neda; Prastawa, Marcel; Fletcher, P Thomas; Wolff, Jason; Gilmore, John H; Gerig, Guido

    2013-03-01

    The human brain undergoes rapid and dynamic development early in life. Assessment of brain growth patterns relevant to neurological disorders and disease requires a normative population model of growth and variability in order to evaluate deviation from typical development. In this paper, we focus on maturation of brain white matter as shown in diffusion tensor MRI (DT-MRI), measured by fractional anisotropy (FA), mean diffusivity (MD), as well as axial and radial diffusivities (AD, RD). We present a novel methodology to model temporal changes of white matter diffusion from longitudinal DT-MRI data taken at discrete time points. Our proposed framework combines nonlinear modeling of trajectories of individual subjects, population analysis, and testing for regional differences in growth pattern. We first perform deformable mapping of longitudinal DT-MRI of healthy infants imaged at birth, 1 year, and 2 years of age, into a common unbiased atlas. An existing template of labeled white matter regions is registered to this atlas to define anatomical regions of interest. Diffusivity properties of these regions, presented over time, serve as input to the longitudinal characterization of changes. We use non-linear mixed effect (NLME) modeling where temporal change is described by the Gompertz function. The Gompertz growth function uses intuitive parameters related to delay, rate of change, and expected asymptotic value; all descriptive measures which can answer clinical questions related to quantitative analysis of growth patterns. Results suggest that our proposed framework provides descriptive and quantitative information on growth trajectories that can be interpreted by clinicians using natural language terms that describe growth. Statistical analysis of regional differences between anatomical regions which are known to mature differently demonstrates the potential of the proposed method for quantitative assessment of brain growth and differences thereof. This will

  7. Blood-Brain Barrier Permeability of Normal Appearing White Matter in Relapsing-Remitting Multiple Sclerosis

    DEFF Research Database (Denmark)

    Lund, Henrik; Krakauer, Martin; Skimminge, Arnold;

    2013-01-01

    and nine healthy controls (4 females) underwent quantitative T1 measurements at 3 tesla before and after injection of a paramagnetic contrast agent (0.2 mmol/kg Gd-DTPA). Mean T1 values were calculated for NAWM in patients and total cerebral white matter in healthy subjects for the T1 measurements before...

  8. Comparison of the pathology of cerebral white matter with post-mortem magnetic resonance imaging (MRI) in the elderly brain.

    Science.gov (United States)

    Fernando, M S; O'Brien, J T; Perry, R H; English, P; Forster, G; McMeekin, W; Slade, J Y; Golkhar, A; Matthews, F E; Barber, R; Kalaria, R N; Ince, P G

    2004-08-01

    White matter lesions (WML) on magnetic resonance imaging (MRI) brain scans are associated with ageing. They are unrelated to specific disorders, and their impact on cognitive and other brain functions is poorly characterized. Pathological studies often omit systematic survey of WML because of the need to study multiple full coronal tissue blocks, and uncertainty over the significance of lesions identified in periventricular and deep subcortical regions. Post-mortem MRI provides a means of mapping WML but the sensitivity and specificity of the method are unresolved. In this study post-mortem MRI of WML in fixed brain slices was compared with pathology in 33 brains donated to the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). This study shows that MRI detection of WML was less sensitive than pathology: periventricaular lesions (PVL) sensitivity = 95% (87-99%), specificity = 71% (44-90%); deep subcortical lesions (DSCL) sensitivity = 86% (79-93%), specificity = 80% (72-88%). False negative MRI was associated with milder pathology, but lesions detected by myelin attenuation alone showed both microglial and endothelial activation. Therefore post-mortem MRI of formalin-fixed brain slices is a reliable method to obtain systematic data on the severity and distribution of cerebral white matter disease, and appears to detect those WML most likely to have clinical impact.

  9. White Matter Abnormalities are Associated with Chronic Postconcussion Symptoms in Blast-Related Mild Traumatic Brain Injury

    Science.gov (United States)

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

    2016-01-01

    Blast-related mild traumatic brain injury (mTBI) is a common injury among Iraq and Afghanistan military veterans due to the frequent use of improvised explosive devices. A significant minority of individuals with mTBI report chronic postconcussion symptoms (PCS), which include physical, emotional, and cognitive complaints. However, chronic PCS are non-specific and are also associated with mental health disorders such as posttraumatic stress disorder (PTSD). Identifying the mechanisms that contribute to chronic PCS is particularly challenging in blast-related mTBI, where the incidence of co-morbid PTSD is high. In this study, we examined whether blast-related mTBI is associated with diffuse white matter changes, and whether these neural changes are associated with chronic PCS. Ninety Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans were assigned to one of three groups including a blast-exposed no-TBI group, a blast-related mTBI without loss of consciousness (LOC) group (mTBI−LOC), and a blast-related mTBI with LOC group (mTBI+LOC). PCS were measured with the Rivermead Postconcussion Questionnaire. Results showed that participants in the mTBI+LOC group had more spatially heterogeneous white matter abnormalities than those in the no-TBI group. These white matter abnormalities were significantly associated with physical PCS severity even after accounting for PTSD symptoms, but not with cognitive or emotional PCS severity. A mediation analysis revealed that mTBI+LOC significantly influenced physical PCS severity through its effect on white matter integrity. These results suggest that white matter abnormalities are associated with chronic PCS independent of PTSD symptom severity and that these abnormalities are an important mechanism explaining the relationship between mTBI and chronic physical PCS. PMID:26497829

  10. White matter abnormalities are associated with chronic postconcussion symptoms in blast-related mild traumatic brain injury.

    Science.gov (United States)

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

    2016-01-01

    Blast-related mild traumatic brain injury (mTBI) is a common injury among Iraq and Afghanistan military veterans due to the frequent use of improvised explosive devices. A significant minority of individuals with mTBI report chronic postconcussion symptoms (PCS), which include physical, emotional, and cognitive complaints. However, chronic PCS are nonspecific and are also associated with mental health disorders such as posttraumatic stress disorder (PTSD). Identifying the mechanisms that contribute to chronic PCS is particularly challenging in blast-related mTBI, where the incidence of comorbid PTSD is high. In this study, we examined whether blast-related mTBI is associated with diffuse white matter changes, and whether these neural changes are associated with chronic PCS. Ninety Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans were assigned to one of three groups including a blast-exposed no--TBI group, a blast-related mTBI without loss of consciousness (LOC) group (mTBI--LOC), and a blast-related mTBI with LOC group (mTBI + LOC). PCS were measured with the Rivermead Postconcussion Questionnaire. Results showed that participants in the mTBI + LOC group had more spatially heterogeneous white matter abnormalities than those in the no--TBI group. These white matter abnormalities were significantly associated with physical PCS severity even after accounting for PTSD symptoms, but not with cognitive or emotional PCS severity. A mediation analysis revealed that mTBI + LOC significantly influenced physical PCS severity through its effect on white matter integrity. These results suggest that white matter abnormalities are associated with chronic PCS independent of PTSD symptom severity and that these abnormalities are an important mechanism explaining the relationship between mTBI and chronic physical PCS.

  11. An anisotropic hyperelastic constitutive model of brain white matter in biaxial tension and structural-mechanical relationships.

    Science.gov (United States)

    Labus, Kevin M; Puttlitz, Christian M

    2016-09-01

    Computational models of the brain require accurate and robust constitutive models to characterize the mechanical behavior of brain tissue. The anisotropy of white matter has been previously demonstrated; however, there is a lack of data describing the effects of multi-axial loading, even though brain tissue experiences multi-axial stress states. Therefore, a biaxial tensile experiment was designed to more fully characterize the anisotropic behavior of white matter in a quasi-static loading state, and the mechanical data were modeled with an anisotropic hyperelastic continuum model. A probabilistic analysis was used to quantify the uncertainty in model predictions because the mechanical data of brain tissue can show a high degree of variability, and computational studies can benefit from reporting the probability distribution of model responses. The axonal structure in white matter can be heterogeneous and regionally dependent, which can affect computational model predictions. Therefore, corona radiata and corpus callosum regions were tested, and histology and transmission electron microscopy were performed on tested specimens to relate the distribution of axon orientations and the axon volume fraction to the mechanical behavior. These measured properties were implemented into a structural constitutive model. Results demonstrated a significant, but relatively low anisotropic behavior, yet there were no conclusive mechanical differences between the two regions tested. The inclusion of both biaxial and uniaxial tests in model fits improved the accuracy of model predictions. The mechanical anisotropy of individual specimens positively correlated with the measured axon volume fraction, and, accordingly, the structural model exhibited slightly decreased uncertainty in model predictions compared to the model without structural properties.

  12. White matter and cognition: making the connection.

    Science.gov (United States)

    Filley, Christopher M; Fields, R Douglas

    2016-11-01

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

  13. The early development of brain white matter: a review of imaging studies in fetuses, newborns and infants.

    Science.gov (United States)

    Dubois, J; Dehaene-Lambertz, G; Kulikova, S; Poupon, C; Hüppi, P S; Hertz-Pannier, L

    2014-09-12

    Studying how the healthy human brain develops is important to understand early pathological mechanisms and to assess the influence of fetal or perinatal events on later life. Brain development relies on complex and intermingled mechanisms especially during gestation and first post-natal months, with intense interactions between genetic, epigenetic and environmental factors. Although the baby's brain is organized early on, it is not a miniature adult brain: regional brain changes are asynchronous and protracted, i.e. sensory-motor regions develop early and quickly, whereas associative regions develop later and slowly over decades. Concurrently, the infant/child gradually achieves new performances, but how brain maturation relates to changes in behavior is poorly understood, requiring non-invasive in vivo imaging studies such as magnetic resonance imaging (MRI). Two main processes of early white matter development are reviewed: (1) establishment of connections between brain regions within functional networks, leading to adult-like organization during the last trimester of gestation, (2) maturation (myelination) of these connections during infancy to provide efficient transfers of information. Current knowledge from post-mortem descriptions and in vivo MRI studies is summed up, focusing on T1- and T2-weighted imaging, diffusion tensor imaging, and quantitative mapping of T1/T2 relaxation times, myelin water fraction and magnetization transfer ratio.

  14. White matter lesion progression

    DEFF Research Database (Denmark)

    Hofer, Edith; Cavalieri, Margherita; Bis, Joshua C;

    2015-01-01

    BACKGROUND AND PURPOSE: White matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants...

  15. Brain Swelling and Loss of Gray and White Matter Differentiation in Human Postmortem Cases by Computed Tomography.

    Directory of Open Access Journals (Sweden)

    Go Shirota

    Full Text Available The purpose of this study was to evaluate the brain by postmortem computed tomography (PMCT versus antemortem computed tomography (AMCT using brains from the same patients. We studied 36 nontraumatic subjects who underwent AMCT, PMCT, and pathological autopsy in our hospital between April 2009 and December 2013. PMCT was performed within 20 h after death, followed by pathological autopsy including the brain. Autopsy confirmed the absence of intracranial disorders that might be related to the cause of death or might affect measurements in our study. Width of the third ventricle, width of the central sulcus, and attenuation in gray matter (GM and white matter (WM from the same area of the basal ganglia, centrum semiovale, and high convexity were statistically compared between AMCT and PMCT. Both the width of the third ventricle and the central sulcus were significantly shorter in PMCT than in AMCT (P < 0.0001. GM attenuation increased after death at the level of the centrum semiovale and high convexity, but the differences were not statistically significant considering the differences in attenuation among the different computed tomography scanners. WM attenuation significantly increased after death at all levels (P<0.0001. The differences were larger than the differences in scanners. GM/WM ratio of attenuation was significantly lower by PMCT than by AMCT at all levels (P<0.0001. PMCT showed an increase in WM attenuation, loss of GM-WM differentiation, and brain swelling, evidenced by a decrease in the size of ventricles and sulci.

  16. Age-related white matter degradation rule of normal human brain: the evidence from diffusion tensor magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    Zhang Xiang; Li Baoqing; Shan Baoci

    2014-01-01

    Background Diffusion tensor imaging can evaluate white matter function in human brain.Fractional anisotropy is the most important parameter.This study aimed to find regional reduction of fractional anisotropy (FA) with aging in the whole brain and the changing rules of anisotropy with aging.Methods Fifty volunteers from 20 to 75 years old were divided into five consecutive age groups; a young group and four senior groups.FA values were calculated with diffusion tensor imaging (DTI) studio software.The difference of FA between the young group and the four senior groups were analyzed by analysis of voxel-level height threshold in Statistic Parametric Mapping (SPM),and the regions with decreased FA were obtained.The FA values of these regions were then extracted using an in-house developed program,and a multiple linear regression model was built to assess the influence of age and sex on the FA values of these regions.Results Eight regions,including frontal lobe,postcentral gyrus,optic radiation,hippocampus,cerebella hemisphere,corona radiate,corpus callosum and internal capsule,were found to have decreased FA.There was a strong negative correlation between age and the FA in the frontal lobe,postcentral gyrus,optic radiation,hippocampus,and cerebella hemisphere,while a weaker negative correlation in the corona radiate,corpus callosum,and internal capsule was found.The FA reduction in the frontal lobe,postcentral gyrus,optic radiation,hippocampus and cerebella hemisphere were found earlier than in the corona radiate,corpus callosum and internal capsule.There was no correlation between sex and FA in these regions.Conclusions The FA in the subcortical white matter area reduces earlier than that in deep white matter.The areas with decreased FA continuously enlarge with aqing.The FAs in these regions have a strong negative correlation with age.

  17. New light on white matter damage of the premature brain: a neonatologist’s point of view

    Directory of Open Access Journals (Sweden)

    Maria Antonietta Marcialis

    2014-06-01

    Full Text Available Periventricular leucomalacia (PVL is traditionally considered a multifactorial lesion related to three main mechanisms: ischemia, inflammation and excitotoxicity. For years it was believed that hypoperfusion, associated with the peculiar vascular anatomy of the premature brain (border zones, was the conditio sine qua non in the pathogenesis of PVL. More recently this theory has been questioned. Many studies have stressed the importance of the association between inflammation/infection and white matter injury and have supported the multi hit hypothesis according to which several (genetic, hormonal, immune and nutritional factors may team up in a multi-hit fashion. The emerging concept is that the fetal white cell activation together with the interaction between the innate and adaptive immune system play a main role in white matter damage. Currently there are increasing evidence that PVL is a disease of connectivity. In this article we review the news in the basics of pathogenesis, the incidence, the definition and the diagnosis of PVL. Furthermore, recent follow-up studies and neuroprotective therapies are mentioned. Proceedings of the International Course on Perinatal Pathology (part of the 10th International Workshop on Neonatology · October 22nd-25th, 2014 · Cagliari (Italy · October 25th, 2014 · The role of the clinical pathological dialogue in problem solving Guest Editors: Gavino Faa, Vassilios Fanos, Peter Van Eyken

  18. Automatic segmentation of white matter lesions on magnetic resonance images of the brain by using an outlier detection strategy.

    Science.gov (United States)

    Wang, Rui; Li, Chao; Wang, Jie; Wei, Xiaoer; Li, Yuehua; Hui, Chun; Zhu, Yuemin; Zhang, Su

    2014-12-01

    White matter lesions (WMLs) are commonly observed on the magnetic resonance (MR) images of normal elderly in association with vascular risk factors, such as hypertension or stroke. An accurate WML detection provides significant information for disease tracking, therapy evaluation, and normal aging research. In this article, we present an unsupervised WML segmentation method that uses Gaussian mixture model to describe the intensity distribution of the normal brain tissues and detects the WMLs as outliers to the normal brain tissue model based on extreme value theory. The detection of WMLs is performed by comparing the probability distribution function of a one-sided normal distribution and a Gumbel distribution, which is a specific extreme value distribution. The performance of the automatic segmentation is validated on synthetic and clinical MR images with regard to different imaging sequences and lesion loads. Results indicate that the segmentation method has a favorable accuracy competitive with other state-of-the-art WML segmentation methods.

  19. Alzheimer's disease susceptibility genes APOE and TOMM40, and brain white matter integrity in the Lothian Birth Cohort 1936☆

    Science.gov (United States)

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

    2014-01-01

    Apolipoprotein E (APOE) ε genotype has previously been significantly associated with cognitive, brain imaging, and Alzheimer's disease-related phenotypes (e.g., age of onset). In the TOMM40 gene, the rs10524523 (“523”) variable length poly-T repeat polymorphism has more recently been associated with similar ph/enotypes, although the allelic directions of these associations have varied between initial reports. Using diffusion magnetic resonance imaging tractography, the present study aimed to investigate whether there are independent effects of apolipoprotein E (APOE) and TOMM40 genotypes on human brain white matter integrity in a community-dwelling sample of older adults, the Lothian Birth Cohort 1936 (mean age = 72.70 years, standard deviation = 0.74, N approximately = 640–650; for most analyses). Some nominally significant effects were observed (i.e., covariate-adjusted differences between genotype groups at p < 0.05). For APOE, deleterious effects of ε4 “risk” allele presence (vs. absence) were found in the right ventral cingulum and left inferior longitudinal fasciculus. To test for biologically independent effects of the TOMM40 523 repeat, participants were stratified into APOE genotype subgroups, so that any significant effects could not be attributed to APOE variation. In participants with the APOE ε3/ε4 genotype, effects of TOMM40 523 status were found in the left uncinate fasciculus, left rostral cingulum, left ventral cingulum, and a general factor of white matter integrity. In all 4 of these tractography measures, carriers of the TOMM40 523 “short” allele showed lower white matter integrity when compared with carriers of the “long” and “very-long” alleles. Most of these effects survived correction for childhood intelligence test scores and vascular disease history, though only the effect of TOMM40 523 on the left ventral cingulum integrity survived correction for false discovery rate. The effects of APOE in this older

  20. Differences in the molecular structure of the blood-brain barrier in the cerebral cortex and white matter: an in silico, in vitro, and ex vivo study.

    Science.gov (United States)

    Nyúl-Tóth, Ádám; Suciu, Maria; Molnár, Judit; Fazakas, Csilla; Haskó, János; Herman, Hildegard; Farkas, Attila E; Kaszaki, József; Hermenean, Anca; Wilhelm, Imola; Krizbai, István A

    2016-06-01

    The blood-brain barrier (BBB) is the main interface controlling molecular and cellular traffic between the central nervous system (CNS) and the periphery. It consists of cerebral endothelial cells (CECs) interconnected by continuous tight junctions, and closely associated pericytes and astrocytes. Different parts of the CNS have diverse functions and structures and may be subject of different pathologies, in which the BBB is actively involved. It is largely unknown, however, what are the cellular and molecular differences of the BBB in different regions of the brain. Using in silico, in vitro, and ex vivo techniques we compared the expression of BBB-associated genes and proteins (i.e., markers of CECs, brain pericytes, and astrocytes) in the cortical grey matter and white matter. In silico human database analysis (obtained from recalculated data of the Allen Brain Atlas), qPCR, Western blot, and immunofluorescence studies on porcine and mouse brain tissue indicated an increased expression of glial fibrillary acidic protein in astrocytes in the white matter compared with the grey matter. We have also found increased expression of genes of the junctional complex of CECs (occludin, claudin-5, and α-catenin) in the white matter compared with the cerebral cortex. Accordingly, occludin, claudin-5, and α-catenin proteins showed increased expression in CECs of the white matter compared with endothelial cells of the cortical grey matter. In parallel, barrier properties of white matter CECs were superior as well. These differences might be important in the pathogenesis of diseases differently affecting distinct regions of the brain.

  1. Objectively measured physical activity, brain atrophy, and white matter lesions in older adults with mild cognitive impairment.

    Science.gov (United States)

    Doi, Takehiko; Makizako, Hyuma; Shimada, Hiroyuki; Tsutsumimoto, Kota; Hotta, Ryo; Nakakubo, Sho; Park, Hyuntae; Suzuki, Takao

    2015-02-01

    Physical activity may help to prevent or delay brain atrophy. Numerous studies have shown associations between physical activity and age-related changes in the brain. However, most of these studies involved self-reported physical activity, not objectively measured physical activity. Therefore, the aim of this study was to examine the association between objectively measured physical activity, as determined using accelerometers, and brain magnetic resonance imaging (MRI) measures in older adults with mild cognitive impairment (MCI). We analyzed 323 older subjects with MCI (mean age 71.4 years) who were recruited from the participants of the Obu Study of Health Promotion for the Elderly. We recorded demographic data and measured physical activity using a tri-axial accelerometer. Physical activity was classified as light-intensity physical activity (LPA) or moderate-to-vigorous physical activity (MVPA). Brain atrophy and the severity of white matter lesions (WML) were determined by MRI. Low levels of LPA and MVPA were associated with severe WML. Subjects with severe WML were older, had lower mobility, and had greater brain atrophy than subjects with mild WML (all P<0.05). Multivariate analysis revealed that more MVPA was associated with less brain atrophy, even after adjustment for WML (β=-0.126, P=0.015), but LPA was not (β=-0.102, P=0.136). Our study revealed that objectively measured physical activity, especially MVPA, was associated with brain atrophy in MCI subjects, even after adjusting for WML. These findings support the hypothesis that physical activity plays a crucial role in maintaining brain health.

  2. Pathological Assessment of Brain White Matter in Relapsing-Remitting MS Patients using Quantitative Magnetization Transfer Imaging

    Directory of Open Access Journals (Sweden)

    Khodarahm Pahlevan

    2011-09-01

    Full Text Available Introduction: Multiple sclerosis (MS is characterized by lesions in the white matter (WM of the central nervous system. Magnetic resonance imaging is the most specific and sensitive method for diagnosis of multiple sclerosis. However, the ability of conventional MRI to show histopathologic heterogeneity of MS lesions is insufficient. Quantitative magnetization transfer imaging (qMTI is a relatively new method to investigate pathologic processes of the brain tissue occurring in MS patients. Material and Methods: Voxel-based analyses allow regional comparisons between groups to be made for the whole brain in a single analysis. This is done by coregistering data from all individual subjects to a reference brain, generally referred to as the "standard space", and then comparing them on a voxel-by-voxel basis. This study aimed to analyze whole-brain quantitative T1 maps, not to find global changes or changes in selected regions, but specifically to investigate the spatial distribution throughout the brain of T1 increases in MS WM with respect to control WM. In this study, 11 healthy controls, 10 relapsing-remitting (RR MS patients and 13 CIS patients were studied using MT-MRI imaging. MT parameters, including magnetization transfer ratio (MTR, magnetization transfer rate between free protons and restricted macromolecular protons, Ksat and longitudinal relaxation times (with and without MT saturation pulse, T1sat and T1free values were evaluated. Results: The results showed that, at a group level, there is widespread involvement of WM throughout the brain in CIS MS and especially in RRMS, where a significant T1 increase was found in 15.58% of WM voxels (normals < RR. Discussion and Conclusion: This study demonstrates that WM in large parts of the brain is susceptible to disease processes in RR and CIS MS

  3. Delayed increases in microvascular pathology after experimental traumatic brain injury are associated with prolonged inflammation, blood-brain barrier disruption, and progressive white matter damage.

    Science.gov (United States)

    Glushakova, Olena Y; Johnson, Danny; Hayes, Ronald L

    2014-07-01

    Traumatic brain injury (TBI) is a significant risk factor for chronic traumatic encephalopathy (CTE), Alzheimer's disease (AD), and Parkinson's disease (PD). Cerebral microbleeds, focal inflammation, and white matter damage are associated with many neurological and neurodegenerative disorders including CTE, AD, PD, vascular dementia, stroke, and TBI. This study evaluates microvascular abnormalities observed at acute and chronic stages following TBI in rats, and examines pathological processes associated with these abnormalities. TBI in adult rats was induced by controlled cortical impact (CCI) of two magnitudes. Brain pathology was assessed in white matter of the corpus callosum for 24 h to 3 months following injury using immunohistochemistry (IHC). TBI resulted in focal microbleeds that were related to the magnitude of injury. At the lower magnitude of injury, microbleeds gradually increased over the 3 month duration of the study. IHC revealed TBI-induced focal abnormalities including blood-brain barrier (BBB) damage (IgG), endothelial damage (intercellular adhesion molecule 1 [ICAM-1]), activation of reactive microglia (ionized calcium binding adaptor molecule 1 [Iba1]), gliosis (glial fibrillary acidic protein [GFAP]) and macrophage-mediated inflammation (cluster of differentiation 68 [CD68]), all showing different temporal profiles. At chronic stages (up to 3 months), apparent myelin loss (Luxol fast blue) and scattered deposition of microbleeds were observed. Microbleeds were surrounded by glial scars and co-localized with CD68 and IgG puncta stainings, suggesting that localized BBB breakdown and inflammation were associated with vascular damage. Our results indicate that evolving white matter degeneration following experimental TBI is associated with significantly delayed microvascular damage and focal microbleeds that are temporally and regionally associated with development of punctate BBB breakdown and progressive inflammatory responses. Increased

  4. The Left, The Better: White-Matter Brain Integrity Predicts Foreign Language Imitation Ability.

    Science.gov (United States)

    Vaquero, Lucía; Rodríguez-Fornells, Antoni; Reiterer, Susanne M

    2016-07-26

    Speech imitation is crucial for language acquisition and second-language learning. Interestingly, large individual differences regarding the ability in imitating foreign-language sounds have been observed. The origin of this interindividual diversity remains unknown, although it might be partially explained by structural predispositions. Here we correlated white-matter structural properties of the arcuate fasciculus (AF) with the performance of 52 German-speakers in a Hindi sentence- and word-imitation task. First, a manual reconstruction was performed, permitting us to extract the mean values along the three branches of the AF. We found that a larger lateralization of the AF volume toward the left hemisphere predicted the performance of our participants in the imitation task. Second, an automatic reconstruction was carried out, allowing us to localize the specific region within the AF that exhibited the largest correlation with foreign language imitation. Results of this reconstruction also showed a left lateralization trend: greater fractional anisotropy values in the anterior half of the left AF correlated with the performance in the Hindi-imitation task. From the best of our knowledge, this is the first time that foreign language imitation aptitude is tested using a more ecological imitation task and correlated with DTI tractography, using both a manual and an automatic method.

  5. Assessing White Matter Microstructure in Brain Regions with Different Myelin Architecture Using MRI

    Science.gov (United States)

    Schultz, Thomas; Balla, Dávid Z.; Klose, Uwe; Hauser, Till-Karsten; Nägele, Thomas; Bieri, Oliver; Prasloski, Thomas; MacKay, Alex L.; Krägeloh-Mann, Ingeborg; Scheffler, Klaus

    2016-01-01

    Objective We investigate how known differences in myelin architecture between regions along the cortico-spinal tract and frontal white matter (WM) in 19 healthy adolescents are reflected in several quantitative MRI parameters that have been proposed to non-invasively probe WM microstructure. In a clinically feasible scan time, both conventional imaging sequences as well as microstructural MRI parameters were assessed in order to quantitatively characterise WM regions that are known to differ in the thickness of their myelin sheaths, and in the presence of crossing or parallel fibre organisation. Results We found that diffusion imaging, MR spectroscopy (MRS), myelin water fraction (MWF), Magnetization Transfer Imaging, and Quantitative Susceptibility Mapping were myelin-sensitive in different ways, giving complementary information for characterising WM microstructure with different underlying fibre architecture. From the diffusion parameters, neurite density (NODDI) was found to be more sensitive than fractional anisotropy (FA), underlining the limitation of FA in WM crossing fibre regions. In terms of sensitivity to different myelin content, we found that MWF, the mean diffusivity and chemical-shift imaging based MRS yielded the best discrimination between areas. Conclusion Multimodal assessment of WM microstructure was possible within clinically feasible scan times using a broad combination of quantitative microstructural MRI sequences. By assessing new microstructural WM parameters we were able to provide normative data and discuss their interpretation in regions with different myelin architecture, as well as their possible application as biomarker for WM disorders. PMID:27898701

  6. Brain magnetic resonance imaging findings in adult patients with congenital adrenal hyperplasia: Increased frequency of white matter impairment and temporal lobe structures dysgenesis

    Directory of Open Access Journals (Sweden)

    Mouna Feki Mnif

    2013-01-01

    Full Text Available Background: Congenital adrenal hyperplasia (CAH is an inherited recessive disorder of adrenal steroidogenesis. The enzymes most commonly affected are 21-hydroxylase. Past reports suggested brain magnetic resonance imaging (MRI abnormalities in CAH patients, affecting white matter signal, temporal lobe and amygdala structure and function. Aims: In the present study, we aimed to investigate the frequency of white matter changes and temporal lobes structures dysgenesis in a population of patients having CAH due to 21-hydroxylase deficiency. Materials and Methods: Neurological examination and brain MRI were performed in 26 patients. Results: Neurological examination revealed mental retardation in three patients, tremor in two patients, tendon reflexes asymmetry in one patient, and cerebellar syndrome in one patient. Eleven patients (42.3% showed MRI abnormalities: Eight of them had white matter hyperintensities, one patient had moderate atrophy in the right temporal, and hippocampal dysgenesis was found in the remaining two patients. Conclusions: Brain MRI abnormalities in CAH patients include white matter hyperintensities and temporal lobe structures dysgenesis. The mechanisms involved seem related to hormonal imbalances during brain development and exposure to excess exogenous glucocorticoids. Clinical implications of such lesions remain unclear. More extensive studies are required to define better the relationships between brain involvement and different CAH phenotypes and treatment regimens.

  7. Diffusion tensor imaging detects chronic microstructural changes in white and grey matter after traumatic brain injury in rat

    Directory of Open Access Journals (Sweden)

    Teemu eLaitinen

    2015-04-01

    Full Text Available Traumatic brain injury (TBI is a major cause of disability and death in people of all ages worldwide. An initial brain injury caused by external mechanical forces triggers a cascade of tissue changes that lead to a wide spectrum of symptoms and disabilities, such as cognitive deficits, mood or anxiety disorders, motor impairments, chronic pain, and epilepsy. We investigated the detectability of secondary injury at a chronic time-point using ex vivo diffusion tensor imaging (DTI in a rat model of TBI, lateral fluid percussion injury. Our analysis of ex vivo DTI data revealed persistent microstructural tissue changes in white matter tracts, such as the splenium of the corpus callosum, angular bundle, and internal capsule. Histologic examination revealed mainly loss of myelinated axons and/or iron accumulation. Grey matter areas in the thalamus exhibited an increase in fractional anisotropy associated with neurodegeneration, myelinated fiber loss, and/or calcifications at the chronic phase. In addition, we examined whether these changes could also be detected with in vivo settings at the same chronic time-point. Our results provide insight into DTI detection of microstructural changes in the chronic phase of TBI, and elucidate how these changes correlate with cellular level alterations. These findings suggest that DTI could be a useful tool for detecting potential imaging biomarkers after TBI as indicators of progressive damage or recovery

  8. The prognostic value of multivoxel magnetic resonance spectroscopy determined metabolite levels in white and grey matter brain tissue for adverse outcome in term newborns following perinatal asphyxia

    Energy Technology Data Exchange (ETDEWEB)

    Doormaal, Pieter Jan van [University Medical Center Groningen and University of Groningen, Department of Pediatrics, Division of Neonatology, Groningen (Netherlands); Meander Medical Center Amersfoort, Department of Radiology, PO Box 1502, Amersfoort (Netherlands); Meiners, Linda C.; Sijens, Paul E. [University Medical Center Groningen and University of Groningen, Department of Radiology, Groningen (Netherlands); Horst, Hendrik J. ter; Veere, Christa N. van der [University Medical Center Groningen and University of Groningen, Department of Pediatrics, Division of Neonatology, Groningen (Netherlands)

    2012-04-15

    Magnetic resonance spectroscopy can identify brain metabolic changes in perinatal asphyxia by providing ratios of metabolites, such as choline (Cho), creatine (Cr), N-acetyl aspartate (NAA) and lactate (Lact) [Cho/Cr, Lact/NAA, etc.]. The purpose of this study was to quantify the separate white and grey matter metabolites in a slab cranial to the ventricles and relate these to the outcome. A standard 2D-chemical shift imaging protocol was used for measuring a transverse volume of interest located cranial to the ventricles allowing for direct comparison of the metabolites in white and grey matter brain tissue in 24 term asphyxiated newborns aged 3 to 16 days. Cho, NAA and Lact showed significant differences between four subgroups of asphyxiated infants with more and less favourable outcomes. High levels of Cho and Lact in the grey matter differentiated non-survivors from survivors (P = 0.003 and P = 0.017, respectively). In perinatal asphyxia the levels of Cho, NAA and Lact in both white and grey matter brain tissue are affected. The levels of Cho and Lact measured in the grey matter are the most indicative of survival. It is therefore advised to include grey matter brain tissue in the region of interest examined by multivoxel MR spectroscopy. (orig.)

  9. Investigating Brain Network Characteristics Interrupted by Covert White Matter Injury in Patients with Moyamoya Disease: Insights from Graph Theoretical Analysis.

    Science.gov (United States)

    Kazumata, Ken; Tha, Khin Khin; Narita, Hisashi; Shichinohe, Hideo; Ito, Masaki; Uchino, Haruto; Abumiya, Takeo

    2016-05-01

    Chronic ischemia in adult moyamoya disease (MMD) reduces the integrity of normal-appearing white matter (WM). We investigated whether covert WM impairment alters large-scale brain networks and specific neural circuits associated with neurocognitive dysfunction in MMD. Forty-six participants (control, n = 23; MMD, n = 23) were examined using diffusion tensor imaging and streamline tractography. Structural connectivity among 90 cortical and subcortical brain regions was evaluated using the mean fractional anisotropy along the fiber tracts. Graph theoretical analysis was used to measure network parameters and inter-regional connectivity. Global network parameters were reduced in patients with MMD, including cluster coefficient (controls vs. MMD: 3.62 ± 0.24 vs. 3.26 ± 0.36; P < 0.0001), characteristic path length (controls vs. MMD: 1.20 ± 0.02 vs. 1.17 ± 0.01; P < 0.001), and small-world property (controls vs. MMD: 3.07 ± 0.18 vs. 2.83 ± 0.27; P < 0.001). Reduced pairwise connectivity was found in prefrontal neural circuits within the middle/inferior frontal gyrus; supplementary motor area; and insular, inferior temporal, and dorsal cingulate cortices. Covert WM microstructural changes in patients with MMD alter large-scale brain networks, as well as lateral prefrontal neural circuits. Evaluation of structural connectivity may be useful to assess the severity of chronic ischemic injury from a network perspective.

  10. White matter injury detection in neonatal MRI

    Science.gov (United States)

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

    2013-02-01

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

  11. Comparing brain white matter on sequential cranial ultrasound and MRI in very preterm infants

    Energy Technology Data Exchange (ETDEWEB)

    Leijser, Lara M.; Veen, Sylvia; Boer, Inge P. de; Walther, Frans J.; Wezel-Meijler, Gerda van [Leiden University Medical Center, Department of Pediatrics, Division of Neonatology, Albinusdreef 2, P.O. Box 9600, Leiden (Netherlands); Liauw, Lishya [Leiden University Medical Center, Department of Radiology, Division of Neuroradiology, Albinusdreef 2, P.O. Box 9600, Leiden (Netherlands)

    2008-09-15

    Periventricular white matter (WM) echodensities, frequently seen in preterm infants, can be associated with suboptimal neurodevelopment. Major WM injury is well detected on cranial ultrasound (cUS). cUS seems less sensitive for diffuse or more subtle WM injury. Our aim was to assess the value of cUS and magnetic resonance imaging (MRI) for evaluating WM changes and the predictive value of cUS and/or MRI findings for neurodevelopmental outcome in very preterm infants with normal to severely abnormal WM on sequential high-quality cUS. Very preterm infants (<32 weeks) who had sequential cUS and one MRI within the first three postnatal months were included. Periventricular WM on cUS and MRI was compared and correlated with neurodevelopmental outcome at 2 years corrected age. Forty preterm infants were studied; outcome data were available in 32. WM changes on sequential cUS were predictive of WM changes on MRI. Severely abnormal WM on cUS/MRI was predictive of adverse outcome, and normal-mildly abnormal WM of favorable outcome. Moderately abnormal WM on cUS/MRI was associated with variable outcome. Additional MRI slightly increased the predictive value of cUS in severe WM changes. Sequential cUS in preterm infants is reliable for detecting WM changes and predicting favorable and severely abnormal outcome. Conventional and diffusion-weighted MRI sequences before term equivalent age in very preterm infants, suggested on cUS to have mild to moderately abnormal WM, do not seem to be warranted. (orig.)

  12. Regional Differences in Susceptibility to Hypoxic-Ischemic Injury in the Preterm Brain: Exploring the Spectrum from White Matter Loss to Selective Grey Matter Injury in a Rat Model

    Directory of Open Access Journals (Sweden)

    D. B. Selip

    2012-01-01

    Full Text Available Models of premature brain injury have largely focused on the white matter injury thought to underlie periventricular leukomalacia (PVL. However, with increased survival of very low birth weight infants, injury patterns involving grey matter are now recognized. We aimed to determine how grey matter lesions relate to hypoxic-ischemic- (HI mediated white matter injury by modifying our rat model of PVL. Following HI, microglial infiltration, astrocytosis, and neuronal and axonal degeneration increased in a region-specific manner dependent on the severity of myelin loss in pericallosal white matter. The spectrum of injury ranged from mild, where diffuse white matter abnormalities were dominant and were associated with mild axonal injury and local microglial activation, to severe HI injury characterized by focal MBP loss, widespread neuronal degeneration, axonal damage, and gliosis throughout the neocortex, caudate putamen, and thalamus. In sum, selective regional white matter loss occurs in the preterm rat concomitantly with a clinically relevant spectrum of grey matter injury. These data demonstrate an interspecies similarity of brain injury patterns and further substantiates the reliable use of this model for the study of preterm brain injury.

  13. Smoking and the developing brain: altered white matter microstructure in attention-deficit/hyperactivity disorder and healthy controls.

    Science.gov (United States)

    van Ewijk, Hanneke; Groenman, Annabeth P; Zwiers, Marcel P; Heslenfeld, Dirk J; Faraone, Stephen V; Hartman, Catharina A; Luman, Marjolein; Greven, Corina U; Hoekstra, Pieter J; Franke, Barbara; Buitelaar, Jan; Oosterlaan, Jaap

    2015-03-01

    Brain white matter (WM) tracts, playing a vital role in the communication between brain regions, undergo important maturational changes during adolescence and young adulthood, a critical period for the development of nicotine dependence. Attention-deficit/hyperactivity disorder (ADHD) is associated with increased smoking and widespread WM abnormalities, suggesting that the developing ADHD brain might be especially vulnerable to effects of smoking. This study aims to investigate the effect of smoking on (WM) microstructure in adolescents and young adults with and without ADHD. Diffusion tensor imaging was performed in an extensively phenotyped sample of nonsmokers (n = 95, 50.5% ADHD), irregular smokers (n = 41, 58.5% ADHD), and regular smokers (n = 50, 82.5% ADHD), aged 14-24 years. A whole-brain voxelwise approach investigated associations of smoking, ADHD and their interaction, with WM microstructure as measured by fractional anisotropy (FA) and mean diffusivity (MD). Widespread alterations in FA and MD were found for regular smokers compared to irregular and nonsmokers, mainly located in the corpus callosum and WM tracts surrounding the basal ganglia. Several regions overlapped with regions of altered FA for ADHD versus controls, albeit in different directions. Irregular and nonsmokers did not differ, and ADHD and smoking did not interact. Results implicate that smoking and ADHD have independent effects on WM microstructure, and possibly do not share underlying mechanisms. Two mechanisms may play a role in the current results. First, smoking may cause alterations in WM microstructure in the maturing brain. Second, pre-existing WM microstructure differences possibly reflect a risk factor for development of a smoking addiction.

  14. Cortex-sparing fiber dissection: an improved method for the study of white matter anatomy in the human brain

    Science.gov (United States)

    Martino, Juan; De Witt Hamer, Philip C; Vergani, Francesco; Brogna, Christian; de Lucas, Enrique Marco; Vázquez-Barquero, Alfonso; García-Porrero, Juan A; Duffau, Hugues

    2011-01-01

    Classical fiber dissection of post mortem human brains enables us to isolate a fiber tract by removing the cortex and overlying white matter. In the current work, a modification of the dissection methodology is presented that preserves the cortex and the relationships within the brain during all stages of dissection, i.e. ‘cortex-sparing fiber dissection’. Thirty post mortem human hemispheres (15 right side and 15 left side) were dissected using cortex-sparing fiber dissection. Magnetic resonance imaging study of a healthy brain was analyzed using diffusion tensor imaging (DTI)-based tractography software. DTI fiber tract reconstructions were compared with cortex-sparing fiber dissection results. The fibers of the superior longitudinal fasciculus (SLF), inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF) and uncinate fasciculus (UF) were isolated so as to enable identification of their cortical terminations. Two segments of the SLF were identified: first, an indirect and superficial component composed of a horizontal and vertical segment; and second, a direct and deep component or arcuate fasciculus. The IFOF runs within the insula, temporal stem and sagittal stratum, and connects the frontal operculum with the occipital, parietal and temporo-basal cortex. The UF crosses the limen insulae and connects the orbito-frontal gyri with the anterior temporal lobe. Finally, a portion of the ILF was isolated connecting the fusiform gyrus with the occipital gyri. These results indicate that cortex-sparing fiber dissection facilitates study of the 3D anatomy of human brain tracts, enabling the tracing of fibers to their terminations in the cortex. Consequently, it is an important tool for neurosurgical training and neuroanatomical research. PMID:21767263

  15. Diffusion tensor imaging measures of white matter compared to myelin basic protein immunofluorescence in tissue cleared intact brains

    Directory of Open Access Journals (Sweden)

    Eric H. Chang

    2017-02-01

    Full Text Available We provide datasets from combined ex vivo diffusion tensor imaging (DTI and Clear Lipid-exchanged, Anatomically Rigid, Imaging/immunostaining compatible, Tissue hYdrogel (CLARITY performed on intact mouse brains. DTI-derived measures of fractional anisotropy (FA, radial diffusivity (RD, and axial diffusivity (AD were compared to antibody-based labeling of myelin basic protein (MBP, as measured by fluorescence microscopy. We used a customized CLARITY hydrogel solution to facilitate whole brain tissue clearing and subsequent immunolabeling. We describe how CLARITY was made compatible with magnetic resonance imaging with the intention of facilitating future multimodal imaging studies that may combine noninvasive imaging with 3D immunohistochemistry. These data and methods are related to the accompanying research article entitled, ‘The role of myelination in measures of white matter integrity: Combination of diffusion tensor imaging and two-photon microscopy of CLARITY intact brains’ (E.H. Chang, M. Argyelan, M. Aggarwal, T-S. Chandon, K.H. Karlsgodt, S. Mori, A.K. Malhotra, 2016 [1].

  16. Atlasing location, asymmetry and inter-subject variability of white matter tracts in the human brain with MR diffusion tractography.

    Science.gov (United States)

    Thiebaut de Schotten, Michel; Ffytche, Dominic H; Bizzi, Alberto; Dell'Acqua, Flavio; Allin, Matthew; Walshe, Muriel; Murray, Robin; Williams, Steven C; Murphy, Declan G M; Catani, Marco

    2011-01-01

    The purpose of this study is to create a white matter atlas of the human brain using diffusion tensor imaging (DTI) tractography and to describe the constant and variable features of the major pathways. DTI was acquired from 40 healthy right-handed adults and reconstructed tracts mapped within a common reference space (MNI). Group effect maps of each tract defined constant anatomical features while overlap maps were generated to study inter-subject variability and to compare DTI derived anatomy with a histological atlas. Two patients were studied to assess the localizing validity of the atlas. The DTI-derived maps are overall consistent with a previously published histological atlas. A statistically significant leftward asymmetry was found for the volume and number of streamlines of the cortico-spinal tract and the direct connections between Broca's and Wernicke's territories (long segment). A statistically significant rightward asymmetry was found for the inferior fronto-occipital fasciculus and the fronto-parietal connections (anterior segment) of the arcuate fasciculus. Furthermore, males showed a left lateralization of the fronto-temporal segment of the arcuate fasciculus (long segment), while females had a more bilateral distribution. In two patients with brain lesions, DTI was acquired and tractography used to show that the tracts affected by the lesions were correctly identified by the atlas. This study suggests that DTI-derived maps can be used together with a previous histological atlas to establish the relationship of focal lesions with nearby tracts and improve clinico-anatomical correlation.

  17. Regional white matter volume and the relation with attentional functioning in survivors of malignant pediatric brain tumors

    Science.gov (United States)

    Glass, John O.; Mulhern, Raymond K.; White, Holly A.; Wilkinson, Gina M.; Reddick, Wilburn E.

    2003-05-01

    Quantitative assessment of MR examinations in 37 survivors of childhood cancer treated with central nervous system prophylaxis revealed that normal appearing white matter (NAWM) volume is associated with attention-related problems, localized specifically in the right prefrontal region. T1-, T2-, and PD-weighted images were segmented and divided into pre-frontal, frontal, parietal/temporal, and parietal/occipital regions for each hemisphere. These eight regions were analyzed in five slices centered at the level of the basal ganglia. The patient's age at diagnosis and time elapsed from diagnosis were used as covariates in the regressions. Attentional measures showed significant deficiency when compared to age and gender normative values. Total, frontal and/or prefrontal NAWM volumes from the range of slices examined were significantly associated with 5 of the 8 attentional measures. The frontal/prefrontal region of the brain is associated with executive functioning tasks and could potentially be spared as much as possible during therapy planning. The results of the present study further support the contention that NAWM is an important substrate for treatment-induced neurocognitive problems among survivors of malignant brain tumors of childhood.

  18. White matter microstructural characteristics in newly diagnosed Parkinson’s disease: An unbiased whole-brain study

    Science.gov (United States)

    Wen, Ming-Ching; Heng, Hannah S. E.; Ng, Samuel Y. E.; Tan, Louis C. S.; Chan, Ling Ling; Tan, Eng King

    2016-01-01

    Parkinson’s disease (PD) is a debilitating neurodegenerative disorder. Findings on specific white matter (WM) alterations in PD have been inconsistent. We hypothesized that WM changes occur in early PD patients and unbiased whole-brain analysis may provide additional evidence of pathological WM changes in PD. In this study, we examined various indexes of WM microstructure in newly diagnosed PD patients at the whole-brain level. 64 PDs with Hoehn & Yahr stage 1 (HY1PDs), 87 PDs with Hoehn & Yahr stage 2 (HYPD2s), and 60 controls (HCs) were recruited. Tract-based spatial statistics (TBSS) and diffusion connectometry were used to identify changes of WM pathways associated with PD. There were no significant differences in axial diffusivity, but HY1PDs exhibited greater fractional anisotropy (FA) and decreased mean and radial diffusivities (MD and RD) in callosal, projection, and association fibres than HCs and HY2PDs. Motor severity was inversely correlated with FA, but positively correlated with MD and RD in PD patients. Connectometry analysis also revealed increased WM density in the aforementioned tracts in PD patients, compared with HCs. Our study reveals WM enhancement, suggesting neural compensations in early PD. Longitudinal follow-up studies are warranted to identify the trajectory of WM changes alongside the progression of PD. PMID:27762307

  19. Characterizing the contrast of white matter and grey matter in high-resolution phase difference enhanced imaging of human brain at 3.0 T

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Li [Fudan University, Department of Radiology, Shanghai Institute of Medical Imaging, Zhongshan Hospital, Shanghai (China); Shandong University, Shandong Medical Imaging Research Institute, Shandong Provincial Key Laboratory of Diagnosis and Treatment of Cardio-cerebral Vascular Diseases, Jinan, Shandong (China); Wang, Shanshan; Yao, Bin; Li, Lili; Guo, Lingfei; Zhang, Xinjuan; Wang, Guangbin [Shandong University, Shandong Medical Imaging Research Institute, Shandong Provincial Key Laboratory of Diagnosis and Treatment of Cardio-cerebral Vascular Diseases, Jinan, Shandong (China); Xu, Xiaofei [Erasmus University Rotterdam, Laboratory of Experimental Tumor Immunology, Department of Medical Oncology, Erasmus Medical Center Cancer Institute, Rotterdam (Netherlands); Zhao, Lianxin [Shandong University, Department of Radiology, Qilu Hospital, Jinan, Shandong (China); Chen, Weibo; Chan, Queenie [Philips Healthcare, Shanghai (China)

    2015-04-01

    The purpose of this study was to address the feasibility of characterizing the contrast both between and within grey matter and white matter using the phase difference enhanced (PADRE) technique. PADRE imaging was performed in 33 healthy volunteers. Vessel enhancement (VE), tissue enhancement (TE), and PADRE images were reconstructed from source images and were evaluated with regard to differentiation of grey-to-white matter interface, the stria of Gennari, and the two layers, internal sagittal stratum (ISS) and external sagittal stratum (ESS), of optic radiation. White matter regions showed decreased signal intensity compared to grey matter regions. Discrimination was sharper between white matter and cortical grey matter in TE images than in PADRE images, but was poorly displayed in VE images. The stria of Gennari was observed on all three image sets. Low-signal-intensity bands displayed in VE images representing the optic radiation were delineated as two layers of different signal intensities in TE and PADRE images. Statistically significant differences in phase shifts were found between frontal grey and white matter, as well as between ISS and ESS (p < 0.01). The PADRE technique is capable of identifying grey-to-white matter interface, the stria of Gennari, and ISS and ESS, with improved contrast in PADRE and TE images compared to VE images. (orig.)

  20. The Brain Dynamics of Intellectual Development: Waxing and Waning White and Gray Matter

    Science.gov (United States)

    Tamnes, Christian K.; Fjell, Anders M.; Ostby, Ylva; Westlye, Lars T.; Due-Tonnessen, Paulina; Bjornerud, Atle; Walhovd, Kristine B.

    2011-01-01

    Distributed brain areas support intellectual abilities in adults. How structural maturation of these areas in childhood enables development of intelligence is not established. Neuroimaging can be used to monitor brain development, but studies to date have typically considered single imaging modalities. To explore the impact of structural brain…

  1. Diffusion-tensor magnetic resonance imaging in brain white matter diseases%弥散张量成像在脑白质病变中的应用价值初探

    Institute of Scientific and Technical Information of China (English)

    初曙光; 沈天真; 陈星荣

    2002-01-01

    Objective To evaluate the usefulness of diffusion-tensor MR imaging in brain white matter diseases. Methods A combined conventional and diffusion tensor MRI were obtained from 10 multiple sclerosis ,10 multiple lacunar infarction,3 cysticercosis,1 angiitis ,1 morphinist and 10 healthy control volunteers. After obtaining mean diffusivity (D) and fractional anisotropy images and image coregistration, the correlations of the lesions and the white matter pathways were investigated. D and AI values were measured form four big lesions which can be seen in T2WI and compared to contralateral white matter. Also D and AI value of four different anatomic locations of normal-appearing white matter regions were measured in all patients and controls. Results Whereas the lesions of infarction, cysticercosis and angiitis were in and outside the white matter pathways, all plaques of multiple sclerosis were inside the whit matter pathways. The brain white matter lesions by 1 morphinist were beside the lateral ventricle with big patchy appearance, which was partly inside white matter. For MS, D value was higher in lesions than control white matter. But for other diseases, D value could be seen higher or lower compared to healthy side. AI values were lower in all lesions. D value was higher and AI was lower in normal appearing brain white matter when comparing MS to other cases or healthy control volunteers. Conclusion Diffusion tensor MR images can determine the correlations of the lesions and brain white matter pathways. The changes of D and AI values can improve specificity in differential diagnoses though quantitatively analyzing the tissue damage in lesions and normal-appearing brain white matter.

  2. The apparent diffusion coefficient of water in gray and white matter of the infant brain

    DEFF Research Database (Denmark)

    Toft, P B; Leth, H; Peitersen, Birgit;

    1996-01-01

    PURPOSE: The purpose was to obtain normal values of the apparent diffusion coefficient (ADC) in the infant brain and to compare ADC maps with T1- and T2-weighted images. METHOD: Diffusion was measured in nine infants with an ECG-gated SE sequence compensated for first-order motion. One axial slic...... of the ADC increased with age and approached 1 at the age of 30 weeks. CONCLUSION: ADC maps add information to the T1 and T2 images about the size and course of unmyelinated as well as myelinated tracts in the immature brain.......PURPOSE: The purpose was to obtain normal values of the apparent diffusion coefficient (ADC) in the infant brain and to compare ADC maps with T1- and T2-weighted images. METHOD: Diffusion was measured in nine infants with an ECG-gated SE sequence compensated for first-order motion. One axial slice...

  3. Training-induced improvements in postural control are accompanied by alterations in cerebellar white matter in brain injured patients

    Directory of Open Access Journals (Sweden)

    David Drijkoningen

    2015-01-01

    Full Text Available We investigated whether balance control in young TBI patients can be promoted by an 8-week balance training program and whether this is associated with neuroplastic alterations in brain structure. The cerebellum and cerebellar peduncles were selected as regions of interest because of their importance in postural control as well as their vulnerability to brain injury. Young patients with moderate to severe TBI and typically developing (TD subjects participated in balance training using PC-based portable balancers with storage of training data and real-time visual feedback. An additional control group of TD subjects did not attend balance training. Mean diffusivity and fractional anisotropy were determined with diffusion MRI scans and were acquired before, during (4 weeks and at completion of training (8 weeks together with balance assessments on the EquiTest® System (NeuroCom which included the Sensory Organization Test, Rhythmic Weight Shift and Limits of Stability protocols. Following training, TBI patients showed significant improvements on all EquiTest protocols, as well as a significant increase in mean diffusivity in the inferior cerebellar peduncle. Moreover, in both training groups, diffusion metrics in the cerebellum and/or cerebellar peduncles at baseline were predictive of the amount of performance increase after training. Finally, amount of training-induced improvement on the Rhythmic Weight Shift test in TBI patients was positively correlated with amount of change in fractional anisotropy in the inferior cerebellar peduncle. This suggests that training-induced plastic changes in balance control are associated with alterations in the cerebellar white matter microstructure in TBI patients.

  4. Canavan Disease: A White Matter Disorder

    Science.gov (United States)

    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.…

  5. Increased apoptosis and hypomyelination in cerebral white matter of macular mutant mouse brain

    Directory of Open Access Journals (Sweden)

    Shoichi Takikita

    2015-09-01

    Full Text Available Hypomyelination in developing brain is often accompanied by congenital metabolic disorders. Menkes kinky hair disease is an X-linked neurodegenerative disease of impaired copper transport, resulting from a mutation of the Menkes disease gene, a transmembrane copper-transporting p-type ATPase gene (ATP7A. In a macular mutant mouse model, the murine ortholog of Menkes gene (mottled gene is mutated, and widespread neurodegeneration and subsequent death are observed. Although some biochemical analysis of myelin protein in macular mouse has been reported, detailed histological study of myelination in this mouse model is currently lacking. Since myelin abnormality is one of the neuropathologic findings of human Menkes disease, in this study early myelination in macular mouse brain was evaluated by immunohistochemistry. Two-week-old macular mice and normal littermates were perfused with 4% paraformaldehyde. Immunohistochemical staining of paraffin embedded and vibratome sections was performed using antibodies against either CNPase, cleaved caspase-3 or O4 (marker of immature oligodendrocytes. This staining showed that cerebral myelination in macular mouse was generally hypoplastic and that hypomyelination was remarkable in internal capsule, corpus callosum, and cingulate cortex. In addition, an increased number of cleaved caspase-3 positive cells were observed in corpus callosum and internal capsule. Copper deficiency induced by low copper diet has been reported to induce oligodendrocyte dysfunction and leads to hypomyelination in this mouse model. Taken together, hypomyelination observed in this study in a mouse model of Menkes disease is assumed to be induced by increased apoptosis of immature oligodendrocytes in developing cerebrum, through deficient intracellular copper metabolism.

  6. Increased apoptosis and hypomyelination in cerebral white matter of macular mutant mouse brain.

    Science.gov (United States)

    Takikita, Shoichi; Takano, Tomoyuki; Narita, Tsutomu; Maruo, Yoshihiro

    2015-09-01

    Hypomyelination in developing brain is often accompanied by congenital metabolic disorders. Menkes kinky hair disease is an X-linked neurodegenerative disease of impaired copper transport, resulting from a mutation of the Menkes disease gene, a transmembrane copper-transporting p-type ATPase gene (ATP7A). In a macular mutant mouse model, the murine ortholog of Menkes gene (mottled gene) is mutated, and widespread neurodegeneration and subsequent death are observed. Although some biochemical analysis of myelin protein in macular mouse has been reported, detailed histological study of myelination in this mouse model is currently lacking. Since myelin abnormality is one of the neuropathologic findings of human Menkes disease, in this study early myelination in macular mouse brain was evaluated by immunohistochemistry. Two-week-old macular mice and normal littermates were perfused with 4% paraformaldehyde. Immunohistochemical staining of paraffin embedded and vibratome sections was performed using antibodies against either CNPase, cleaved caspase-3 or O4 (marker of immature oligodendrocytes). This staining showed that cerebral myelination in macular mouse was generally hypoplastic and that hypomyelination was remarkable in internal capsule, corpus callosum, and cingulate cortex. In addition, an increased number of cleaved caspase-3 positive cells were observed in corpus callosum and internal capsule. Copper deficiency induced by low copper diet has been reported to induce oligodendrocyte dysfunction and leads to hypomyelination in this mouse model. Taken together, hypomyelination observed in this study in a mouse model of Menkes disease is assumed to be induced by increased apoptosis of immature oligodendrocytes in developing cerebrum, through deficient intracellular copper metabolism.

  7. Intellectual impairment and brain MRI findings in myotonic dystrophy. With a special reference to hippocampal atrophy and white matter lesions

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Etsuko; Takahashi, Satoshi; Yonezawa, Hisashi [Iwate Medical Univ., Morioka (Japan). School of Medicine

    1995-08-01

    We performed a correlative study between intellectual impairment, CTG repeat expansion and magnetic resonance imaging (MRI) abnormalities, including hippocampal atrophy, white matter lesions and ventricular dilatation in 15 patients with myotonic dystrophy (MD). They included 4 males and 11 females aged from 20 to 66 years, averaging 43 years of age and 15 years of duration of illness. Nine patients had intellectual impairment (WAIS-R<80). Negative correlations were found between full scale IQ (FSIQ), duration of illness (p<0.05) and CTG repeat expansion (p<0.05). Compared with normal controls, the patients with MD showed a significant reduction in size of the hippocampal head (p<0.01), which was positively correlated to FSIQ, verbal IQ and performance IQ levels (p<0.05). Ten patients had white matter lesions. Severer white matter lesions tended to be recognized in patients with longer duration of illness and with decreased FSIQ level. These results suggest that hippocampal atrophy and white matter lesions are related to intellectual impairment in patients with MD. (author).

  8. Calcium, potassium, iron, copper and zinc concentrations in the white and gray matter of the cerebellum and corpus callosum in brain of four genetic mouse strains

    Science.gov (United States)

    Sergeant, C.; Vesvres, M. H.; Devès, G.; Guillou, F.

    2005-04-01

    In the central nervous system, metallic cations are involved in oligodendrocyte maturation and myelinogenesis. Moreover, the metallic cations have been associated with pathogenesis, particularly multiple sclerosis and malignant gliomas. The brain is vulnerable to either a deficit or an excess of available trace elements. Relationship between trace metals and myelinogenesis is important in understanding a severe human pathology : the multiple sclerosis, which remains without efficient treatment. One approach to understand this disease has used mutant or transgenic mice presenting myelin deficiency or excess. But to date, the concentration of trace metals and mineral elements in white and gray matter areas in wild type brain is unknown. The aim of this study is to establish the reference concentrations of trace metals (iron, copper and zinc) and minerals (potassium and calcium) in the white and gray matter of the mouse cerebellum and corpus callosum. The brains of four different genetic mouse strains (C57Black6/SJL, C57Black6/D2, SJL and C3H) were analyzed. The freeze-dried samples were prepared to allow PIXE (Proton-induced X-ray emission) and RBS (Rutherford backscattering spectrometry) analyses with the nuclear microprobe in Bordeaux. The results obtained give the first reference values. Furthermore, one species out of the fours testes exhibited differences in calcium, iron and zinc concentrations in the white matter.

  9. Astrocyte-derived proinflammatory cytokines induce hypomyelination in the periventricular white matter in the hypoxic neonatal brain.

    Directory of Open Access Journals (Sweden)

    Yiyu Deng

    Full Text Available Hypoxic exposure in the perinatal period causes periventricular white matter damage (PWMD, a condition associated with myelination abnormalities. Under hypoxic conditions, glial cells were activated and released a large number of inflammatory mediators in the PWM in neonatal brain, which may result in oligodendrocyte (OL loss and axonal injury. This study aims to determine if astrocytes are activated and generate proinflammatory cytokines that may be coupled with the oligodendroglial loss and hypomyelination observed in hypoxic PWMD. Twenty-four 1-day-old Wistar rats were exposed to hypoxia for 2 h. The rats were then allowed to recover under normoxic conditions for 7 or 28 days before being killed. Another group of 24 rats kept outside the chamber was used as age-matched controls. Upregulated expression of TNF-α and IL-1β was observed in astrocytes in the PWM of P7 hypoxic rats by double immunofluorescence, western blotting and real time RT-PCR. This was linked to apoptosis and enhanced expression of TNF-R1 and IL-1R1 in APC(+ OLs. PLP expression was decreased significantly in the PWM of P28d hypoxic rats. The proportion of myelinated axons was markedly reduced by electron microscopy (EM and the average g-ratios were higher in P28d hypoxic rats. Upregulated expression of TNF-α and IL-1β in primary cultured astrocytes as well as their corresponding receptors in primary culture APC(+ oligodendrocytes were detected under hypoxic conditions. Our results suggest that following a hypoxic insult, astrocytes in the PWM of neonatal rats produce inflammatory cytokines such as TNF-α and IL-1β, which induce apoptosis of OLs via their corresponding receptors associated with them. This results in hypomyelination in the PWM of hypoxic rats.

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

    OpenAIRE

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

    2012-01-01

    White matter development is important for efficient communication between brain regions, higher order cognitive functioning, and complex behaviors. Adolescents have a higher propensity for engaging in risky behaviors, yet few studies have explored associations between white matter integrity and risk taking directly. Altered white matter integrity in mid-adolescence was hypothesized to predict subsequent risk taking behaviors 1.5 years later. Adolescent substance users (predominantly alcohol a...

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

    Directory of Open Access Journals (Sweden)

    Haiyun Xu

    2011-01-01

    Full Text Available 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.

  12. Magnetic resonance signal intensity ratio of gray/white matter in children; Quantitative assessment in developing brain

    Energy Technology Data Exchange (ETDEWEB)

    Maezawa, Mariko (Tokyo Saiseikai Central Hospital (Japan)); Seki, Tohru; Imura, Soichi; Akiyama, Kazunori; Takikawa, Itsuro; Yuasa, Yuji

    Magnetic resonance imaging (MRI) findings in 87 children with various clinical entities were used to determine the signal intensity ratio of gray/white matter in T[sub 1]-weighted and T[sub 2]-weighted images using a 1.5 T MR scanner. Signal intensity ratio changes in both T[sub 1]- and T[sub 2]-weighted images correlated well with advancing age (y=0.9349-0.001575, r=0.584, P<0.0001 in T[sub 1]-weighted images; y=0.9798+0.002854, r=0.723, P<0.0001 in T[sub 2]-weighted images), but the correlation was more linear when we included only normally developed (34) children (y=0.9689-0.001967, r=-0.654, P<0.0001 in T[sub 1]-weighted images; y=0.9882+0.002965, r=0.747, P<0.0001 in T[sub 2]-weighted images). Abnormal ratios were observed in patients with congenital hydrocephalus, inherited metabolic diseases and cerebral palsy. Although the gray/white matter differentiation would not delineate the myelination itself, measurement of the signal intensity ratio of gray/white matters is a practical way to evaluate delayed myelination in a busy MR center. (author).

  13. White Matter Development during Adolescence as Shown by Diffusion MRI

    Science.gov (United States)

    Schmithorst, Vincent J.; Yuan, Weihong

    2010-01-01

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

  14. MR spectroscopy and diffusion tensor imaging of the brain in congenital muscular dystrophy with merosin deficiency: metabolite level decreases, fractional anisotropy decreases, and apparent diffusion coefficient increases in the white matter.

    Science.gov (United States)

    Sijens, P E; Fock, J M; Meiners, L C; Potze, J H; Irwan, R; Oudkerk, M

    2007-06-01

    Brain magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) in one patient with merosin-deficient congenital muscular dystrophy (MDCMD) revealed significant metabolite (choline, creatine, N-acetyl aspartate) level reductions, fractional anisotropy (FA) reduction and increased apparent diffusion coefficient (ADC) in the white matter (p<0.01, all). In the gray matter, the MRS properties did not differ significantly from those in controls. The ADC and FA, however, differed significantly as in the white matter, although the differences were less pronounced. This is the first quantitative MR study of the brain in a patient with MDCMD, which revealed that the concentrations of all MRS measured metabolites were decreased only in the white matter. This observation, combined with the DTI observed ADC increases and FA decrease, indicated a presence of vasogenic edema in the white matter.

  15. The ameliorative effects of exercise on cognitive impairment and white matter injury from blood-brain barrier disruption induced by chronic cerebral hypoperfusion in adolescent rats.

    Science.gov (United States)

    Lee, Jae-Min; Park, Jong-Min; Song, Min Kyung; Oh, Yoo Joung; Kim, Chang-Ju; Kim, Youn-Jung

    2017-01-18

    Vascular dementia is the progressive change in blood vessels that leads to neuronal injuries in vulnerable areas induced by chronic cerebral hypoperfusion (CCH). CCH induces disruption of blood-brain barrier (BBB), and this BBB disruption can initiate the cognitive impairment and white matter injury. In the present study, we evaluated the effect of treadmill exercise on the cognitive impairment, white matter injury, and BBB disruption induced by CCH. Vascular dementia was induced by permanent bilateral common carotid arteries occlusion (BCCAO) in rats. The rats in the exercise group were made to run on a treadmill for 30min once a day for 14 weeks, starting 4 weeks after birth. Our results revealed that treadmill exercise group was alleviated the cognitive impairment and myelin degradation induced by CCH. The disruption of BBB after CCH indicates degradation of occludin, zonula occluden-1 (ZO-1), and up-regulation of matrix metalloproteinases (MMPs). Treadmill exercise may provide protective effects on BBB disruption from degradation of occludin, ZO-1, and overexpression of MMP-9 after CCH. These findings suggest that treadmill exercise ameliorates cognitive impairment and white matter injury from BBB disruption induced by CCH in rats. The present study will be valuable for means of prophylactic and therapeutic intervention for patients with CCH.

  16. Quantitation of brain tissue changes associated with white matter hyperintensities by diffusion-weighted and magnetization transfer imaging: the LADIS (Leukoaraiosis and Disability in the Elderly) study

    DEFF Research Database (Denmark)

    Ropele, Stefan; Seewann, Alexandra; Gouw, Alida A;

    2009-01-01

    PURPOSE: To explore the value of diffusion-weighted imaging (DWI) and magnetization transfer imaging (MTI) for the improved detection and quantification of cerebral tissue changes associated with ageing and white matter hyperintensities (WMH). MATERIALS AND METHODS: DWI (n = 340) and MTI (n = 177...... brain tissue (NABT) and within WMH and related them to subjects' age and WHM severity according to the Fazekas score. RESULTS: ADC and MTR values showed a significant inter-site variation, which was stronger for the MTR. After z-transformation multiple regression analysis revealed WMH severity and age...

  17. Brainstem white matter integrity is related to loss of consciousness and postconcussive symptomatology in veterans with chronic mild to moderate traumatic brain injury.

    Science.gov (United States)

    Delano-Wood, L; Bangen, K J; Sorg, S F; Clark, A L; Schiehser, D M; Luc, N; Bondi, M W; Werhane, M; Kim, R T; Bigler, E D

    2015-09-01

    We investigated associations between DTI indices of three brainstem white matter tracts, traumatic brain injury (TBI) injury characteristics, and postconcussive symptomatology (PCS) in a well-characterized sample of veterans with history of mild to moderate TBI (mTBI). 58 military veterans (mTBI: n = 38, mean age = 33.2, mean time since injury = 90.9 months; military controls [MC]; n = 20; mean age = 29.4) were administered 3T DTI scans as well as a comprehensive neuropsychiatric evaluation including evaluation of TBI injury characteristics and PCS symptoms (e.g., negative mood, dizziness, balance and coordination difficulties). Tractography was employed by seeding ROIs along 3 brainstem white matter tracts (i.e., medial lemniscus-central tegmentum tract [ML-CTT]; corticospinal tracts [CST], and pontine tegmentum [PT]), and mean DTI values were derived from fractional anisotropic (FA) maps. Results showed that there were no significant difference in FA between the MC and TBI groups across the 3 regions of interest; however, among the TBI group, CST FA was significantly negatively associated with LOC duration. Additionally, lower FA of certain tracts-most especially the PT-was significantly associated with increased PCS symptoms (i.e., more severe vestibular symptoms, poorer physical functioning, and greater levels of fatigue), even after adjusting for PTSD symptoms. Our findings show that, in our sample of veterans with mTBI, tractography-based DTI indices of brainstem white matter tracts of interest are related to the presence and severity of PCS symptoms. Findings are promising as they show linkages between brainstem white matter integrity and injury severity (LOC), and they raise the possibility that the pontine tegmentum in particular may be a useful marker of PCS symptoms. Collectively, these data point to important neurobiological substrates of the chronic and complex constellation of symptoms following the 'signature injury' of our

  18. Excitotoxic damage to white matter

    Science.gov (United States)

    Matute, Carlos; Alberdi, Elena; Domercq, María; Sánchez-Gómez, María-Victoria; Pérez-Samartín, Alberto; Rodríguez-Antigüedad, Alfredo; Pérez-Cerdá, Fernando

    2007-01-01

    Glutamate kills neurons by excitotoxicity, which is caused by sustained activation of glutamate receptors. In recent years, it has been shown that glutamate can also be toxic to white matter oligodendrocytes and to myelin by this mechanism. In particular, glutamate receptor-mediated injury to these cells can be triggered by activation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, kainate and N-methyl-d-aspartate glutamate receptor types. Thus, these receptor classes, and the intermediaries of the signal cascades they activate, are potential targets for drug development to treat white matter damage in acute and chronic diseases. In addition, alterations of glutamate homeostasis in white matter can determine glutamate injury to oligodendrocytes and myelin. Astrocytes are responsible for most glutamate uptake in synaptic and non-synaptic areas and consequently are the major regulators of glutamate homeostasis. Activated microglia in turn may secrete cytokines and generate radical oxygen species, which impair glutamate uptake and reduce the expression of glutamate transporters. Finally, oligodendrocytes also contribute to glutamate homeostasis. This review aims at summarizing the current knowledge about the mechanisms leading to oligodendrocyte cell death and demyelination as a consequence of alterations in glutamate signalling, and their clinical relevance to disease. In addition, we show evidence that oligodendrocytes can also be killed by ATP acting at P2X receptors. A thorough understanding of how oligodendrocytes and myelin are damaged by excitotoxicity will generate knowledge that can lead to improved therapeutic strategies to protect white matter. PMID:17504270

  19. Amyloid precursor protein and growth-associated protein 43 expression in brain white matter and spinal cord tissues in a rat model of experimental autoimmune encephalomyelitis

    Institute of Scientific and Technical Information of China (English)

    Yizhou Wang; Shuang Kou; Jingcheng Tang; Ping Zhang; Qiuxia Zhang; Yan Liu; Qi Zheng; Hui Zhao; Lei Wang

    2011-01-01

    Studies have demonstrated that amyloid precursor protein (APP) expression increases in multiple sclerosis tissues during acutely and chronically active stages.To determine the relationship between axonal injury and regeneration in multiple sclerosis, an animal model of experimental autoimmune encephalomyelitis was induced using different doses of myelin basic protein peptide.APP and growth-associated protein 43 (GAP-43), which is considered a specific marker of neural regeneration, were assessed by western blot analysis.Expression of APP and GAP-43, as well as the correlation between these two proteins, in brain white matter and spinal cord tissues of experimental autoimmune encephalomyelitis rats at different pathological stages was analyzed.Results showed that APP and GAP-43 expression increased during the acute stage and decreased during remission, with a positive correlation between APP and GAP-43 expression in brain white matter and spinal cord tissues.These results suggest that APP and GAP-43 could provide nutritional and protective effects on damaged neurons.

  20. White matter abnormalities of microstructure and physiological noise in schizophrenia.

    Science.gov (United States)

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

    2015-12-01

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

  1. Increased concentrations of glutamate and glutamine in normal-appearing white matter of patients with multiple sclerosis and normal MR imaging brain scans.

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    Anders Tisell

    Full Text Available In Multiple Sclerosis (MS the relationship between disease process in normal-appearing white matter (NAWM and the development of white matter lesions is not well understood. In this study we used single voxel proton 'Quantitative Magnetic Resonance Spectroscopy' (qMRS to characterize the NAWM and thalamus both in atypical 'Clinically Definite MS' (CDMS patients, MRI(neg (N = 15 with very few lesions (two or fewer lesions, and in typical CDMS patients, MRI(pos (N = 20 with lesions, in comparison with healthy control subjects (N = 20. In addition, the metabolite concentrations were also correlated with extent of brain atrophy measured using Brain Parenchymal Fraction (BPF and severity of the disease measured using 'Multiple Sclerosis Severity Score' (MSSS. Elevated concentrations of glutamate and glutamine (Glx were observed in both MS groups (MRI(neg 8.12 mM, p<0.001 and MRI(pos 7.96 mM p<0.001 compared to controls, 6.76 mM. Linear regressions of Glx and total creatine (tCr with MSSS were 0.16 ± 0.06 mM/MSSS (p = 0.02 for Glx and 0.06 ± 0.03 mM/MSSS (p = 0.04 for tCr, respectively. Moreover, linear regressions of tCr and myo-Inositol (mIns with BPF were -6.22 ± 1.63 mM/BPF (p<0.001 for tCr and -7.71 ± 2.43 mM/BPF (p = 0.003 for mIns. Furthermore, the MRI(pos patients had lower N-acetylaspartate and N-acetylaspartate-glutamate (tNA and elevated mIns concentrations in NAWM compared to both controls (tNA: p = 0.04 mIns p<0.001 and MRI(neg (tNA: p = 0.03 , mIns: p = 0.002. The results suggest that Glx may be an important marker for pathology in non-lesional white matter in MS. Moreover, Glx is related to the severity of MS independent of number of lesions in the patient. In contrast, increased glial density indicated by increased mIns and decreased neuronal density indicated by the decreased tNA, were only observed in NAWM of typical CDMS patients with white matter lesions.

  2. Gray matter and white matter abnormalities in online game addiction

    Energy Technology Data Exchange (ETDEWEB)

    Weng, Chuan-Bo, E-mail: send007@163.com [Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, 17 Lujiang Road, Hefei, Ahui Province 230001 (China); School of Neurosurgery, Anhui Medical University, 81 Meishang Road, Hefei, Anhui Province 230032 (China); Qian, Ruo-Bing, E-mail: rehomail@163.com [Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, 17 Lujiang Road, Hefei, Ahui Province 230001 (China); Anhui Provincial Institute of Stereotactic Neurosurgery, 9 Lujiang Road, Hefei, Ahui Province 230001 (China); Fu, Xian-Ming, E-mail: 506537677@qq.com [Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, 17 Lujiang Road, Hefei, Ahui Province 230001 (China); Anhui Provincial Institute of Stereotactic Neurosurgery, 9 Lujiang Road, Hefei, Ahui Province 230001 (China); Lin, Bin, E-mail: 274722758@qq.com [School of Neurosurgery, Anhui Medical University, 81 Meishang Road, Hefei, Anhui Province 230032 (China); Han, Xiao-Peng, E-mail: hanxiaopeng@163.com [Department of Psychology, Anhui Provincial Hospital Affiliated to Anhui Medical University, 17 Lujiang Road, Hefei, Ahui Province 230001 (China); Niu, Chao-Shi, E-mail: niuchaoshi@163.com [Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, 17 Lujiang Road, Hefei, Ahui Province 230001 (China); Anhui Provincial Institute of Stereotactic Neurosurgery, 9 Lujiang Road, Hefei, Ahui Province 230001 (China); Wang, Ye-Han, E-mail: wangyehan@163.com [Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, 17 Lujiang Road, Hefei, Ahui Province 230001 (China); Anhui Provincial Institute of Stereotactic Neurosurgery, 9 Lujiang Road, Hefei, Ahui Province 230001 (China)

    2013-08-15

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

  3. Density abnormalities in normal-appearing gray matter in the middle-aged brain with white matter hyperintense lesions: a DARTEL-enhanced voxel-based morphometry study

    Directory of Open Access Journals (Sweden)

    Peng Y

    2016-05-01

    Full Text Available Yan Peng,1,* Shenhong Li,2,* Ying Zhuang,3,* Xiaojia Liu,4 Lin Wu,2 Honghan Gong,2 Dewu Liu,1 Fuqing Zhou2 1Burn Center, 2Department of Radiology, The First Affiliated Hospital, Nanchang University, 3Department of Oncology, The Second Hospital of Nanchang, Nanchang, Jiangxi Province, 4Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, People’s Republic of China *These authors contributed equally to this work Background and purpose: Little is known about the structural alterations within gray matter (GM in middle-aged subjects with white matter hyperintense (WMH lesions. Here, we aimed to examine the anatomical changes within the GM and their relationship to WMH lesion loads in middle-aged subjects. Participants and methods: Twenty-three middle-aged subjects with WMH lesions (WMH group and 23 demographically matched healthy control subjects participated in the study. A Diffeomorphic Anatomical Registration Through Exponentiated Liealgebra-enhanced voxel-based morphometry was used to measure the GM density, and the correlations between WMH lesion volume and extracted GM values in abnormal regions were identified by voxel-based morphometry analysis. Results: Compared with the healthy control subjects, the WMH group had a significantly decreased GM density in the left middle frontal gyrus, bilateral anterior cingulate cortex, left and right premotor cortex, and left and right middle cingulate cortex and an increased GM density in the bilateral cerebellum anterior lobe, left middle temporal gyrus, right temporoparietal junction, left and right prefrontal cortex (PFC, and left inferior parietal lobule. A relationship was observed between the normalized WMH lesion volume and the decreased GM density, including the left middle frontal gyrus (ρ=-0.629, P=0.002, bilateral anterior cingulate cortex (ρ=-0.507, P=0.019, right middle cingulate cortex (ρ=-0.484, P=0.026, and

  4. Automated Spatial Brain Normalization and Hindbrain White Matter Reference Tissue Give Improved [(18)F]-Florbetaben PET Quantitation in Alzheimer's Model Mice.

    Science.gov (United States)

    Overhoff, Felix; Brendel, Matthias; Jaworska, Anna; Korzhova, Viktoria; Delker, Andreas; Probst, Federico; Focke, Carola; Gildehaus, Franz-Josef; Carlsen, Janette; Baumann, Karlheinz; Haass, Christian; Bartenstein, Peter; Herms, Jochen; Rominger, Axel

    2016-01-01

    Preclinical PET studies of β-amyloid (Aβ) accumulation are of growing importance, but comparisons between research sites require standardized and optimized methods for quantitation. Therefore, we aimed to evaluate systematically the (1) impact of an automated algorithm for spatial brain normalization, and (2) intensity scaling methods of different reference regions for Aβ-PET in a large dataset of transgenic mice. PS2APP mice in a 6 week longitudinal setting (N = 37) and another set of PS2APP mice at a histologically assessed narrow range of Aβ burden (N = 40) were investigated by [(18)F]-florbetaben PET. Manual spatial normalization by three readers at different training levels was performed prior to application of an automated brain spatial normalization and inter-reader agreement was assessed by Fleiss Kappa (κ). For this method the impact of templates at different pathology stages was investigated. Four different reference regions on brain uptake normalization were used to calculate frontal cortical standardized uptake value ratios (SUVRCTX∕REF), relative to raw SUVCTX. Results were compared on the basis of longitudinal stability (Cohen's d), and in reference to gold standard histopathological quantitation (Pearson's R). Application of an automated brain spatial normalization resulted in nearly perfect agreement (all κ≥0.99) between different readers, with constant or improved correlation with histology. Templates based on inappropriate pathology stage resulted in up to 2.9% systematic bias for SUVRCTX∕REF. All SUVRCTX∕REF methods performed better than SUVCTX both with regard to longitudinal stability (d≥1.21 vs. d = 0.23) and histological gold standard agreement (R≥0.66 vs. R≥0.31). Voxel-wise analysis suggested a physiologically implausible longitudinal decrease by global mean scaling. The hindbrain white matter reference (R mean = 0.75) was slightly superior to the brainstem (R mean = 0.74) and the cerebellum (R mean = 0.73). Automated

  5. Automated spatial brain normalization and hindbrain white matter reference tissue give improved [18F]-florbetaben PET quantitation in Alzheimer´s model mice

    Directory of Open Access Journals (Sweden)

    Felix eOverhoff

    2016-02-01

    Full Text Available Preclinical PET studies of β-amyloid (Aβ accumulation are of growing importance, but comparisons between research sites require standardized and optimized methods for quantitation. Therefore we aimed to evaluate systematically the 1 impact of an automated algorithm for spatial brain normalization, and 2 intensity scaling methods of different reference regions for Aβ-PET in a large dataset of transgenic mice. PS2APP mice in a six week longitudinal setting (N = 37 and another set of PS2APP mice at a histologically assessed narrow range of Aβ burden (N = 40 were investigated by [18F]-florbetaben PET. Manual spatial normalization by three readers at different training levels was performed prior to application of an automated brain spatial normalization and inter-reader agreement was assessed by Fleiss Kappa (κ. For this method the impact of templates at different pathology stages was investigated. Four different reference regions on brain uptake normalization were used to calculate frontal cortical standardized uptake value ratios (SUVRCTX/REF, relative to raw SUVCTX. Results were compared on the basis of longitudinal stability (Cohen’s d, and in reference to gold standard histopathological quantitation (Pearson’s R.Application of an automated brain spatial normalization resulted in nearly perfect agreement (all κ ≥ 0.99 between different readers, with constant or improved correlation with histology. Templates based on inappropriate pathology stage resulted in up to 2.9% systematic bias for SUVRCTX/REF. All SUVRCTX/REF methods performed better than SUVCTX both with regard to longitudinal stability (d ≥ 1.21 vs. d = 0.23 and histological gold standard agreement (R ≥ 0.66 vs. R ≥ 0.31. Voxel-wise analysis suggested a physiologically implausible longitudinal decrease of global mean scaling. The hindbrain white matter reference (Rmean = 0.75 was slightly superior to the brainstem (Rmean = 0.74 and the cerebellum (Rmean = 0

  6. White matter development in adolescence: a DTI study.

    Science.gov (United States)

    Asato, M R; Terwilliger, R; Woo, J; Luna, B

    2010-09-01

    Adolescence is a unique period of physical and cognitive development that includes concurrent pubertal changes and sex-based vulnerabilities. While diffusion tensor imaging (DTI) studies show white matter maturation throughout the lifespan, the state of white matter integrity specific to adolescence is not well understood as are the contributions of puberty and sex. We performed whole-brain DTI studies of 114 children, adolescents, and adults to identify age-related changes in white matter integrity that characterize adolescence. A distinct set of regions across the brain were found to have decreasing radial diffusivity across age groups. Region of interest analyses revealed that maturation was attained by adolescence in broadly distributed association and projection fibers, including those supporting cortical and brain stem integration that may underlie known enhancements in reaction time during this period. Maturation after adolescence included association and projection tracts, including prefrontal-striatal connections, known to support top-down executive control of behavior and interhemispheric connectivity. Maturation proceeded in parallel with pubertal changes to the postpubertal stage, suggesting hormonal influences on white matter development. Females showed earlier maturation of white matter integrity compared with males. Together, these findings suggest that white matter connectivity supporting executive control of behavior is still immature in adolescence.

  7. Improved delineation of short cortical association fibers and gray/white matter boundary using whole-brain three-dimensional diffusion tensor imaging at submillimeter spatial resolution.

    Science.gov (United States)

    Song, Allen W; Chang, Hing-Chiu; Petty, Christopher; Guidon, Arnaud; Chen, Nan-Kuei

    2014-11-01

    Recent emergence of human connectome imaging has led to a high demand on angular and spatial resolutions for diffusion magnetic resonance imaging (MRI). While there have been significant growths in high angular resolution diffusion imaging, the improvement in spatial resolution is still limited due to a number of technical challenges, such as the low signal-to-noise ratio and high motion artifacts. As a result, the benefit of a high spatial resolution in the whole-brain connectome imaging has not been fully evaluated in vivo. In this brief report, the impact of spatial resolution was assessed in a newly acquired whole-brain three-dimensional diffusion tensor imaging data set with an isotropic spatial resolution of 0.85 mm. It was found that the delineation of short cortical association fibers is drastically improved as well as the definition of fiber pathway endings into the gray/white matter boundary-both of which will help construct a more accurate structural map of the human brain connectome.

  8. TVA–based assessment of attentional capacities – associations with age and indices of brain white matter microstructure

    Directory of Open Access Journals (Sweden)

    Thomas eEspeseth

    2014-10-01

    Full Text Available In this study the primary aims were to characterize the effects of age on basic components of visual attention derived from assessments based on a theory of visual attention (TVA in 325 healthy volunteers covering the adult lifespan (19-81 years. Furthermore, we aimed to investigate how age-related differences on TVA parameters are associated with white matter (WM microstructure as indexed by diffusion tensor imaging (DTI. Finally, we explored how TVA parameter estimates were associated with complex, or multicomponent indices of processing speed (Digit-symbol substitution, DSS and fluid intelligence (gF. The results indicated that the TVA parameters for visual short-term memory capacity, K, and for attentional selectivity, α, were most strongly associated with age before the age of 50. However, in this age range, it was the parameter for processing speed, C, that was most clearly associated with DTI indices, in this case fractional anisotropy (FA, particularly in the genu and body of the corpus callosum. Furthermore, differences in the C parameter partially mediated differences in DSS within this age range. After the age of 50, the TVA parameter for the perceptual threshold, t0, as well as K, were most strongly related to participant age. Both parameters, but t0 more strongly so than K, were associated WM diffusivity, particularly in projection fibers such as the internal capsule, the sagittal stratum, and the corona radiata. Within this age range, t0 partially mediated age-related differences in gF. The results are consistent with, and provide novel empirical support for the neuroanatomical localization of TVA computations as outlined in the neuronal interpretation of TVA (NTVA. Furthermore, the results indicate that to understand the biological sources of age-related changes in processing speed and fluid cognition, it may be useful to employ methods that allow for computational fractionation of these multicomponent measures.

  9. An allometric scaling law between gray matter and white matter of cerebral cortex

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    He Jihuan [College of Science, Donghua University, Shanghai, 1882 Yan' an Xilu Road, Shanghai 200051 (China)] e-mail: jhhe@dhu.edu.cn

    2006-02-01

    An allometric scaling relationship between cortical white and gray volumes is derived from a general model that describes brain's remarkable efficiency and prodigious communications between brain areas. The model assumes that (1) a cell's metabolic rate depends upon cell's surface; (2) the overall basal metabolic rates of brain areas depend upon their fractal structures; (3) differential brain areas have same basal metabolic rate at slow wave sleep. The obtained allometric exponent scaling white matter to gray matter is 1.2, which is very much close to Zhang and Sejnowski's observation data.

  10. Gender differences in white matter microstructure.

    Directory of Open Access Journals (Sweden)

    Richard A Kanaan

    Full Text Available BACKGROUND: Sexual dimorphism in human brain structure is well recognised, but little is known about gender differences in white matter microstructure. We used diffusion tensor imaging to explore differences in fractional anisotropy (FA, an index of microstructural integrity. METHODS: A whole brain analysis of 135 matched subjects (90 men and 45 women using a 1.5 T scanner. A region of interest (ROI analysis was used to confirm those results where proximity to CSF raised the possibility of partial-volume artefact. RESULTS: Men had higher fractional anisotropy (FA in cerebellar white matter and in the left superior longitudinal fasciculus; women had higher FA in the corpus callosum, confirmed by ROI. DISCUSSION: The size of the differences was substantial--of the same order as that attributed to some pathology--suggesting gender may be a potentially significant confound in unbalanced clinical studies. There are several previous reports of difference in the corpus callosum, though they disagree on the direction of difference; our findings in the cerebellum and the superior longitudinal fasciculus have not previously been noted. The higher FA in women may reflect greater efficiency of a smaller corpus callosum. The relatively increased superior longitudinal fasciculus and cerebellar FA in men may reflect their increased language lateralisation and enhanced motor development, respectively.

  11. Gender Differences in White Matter Microstructure

    Science.gov (United States)

    Kanaan, Richard A.; Allin, Matthew; Picchioni, Marco; Barker, Gareth J.; Daly, Eileen; Shergill, Sukhwinder S.; Woolley, James; McGuire, Philip K.

    2012-01-01

    Background Sexual dimorphism in human brain structure is well recognised, but little is known about gender differences in white matter microstructure. We used diffusion tensor imaging to explore differences in fractional anisotropy (FA), an index of microstructural integrity. Methods A whole brain analysis of 135 matched subjects (90 men and 45 women) using a 1.5 T scanner. A region of interest (ROI) analysis was used to confirm those results where proximity to CSF raised the possibility of partial-volume artefact. Results Men had higher fractional anisotropy (FA) in cerebellar white matter and in the left superior longitudinal fasciculus; women had higher FA in the corpus callosum, confirmed by ROI. Discussion The size of the differences was substantial - of the same order as that attributed to some pathology – suggesting gender may be a potentially significant confound in unbalanced clinical studies. There are several previous reports of difference in the corpus callosum, though they disagree on the direction of difference; our findings in the cerebellum and the superior longitudinal fasciculus have not previously been noted. The higher FA in women may reflect greater efficiency of a smaller corpus callosum. The relatively increased superior longitudinal fasciculus and cerebellar FA in men may reflect their increased language lateralisation and enhanced motor development, respectively. PMID:22701619

  12. Linked alterations in gray and white matter morphology in adults with high-functioning autism spectrum disorder: A multimodal brain imaging study

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    Takashi Itahashi

    2015-01-01

    Full Text Available Growing evidence suggests that a broad range of behavioral anomalies in people with autism spectrum disorder (ASD can be linked with morphological and functional alterations in the brain. However, the neuroanatomical underpinnings of ASD have been investigated using either structural magnetic resonance imaging (MRI or diffusion tensor imaging (DTI, and the relationships between abnormalities revealed by these two modalities remain unclear. This study applied a multimodal data-fusion method, known as linked independent component analysis (ICA, to a set of structural MRI and DTI data acquired from 46 adult males with ASD and 46 matched controls in order to elucidate associations between different aspects of atypical neuroanatomy of ASD. Linked ICA identified two composite components that showed significant between-group differences, one of which was significantly correlated with age. In the other component, participants with ASD showed decreased gray matter (GM volumes in multiple regions, including the bilateral fusiform gyri, bilateral orbitofrontal cortices, and bilateral pre- and post-central gyri. These GM changes were linked with a pattern of decreased fractional anisotropy (FA in several white matter tracts, such as the bilateral inferior longitudinal fasciculi, bilateral inferior fronto-occipital fasciculi, and bilateral corticospinal tracts. Furthermore, unimodal analysis for DTI data revealed significant reductions of FA along with increased mean diffusivity in those tracts for ASD, providing further evidence of disrupted anatomical connectivity. Taken together, our findings suggest that, in ASD, alterations in different aspects of brain morphology may co-occur in specific brain networks, providing a comprehensive view for understanding the neuroanatomy of this disorder.

  13. Major Superficial White Matter Abnormalities in Huntington's Disease

    Science.gov (United States)

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

    2016-01-01

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

  14. Major Superficial White Matter Abnormalities in Huntington disease

    Directory of Open Access Journals (Sweden)

    Owen Robert Phillips

    2016-05-01

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

  15. Magnetic resonance imaging of white matter diseases of prematurity

    Energy Technology Data Exchange (ETDEWEB)

    Rutherford, Mary A.; Supramaniam, Veena; Ederies, Ashraf; Chew, Andrew; Anjari, Mustafa; Counsell, Serena [Imperial College, Hammersmith Hospital, Robert Steiner MR Unit, MRC Clinical Sciences Centre, London (United Kingdom); Bassi, Laura; Groppo, Michela; Ramenghi, Luca A. [University of Milan, NICU, Institute of Pediatrics and Neonatology, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan (Italy)

    2010-06-15

    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. (orig.)

  16. Unraveling the secrets of white matter – Bridging the gap between cellular, animal and human imaging studies

    OpenAIRE

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

    2014-01-01

    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. Collab...

  17. Abnormal white matter properties in adolescent girls with anorexia nervosa

    Science.gov (United States)

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

    2015-01-01

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

  18. Abnormal white matter properties in adolescent girls with anorexia nervosa

    Directory of Open Access Journals (Sweden)

    Katherine E. Travis

    2015-01-01

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

  19. White matter connectivity and Internet gaming disorder.

    Science.gov (United States)

    Jeong, Bum Seok; Han, Doug Hyun; Kim, Sun Mi; Lee, Sang Won; Renshaw, Perry F

    2016-05-01

    Internet use and on-line game play stimulate corticostriatal-limbic circuitry in both healthy subjects and subjects with Internet gaming disorder (IGD). We hypothesized that increased fractional anisotropy (FA) with decreased radial diffusivity (RD) would be observed in IGD subjects, compared with healthy control subjects, and that these white matter indices would be associated with clinical variables including duration of illness and executive function. We screened 181 male patients in order to recruit a large number (n = 58) of IGD subjects without psychiatric co-morbidity as well as 26 male healthy comparison subjects. Multiple diffusion-weighted images were acquired using a 3.0 Tesla magnetic resonance imaging scanner. Tract-based spatial statistics was applied to compare group differences in diffusion tensor imaging (DTI) metrics between IGD and healthy comparison subjects. IGD subjects had increased FA values within forceps minor, right anterior thalamic radiation, right corticospinal tract, right inferior longitudinal fasciculus, right cingulum to hippocampus and right inferior fronto-occipital fasciculus (IFOF) as well as parallel decreases in RD value within forceps minor, right anterior thalamic radiation and IFOF relative to healthy control subjects. In addition, the duration of illness in IGD subjects was positively correlated with the FA values (integrity of white matter fibers) and negatively correlated with RD scores (diffusivity of axonal density) of whole brain white matter. In IGD subjects without psychiatric co-morbidity, our DTI results suggest that increased myelination (increased FA and decreased RD values) in right-sided frontal fiber tracts may be the result of extended game play.

  20. IMAGING WHITE MATTER IN HUMAN BRAINSTEM

    Directory of Open Access Journals (Sweden)

    Anastasia A Ford

    2013-07-01

    Full Text Available The human brainstem is critical for the control of many life-sustaining functions, such as consciousness, respiration, sleep, and transfer of sensory and motor information between the brain and the spinal cord. Most of our knowledge about structure and organization of white and gray matter within the brainstem is derived from ex vivo dissection and histology studies. However, these methods cannot be applied to study structural architecture in live human participants. Tractography from diffusion-weighted MRI may provide valuable insights about white matter organization within the brainstem in vivo. However, this method presents technical challenges in vivo due to susceptibility artifacts, functionally dense anatomy, as well as pulsatile and respiratory motion. To investigate the limits of MR tractography, we present results from high angular resolution diffusion imaging (HARDI of an intact excised human brainstem performed at 11.1T using isotropic resolution of 0.333, 1, and 2 mm, with the latter reflecting resolution currently used clinically. At the highest resolution, the dense fiber architecture of the brainstem is evident, but the definition of structures degrades as resolution decreases. In particular, the inferred corticopontine/corticospinal tracts (CPT/CST, superior (SCP and middle cerebellar peduncle (MCP, and medial lemniscus (ML pathways are clearly discernable and follow known anatomical trajectories at the highest spatial resolution. At lower resolutions, the CST/CPT, SCP, and MCP pathways are artificially enlarged due to inclusion of collinear and crossing fibers not inherent to these three pathways. The inferred ML pathways appear smaller at lower resolutions, indicating insufficient spatial information to successfully resolve smaller fiber pathways. Our results suggest that white matter tractography maps derived from the excised brainstem can be used to guide the study of the brainstem architecture using diffusion MRI in vivo.

  1. Physical Exercise Keeps the Brain Connected : Biking Increases White Matter Integrity in Patients With Schizophrenia and Healthy Controls

    NARCIS (Netherlands)

    Svatkova, Alena; Mandl, Rene C. W.; Scheewe, Thomas W.; Cahn, Wiepke; Kahn, Rene S.; Pol, Hilleke E. Hulshoff

    2015-01-01

    It has been shown that learning a new skill leads to structural changes in the brain. However, it is unclear whether it is the acquisition or continuous practicing of the skill that causes this effect and whether brain connectivity of patients with schizophrenia can benefit from such practice. We ex

  2. Q-ball imaging models: comparison between high and low angular resolution diffusion-weighted MRI protocols for investigation of brain white matter integrity

    Energy Technology Data Exchange (ETDEWEB)

    Caiazzo, Giuseppina; Trojsi, Francesca; Cirillo, Mario; Tedeschi, Gioacchino [MRI Research Center SUN-FISM-Neurological Institute for Diagnosis and Care ' ' Hermitage Capodimonte' ' , Naples (Italy); Second University of Naples, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Naples (Italy); Esposito, Fabrizio [University of Salerno, Department of Medicine and Surgery, Baronissi (Salerno) (Italy); Maastricht University, Department of Cognitive Neuroscience, Maastricht (Netherlands)

    2016-02-15

    Q-ball imaging (QBI) is one of the typical data models for quantifying white matter (WM) anisotropy in diffusion-weighted MRI (DwMRI) studies. Brain and spinal investigation by high angular resolution DwMRI (high angular resolution imaging (HARDI)) protocols exhibits higher angular resolution in diffusion imaging compared to low angular resolution models, although with longer acquisition times. We aimed to assess the difference between QBI-derived anisotropy values from high and low angular resolution DwMRI protocols and their potential advantages or shortcomings in neuroradiology. Brain DwMRI data sets were acquired in seven healthy volunteers using both HARDI (b = 3000 s/mm{sup 2}, 54 gradient directions) and low angular resolution (b = 1000 s/mm{sup 2}, 32 gradient directions) acquisition schemes. For both sequences, tract of interest tractography and generalized fractional anisotropy (GFA) measures were extracted by using QBI model and were compared between the two data sets. QBI tractography and voxel-wise analyses showed that some WM tracts, such as corpus callosum, inferior longitudinal, and uncinate fasciculi, were reconstructed as one-dominant-direction fiber bundles with both acquisition schemes. In these WM tracts, mean percent different difference in GFA between the two data sets was less than 5 %. Contrariwise, multidirectional fiber bundles, such as corticospinal tract and superior longitudinal fasciculus, were more accurately depicted by HARDI acquisition scheme. Our results suggest that the design of optimal DwMRI acquisition protocols for clinical investigation of WM anisotropy by QBI models should consider the specific brain target regions to be explored, inducing researchers to a trade-off choice between angular resolution and acquisition time. (orig.)

  3. Optimal voxel size for measuring global gray and white matter proton metabolite concentrations using chemical shift imaging

    DEFF Research Database (Denmark)

    Hanson, Lars Peter Grüner; Adalsteinsson, E; Pfefferbaum, A;

    2000-01-01

    Quantification of gray and white matter levels of spectroscopically visible metabolites can provide important insights into brain development and pathological conditions. Chemical shift imaging offers a gain in efficiency for estimation of global gray and white matter metabolite concentrations...

  4. Brain intracellular metabolites are freely diffusing along cell fibers in grey and white matter, as measured by diffusion-weighted MR spectroscopy in the human brain at 7 T.

    Science.gov (United States)

    Najac, Chloé; Branzoli, Francesca; Ronen, Itamar; Valette, Julien

    2016-04-01

    Due to the specific compartmentation of brain metabolites, diffusion-weighted magnetic resonance spectroscopy opens unique insight into neuronal and astrocytic microstructures. The apparent diffusion coefficient (ADC) of brain metabolites depends on various intracellular parameters including cytosol viscosity and molecular crowding. When diffusion time (t d) is long enough, the size and geometry of the compartment in which the metabolites diffuse strongly influence metabolites ADC. In a previous study, performed in the macaque brain, we measured neuronal and astrocytic metabolites ADC at long t d (from 86 to 1,011 ms) in a large voxel enclosing an equal proportion of white and grey matter. We showed that metabolites apparently diffuse freely along the axis of dendrites, axons and astrocytic processes. To assess potential differences between these two tissue types, here we measured for the first time in the Human brain the t d-dependency of metabolites trace/3 ADC at 7 teslas using a localized diffusion-weighted STEAM sequence, in parietal and occipital voxels, respectively, containing mainly white and grey matter. We show that, in both tissues and over the observed timescale (t d varying from 92 to 712 ms) metabolite ADC reaches a non-zero plateau, suggesting that metabolites are not confined inside subcellular regions such as cell bodies, or inside subcellular compartments such as organelles, but are rather free to diffuse in the whole fiber-like structure of neurons and astrocytes. Beyond the fundamental insights into intracellular compartmentation of metabolites, this work also provides a new framework for interpreting results of neuroimaging techniques based on molecular diffusion, such as diffusion-weighted magnetic resonance spectroscopy and imaging.

  5. White Matter Maturation Supports the Development of Reasoning Ability through Its Influence on Processing Speed

    Science.gov (United States)

    Ferrer, Emilio; Whitaker, Kirstie J.; Steele, Joel S.; Green, Chloe T.; Wendelken, Carter; Bunge, Silvia A.

    2013-01-01

    The structure of the human brain changes in several ways throughout childhood and adolescence. Perhaps the most salient of these changes is the strengthening of white matter tracts that enable distal brain regions to communicate with one another more quickly and efficiently. Here, we sought to understand whether and how white matter changes…

  6. Training-induced improvements in postural control are accompanied by alterations in cerebellar white matter in brain injured patients

    NARCIS (Netherlands)

    Drijkoningen, D.; Caeyenberghs, K.; Leunissen, I.; Linden, C. van der; Leemans, A.; Sunaert, S.; Duysens, J.E.J.; Swinnen, S.P.

    2015-01-01

    We investigated whether balance control in young TBI patients can be promoted by an 8-week balance training program and whether this is associated with neuroplastic alterations in brain structure. The cerebellum and cerebellar peduncles were selected as regions of interest because of their importanc

  7. Prefrontal Lobe Brain Reserve Capacity with Resistance to Higher Global Amyloid Load and White Matter Hyperintensity Burden in Mild Stage Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Ya-Ting Chang

    Full Text Available Amyloid deposition and white matter lesions (WMLs in Alzheimer's disease (AD are both considered clinically significant while a larger brain volume is thought to provide greater brain reserve (BR against these pathological effects. This study identified the topography showing BR in patients with mild AD and explored the clinical balances among BR, amyloid, and WMLs burden.Thirty patients with AD were enrolled, and AV-45 positron emission tomography was conducted to measure the regional standardized uptake value ratio (SUVr in 8 cortical volumes-of- interests (VOIs. The quantitative WMLs burden was measured from magnetic resonance imaging while the normalized VOIs volumes represented BR in this study. The cognitive test represented major clinical correlates.Significant correlations between the prefrontal volume and global (r = 0.470, p = 0.024, but not regional (r = 0.264, p = 0.223 AV-45 SUVr were found. AD patients having larger regional volume in the superior- (r = 0.572, p = 0.004, superior medial- (r = 0.443, p = 0.034, and middle-prefrontal (r = 0.448, p = 0.032 regions had higher global AV-45 SUVr. For global WML loads, the prefrontal (r = -0.458, p = 0.019 and hippocampal volume (r = -0.469, p = 0.016 showed significant correlations while the prefrontal (r = -0.417, p = 0.043 or hippocampal volume (r = -0.422, p = 0.04 also predicted better composite memory scores. There were no interactions between amyloid SUVr and WML loads on the prefrontal volume.BR of the prefrontal region might modulate the adverse global pathological burden caused by amyloid deposition. While prefrontal volume positively associated with hippocampal volume, WMLs had an adverse impact on the hippocampal volume that predicts memory performance in mild stage AD.

  8. White matter tracts critical for recognition of sarcasm.

    Science.gov (United States)

    Davis, Cameron L; Oishi, Kenichi; Faria, Andreia V; Hsu, John; Gomez, Yessenia; Mori, Susumu; Hillis, Argye E

    2016-01-01

    Failure to recognize sarcasm can lead to important miscommunications. Few previous studies have identified brain lesions associated with impaired recognition of sarcasm. We tested the hypothesis that percent damage to specific white matter tracts, age, and education together predict accuracy in sarcasm recognition. Using multivariable linear regression, with age, education, and percent damage to each of eight white matter tracts as independent variables, and percent accuracy on sarcasm recognition as the dependent variable, we developed a model for predicting sarcasm recognition. Percent damage to the sagittal stratum had the greatest weight and was the only independent predictor of sarcasm recognition.

  9. Moderate and late preterm infants exhibit widespread brain white matter microstructure alterations at term-equivalent age relative to term-born controls

    NARCIS (Netherlands)

    Kelly, Claire E.; Cheong, Jeanie L Y; Gabra Fam, Lillian; Leemans, Alexander; Seal, Marc L.; Doyle, Lex W.; Anderson, Peter J.; Spittle, Alicia J.; Thompson, Deanne K.

    2016-01-01

    Despite the many studies documenting cerebral white matter microstructural alterations associated with very preterm birth (<32 weeks’ gestation), there is a dearth of similar research in moderate and late preterm infants (born 32–36 weeks’ gestation), who experience higher rates of neurodevelopmenta

  10. White matter changes and word finding failures with increasing age.

    Directory of Open Access Journals (Sweden)

    Emmanuel A Stamatakis

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

  11. The prognostic value of multivoxel magnetic resonance spectroscopy determined metabolite levels in white and grey matter brain tissue for adverse outcome in term newborns following perinatal asphyxia

    NARCIS (Netherlands)

    van Doormaal, Pieter Jan; Meiners, Linda C.; ter Horst, Hendrik J.; van der Veere, Christa N.; Sijens, Paul E.

    2012-01-01

    Magnetic resonance spectroscopy can identify brain metabolic changes in perinatal asphyxia by providing ratios of metabolites, such as choline (Cho), creatine (Cr), N-acetyl aspartate (NAA) and lactate (Lact) [Cho/Cr, Lact/NAA, etc.]. The purpose of this study was to quantify the separate white and

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Andreia V. Faria

    2016-01-01

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

  14. Impaired empathic abilities and reduced white matter integrity in schizophrenia.

    Science.gov (United States)

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

    2014-01-01

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

  15. Comparison of cortical and white matter traumatic brain injury models reveals differential effects in the subventricular zone and divergent Sonic hedgehog signaling pathways in neuroblasts and oligodendrocyte progenitors.

    Science.gov (United States)

    Mierzwa, Amanda J; Sullivan, Genevieve M; Beer, Laurel A; Ahn, Sohyun; Armstrong, Regina C

    2014-01-01

    The regenerative capacity of the central nervous system must be optimized to promote repair following traumatic brain injury (TBI) and may differ with the site and form of damage. Sonic hedgehog (Shh) maintains neural stem cells and promotes oligodendrogenesis. We examined whether Shh signaling contributes to neuroblast (doublecortin) or oligodendrocyte progenitor (neural/glial antigen 2 [NG2]) responses in two distinct TBI models. Shh-responsive cells were heritably labeled in vivo using Gli1-CreER(T2);R26-YFP bitransgenic mice with tamoxifen administration on Days 2 and 3 post-TBI. Injury to the cerebral cortex was produced with mild controlled cortical impact. Yellow fluorescent protein (YFP) cells decreased in cortical lesions. Total YFP cells increased in the subventricular zone (SVZ), indicating Shh pathway activation in SVZ cells, including doublecortin-labeled neuroblasts. The alternate TBI model produced traumatic axonal injury in the corpus callosum. YFP cells decreased within the SVZ and were rarely double labeled as NG2 progenitors. NG2 progenitors increased in the cortex, with a similar pattern in the corpus callosum. To further test the potential of NG2 progenitors to respond through Shh signaling, Smoothened agonist was microinjected into the corpus callosum to activate Shh signaling. YFP cells and NG2 progenitors increased in the SVZ but were not double labeled. This result indicates that either direct Smoothened activation in NG2 progenitors does not signal through Gli1 or that Smoothened agonist acts indirectly to increase NG2 progenitors. Therefore, in all conditions, neuroblasts exhibited differential Shh pathway utilization compared with oligodendrocyte progenitors. Notably, cortical versus white matter damage from TBI produced opposite responses of Shh-activated cells within the SVZ.

  16. Comparison of Cortical and White Matter Traumatic Brain Injury Models Reveals Differential Effects in the Subventricular Zone and Divergent Sonic Hedgehog Signaling Pathways in Neuroblasts and Oligodendrocyte Progenitors

    Directory of Open Access Journals (Sweden)

    Amanda J. Mierzwa

    2014-09-01

    Full Text Available The regenerative capacity of the central nervous system must be optimized to promote repair following traumatic brain injury (TBI and may differ with the site and form of damage. Sonic hedgehog (Shh maintains neural stem cells and promotes oligodendrogenesis. We examined whether Shh signaling contributes to neuroblast (doublecortin or oligodendrocyte progenitor (neural/glial antigen 2 [NG2] responses in two distinct TBI models. Shh-responsive cells were heritably labeled in vivo using Gli1-CreERT2;R26-YFP bitransgenic mice with tamoxifen administration on Days 2 and 3 post-TBI. Injury to the cerebral cortex was produced with mild controlled cortical impact. Yellow fluorescent protein (YFP cells decreased in cortical lesions. Total YFP cells increased in the subventricular zone (SVZ, indicating Shh pathway activation in SVZ cells, including doublecortin-labeled neuroblasts. The alternate TBI model produced traumatic axonal injury in the corpus callosum. YFP cells decreased within the SVZ and were rarely double labeled as NG2 progenitors. NG2 progenitors increased in the cortex, with a similar pattern in the corpus callosum. To further test the potential of NG2 progenitors to respond through Shh signaling, Smoothened agonist was microinjected into the corpus callosum to activate Shh signaling. YFP cells and NG2 progenitors increased in the SVZ but were not double labeled. This result indicates that either direct Smoothened activation in NG2 progenitors does not signal through Gli1 or that Smoothened agonist acts indirectly to increase NG2 progenitors. Therefore, in all conditions, neuroblasts exhibited differential Shh pathway utilization compared with oligodendrocyte progenitors. Notably, cortical versus white matter damage from TBI produced opposite responses of Shh-activated cells within the SVZ.

  17. Tigroid pattern of the white matter: a previously unrecognized MR finding in lissencephaly with cerebellar hypoplasia

    Energy Technology Data Exchange (ETDEWEB)

    Kono, Tatsuo [Dokkyo University, Department of Radiology, Mibu, Shimotsuga, Tochigi (Japan); Moriyama, Nobuko [Ibaraki Children' s Hospital, Department of Paediatrics, Mito, Ibaraki (Japan); Tanaka, Ryuta [University of Tsukuba, Department of Paediatrics, Tsukubu, Ibaraki (Japan); Iwasaki, Nobuaki [Ibaraki Prefectural University of Health Sciences, Department of Paediatrics, Ami, Ibaraki (Japan); Arai, Jun-ichi [Ibaraki Children' s Hospital, Department of Neonatology, Mito, Ibaraki (Japan)

    2008-10-15

    Brain MR images of a 14-month-old boy with lissencephaly and cerebellar hypoplasia showed numerous radiating linear structures in the white matter. This finding was identical to the tigroid or leopard-skin pattern that is seen in Pelizaeus-Merzbacher disease or metachromatic leukodystrophy and represents the perivascular white matter spared from demyelination. We speculate that mutations of the reelin gene, expressed both in the cortex and in the white matter, may play an important role in its development. (orig.)

  18. Subcortical white matter pathology as a mediating factor for age-related decreased performance in dichotic listening

    NARCIS (Netherlands)

    Gootjes, Liselotte; Scheltens, Philip; Van Strien, Jan W.; Bouma, Anke

    2007-01-01

    Cortical 'disconnection', involving disruption of white matter tracts in the brain, has been hypothesized as a mechanism of age-related cognitive decline. Diffuse hyperintensities in the white matter (so called white matter hyperintensities, WMH) on T2-weighted MRI scans are regarded to represent is

  19. White matter development and early cognition in babies and toddlers.

    Science.gov (United States)

    O'Muircheartaigh, Jonathan; Dean, Douglas C; Ginestet, Cedric E; Walker, Lindsay; Waskiewicz, Nicole; Lehman, Katie; Dirks, Holly; Piryatinsky, Irene; Deoni, Sean C L

    2014-09-01

    The normal myelination of neuronal axons is essential to neurodevelopment, allowing fast inter-neuronal communication. The most dynamic period of myelination occurs in the first few years of life, in concert with a dramatic increase in cognitive abilities. How these processes relate, however, is still unclear. Here we aimed to use a data-driven technique to parcellate developing white matter into regions with consistent white matter growth trajectories and investigate how these regions related to cognitive development. In a large sample of 183 children aged 3 months to 4 years, we calculated whole brain myelin volume fraction (VFM ) maps using quantitative multicomponent relaxometry. We used spatial independent component analysis (ICA) to blindly segment these quantitative VFM images into anatomically meaningful parcels with distinct developmental trajectories. We further investigated the relationship of these trajectories with standardized cognitive scores in the same children. The resulting components represented a mix of unilateral and bilateral white matter regions (e.g., cortico-spinal tract, genu and splenium of the corpus callosum, white matter underlying the inferior frontal gyrus) as well as structured noise (misregistration, image artifact). The trajectories of these regions were associated with individual differences in cognitive abilities. Specifically, components in white matter underlying frontal and temporal cortices showed significant relationships to expressive and receptive language abilities. Many of these relationships had a significant interaction with age, with VFM becoming more strongly associated with language skills with age. These data provide evidence for a changing coupling between developing myelin and cognitive development.

  20. Combining Fiber Dissection, Plastination, and Tractography for Neuroanatomical Education: Revealing the Cerebellar Nuclei and Their White Matter Connections

    Science.gov (United States)

    Arnts, Hisse; Kleinnijenhuis, Michiel; Kooloos, Jan G. M.; Schepens-Franke, Annelieke N.; van Cappellen van Walsum, Anne-Marie

    2014-01-01

    In recent years, there has been a growing interest in white matter anatomy of the human brain. With advances in brain imaging techniques, the significance of white matter integrity for brain function has been demonstrated in various neurological and psychiatric disorders. As the demand for interpretation of clinical and imaging data on white…

  1. Combining fiber dissection, plastination, and tractography for neuroanatomical education: Revealing the cerebellar nuclei and their white matter connections.

    NARCIS (Netherlands)

    Arnts, H.; Kleinnijenhuis, M.; Kooloos, J.G.M.; Schepens-Franke, A.N.; Cappellen van Walsum, A.M. van

    2014-01-01

    In recent years, there has been a growing interest in white matter anatomy of the human brain. With advances in brain imaging techniques, the significance of white matter integrity for brain function has been demonstrated in various neurological and psychiatric disorders. As the demand for interpret

  2. Alterations in Cortical Thickness and White Matter Integrity in Mild-to-Moderate Communicating Hydrocephalic School-Aged Children Measured by Whole-Brain Cortical Thickness Mapping and DTI

    Science.gov (United States)

    Ye, Xinjian; Bai, Guanghui; Fu, Yuchuan; Mao, Chuanwan; Wu, Aiqin

    2017-01-01

    Follow-up observation is required for mild-to-moderate hydrocephalic patients because of the potential damage to brain. However, effects of mild-to-moderate hydrocephalus on gray and white matter remain unclear in vivo. Using structural MRI and diffusion tensor imaging (DTI), current study compared the cortical thickness and white matter integrity between children with mild-to-moderate communicating hydrocephalus and healthy controls. The relationships between cortical changes and intelligence quota were also examined in patients. We found that cortical thickness in the left middle temporal and left rostral middle frontal gyrus was significantly lower in the hydrocephalus group compared with that of controls. Fractional anisotropy in the right corpus callosum body was significantly lower in the hydrocephalus group compared with that of controls. In addition, there was no association of cortical thinning or white matter fractional anisotropy with intelligence quota in either group. Thus, our findings provide clues to that mild-to-moderate hydrocephalus could lead to structural brain deficits especially in the middle temporal and middle frontal gyrus prior to the behavior changes.

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Science.gov (United States)

    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...

  5. White matter structure changes as adults learn a second language.

    Science.gov (United States)

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

    2012-08-01

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

  6. White Matter Integrity Reductions in Intermittent Explosive Disorder.

    Science.gov (United States)

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

    2016-10-01

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

  7. White matter fractional anisotropy predicts balance performance in older adults.

    Science.gov (United States)

    Van Impe, Annouchka; Coxon, James P; Goble, Daniel J; Doumas, Mihail; Swinnen, Stephan P

    2012-09-01

    Aging is characterized by brain structural changes that may compromise motor functions. In the context of postural control, white matter integrity is crucial for the efficient transfer of visual, proprioceptive and vestibular feedback in the brain. To determine the role of age-related white matter decline as a function of the sensory feedback necessary to correct posture, we acquired diffusion weighted images in young and old subjects. A force platform was used to measure changes in body posture under conditions of compromised proprioceptive and/or visual feedback. In the young group, no significant brain structure-balance relations were found. In the elderly however, the integrity of a cluster in the frontal forceps explained 21% of the variance in postural control when proprioceptive information was compromised. Additionally, when only the vestibular system supplied reliable information, the occipital forceps was the best predictor of balance performance (42%). Age-related white matter decline may thus be predictive of balance performance in the elderly when sensory systems start to degrade.

  8. White matter microstructure correlates of mathematical giftedness and intelligence quotient.

    Science.gov (United States)

    Navas-Sánchez, Francisco J; Alemán-Gómez, Yasser; Sánchez-Gonzalez, Javier; Guzmán-De-Villoria, Juan A; Franco, Carolina; Robles, Olalla; Arango, Celso; Desco, Manuel

    2014-06-01

    Recent functional neuroimaging studies have shown differences in brain activation between mathematically gifted adolescents and controls. The aim of this study was to investigate the relationship between mathematical giftedness, intelligent quotient (IQ), and the microstructure of white matter tracts in a sample composed of math-gifted adolescents and aged-matched controls. Math-gifted subjects were selected through a national program based on detecting enhanced visuospatial abilities and creative thinking. We used diffusion tensor imaging to assess white matter microstructure in neuroanatomical connectivity. The processing included voxel-wise and region of interest-based analyses of the fractional anisotropy (FA), a parameter which is purportedly related to white matter microstructure. In a whole-sample analysis, IQ showed a significant positive correlation with FA, mainly in the corpus callosum, supporting the idea that efficient information transfer between hemispheres is crucial for higher intellectual capabilities. In addition, math-gifted adolescents showed increased FA (adjusted for IQ) in white matter tracts connecting frontal lobes with basal ganglia and parietal regions. The enhanced anatomical connectivity observed in the forceps minor and splenium may underlie the greater fluid reasoning, visuospatial working memory, and creative capabilities of these children.

  9. Recombinant human erythropoietin for repair of white matter damage

    Institute of Scientific and Technical Information of China (English)

    Wei Zhou; Xiao Rong; Li Tao; Weineng Lu

    2011-01-01

    Erythropoietin has been shown to exhibit neuroprotective effects in animal models. A neonatal rat model of hypoxic-ischemic white matter damage was established via bilateral carotid artery ligation in 4-day-old Sprague-Dawley rats. The rats were subsequently treated with recombinant human erythropoietin to observe pathological changes in the brain and long-term neurobehavioral functions before and after intervention. Results showed that the number of myelin basic protein-positive cells, which reflected myelin/oligodendrocyte damage, significantly increased, although the number of amyloid precursor protein-positive cells, which reflected axonal injury, significantly decreased in periventricular white matter at 72 hours and 7 days following erythropoietin intervention. The number of glial fibrillary acidic protein-positive cells, indicating astrocytic damage, significantly decreased in periventricular white matter of erythropoietin-treated rats at 48 hours, 72 hours, 7 days, and 26 days. Following erythropoietin intervention in the 30-day-old rats, head-turning time in the slope test was shortened and open-field test scores increased. These results suggested that erythropoietin promoted repair of white matter damage, as well as improved neurobehavioral functions in a rat model of hypoxic-ischemic injury.

  10. Empty-nest-related psychological distress is associated with progression of brain white matter lesions and cognitive impairment in the elderly

    Science.gov (United States)

    Duan, Dandan; Dong, Yuanli; Zhang, Hua; Zhao, Yingxin; Diao, Yutao; Cui, Yi; Wang, Juan; Chai, Qiang; Liu, Zhendong

    2017-01-01

    This study evaluated the association between empty-nest-related psychological distress and the progression of white matter lesions (WMLs) and cognitive impairment in 219 elderly subjects aged 60 years or over. Psychological distress was assessed using the University of California at Los Angeles Loneliness Scale (UCLA-LS) and Geriatric Depression Scale (GDS) Short-Form. Cognitive function was evaluated using the MMSE and MoCA. White matter hyperintensities (WMH) were assessed using magnetic resonance imaging. After 5.2-year follow-up, the reductions in MMSE and MoCA scores and the increases in periventricular (P)WMH, deep (D)WMH, and total WMH volumes in the empty-nest elderly were greater than those in the non-empty-nest elderly (P < 0.05). The reduced MMSE and MoCA scores and increased volumes of PWMH and total WMH in the empty-nest elderly living alone were greater than those in the empty-nest elderly living with a spouse (P < 0.05). UCLA-LS and GDS scores were significantly and independently associated with reduced MMSE and MoCA scores and the increased volumes of PWMH, DWMH, and total WMH. The results indicate that empty-nest-related psychological distress is associated with progression of WMLs and cognitive impairment in the elderly. PMID:28256594

  11. White matter microstructural organization and gait stability in older adults

    Directory of Open Access Journals (Sweden)

    Sjoerd M. Bruijn

    2014-06-01

    Full Text Available Understanding age-related decline in gait stability and the role of alterations in brain structure is crucial. Here, we studied the relationship between white matter microstructural organization using Diffusion Tensor Imaging (DTI and advanced gait stability measures in 15 healthy young adults (range 18-30 years and 25 healthy older adults (range 62-82 years.Among the different gait stability measures, only stride time and the maximum Lyapunov exponent (which quantifies how well participants are able to attenuate small perturbations were found to decline with age. White matter microstructural organization (FA was lower throughout the brain in older adults. We found a strong correlation between FA in the left anterior thalamic radiation and left corticospinal tract on the one hand, and step width and safety margin (indicative of how close participants are to falling over on the other. These findings suggest that white matter FA in tracts connecting subcortical and prefrontal areas is associated with the implementation of an effective stabilization strategy during gait.

  12. White matter connectivity and aerobic fitness in male adolescents

    Directory of Open Access Journals (Sweden)

    Megan M. Herting

    2014-01-01

    Full Text Available 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.

  13. White matter changes in Wilson's disease: A radiological enigma

    Directory of Open Access Journals (Sweden)

    Soumava Mukherjee

    2016-01-01

    Full Text Available Wilson's disease is a metabolic disorder which presents with hepatitis or hepatic decompensation commonly. Neurologic manifestations are late and include movement disorders, personality changes, and seizures. Magnetic resonance imaging (MRI brain shows high signal changes in putamen, lentiform nucleus, thalamus, and brainstem. White matter lesions are rare. We report a child of Wilson's disease who presented to us with dystonia, rigidity, myoclonus and had symmetrical white matter changes in the fronto-parietooccipital region. Diffusion restriction in bilateral frontoparietal areas was also seen which is rare in chronic cases like ours. Atypical MRI characteristics should be considered in patients with clinical signs of neurological involvement in Wilson's disease as it is a devastating but treatable disease.

  14. White matter changes in Wilson's disease: A radiological enigma.

    Science.gov (United States)

    Mukherjee, Soumava; Solanki, Bhavesh; Guha, Goutam; Saha, Shankar Prasad

    2016-01-01

    Wilson's disease is a metabolic disorder which presents with hepatitis or hepatic decompensation commonly. Neurologic manifestations are late and include movement disorders, personality changes, and seizures. Magnetic resonance imaging (MRI) brain shows high signal changes in putamen, lentiform nucleus, thalamus, and brainstem. White matter lesions are rare. We report a child of Wilson's disease who presented to us with dystonia, rigidity, myoclonus and had symmetrical white matter changes in the fronto-parietooccipital region. Diffusion restriction in bilateral frontoparietal areas was also seen which is rare in chronic cases like ours. Atypical MRI characteristics should be considered in patients with clinical signs of neurological involvement in Wilson's disease as it is a devastating but treatable disease.

  15. Multiple Factors Involved in the Pathogenesis of White Matter Lesions

    Science.gov (United States)

    Lin, Jing; Wang, Dilong; Lan, Linfang

    2017-01-01

    White matter lesions (WMLs), also known as leukoaraiosis (LA) or white matter hyperintensities (WMHs), are characterized mainly by hyperintensities on T2-weighted or fluid-attenuated inversion recovery (FLAIR) images. With the aging of the population and the development of imaging technology, the morbidity and diagnostic rates of WMLs are increasing annually. WMLs are not a benign process. They clinically manifest as cognitive decline and the subsequent development of dementia. Although WMLs are important, their pathogenesis is still unclear. This review elaborates on the advances in the understanding of the pathogenesis of WMLs, focusing on anatomy, cerebral blood flow autoregulation, venous collagenosis, blood brain barrier disruption, and genetic factors. In particular, the attribution of WMLs to chronic ischemia secondary to venous collagenosis and cerebral blood flow autoregulation disruption seems reasonable. With the development of gene technology, the effect of genetic factors on the pathogenesis of WMLs is gaining gradual attention. PMID:28316994

  16. Plasticity of white matter connectivity in phonetics experts.

    Science.gov (United States)

    Vandermosten, Maaike; Price, Cathy J; Golestani, Narly

    2016-09-01

    Phonetics experts are highly trained to analyze and transcribe speech, both with respect to faster changing, phonetic features, and to more slowly changing, prosodic features. Previously we reported that, compared to non-phoneticians, phoneticians had greater local brain volume in bilateral auditory cortices and the left pars opercularis of Broca's area, with training-related differences in the grey-matter volume of the left pars opercularis in the phoneticians group (Golestani et al. 2011). In the present study, we used diffusion MRI to examine white matter microstructure, indexed by fractional anisotropy, in (1) the long segment of arcuate fasciculus (AF_long), which is a well-known language tract that connects Broca's area, including left pars opercularis, to the temporal cortex, and in (2) the fibers arising from the auditory cortices. Most of these auditory fibers belong to three validated language tracts, namely to the AF_long, the posterior segment of the arcuate fasciculus and the middle longitudinal fasciculus. We found training-related differences in phoneticians in left AF_long, as well as group differences relative to non-experts in the auditory fibers (including the auditory fibers belonging to the left AF_long). Taken together, the results of both studies suggest that grey matter structural plasticity arising from phonetic transcription training in Broca's area is accompanied by changes to the white matter fibers connecting this very region to the temporal cortex. Our findings suggest expertise-related changes in white matter fibers connecting fronto-temporal functional hubs that are important for phonetic processing. Further studies can pursue this hypothesis by examining the dynamics of these expertise related grey and white matter changes as they arise during phonetic training.

  17. Gray matter volume and white matter lesions in chronic kidney disease : exploring the association with depressive symptoms

    NARCIS (Netherlands)

    Meurs, Maaike; Roest, Annelieke M.; Groenewold, Nynke A.; Franssen, Casper F. M.; Westerhuis, Ralf; Kloppenburg, Wybe Douwe; Doornbos, Bennard; Beukema, Lindy; Lindmae, Hanna; de Groot, Jan Cees; van Tol, Marie-Jose; de Jonge, Peter

    2016-01-01

    Objective: Chronic kidney disease (CKD) is associated with structural brain damage and with a high prevalence of depression. We therefore investigated structural brain alterations in both gray and white matter in CKD patients, focusing on depression-related (frontal-subcortical) regions. Method: Thi

  18. White matter atrophy and cognitive dysfunctions in neuromyelitis optica.

    Directory of Open Access Journals (Sweden)

    Frederic Blanc

    Full Text Available 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

  19. White matter neuroanatomical differences in young children who stutter.

    Science.gov (United States)

    Chang, Soo-Eun; Zhu, David C; Choo, Ai Leen; Angstadt, Mike

    2015-03-01

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

  20. White matter correlates of sensory processing in autism spectrum disorders

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    Jennifer R. Pryweller

    2014-01-01

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

  1. Atypical white matter microstructure in left-handed individuals.

    Science.gov (United States)

    McKay, Nicole S; Iwabuchi, Sarina J; Häberling, Isabelle S; Corballis, Michael C; Kirk, Ian J

    2016-04-27

    Information regarding anatomical connectivity in the human brain can be gathered using diffusion tensor imaging (DTI). Fractional anisotropy (FA) is the most commonly derived value, and reflects how strongly directional are the underlying tracts. Differences in FA are thus associated with differences in the underlying microstructure of the brain. The relationships between these differences in microstructure and functional differences in corresponding regions have also been examined. Previous studies have found an effect of handedness on functional lateralization in the brain and corresponding microstructural differences. Here, using tract-based spatial statistics to analyse DTI-derived FA values, we further investigated the structural white matter architecture in the brains of right- and left-handed males. We found significantly higher FA values for left-handed, relatively to right-handed, individuals, in all major lobes, and in the corpus callosum. In support of previous suggestions, we find that there is a difference in the microstructure of white matter in left- and right-handed males that could underpin reduced lateralization of function in left-handed individuals.

  2. White Matter Glial Pathology in Autism

    Science.gov (United States)

    2015-11-01

    and oxidative stress as observed in depressed suicide victims. To examine this, oligodendrocytes will be captured from the region of the brainstem...captured materials. This decision was made on both a scientific and financial basis. All superficial white matter and pyramidal neuron samples were...9/09-2/8/11 American Foundation for Suicide Prevention. “Glutamatergic signaling in the locus coeruleus in depression and suicide ” The major goal

  3. Postinfectious encephalitis with multifocal white matter lesions.

    Science.gov (United States)

    Boulloche, J; Parain, D; Mallet, E; Tron, P

    1989-08-01

    Two cases of multifocal white matter lesions occurring after viral illness are reported. Evoked potentials study and cranial magnetic resonance imaging (T2-weighted image) showed early abnormalities while CT scan was initially normal. Patients improved dramatically with steroid therapy. It would seem that because of a considerable responsiveness to steroids this affection should be differentiated from other types of encephalitis. Relations with multiple sclerosis are discussed.

  4. Considerations for the optimization of induced white matter injury preclinical models

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    Abdullah Shafique Ahmad

    2015-08-01

    Full Text Available The white matter injury in relation to acute neurologic conditions, especially stroke, has remained obscure until recently. Current advances in the imaging technologies in the field of stroke have confirmed that white matter injury plays an important role in the prognosis of stroke and suggest that white matter protection is essential for functional recovery and post-stroke rehabilitation. However, due to the lack of a reproducible animal model of white matter injury, the pathophysiology and mechanisms of this injury are not well studied. Moreover, producing selective white matter injury in animals, especially in rodents, has proven to be challenging. Problems associated with inducing selective white matter ischemic injury in the rodent derive from differences in the architecture of the brain, most particularly the ratio of white matter to gray matter in rodents compared to humans, the agents used to induce the injury, and the location of the injury. Aging, gender differences, and comorbidities further add to this complexity. This review provides a brief account of the techniques commonly used to induce general white matter injury in animal models (stroke and non-stroke related and highlights relevance, optimization issues, and translational potentials associated with this particular form of injury.

  5. Comparison of the Relationship between Cerebral White Matter and Grey Matter in Normal Dogs and Dogs with Lateral Ventricular Enlargement.

    Directory of Open Access Journals (Sweden)

    Martin J Schmidt

    Full Text Available Large cerebral ventricles are a frequent finding in brains of dogs with brachycephalic skull conformation, in comparison with mesaticephalic dogs. It remains unclear whether oversized ventricles represent a normal variant or a pathological condition in brachycephalic dogs. There is a distinct relationship between white matter and grey matter in the cerebrum of all eutherian mammals. The aim of this study was to determine if this physiological proportion between white matter and grey matter of the forebrain still exists in brachycephalic dogs with oversized ventricles. The relative cerebral grey matter, white matter and cerebrospinal fluid volume in dogs were determined based on magnetic-resonance-imaging datasets using graphical software. In an analysis of covariance (ANCOVA using body mass as the covariate, the adjusted means of the brain tissue volumes of two groups of dogs were compared. Group 1 included 37 mesaticephalic dogs of different sizes with no apparent changes in brain morphology, and subjectively normal ventricle size. Group 2 included 35 brachycephalic dogs in which subjectively enlarged cerebral ventricles were noted as an incidental finding in their magnetic-resonance-imaging examination. Whereas no significant different adjusted means of the grey matter could be determined, the group of brachycephalic dogs had significantly larger adjusted means of lateral cerebral ventricles and significantly less adjusted means of relative white matter volume. This indicates that brachycephalic dogs with subjective ventriculomegaly have less white matter, as expected based on their body weight and cerebral volume. Our study suggests that ventriculomegaly in brachycephalic dogs is not a normal variant of ventricular volume. Based on the changes in the relative proportion of WM and CSF volume, and the unchanged GM proportions in dogs with ventriculomegaly, we rather suggest that distension of the lateral ventricles might be the underlying cause

  6. Comparison of the Relationship between Cerebral White Matter and Grey Matter in Normal Dogs and Dogs with Lateral Ventricular Enlargement.

    Science.gov (United States)

    Schmidt, Martin J; Laubner, Steffi; Kolecka, Malgorzata; Failing, Klaus; Moritz, Andreas; Kramer, Martin; Ondreka, Nele

    2015-01-01

    Large cerebral ventricles are a frequent finding in brains of dogs with brachycephalic skull conformation, in comparison with mesaticephalic dogs. It remains unclear whether oversized ventricles represent a normal variant or a pathological condition in brachycephalic dogs. There is a distinct relationship between white matter and grey matter in the cerebrum of all eutherian mammals. The aim of this study was to determine if this physiological proportion between white matter and grey matter of the forebrain still exists in brachycephalic dogs with oversized ventricles. The relative cerebral grey matter, white matter and cerebrospinal fluid volume in dogs were determined based on magnetic-resonance-imaging datasets using graphical software. In an analysis of covariance (ANCOVA) using body mass as the covariate, the adjusted means of the brain tissue volumes of two groups of dogs were compared. Group 1 included 37 mesaticephalic dogs of different sizes with no apparent changes in brain morphology, and subjectively normal ventricle size. Group 2 included 35 brachycephalic dogs in which subjectively enlarged cerebral ventricles were noted as an incidental finding in their magnetic-resonance-imaging examination. Whereas no significant different adjusted means of the grey matter could be determined, the group of brachycephalic dogs had significantly larger adjusted means of lateral cerebral ventricles and significantly less adjusted means of relative white matter volume. This indicates that brachycephalic dogs with subjective ventriculomegaly have less white matter, as expected based on their body weight and cerebral volume. Our study suggests that ventriculomegaly in brachycephalic dogs is not a normal variant of ventricular volume. Based on the changes in the relative proportion of WM and CSF volume, and the unchanged GM proportions in dogs with ventriculomegaly, we rather suggest that distension of the lateral ventricles might be the underlying cause of pressure

  7. Longitudinal changes in white matter microstructure after heavy cannabis use.

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

    2015-12-01

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

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

    Science.gov (United States)

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

    2012-07-23

    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.

  9. Fast quantitative diffusion-tensor imaging of cerebral white matter from the neonatal period to adolescence

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    Schneider, J.F.L.; Martin, E. [Department of Neuroradiology and Magnetic Resonance Imaging, University Children' s Hospital, Steinwiesstrasse 75, 8032, Zuerich (Switzerland); Il' yasov, K.A.; Hennig, J. [Department of Diagnostic Radiology, Section of Medical Physics, University Medical Centre, Hugstetter Strasse 55, 79106, Freiburg (Germany)

    2004-04-01

    We investigated the isotropic diffusion coefficient (D') and fractional anisotropy (FA) in white matter (WM) during brain development, using an optimised diffusion-tensor imaging (DTI) method with whole brain coverage in a clinically acceptable time. We images 52 children with no evident neurological abnormality (30 boys, 22 girls aged 1 day-16 years) using high-angle DTI with optimised temporal gradient performance. D' and FA were calculated in 10 regions of interest in white matter. We saw that the age-related reduction in D' and increase in FA follow a mono- or biexponential model in white matter, probably depending on the compactness and myelination rate of the fibre tracts. In contrast to other areas, in which adult values were reached during the third year, there is a trend to continuous increase in FA in all deep white-matter areas, suggesting continuing maturation and organisation of deep tracts not detected on conventional MRI. (orig.)

  10. White matter maturation in visual and motor areas predicts the latency of visual activation in children.

    Science.gov (United States)

    Dockstader, Colleen; Gaetz, William; Rockel, Conrad; Mabbott, Donald J

    2012-01-01

    In humans, white matter maturation is important for the improvement of cognitive function and performance with age. Across studies the variables of white matter maturity and age are highly correlated; however, the unique contributions of white matter to information processing speed remain relatively unknown. We investigated the relations between the speed of the visually-evoked P100m response and the biophysical properties of white matter in 11 healthy children performing a simple, visually-cued finger movement. We found that: (1) the latency of the early, visually-evoked response was related to the integrity of white matter in both visual and motor association areas and (2) white matter maturation in these areas accounted for the variations in visual processing speed, independent of age. Our study is a novel investigation of spatial-temporal dynamics in the developing brain and provides evidence that white matter maturation accounts for age-related decreases in the speed of visual response. Developmental models of cortical specialization should incorporate the unique role of white matter maturation in mediating changes in performance during tasks involving visual processing.

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

    Science.gov (United States)

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

    2016-04-15

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

  12. White matter microstructure asymmetry: effects of volume asymmetry on fractional anisotropy asymmetry.

    Science.gov (United States)

    Takao, H; Hayashi, N; Ohtomo, K

    2013-02-12

    Diffusion tensor imaging (DTI) provides information regarding white matter microstructure; however, macroscopic fiber architectures can affect DTI measures. A larger brain (fiber tract) has a 'relatively' smaller voxel size, and the voxels are less likely to contain more than one fiber orientation and more likely to have higher fractional anisotropy (FA). Previous DTI studies report left-to-right differences in the white matter; however, these may reflect true microscopic differences or be caused purely by volume differences. Using tract-based spatial statistics, we investigated left-to-right differences in white matter microstructure across the whole brain. Voxel-wise analysis revealed a large number of white matter volume asymmetries, including leftward asymmetry of the arcuate fasciculus and cingulum. In many white matter regions, FA asymmetry was positively correlated with volume asymmetry. Voxel-wise analysis with adjustment for volume asymmetry revealed many white matter FA asymmetries, including leftward asymmetry of the arcuate fasciculus and cingulum. The voxel-wise analysis showed a reduced number of regions with significant FA asymmetry compared with analysis performed without adjustment for volume asymmetry; however, the overall trend of the results was unchanged. The results of the present study suggest that these FA asymmetries are not caused by volume differences and reflect microscopic differences in the white matter.

  13. White matter changes in paediatric multiple sclerosis and monophasic demyelinating disorders.

    Science.gov (United States)

    Longoni, Giulia; Brown, Robert A; MomayyezSiahkal, Parya; Elliott, Colm; Narayanan, Sridar; Bar-Or, Amit; Ann Marrie, Ruth; Ann Yeh, E; Filippi, Massimo; Banwell, Brenda; Arnold, Douglas L

    2017-03-14

    Most children who experience an acquired demyelinating syndrome of the central nervous system will have a monophasic disease course, with no further clinical or radiological symptoms. A subset will be diagnosed with multiple sclerosis, a life-long disorder. Using linear mixed effects models we examined longitudinal diffusion properties of normal-appearing white matter in 505 serial scans of 132 paediatric participants with acquired demyelinating syndromes followed for a median of 4.4 years, many from first clinical presentation, and 106 scans of 80 healthy paediatric participants. Fifty-three participants with demyelinating syndromes eventually received a diagnosis of paediatric-onset multiple sclerosis. Diffusion tensor imaging measures properties of water diffusion through tissue, which normally becomes increasingly restricted and anisotropic in the brain during childhood and adolescence, as fibre bundles develop and myelinate. In the healthy paediatric participants, our data demonstrate the expected trajectory of more restricted and anisotropic white matter diffusivity with increasing age. However, in participants with multiple sclerosis, fractional anisotropy decreased and mean diffusivity of non-lesional, normal-appearing white matter progressively increased after clinical presentation, suggesting not only a failure of age-expected white matter development but also a progressive loss of tissue integrity. Surprisingly, patients with monophasic disease failed to show age-expected changes in diffusion parameters in normal-appearing white matter, although they did not show progressive loss of integrity over time. Further analysis demonstrated that participants with monophasic disease experienced different post-onset trajectories in normal-appearing white matter depending on their presenting phenotype: those with acute disseminated encephalomyelitis demonstrated abnormal trajectories of diffusion parameters compared to healthy paediatric participants, as did

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

    NARCIS (Netherlands)

    Vercruysse, S.; Leunissen, I.; Vervoort, G.M.; Vandenberghe, W.; Swinnen, S.; Nieuwboer, A.

    2015-01-01

    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 dete

  15. Tissue transglutaminase in Marmoset experimental multiple sclerosis : Discrepancy between white and grey matter

    NARCIS (Netherlands)

    Pinzon, Nathaly Espitia; Stroo, Esther; 't Hart, Bert A.; Bol, John G. J. M.; Drukarch, Benjamin; Bauer, Jan; van Dam, Anne-Marie

    2014-01-01

    Infiltration of leukocytes is a major pathological event in white matter lesion formation in the brain of multiple sclerosis (MS) patients. In grey matter lesions, less infiltration of these cells occur, but microglial activation is present. Thus far, the interaction of beta-integrins with extracell

  16. No change in total length of white matter fibers in Alzheimer's disease

    DEFF Research Database (Denmark)

    Jorgensen, A.M.; Marner, L.; Pakkenberg, B.

    2008-01-01

    White matter changes have been reported as part of Alzheimer dementia. To investigate this, the total subcortical myelinated nerve fiber length was estimated in postmortem brains from eight females (age 79-88 years) with severe Alzheimer's disease (AD) and compared with brains from 10 female...

  17. Toward objective markers of concussion in sport: a review of white matter and neurometabolic changes in the brain after sports-related concussion.

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    Dimou, Stefan; Lagopoulos, Jim

    2014-03-01

    Abstract Sports-related concussion is an issue that has piqued the public's attention of late as concerns surrounding potential long-term sequelae as well as new methods of characterizing the effects of this form of injury continue to develop. For the most part, diagnosis of concussion is based on subjective clinical measures and thus is prone to under-reporting. In the current environment, where conventional imaging modalities, such as computed tomography and magnetic resonance imaging, are unable to elucidate the degree of white matter damage and neurometabolic change, a discussion of two advanced imaging techniques-diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS)-is undertaken with a view to highlighting their potential utility. Our aim is to outline a variety of the approaches to concussion research that have been employed, with special attention given to the clinical considerations and acute complications attributed to concussive injury. DTI and MRS have been at the forefront of research as a result of their noninvasiveness and ease of acquisition, and hence it is thought that the use of these neuroimaging modalities has the potential to aid clinical decision making and management, including guiding return-to-play protocols.

  18. Changes in white matter microstructure in the developing brain--A longitudinal diffusion tensor imaging study of children from 4 to 11years of age.

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    Krogsrud, Stine K; Fjell, Anders M; Tamnes, Christian K; Grydeland, Håkon; Mork, Lia; Due-Tønnessen, Paulina; Bjørnerud, Atle; Sampaio-Baptista, Cassandra; Andersson, Jesper; Johansen-Berg, Heidi; Walhovd, Kristine B

    2016-01-01

    The purpose of the present study was to detail the childhood developmental course of different white matter (WM) characteristics. In a longitudinal diffusion tensor imaging (DTI) study of 159 healthy children between 4 and 11years scanned twice, we used tract-based spatial statistics as well as delineation of 15 major WM tracts to characterize the regional pattern of change in fractional anisotropy (FA), mean (MD), radial (RD) and axial diffusivity (AD). We tested whether there were decelerations of change with increasing age globally and tract-wise, and also illustrated change along medial-to-lateral, posterior-to-anterior and inferior-to-superior gradients. We found a significant linear increase in global FA, and decrease in MD and RD over time. For mean AD, a weak decrease was observed. The developmental changes in specific WM tracts showed regional differences. Eight WM tracts showed non-linear development patterns for one or several DTI metrics, with a deceleration in change with age. Sex did not affect change in any DTI metric. Overall, greater rate of change was found in the left hemisphere. Spatially, there was a posterior-to-anterior gradient of change with greater change in frontal regions for all metrics. The current study provides a comprehensive characterization of the regional patters of change in WM microstructure across pre-adolescence childhood.

  19. Whole genome grey and white matter DNA methylation profiles in dorsolateral prefrontal cortex.

    Science.gov (United States)

    Sanchez-Mut, Jose Vicente; Heyn, Holger; Vidal, Enrique; Delgado-Morales, Raúl; Moran, Sebastian; Sayols, Sergi; Sandoval, Juan; Ferrer, Isidre; Esteller, Manel; Gräff, Johannes

    2017-01-20

    The brain's neocortex is anatomically organized into grey and white matter, which are mainly composed by neuronal and glial cells, respectively. The neocortex can be further divided in different Brodmann areas according to their cytoarchitectural organization, which are associated with distinct cortical functions. There is increasing evidence that brain development and function are governed by epigenetic processes, yet their contribution to the functional organization of the neocortex remains incompletely understood. Herein, we determined the DNA methylation patterns of grey and white matter of dorsolateral prefrontal cortex (Brodmann area 9), an important region for higher cognitive skills that is particularly affected in various neurological diseases. For avoiding interindividual differences, we analyzed white and grey matter from the same donor using whole genome bisulfite sequencing, and for validating their biological significance, we used Infinium HumanMethylation450 BeadChip and pyrosequencing in ten and twenty independent samples, respectively. The combination of these analysis indicated robust grey-white matter differences in DNA methylation. What is more, cell type-specific markers were enriched among the most differentially methylated genes. Interestingly, we also found an outstanding number of grey-white matter differentially methylated genes that have previously been associated with Alzheimer's, Parkinson's, and Huntington's disease, as well as Multiple and Amyotrophic lateral sclerosis. The data presented here thus constitute an important resource for future studies not only to gain insight into brain regional as well as grey and white matter differences, but also to unmask epigenetic alterations that might underlie neurological and neurodegenerative diseases.

  20. Fractional anisotropy for assessment of white matter tracts injury in methylmalonic acidemia

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    GAO Yu; GUAN Wen-ye; WANG Jiang; ZHANG Yu-zhen; LI Yu-hua; HAN Lian-shu

    2009-01-01

    Background Methylmalonic acidemia (MMA) is a multifactorial autosomal recessive inborn error of organic acid metabolism, often presenting with neurological symptoms. As neurological disorders are often related to white matter injury, diffusion tensor imaging (DTI) is an excellent tool for assessment of white matter injury and possibly for diagnosing this disorder.Methods We retrospectively analyzed DTI images of 12 patients with MMA (7 males, 5 females, age range: 7-12 months, mean age: 9.25±1.70 months) with negative MRI findings. And another 12 age-matched and gender-matched infants were enrolled as control subjects. Fractional anisotropy (FA) of different white matter tracts of the brain was measured in both groups.Results For patients with negative MRI findings, compared with healthy infants, a statistically significant reduction in DTI FA value of the frontal white matter, temporal white matter, and occipital white matter was observed (P<0.01).Conclusions In addition to conventional T1W and T2W MR Image, Brain DTI presents a useful, sensitive and complementary tool for the assessment of brain damage in patients with MMA.

  1. Josef Klingler's models of white matter tracts: influences on neuroanatomy, neurosurgery, and neuroimaging.

    Science.gov (United States)

    Agrawal, Abhishek; Kapfhammer, Josef P; Kress, Annetrudi; Wichers, Hermann; Deep, Aman; Feindel, William; Sonntag, Volker K H; Spetzler, Robert F; Preul, Mark C

    2011-08-01

    During the 1930s, white matter tracts began to assume relevance for neurosurgery, especially after Cajal's work. In many reviews of white matter neurobiology, the seminal contributions of Josef Klingler (1888-1963) and their neurological applications have been overlooked. In 1934 at the University of Basel under Eugen Ludwig, Klingler developed a new method of dissection based on a freezing technique for brain tissue that eloquently revealed the white matter tracts. Klingler worked with anatomists, surgeons, and other scientists, and his models and dissections of white matter tracts remain arguably the most elegant ever created. He stressed 3-dimensional anatomic relationships and laid the foundation for defining mesial temporal, limbic, insular, and thalamic fiber and functional relationships and contributed to the potential of stereotactic neurosurgery. Around 1947, Klingler was part of a Swiss-German group that independently performed the first stereotactic thalamotomies, basing their targeting and logic on Klingler's white matter studies, describing various applications of stereotaxy and showing Klingler's work integrated into a craniocerebral topographic system for targeting with external localization of eloquent brain structures and stimulation of deep thalamic nuclei. Klingler's work has received renewed interest because it is applicable for correlating the results of the fiber-mapping paradigms from diffusion tensor imaging to actual anatomic evidence. Although others have described white matter tracts, none have had as much practical impact on neuroscience as Klinger's work. More importantly, Josef Klingler was an encouraging mentor, influencing neurosurgeons, neuroscientists, and brain imaging for more than three quarters of a century.

  2. Pattern of normal age-related regional differences in white matter microstructure is modified by vascular risk.

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    Kennedy, Kristen M; Raz, Naftali

    2009-11-10

    Even successful aging is associated with regional brain shrinkage and deterioration of the cerebral white matter. Aging also brings about an increase in vascular risk, and vascular impairment may be a potential mechanism behind the observed patterns of aging. The goals of this study were to characterize the normal age differences in white matter integrity in several brain regions across the adult life span and to assess the modifying effect of vascular risk on the observed pattern of regional white matter integrity. We estimated fractional anisotropy and diffusivity of white matter in nine cerebral regions of interest in 77 healthy adults (19-84 years old). There was a widespread reduction of white matter anisotropy with age, and prefrontal and occipital regions evidenced the greatest age-related differences. Diffusivity increased with age, and the magnitude of age differences increased beginning with the middle of the fifth decade. Vascular risk factors modified age differences in white matter integrity. Clinically diagnosed and treated arterial hypertension was associated with reduced white matter anisotropy and increased diffusivity beyond the effects of age. In the normotensive participants, elevation of arterial pulse pressure (a surrogate of arterial stiffness) was linked to deterioration of the white matter integrity in the frontal regions. Although the causal role of vascular risk in brain aging is unclear, the observed pattern of effects suggests that vascular risk may drive the expansion of age-related white matter damage from anterior to posterior regions.

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

    Directory of Open Access Journals (Sweden)

    Jodie Reanna Gawryluk

    2014-08-01

    Full Text Available 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.

  4. Brain white matter lesions correlated to newborns death and lethality Fatores correlacionados ao óbito e à letalidade hospitalar em neonatos com lesão da substância branca cerebral

    Directory of Open Access Journals (Sweden)

    Nayara Argollo

    2006-06-01

    Full Text Available OBJECTIVES: to describe hospital lethality rates and factors correlated to death in neonates with brain white matter lesions. METHODS: a retrospective study was performed from January 1994 to December 2001. Neonates with white brain matter lesions were divided into survival and death groups and their medical files reviewed through the single blind method to determine evolution. Death certificates provided the cause of death. The groups were compared through correlation coefficients. Hospital lethality rate was calculated. RESULTS: ninety three cases of white brain matter lesions and seven deaths were determined. Hospital lethality rate was of 8.2.% (95%CI: 2.4-14.0 independently from lesion occurrence time, and of 10.3% (95%CI: 3.3-17.3 for deaths occurred during prenatal and perinatal periods. Death was correlated to: Apgar score, non-cephalic presentation, gestational age, hyperglicemia, hypercalcemia, convulsion, respiratory insufficiency and atelectasy. CONCLUSIONS: hospital lethality was of 10.3% generating the following hypothesis: perinatal asphyxia must be the principal direct and indirect etiologic factor (aggravating the expression of prematurity and infection diseases, of prenatal and perinatal mortality among newborns with white brain matter lesions; and OBJETIVOS: descrever a taxa de letalidade hospitalar e fatores correlacionados com o óbito em crianças com lesão da substância branca cerebral (LSB. MÉTODOS: estudo retrospectivo realizado de janeiro de 1994 a dezembro de 2001. Os neonatos com LSB foram divididos em sobreviventes ou óbito, e seus prontuários revisados de forma cega para a evolução. Dos atestados de óbito, a causa de morte. Os grupos foram comparados por coeficientes de correlação. Calculada a taxa de letalidade hospitalar. RESULTADOS: foram encontrados 93 casos de LSB e sete óbitos. A taxa de letalidade hospitalar foi de 8,2%, (IC95%: 2,4-14,0, independentemente da época de instalação da lesão, e de

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

    Science.gov (United States)

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

    2016-01-01

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

  6. White matter hyperintensities are associated with disproportionate progressive hippocampal atrophy.

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    Fiford, Cassidy M; Manning, Emily N; Bartlett, Jonathan W; Cash, David M; Malone, Ian B; Ridgway, Gerard R; Lehmann, Manja; Leung, Kelvin K; Sudre, Carole H; Ourselin, Sebastien; Biessels, Geert Jan; Carmichael, Owen T; Fox, Nick C; Cardoso, M Jorge; Barnes, Josephine

    2017-03-01

    This study investigates relationships between white matter hyperintensity (WMH) volume, cerebrospinal fluid (CSF) Alzheimer's disease (AD) pathology markers, and brain and hippocampal volume loss. Subjects included 198 controls, 345 mild cognitive impairment (MCI), and 154 AD subjects with serial volumetric 1.5-T MRI. CSF Aβ42 and total tau were measured (n = 353). Brain and hippocampal loss were quantified from serial MRI using the boundary shift integral (BSI). Multiple linear regression models assessed the relationships between WMHs and hippocampal and brain atrophy rates. Models were refitted adjusting for (a) concurrent brain/hippocampal atrophy rates and (b) CSF Aβ42 and tau in subjects with CSF data. WMH burden was positively associated with hippocampal atrophy rate in controls (P = 0.002) and MCI subjects (P = 0.03), and with brain atrophy rate in controls (P = 0.03). The associations with hippocampal atrophy rate remained following adjustment for concurrent brain atrophy rate in controls and MCIs, and for CSF biomarkers in controls (P = 0.007). These novel results suggest that vascular damage alongside AD pathology is associated with disproportionately greater hippocampal atrophy in nondemented older adults. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.

  7. Enhanced white matter tracts integrity in children with abacus training.

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    Hu, Yuzheng; Geng, Fengji; Tao, Lixia; Hu, Nantu; Du, Fenglei; Fu, Kuang; Chen, Feiyan

    2011-01-01

    Experts of abacus, who have the skills of abacus-based mental calculation (AMC), are able to manipulate numbers via an imagined abacus in mind and demonstrate extraordinary ability in mental calculation. Behavioral studies indicated that abacus experts utilize visual strategy in solving numerical problems, and fMRI studies confirmed the enhanced involvement of visuospatial-related neural resources in AMC. This study aims to explore the possible changes in brain white matter induced by long-term training of AMC. Two matched groups participated: the abacus group consisting of 25 children with over 3-year training in abacus calculation and AMC, the controls including 25 children without any abacus experience. We found that the abacus group showed higher average fractional anisotropy (FA) in whole-brain fiber tracts, and the regions with increased FA were found in corpus callosum, left occipitotemporal junction and right premotor projection. No regions, however, showed decreased FA in the abacus group. Further analysis revealed that the differences in FA values were mainly driven by the alternation of radial rather than axial diffusivities. Furthermore, in forward digit and letter memory span tests, AMC group showed larger digit/letter memory spans. Interestingly, individual differences in white matter tracts were found positively correlated with the memory spans, indicating that the widespread increase of FA in the abacus group result possibly from the AMC training. In conclusion, our findings suggested that long-term AMC training from an early age may improve the memory capacity and enhance the integrity in white matter tracts related to motor and visuospatial processes.

  8. Social network diversity and white matter microstructural integrity in humans.

    Science.gov (United States)

    Molesworth, Tara; Sheu, Lei K; Cohen, Sheldon; Gianaros, Peter J; Verstynen, Timothy D

    2015-09-01

    Diverse aspects of physical, affective and cognitive health relate to social integration, reflecting engagement in social activities and identification with diverse roles within a social network. However, the mechanisms by which social integration interacts with the brain are unclear. In healthy adults (N = 155), we tested the links between social integration and measures of white matter microstructure using diffusion tensor imaging. Across the brain, there was a predominantly positive association between a measure of white matter integrity, fractional anisotropy (FA), and social network diversity. This association was particularly strong in a region near the anterior corpus callosum and driven by a negative association with the radial component of the diffusion signal. This callosal region contained projections between bilateral prefrontal cortices, as well as cingulum and corticostriatal pathways. FA within this region was weakly associated with circulating levels of the inflammatory cytokine interleukin-6 (IL-6), but IL-6 did not mediate the social network and FA relationship. Finally, variation in FA indirectly mediated the relationship between social network diversity and intrinsic functional connectivity of medial corticostriatal pathways. These findings suggest that social integration relates to myelin integrity in humans, which may help explain the diverse aspects of health affected by social networks.

  9. Frontoparietal white matter integrity predicts haptic performance in chronic stroke

    Directory of Open Access Journals (Sweden)

    Alexandra L. Borstad

    2016-01-01

    Full Text Available Frontoparietal white matter supports information transfer between brain areas involved in complex haptic tasks such as somatosensory discrimination. The purpose of this study was to gain an understanding of the relationship between microstructural integrity of frontoparietal network white matter and haptic performance in persons with chronic stroke and to compare frontoparietal network integrity in participants with stroke and age matched control participants. Nineteen individuals with stroke and 16 controls participated. Haptic performance was quantified using the Hand Active Sensation Test (HASTe, an 18-item match-to-sample test of weight and texture discrimination. Three tesla MRI was used to obtain diffusion-weighted and high-resolution anatomical images of the whole brain. Probabilistic tractography was used to define 10 frontoparietal tracts total; Four intrahemispheric tracts measured bilaterally 1 thalamus to primary somatosensory cortex (T–S1, 2 thalamus to primary motor cortex (T–M1, 3 primary to secondary somatosensory cortex (S1 to SII and 4 primary somatosensory cortex to middle frontal gyrus (S1 to MFG and, 2 interhemispheric tracts; S1–S1 and precuneus interhemispheric. A control tract outside the network, the cuneus interhemispheric tract, was also examined. The diffusion metrics fractional anisotropy (FA, mean diffusivity (MD, axial (AD and radial diffusivity (RD were quantified for each tract. Diminished FA and elevated MD values are associated with poorer white matter integrity in chronic stroke. Nine of 10 tracts quantified in the frontoparietal network had diminished structural integrity poststroke compared to the controls. The precuneus interhemispheric tract was not significantly different between groups. Principle component analysis across all frontoparietal white matter tract MD values indicated a single factor explained 47% and 57% of the variance in tract mean diffusivity in stroke and control groups respectively

  10. Sex-differences in grey-white matter structure in normal-reading and dyslexic adolescents.

    Science.gov (United States)

    Sandu, Anca-Larisa; Specht, Karsten; Beneventi, Harald; Lundervold, Arvid; Hugdahl, Kenneth

    2008-06-13

    MR images were used to look for brain structure irregularities in adolescent children with dyslexia by use of combined grey and white matter volume measurements and fractal dimension (FD) of the grey-white matter border. The data were collected from 13 dyslexic adolescent (8 boys and 5 girls) that were compared with 18 control subjects (8 boys and 10 girls). The MR images were first segmented, and the volume as well as the FD of the grey/white matter border for the whole brain and for each hemisphere was computed. Changes were found in the measured volumes of both grey and white matter and were best reflected in the ratio of grey/white matter and in FD values, especially in the left hemisphere. The results showed that, although dyslexia is less frequent in women, the structural differences in the brain are more pronounced in their case, pointing to an increased vulnerability of the female brain to morphological changes associated with dyslexia.

  11. White matter and visuospatial processing in autism: a constrained spherical deconvolution tractography study.

    Science.gov (United States)

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

    2013-10-01

    Autism spectrum disorders (ASDs) are associated with a marked disturbance of neural functional connectivity, which may arise from disrupted organization of white matter. The aim of this study was to use constrained spherical deconvolution (CSD)-based tractography to isolate and characterize major intrahemispheric white matter tracts that are important in visuospatial processing. CSD-based tractography avoids a number of critical confounds that are associated with diffusion tensor tractography, and to our knowledge, this is the first time that this advanced diffusion tractography method has been used in autism research. Twenty-five participants with ASD and aged 25, intelligence quotient-matched controls completed a high angular resolution diffusion imaging scan. The inferior fronto-occipital fasciculus (IFOF) and arcuate fasciculus were isolated using CSD-based tractography. Quantitative diffusion measures of white matter microstructural organization were compared between groups and associated with visuospatial processing performance. Significant alteration of white matter organization was present in the right IFOF in individuals with ASD. In addition, poorer visuospatial processing was associated in individuals with ASD with disrupted white matter in the right IFOF. Using a novel, advanced tractography method to isolate major intrahemispheric white matter tracts in autism, this research has demonstrated that there are significant alterations in the microstructural organization of white matter in the right IFOF in ASD. This alteration was associated with poorer visuospatial processing performance in the ASD group. This study provides an insight into structural brain abnormalities that may influence atypical visuospatial processing in autism.

  12. White Matter Lesion Progression in LADIS

    DEFF Research Database (Denmark)

    Schmidt, Reinhold; Berghold, Andrea; Jokinen, Hanna

    2012-01-01

    BACKGROUND AND PURPOSE: White matter lesion (WML) progression has been advocated as a surrogate marker in intervention trials on cerebral small vessel disease. We assessed the rate of visually rated WML progression, studied correlations between lesion progression and cognition, and estimated sample...... relied on the modified Rotterdam Progression Scale. The Vascular Dementia Assessment Scale global score and a composite score of specific executive function tests assessed longitudinal change in cognition. Sample size calculations were based on the assumption that treatment reduces WML progression by 1....... CONCLUSIONS: WML progression is an interesting outcome for proof-of-concept studies in cerebral small vessel disease. If cognitive outcome measures are added to protocols, then sample size estimates increase substantially. Our data support the use of an executive test battery rather than the Vascular Dementia...

  13. White matter hyperintensities are associated with visual search behavior independent of generalized slowing in aging

    Science.gov (United States)

    Lockhart, Samuel N.; Roach, Alexandra E.; Luck, Steven J.; Geng, Joy; Beckett, Laurel; Carmichael, Owen; DeCarli, Charles

    2014-01-01

    A fundamental controversy is whether cognitive decline with advancing age can be entirely explained by decreased processing speed, or whether specific neural changes can elicit cognitive decline, independent of slowing. These hypotheses are anchored by studies of healthy older individuals where age is presumed the sole influence. Unfortunately, advancing age is also associated with asymptomatic brain white matter injury. We hypothesized that differences in white matter injury extent, manifest by MRI white matter hyperintensities (WMH), mediate differences in visual attentional control in healthy aging, beyond processing speed differences. We tested young and cognitively healthy older adults on search tasks indexing speed and attentional control. Increasing age was associated with generally slowed performance. WMH was also associated with slowed search times independent of processing speed differences. Consistent with evidence attributing reduced network connectivity to WMH, these results conclusively demonstrate that clinically silent white matter injury contributes to slower search performance indicative of compromised cognitive control, independent of generalized slowing of processing speed. PMID:24183716

  14. Subcortical White Matter Changes with Normal Aging Detected by Multi-Shot High Resolution Diffusion Tensor Imaging.

    Science.gov (United States)

    Xie, Sheng; Zhang, Zhe; Chang, Feiyan; Wang, Yishi; Zhang, Zhenxia; Zhou, Zhenyu; Guo, Hua

    2016-01-01

    Subcortical white matter builds neural connections between cortical and subcortical regions and constitutes the basis of neural networks. It plays a very important role in normal brain function. Various studies have shown that white matter deteriorates with aging. However, due to the limited spatial resolution provided by traditional diffusion imaging techniques, microstructural information from subcortical white matter with normal aging has not been comprehensively assessed. This study aims to investigate the deterioration effect with aging in the subcortical white matter and provide a baseline standard for pathological disorder diagnosis. We apply our newly developed multi-shot high resolution diffusion tensor imaging, using self-feeding multiplexed sensitivity-encoding, to measure subcortical white matter changes in regions of interest of healthy persons with a wide age range. Results show significant fractional anisotropy decline and radial diffusivity increasing with age, especially in the anterior part of the brain. We also find that subcortical white matter has more prominent changes than white matter close to the central brain. The observed changes in the subcortical white matter may be indicative of a mild demyelination and a loss of myelinated axons, which may contribute to normal age-related functional decline.

  15. Subcortical White Matter Changes with Normal Aging Detected by Multi-Shot High Resolution Diffusion Tensor Imaging.

    Directory of Open Access Journals (Sweden)

    Sheng Xie

    Full Text Available Subcortical white matter builds neural connections between cortical and subcortical regions and constitutes the basis of neural networks. It plays a very important role in normal brain function. Various studies have shown that white matter deteriorates with aging. However, due to the limited spatial resolution provided by traditional diffusion imaging techniques, microstructural information from subcortical white matter with normal aging has not been comprehensively assessed. This study aims to investigate the deterioration effect with aging in the subcortical white matter and provide a baseline standard for pathological disorder diagnosis. We apply our newly developed multi-shot high resolution diffusion tensor imaging, using self-feeding multiplexed sensitivity-encoding, to measure subcortical white matter changes in regions of interest of healthy persons with a wide age range. Results show significant fractional anisotropy decline and radial diffusivity increasing with age, especially in the anterior part of the brain. We also find that subcortical white matter has more prominent changes than white matter close to the central brain. The observed changes in the subcortical white matter may be indicative of a mild demyelination and a loss of myelinated axons, which may contribute to normal age-related functional decline.

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

    Science.gov (United States)

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

    2017-01-01

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

  17. Reliability of quantifying vascular white matter brain lesions - a contribution to reproducible quantitative diagnosis; Reliabilitaet der Quantifizierung von vaskulaeren Laesionen der weissen Hirnsubstanz - ein Beitrag zur replizierbaren quantitativen Diagnostik

    Energy Technology Data Exchange (ETDEWEB)

    Hentschel, F.; Kreis, M.; Damian, M. [Abt. Neuroradiologie, ZI, Fakultaet fuer klinische Medizin Mannheim der Univ. Heidelberg (Germany); Diepers, M. [Abt. Neuroradiologie des Universitaetsklinikums Mannheim (Germany); Disque, C.; Dzialowski, I.; Kitzler, H.; Rodewald, A. [Abt. Neuroradiologie des Universitaetsklinikums Dresden (Germany); Struffert, T. [Abt. Neuroradiologie des Universitaetsklinikums Homburg (Germany); Trittmacher, S. [Abt. Neuroradiologie des Universitaetsklinikums Giessen (Germany); Wille, P.R. [Inst. fuer Neuroradiologie der Univ. Mainz (Germany); Krumm, B. [Abt. Biostatistik, ZI, Fakultaet fuer klinische Medizin Mannheim der Univ. Heidelberg (Germany)

    2005-01-01

    Purpose: microangiopathic lesions of the brain tissue correlate with the clinical diagnosis of vascular subcortical dementia. The ''experience-based'' evaluation is insufficient. Rating scales may contribute to reproducible quantification. Materials and methods: in MRI studies of 10 patients, 9 neuroradiologists quantified vascular white matter lesions (WMLs) at two different points in time for 12 anatomically defined regions with respect to number, size and localization (score). For 9 observers and 10 studies, 90 intra-observer differences were obtained for each of the 12 WML scores. To calculate the inter-observer reliability, rating pairs were formed. Furthermore, 360 differences were computed for each score and rating for 12 anatomically defined WML scores, and the intraclass correlation (ICC) was calculated as a measure of agreement (reliability). Results: as to the intra-observer reliability, the median of the differences was 1.5 for the entire brain as opposed to 0 for defined brain regions. The corresponding values for the inter-observer reliability were 3 and 1, respectively. The mean intra-class correlation coefficient for the 10 studies was 0.88, whereas the mean interclass correlation concerning the inter-observer reliability was 0.70, with the first and second rating being averaged. The rating of each study took about 6 minutes. Conclusion: the rating scale with high intra- and inter-observer reliability can dependably quantify WMLs and correlates with the clinical diagnosis of vascular dementia. Using a reliable rating scale, the diagnostic distinction of age - associated physiological vs. pathological size of the NMC can make a contribution to the reproducible quantifiable diagnostic evaluation of vascular brain tissue lesions within the framework of dementia diagnostics. (orig.)

  18. Superficial white matter: effects of age, sex, and hemisphere.

    Science.gov (United States)

    Phillips, Owen R; Clark, Kristi A; Luders, Eileen; Azhir, Ramin; Joshi, Shantanu H; Woods, Roger P; Mazziotta, John C; Toga, Arthur W; Narr, Katherine L

    2013-01-01

    Structural and diffusion imaging studies demonstrate effects of age, sex, and asymmetry in many brain structures. However, few studies have addressed how individual differences might influence the structural integrity of the superficial white matter (SWM), comprised of short-range association (U-fibers), and intracortical axons. This study thus applied a sophisticated computational analysis approach to structural and diffusion imaging data obtained from healthy individuals selected from the International Consortium for Brain Mapping (ICBM) database across a wide adult age range (n=65, age: 18-74 years, all Caucasian). Fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) were sampled and compared at thousands of spatially matched SWM locations and within regions-of-interest to examine global and local variations in SWM integrity across age, sex, and hemisphere. Results showed age-related reductions in FA that were more pronounced in the frontal SWM than in the posterior and ventral brain regions, whereas increases in RD and AD were observed across large areas of the SWM. FA was significantly greater in left temporoparietal regions in men and in the posterior callosum in women. Prominent leftward FA and rightward AD and RD asymmetries were observed in the temporal, parietal, and frontal regions. Results extend previous findings restricted to the deep white matter pathways to demonstrate regional changes in the SWM microstructure relating to processes of demyelination and/or to the number, coherence, or integrity of axons with increasing age. SWM fiber organization/coherence appears greater in the left hemisphere regions spanning language and other networks, while more localized sex effects could possibly reflect sex-specific advantages in information strategies.

  19. A probabilistic atlas of the cerebellar white matter.

    Science.gov (United States)

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

    2016-01-01

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

  20. Inflammation in White Matter: Clinical and Pathophysiological Aspects

    Science.gov (United States)

    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…

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

    Science.gov (United States)

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

    2016-02-01

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

  2. Abnormal Behaviors and Microstructural Changes in White Matter of Juvenile Mice Repeatedly Exposed to Amphetamine

    Directory of Open Access Journals (Sweden)

    Hong-Ju Yang

    2011-01-01

    Full Text Available Amphetamine (AMP is an addictive CNS stimulant and has been commonly abused by adolescents and young adults, during which period brain white matter is still developing. This study was to examine the effect of a nonneurotoxic AMP on the white matter of juvenile mice. d-AMP (1.0 mg/kg was given to young male C57BL/6 mice once a day for 21 days. The spatial working memory and locomotion of mice were measured at the end. Then, mice were sacrificed and their brains were processed for morphological analyses to examine the white matter structure and for Western blot analysis to measure three main proteins expressed in mature oligodendrocytes. AMP-treated mice displayed higher locomotion and spatial working memory impairment and showed lower levels of Nogo-A and GST-pi proteins in frontal cortex and lower MBP protein in the frontal cortex and hippocampus. They also had fewer mature oligodendrocytes and weak MBP immunofluorescent staining in the same two brain regions. But the striatum was spared. These results suggest that the late-developing white matter is vulnerable to AMP treatment which is able to increase striatal and cortical dopamine. Both the compromised white matter and increased dopamine may contribute to the observed behavioral changes in AMP-treated mice.

  3. Multivariate characterization of white matter heterogeneity in autism spectrum disorder.

    Science.gov (United States)

    Dean, D C; Lange, N; Travers, B G; Prigge, M B; Matsunami, N; Kellett, K A; Freeman, A; Kane, K L; Adluru, N; Tromp, D P M; Destiche, D J; Samsin, D; Zielinski, B A; Fletcher, P T; Anderson, J S; Froehlich, A L; Leppert, M F; Bigler, E D; Lainhart, J E; Alexander, A L

    2017-01-01

    The complexity and heterogeneity of neuroimaging findings in individuals with autism spectrum disorder has suggested that many of the underlying alterations are subtle and involve many brain regions and networks. The ability to account for multivariate brain features and identify neuroimaging measures that can be used to characterize individual variation have thus become increasingly important for interpreting and understanding the neurobiological mechanisms of autism. In the present study, we utilize the Mahalanobis distance, a multidimensional counterpart of the Euclidean distance, as an informative index to characterize individual brain variation and deviation in autism. Longitudinal diffusion tensor imaging data from 149 participants (92 diagnosed with autism spectrum disorder and 57 typically developing controls) between 3.1 and 36.83 years of age were acquired over a roughly 10-year period and used to construct the Mahalanobis distance from regional measures of white matter microstructure. Mahalanobis distances were significantly greater and more variable in the autistic individuals as compared to control participants, demonstrating increased atypicalities and variation in the group of individuals diagnosed with autism spectrum disorder. Distributions of multivariate measures were also found to provide greater discrimination and more sensitive delineation between autistic and typically developing individuals than conventional univariate measures, while also being significantly associated with observed traits of the autism group. These results help substantiate autism as a truly heterogeneous neurodevelopmental disorder, while also suggesting that collectively considering neuroimaging measures from multiple brain regions provides improved insight into the diversity of brain measures in autism that is not observed when considering the same regions separately. Distinguishing multidimensional brain relationships may thus be informative for identifying

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

    Science.gov (United States)

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

    2016-08-30

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

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

    Directory of Open Access Journals (Sweden)

    Aikaterini Xekardaki

    2011-01-01

    Full Text Available 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.

  6. Gray- and white-matter anatomy of absolute pitch possessors.

    Science.gov (United States)

    Dohn, Anders; Garza-Villarreal, Eduardo A; Chakravarty, M Mallar; Hansen, Mads; Lerch, Jason P; Vuust, Peter

    2015-05-01

    Absolute pitch (AP), the ability to identify a musical pitch without a reference, has been examined behaviorally in numerous studies for more than a century, yet only a few studies have examined the neuroanatomical correlates of AP. Here, we used MRI and diffusion tensor imaging to investigate structural differences in brains of musicians with and without AP, by means of whole-brain vertex-wise cortical thickness (CT) analysis and tract-based spatial statistics (TBSS) analysis. APs displayed increased CT in a number of areas including the bilateral superior temporal gyrus (STG), the left inferior frontal gyrus, and the right supramarginal gyrus. Furthermore, we found higher fractional anisotropy in APs within the path of the inferior fronto-occipital fasciculus, the uncinate fasciculus, and the inferior longitudinal fasciculus. The findings in gray matter support previous studies indicating an increased left lateralized posterior STG in APs, yet they differ from previous findings of thinner cortex for a number of areas in APs. Finally, we found a relation between the white-matter results and the CT in the right parahippocampal gyrus. In this study, we present novel findings in AP research that may have implications for the understanding of the neuroanatomical underpinnings of AP ability.

  7. White versus gray matter function as seen on neuropsychological testing following bone marrow transplant for acute leukemia in childhood

    Directory of Open Access Journals (Sweden)

    Fiona S Anderson

    2008-03-01

    Full Text Available Fiona S Anderson1, Alicia S Kunin-Batson1, Joanna L Perkins2, K Scott Baker31Divisions of Pediatric Clinical Neuroscience; 2Department of Pediatric Hematology/Oncology, Children’s Hospitals and Clinics, Minneapolis, MN, USA and 3Hematology/Oncology/BMT, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USAAbstract: Current theory suggests that neurocognitive late effects of treatments for childhood cancer such as difficulties with attention, processing speed and visual-motor ability are the result of white matter damage. Neuroimaging studies have produced a variety of white matter findings. However, although white matter is thought to be differentially affected, previous studies have not demonstrated a discrepancy between white and gray matter function. The present study included 36 children treated for childhood leukemia with hematopoietic stem cell transplant (HCT. Their performance on neurocognitive measures traditionally thought to measure white matter was compared to performance on measures thought to measure gray matter function. Composite white and gray matter standard scores were created based on neuropsychological measures that individuals with known white or gray matter damage perform poorly. As predicted, composite white matter scores (mean = 98.1 were significantly lower (t = 2.26, p = 0.03 than composite gray matter scores (mean = 102.5. Additionally, as gray matter performance increased, the difference between gray and white matter scores increased (R = 0.353, p = 0.035. Overall, the results of this study support the current theory that white matter damage is responsible for the more subtle neurocognitive late effects resulting from treatment for childhood leukemia.Keywords: late effects of cancer treatment, leukemia, neuropsychology, white matter, brain function

  8. Four-month enriched environment prevents myelinated fiber loss in the white matter during normal aging of male rats.

    Science.gov (United States)

    Yang, Shu; Lu, Wei; Zhou, De-shan; Tang, Yong

    2015-01-01

    White matter degenerates with normal aging and accordingly results in declines in multiple brain functions. Previous neuroimaging studies have implied that the white matter is plastic by experiences and contributory to the experience-dependent recovery of brain functions. However, it is not clear how and how far enriched environment (EE) plays a role in the white matter remodeling. Male rats exhibit earlier and severer age-related damages in the white matter and its myelinated fibers than female rats; therefore, in this current study, 24 middle-aged (14-month-old) and 24 old-aged (24-month-old) male SD rats were randomly assigned to an EE or standard environment (SE) for 4 months prior to Morris water maze tests. Five rats from each group were then randomly sampled for stereological assessment of the white matter. Results revealed that EE could somewhat induce improvement of spatial learning and significantly increase the white matter volume, the myelinated fiber volume and the myelinated fiber length during normal aging. The EE-induced improvement of spatial learning ability was significantly correlated with the EE-induced increase of the white matter and its myelinated fibers. We suggested that exposure to an EE could delay the progress of age-related changes in the white matter and the effect could extend to old age.

  9. Individual differences in left parietal white matter predict math scores on the Preliminary Scholastic Aptitude Test.

    Science.gov (United States)

    Matejko, Anna A; Price, Gavin R; Mazzocco, Michèle M M; Ansari, Daniel

    2013-02-01

    Mathematical skills are of critical importance, both academically and in everyday life. Neuroimaging research has primarily focused on the relationship between mathematical skills and functional brain activity. Comparatively few studies have examined which white matter regions support mathematical abilities. The current study uses diffusion tensor imaging (DTI) to test whether individual differences in white matter predict performance on the math subtest of the Preliminary Scholastic Aptitude Test (PSAT). Grades 10 and 11 PSAT scores were obtained from 30 young adults (ages 17-18) with wide-ranging math achievement levels. Tract based spatial statistics was used to examine the correlation between PSAT math scores, fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD). FA in left parietal white matter was positively correlated with math PSAT scores (specifically in the left superior longitudinal fasciculus, left superior corona radiata, and left corticospinal tract) after controlling for chronological age and same grade PSAT critical reading scores. Furthermore, RD, but not AD, was correlated with PSAT math scores in these white matter microstructures. The negative correlation with RD further suggests that participants with higher PSAT math scores have greater white matter integrity in this region. Individual differences in FA and RD may reflect variability in experience dependent plasticity over the course of learning and development. These results are the first to demonstrate that individual differences in white matter are associated with mathematical abilities on a nationally administered scholastic aptitude measure.

  10. Magnified effects of the COMT gene on white-matter microstructure in very old age.

    Science.gov (United States)

    Papenberg, Goran; Lövdén, Martin; Laukka, Erika J; Kalpouzos, Grégoria; Keller, Lina; Graff, Caroline; Köhncke, Ylva; Li, Tie-Qiang; Fratiglioni, Laura; Bäckman, Lars

    2015-09-01

    Genetic factors may partly account for between-person differences in brain integrity in old age. Evidence from human and animal studies suggests that the dopaminergic system is implicated in the modulation of white-matter integrity. We investigated whether a genetic variation in the Catechol-O-Methyltransferase (COMT) Val158Met polymorphism, which influences dopamine availability in prefrontal cortex, contributes to interindividual differences in white-matter microstructure, as measured with diffusion-tensor imaging. In a sample of older adults from a population-based study (60-87 years; n = 238), we found that the COMT polymorphism affects white-matter microstructure, indexed by fractional anisotropy and mean diffusivity, of several white-matter tracts in the oldest age group (81-87 years), although there were no reliable associations between COMT and white-matter microstructure in the two younger age groups (60-66 and 72-78 years). These findings extend previous observations of magnified genetic effects on cognition in old age to white-matter integrity.

  11. Deep white matter in Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Owen Phillips

    Full Text Available 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.

  12. Occult White Matter Damage Contributes to Intellectual Disability in Tuberous Sclerosis Complex

    Science.gov (United States)

    Yu, Chunshui; Lin, Fuchun; Zhao, Li; Ye, Jing; Qin, Wen

    2009-01-01

    Whether patients with tuberous sclerosis complex (TSC) have brain normal-appearing white matter (NAWM) damage and whether such damage contributes to their intellectual disability were examined in 15 TSC patients and 15 gender- and age-matched healthy controls using diffusion tensor imaging (DTI). Histogram and region of interest (ROI) analyses of…

  13. Widespread reductions of white matter integrity in patients with long-term remission of Cushing's disease

    Directory of Open Access Journals (Sweden)

    Steven J.A. van der Werff

    2014-01-01

    Conclusion: Patients with a history of endogenous hypercortisolism in present remission show widespread changes of white matter integrity in the brain, with abnormalities in the integrity of the uncinate fasciculus being related to the severity of depressive symptoms, suggesting persistent structural effects of hypercortisolism.

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

    Science.gov (United States)

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

    2011-01-01

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

  15. Brainstem White Matter Predicts Individual Differences in Manual Motor Difficulties and Symptom Severity in Autism

    Science.gov (United States)

    Travers, Brittany G.; Bigler, Erin D.; Tromp, Do P. M.; Adluru, Nagesh; Destiche, Dan; Samsin, Danica; Froehlich, Alyson; Prigge, Molly D. B.; Duffield, Tyler C.; Lange, Nicholas; Alexander, Andrew L.; Lainhart, Janet E.

    2015-01-01

    Mounting evidence suggests that poorer motor skills may be related to more severe autism symptoms. This study investigated if atypical white matter microstructure in the brain mediated the relationship between motor skills and ASD symptom severity. Sixty-seven males with ASD and 42 males with typical development (5-33 years old) completed a…

  16. Accelerated progression of white matter hyperintensities and subsequent risk of mortality

    DEFF Research Database (Denmark)

    Sabayan, Behnam; van der Grond, Jeroen; Westendorp, Rudi G;

    2015-01-01

    We examined the association of accelerated progression of white matter hyperintensities (WMH) with mortality outcomes in 534 older subjects at risk for cardiovascular disease. Using brain magnetic resonance imaging, volume of WMH was measured 2 times in an average of 33 months apart. After...

  17. White Matter and Development in Children with an Autism Spectrum Disorder

    Science.gov (United States)

    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…

  18. White matter abnormalities in adults with 22q11 deletion syndrome with and without schizophrenia

    NARCIS (Netherlands)

    F. da Silva Alves; N. Schmitz; O. Bloemen; J. van der Meer; J. Meijer; E. Boot; A. Nederveen; L. de Haan; D. Linszen; T. van Amelsvoort

    2011-01-01

    Dysfunction of cerebral white matter (WM) is a potential factor underlying the neurobiology of schizophrenia. People with 22q11 deletion syndrome have altered brain morphology and increased risk for schizophrenia, therefore decreased WM integrity may be related to schizophrenia in 22q11DS. We measur

  19. White matter microstructures underlying mathematical abilities in children.

    Science.gov (United States)

    van Eimeren, Lucia; Niogi, Sumit N; McCandliss, Bruce D; Holloway, Ian D; Ansari, Daniel

    2008-07-16

    The role of gray matter function and structure in mathematical cognition has been well researched. Comparatively little is known about white matter microstructures associated with mathematical abilities. Diffusion tensor imaging data from 13 children (7-9 years) and two measures of their mathematical competence were collected. Relationships between children's mathematical competence and fractional anisotropy were found in two left hemisphere white matter regions. Although the superior corona radiata was found to be associated with both numerical operations and mathematical reasoning, the inferior longitudinal fasciculus was correlated with numerical operations specifically. These findings suggest a role for microstructure in left white matter tracts for the development of mathematical skills. Moreover, the findings point to the involvement of different white matter tracts for numerical operations and mathematical reasoning.

  20. Quantitative analysis of [{sup 18}F]FDDNP PET using subcortical white matter as reference region

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Koon-Pong; Shao, Weber; Dahlbom, Magnus; Kepe, Vladimir; Liu, Jie; Satyamurthy, Nagichettiar; Barrio, Jorge R. [David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, Los Angeles, CA (United States); Wardak, Mirwais; Huang, Sung-Cheng [David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, Los Angeles, CA (United States); David Geffen School of Medicine at UCLA, Department of Biomathematics, Los Angeles, CA (United States); Small, Gary W. [David Geffen School of Medicine at UCLA, Department of Psychiatry and Biobehavioral Sciences, Los Angeles, CA (United States); David Geffen School of Medicine at UCLA, Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA (United States); David Geffen School of Medicine at UCLA, UCLA Center on Aging, Los Angeles, CA (United States); Mary S. Easton Center for Alzheimer' s Disease Research, Los Angeles, CA (United States)

    2010-03-15

    Subcortical white matter is known to be relatively unaffected by amyloid deposition in Alzheimer's disease (AD). We investigated the use of subcortical white matter as a reference region to quantify [{sup 18}F]FDDNP binding in the human brain. Dynamic [{sup 18}F]FDDNP PET studies were performed on 7 control subjects and 12 AD patients. Population efflux rate constants (k{sup '}{sub 2}) from subcortical white matter (centrum semiovale) and cerebellar cortex were derived by a simplified reference tissue modeling approach incorporating physiological constraints. Regional distribution volume ratio (DVR) estimates were derived using Logan and simplified reference tissue approaches, with either subcortical white matter or cerebellum as reference input. Discriminant analysis with cross-validation was performed to classify control subjects and AD patients. The population estimates of k{sup '}{sub 2} in subcortical white matter did not differ significantly between control subjects and AD patients but the variability of individual estimates of k{sup '}{sub 2} determined in white matter was lower than that in cerebellum. Logan DVR showed dependence on the efflux rate constant in white matter. The DVR estimates in the frontal, parietal, posterior cingulate, and temporal cortices were significantly higher in the AD group (p<0.01). Incorporating all these regional DVR estimates as predictor variables in discriminant analysis yielded accurate classification of control subjects and AD patients with high sensitivity and specificity, and the results agreed well with those using the cerebellum as the reference region. Subcortical white matter can be used as a reference region for quantitative analysis of [{sup 18}F]FDDNP with the Logan method which allows more accurate and less biased binding estimates, but a population efflux rate constant has to be determined a priori. (orig.)

  1. White matter tract injury and cognitive impairment in human immunodeficiency virus-infected individuals.

    Science.gov (United States)

    Gongvatana, Assawin; Schweinsburg, Brian C; Taylor, Michael J; Theilmann, Rebecca J; Letendre, Scott L; Alhassoon, Omar M; Jacobus, Joanna; Woods, Steven P; Jernigan, Terry L; Ellis, Ronald J; Frank, Lawrence R; Grant, Igor

    2009-04-01

    Approximately half of those infected with the human immunodeficiency virus (HIV) exhibit cognitive impairment, which has been related to cerebral white matter damage. Despite the effectiveness of antiretroviral treatment, cognitive impairment remains common even in individuals with undetectable viral loads. One explanation for this may be subtherapeutic concentrations of some antiretrovirals in the central nervous system (CNS). We utilized diffusion tensor imaging and a comprehensive neuropsychological evaluation to investigate the relationship of white matter integrity to cognitive impairment and antiretroviral treatment variables. Participants included 39 HIV-infected individuals (49% with acquired immunodeficiency syndrome [AIDS]; mean CD4 = 529) and 25 seronegative subjects. Diffusion tensor imaging indices were mapped onto a common whole-brain white matter tract skeleton, allowing between-subject voxelwise comparisons. The total HIV-infected group exhibited abnormal white matter in the internal capsule, inferior longitudinal fasciculus, and optic radiation; whereas those with AIDS exhibited more widespread damage, including in the internal capsule and the corpus callosum. Cognitive impairment in the HIV-infected group was related to white matter injury in the internal capsule, corpus callosum, and superior longitudinal fasciculus. White matter injury was not found to be associated with HIV viral load or estimated CNS penetration of antiretrovirals. Diffusion tensor imaging was useful in identifying changes in white matter tracts associated with more advanced HIV infection. Relationships between diffusion alterations in specific white matter tracts and cognitive impairment support the potential utility of diffusion tensor imaging in examining the anatomical underpinnings of HIV-related cognitive impairment. The study also confirms that CNS injury is evident in persons infected with HIV despite effective antiretroviral treatment.

  2. White matter hyperintensities segmentation: a new semi-automated method

    Directory of Open Access Journals (Sweden)

    Mariangela eIorio

    2013-12-01

    Full Text Available White matter hyperintensities (WMH are brain areas of increased signal on T2-weighted or fluid attenuated inverse recovery magnetic resonance imaging (MRI scans. In this study we present a new semi-automated method to measure WMH load that is based on the segmentation of the intensity histogram of fluid-attenuated inversion recovery images. Thirty patients with Mild Cognitive Impairment with variable WMH load were enrolled. The semi-automated WMH segmentation included: removal of non-brain tissue, spatial normalization, removal of cerebellum and brain stem, spatial filtering, thresholding to segment probable WMH, manual editing for correction of false positives and negatives, generation of WMH map and volumetric estimation of the WMH load. Accuracy was quantitatively evaluated by comparing semi-automated and manual WMH segmentations performed by two independent raters. Differences between the two procedures were assessed using Student’s t tests and similarity was evaluated using linear regression model and Dice Similarity Coefficient (DSC. The volumes of the manual and semi-automated segmentations did not statistically differ (t-value= -1.79, DF=29, p= 0.839 for rater 1; t-value= 1.113, DF=29, p= 0.2749 for rater 2, were highly correlated (R²= 0.921, F (1,29 =155,54, p

  3. White matter damage and brain network alterations in concussed patients: a review of recent diffusion tensor imaging and resting-state functional connectivity data.

    Science.gov (United States)

    Chong, Catherine D; Schwedt, Todd J

    2015-05-01

    Over 2 million people are diagnosed with concussion each year in the USA, resulting in substantial individual and societal burdens. Although 'routine' clinical neuroimaging is useful for the diagnosis of more severe forms of traumatic brain injury, it is insensitive for detecting pathology associated with concussion. Diffusion tensor imaging (DTI) and blood-oxygenation-level-dependent (BOLD) resting-state functional connectivity magnetic resonance imaging (rs-fMRI) are techniques that allow for investigation of brain structural and functional connectivity patterns. DTI and rs-fMRI may be more sensitive than routine neuroimaging for detecting brain sequelae of concussion. This review summarizes recent DTI and rs-fMRI findings of altered structural and functional connectivity patterns in concussed patients.

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

    Science.gov (United States)

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

    2016-01-01

    Aging-related differences in white matter integrity, the presence of amyloid plaques, and density of biomarkers indicative of dopamine functions can be detected and quantified with in vivo human imaging. The primary aim of the present study was to investigate whether these imaging-based measures constitute independent imaging biomarkers in older adults, which would speak to the hypothesis that the aging brain is characterized by multiple independent neurobiological cascades. We assessed MRI-based markers of white matter integrity and PET-based marker of dopamine transporter density and amyloid deposition in the same set of 53 clinically normal individuals (age 65–87). A multiple regression analysis demonstrated that dopamine transporter availability is predicted by white matter integrity, which was detectable even after controlling for chronological age. Further post-hoc exploration revealed that dopamine transporter availability was further associated with systolic blood pressure, mirroring the established association between cardiovascular health and white matter integrity. Dopamine transporter availability was not associated with the presence of amyloid burden. Neurobiological correlates of dopamine transporter measures in aging are therefore likely unrelated to Alzheimer’s disease but are aligned with white matter integrity and cardiovascular risk. More generally, these results suggest that two common imaging markers of the aging brain that are typically investigated separately do not reflect independent neurobiological processes. PMID:26542307

  5. Validity of semi-quantitative scale for brain MRI in unilateral cerebral palsy due to periventricular white matter lesions: Relationship with hand sensorimotor function and structural connectivity

    Directory of Open Access Journals (Sweden)

    Simona Fiori

    2015-01-01

    Conclusion: The sqMRI scale demonstrates first evidence of construct validity against impaired motor and sensory function measures and brain structural connectivity in a cohort of children with UCP due to PWM lesions. More severe lesions correlated with poorer paretic hand sensorimotor function and impaired structural connectivity in the hemisphere contralateral to the clinical side of hemiplegia. The quantitative structural MRI scoring may be a useful clinical tool for studying brain structure–function relationships but requires further validation in other populations of CP.

  6. Changes in perceptual speed and white matter microstructure in the corticospinal tract are associated in very old age.

    Science.gov (United States)

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

    2014-11-15

    The integrity of the brain's white matter is important for neural processing and displays age-related differences, but the contribution of changes in white matter to cognitive aging is unclear. We used latent change modeling to investigate this issue in a sample of very old adults (aged 81-103 years) assessed twice with a retest interval of 2.3 years. Using diffusion-tensor imaging, we probed white matter microstructure by quantifying mean fractional anisotropy and mean diffusivity of six major white matter tracts. Measures of perceptual speed, episodic memory, letter fluency, category fluency, and semantic memory were collected. Across time, alterations of white matter microstructure in the corticospinal tract were associated with decreases of perceptual speed. This association remained significant after statistically controlling for changes in white matter microstructure in the entire brain, in the other demarcated tracts, and in the other cognitive abilities. Changes in brain volume also did not account for the association. We conclude that white matter microstructure is a potent correlate of changes in sensorimotor aspects of behavior in very old age, but that it is unclear whether its impact extends to higher-order cognition.

  7. Gray Matter Concentration Abnormality in Brains of Narcolepsy Patients

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Eun Yeon; Tae, Woo Suk; Kim, Sung Tae; Hong, Seung Bong [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2009-12-15

    To investigate gray matter concentration changes in the brains of narcoleptic patients. Twenty-nine narcoleptic patient with cataplexy and 29 age and sex-matched normal subjects (mean age, 31 years old) underwent volumetric MRIs. The MRIs were spatially normalized to a standard T1 template and subdivided into gray matter, white matter, and cerebrospinal fluid (CSF). These segmented images were then smoothed using a 12-mm full width at half maximum (FWHM) isotropic Gaussian kernel. An optimized voxel-based morphometry protocol was used to analyze brain tissue concentrations using SPM2 (statistical parametric mapping). A one-way analysis of variance was applied to the concentration analysis of gray matter images. Narcoleptics with cataplexy showed reduced gray matter concentration in bilateral thalami, left gyrus rectus, bilateral frontopolar gyri, bilateral short insular gyri, bilateral superior frontal gyri, and right superior temporal and left inferior temporal gyri compared to normal subjects (uncorrected p < 0.001). Furthermore, small volume correction revealed gray matter concentration reduction in bilateral nuclei accumbens, hypothalami, and thalami (false discovery rate corrected p < 0.05). Gray matter concentration reductions were observed in brain regions related to excessive daytime sleepiness, cognition, attention, and memory in narcoleptics with cataplexy

  8. Preclinical cerebral network connectivity evidence of deficits in mild white matter lesions

    Directory of Open Access Journals (Sweden)

    Ying eLiang

    2016-02-01

    Full Text Available White matter lesions (WMLs are notable for their high prevalence and have been demonstrated to be a potential neuroimaging biomarker of early diagnosis of Alzheimer’s disease. This study aimed to identify the brain functional and structural mechanisms underlying cognitive decline observed in mild WMLs. Multi-domain cognitive tests, as well as resting-state, diffusion tensor and structural images were obtained on 42 mild WMLs and 42 age/sex-matched healthy controls. For each participant, we examined the functional connectivity of three resting-state networks related to the changed cognitive domains: the default mode network (DMN and the bilateral fronto-parietal network (FPN. We also performed voxel-based morphometry analysis to compare whole-brain gray matter volume, atlas-based quantification of the white matter tracts interconnecting the RSNs, and the relationship between functional connectivity and structural connectivity. We observed functional connectivity alterations in the DMN and the right FPN combined with related white matter integrity disruption in mild WMLs. However, no significant gray matter atrophy difference was found. Furthermore, the right precuneus functional connectivity in the DMN exhibited a significantly negative correlation with the memory test scores. Our study suggests that in mild WMLs, dysfunction of RSNs might be a consequence of decreased white matter structural connectivity, which further affects cognitive performance.

  9. White matter tract integrity in treatment-resistant gambling disorder

    DEFF Research Database (Denmark)

    Chamberlain, Samuel R.; Derbyshire, Katherine; Daws, Richard E.

    2016-01-01

    Background: Gambling disorder is a relatively common psychiatric disorder recently re-classified within the DSM-5 under the category of ‘substance-related and addictive disorders’. Aims: To compare white matter integrity in patients with gambling disorder with healthy controls; to explore...... relationships between white matter integrity and disease severity in gambling disorder. Method: In total, 16 participants with treatment-resistant gambling disorder and 15 healthy controls underwent magnetic resonance imaging (MRI). White matter integrity was analysed using tract-based spatial statistics....... Results: Gambling disorder was associated with reduced fractional anisotropy in the corpus callosum and superior longitudinal fasciculus. Fractional anisotropy in distributed white matter tracts elsewhere correlated positively with disease severity. Conclusions: Reduced corpus callosum fractional...

  10. Patchy cerebral white matter edema in chronic renal failure

    Energy Technology Data Exchange (ETDEWEB)

    Anlar, B.; Erzen, C.; Saatci, U.

    1989-07-01

    Bilateral patchy cerebral white matter edema was observed in two children with chronic renal failure. Uremia in one case and hypertension or hyponatremia in the other appeared to be the cause of the neurological and radiological findings. (orig.).

  11. Regional White Matter Decreases in Alzheimer's Disease Using Optimized Voxel-Based Morphometry

    Energy Technology Data Exchange (ETDEWEB)

    Shuyu Li; Fang Pu; Feng Shi; Sheng Xie; Yinhua Wang; Tianzi Jiang (Dept. of Bioengineering, Beijing Univ. of Aeronautics and Astronautics, Beijing (China))

    2008-02-15

    Background: Most studies that attempt to clarify structural abnormalities related to functional disconnection in patients with Alzheimer's disease (AD) have focused on exploring pathological changes in cortical gray matter. However, white matter fibers connecting these cerebral areas may also be abnormal. Purpose: To investigate the regional changes of white matter volume in patients with AD compared to healthy subjects. Material and Methods: White matter volume changes in whole-brain magnetic resonance images acquired from 19 patients with AD and 20 healthy subjects (control group) were observed using the optimized voxel-based morphometry (VBM) method. In addition, the corpus callosum (CC) of AD patients and the control group was investigated further by outlining manually the boundary of the CC on a midsagittal slice. Each area of the CC was then corrected by dividing each subject's intracranial area in the midsagittal plane. Results: Compared with the control group, AD patients showed significantly reduced white matter volumes in the posterior part of the CC and the temporal lobe in the left and right hemispheres. Moreover, the voxel showing peak statistical difference in the posterior of the CC was left sided. The five subdivisions of the CC were also significantly smaller among the AD patients relative to the control group. Conclusion: Our findings suggest that these abnormalities in white matter regions may contribute to the functional disconnections in AD

  12. Regional White Matter Decreases in Alzheimer's Disease Using Optimized Voxel-Based Morphometry

    Energy Technology Data Exchange (ETDEWEB)

    Shuyu Li; Fang Pu; Feng Shi; Sheng Xie; Yinhua Wang; Tianzi Jiang [Dept. of Bioengineering, Beijing Univ. of Aeronautics and Astronautics, Beijing (China)

    2008-02-15

    Background: Most studies that attempt to clarify structural abnormalities related to functional disconnection in patients with Alzheimer's disease (AD) have focused on exploring pathological changes in cortical gray matter. However, white matter fibers connecting these cerebral areas may also be abnormal. Purpose: To investigate the regional changes of white matter volume in patients with AD compared to healthy subjects. Material and Methods: White matter volume changes in whole-brain magnetic resonance images acquired from 19 patients with AD and 20 healthy subjects (control group) were observed using the optimized voxel-based morphometry (VBM) method. In addition, the corpus callosum (CC) of AD patients and the control group was investigated further by outlining manually the boundary of the CC on a midsagittal slice. Each area of the CC was then corrected by dividing each subject's intracranial area in the midsagittal plane. Results: Compared with the control group, AD patients showed significantly reduced white matter volumes in the posterior part of the CC and the temporal lobe in the left and right hemispheres. Moreover, the voxel showing peak statistical difference in the posterior of the CC was left sided. The five subdivisions of the CC were also significantly smaller among the AD patients relative to the control group. Conclusion: Our findings suggest that these abnormalities in white matter regions may contribute to the functional disconnections in AD.

  13. Diminished white matter integrity in patients with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Tobias Schmidt-Wilcke

    2014-01-01

    Conclusions: Our data suggest that changes in regional white matter integrity, in terms of a decrease in FA, are present not only in NPSLE patients, but also in non-NPSLE patients, though to a lesser degree. We also demonstrate that the way statistical maps are corrected for multiple comparisons has a profound influence on whether alterations in white matter integrity in non-NPSLE patients are deemed significant.

  14. Magnetic Resonance Diffusion Tensor Imaging in Evaluating Myelinization of White Matter of Brain in Children%儿童脑白质髓鞘发育的磁共振弥散张量成像

    Institute of Scientific and Technical Information of China (English)

    邹松; 曾强; 沈东挥

    2011-01-01

    目的 探讨健康儿童脑白质发育的磁共振弥散张量成像(DTI)参数变化特点及其规律.方法 收集健康儿童49名,按年龄分5组,即第1组≤1岁,第2组>1~3岁,第3组>3~6岁,第4组>6~12岁,第5组>12~18岁.各组均行脑部常规MRI和DTI扫描,对DTI原始数据进行处理获得各感兴趣区的DTI参数,并对所得数据进行统计分析.结果 不同性别儿童的双侧对称共10个部位的DTI参数无明显差别;各部位FA、RA值随年龄而递增,ADC、1-VR值则呈递减趋势;各部位间的DTI参数值的排序:FA、RA值为额叶<顶叶<半卵圆中心<枕叶<颞叶,1-VR值为颞叶<枕叶<半卵圆中心<顶叶<额叶.结论 儿童脑白质髓鞘发育中DTI各参数的变化具有一定的规律特点.%Objective To study the parameters of magnetic resonance diffusion tensor imaging coefficients during the development of white matter of brain in healthy children. Methods 49 healthy children were classified into five groups (≤1 year, >1-3 years, >3-6 years, >6-12 years, >12-18 years) and underwent conventional MRI (magnetic resonance imaging) and DTI (diffusion tensor imaging). Postprocessed the DTI source data to obtain the coefficients of each ROI (region of interest) and made an analysis statistically. Results There were no significant differences between the symmetric bilateral ROIs in DTI coefficients among the 10 locations selected in the brain. The FA (fractional anisotropy) and RA (relative anisotropy) values increased alongside with the increased ages while the tendency of the ADC (apparent diffusion coefficient) and 1-VR (volume ratio) values was opposite. The DTI coefficients of different locations ranged as follows: frontal lobe < parietal lobe < centrum ovale < occipital lobe <temporal lobe (FA and RA values) , temporal lobe < occipital lobe < centrum ovale < parietal lobe <frontal lobe (1-VR values). Conclusions The DTI coefficients showed certain characteristics during

  15. Tissue transglutaminase in marmoset experimental multiple sclerosis: discrepancy between white and grey matter.

    Directory of Open Access Journals (Sweden)

    Nathaly Espitia Pinzon

    Full Text Available Infiltration of leukocytes is a major pathological event in white matter lesion formation in the brain of multiple sclerosis (MS patients. In grey matter lesions, less infiltration of these cells occur, but microglial activation is present. Thus far, the interaction of β-integrins with extracellular matrix proteins, e.g. fibronectin, is considered to be of importance for the influx of immune cells. Recent in vitro studies indicate a possible role for the enzyme tissue Transglutaminase (TG2 in mediating cell adhesion and migration. In the present study we questioned whether TG2 is present in white and grey matter lesions observed in the marmoset model for MS. To this end, immunohistochemical studies were performed. We observed that TG2, expressed by infiltrating monocytes in white matter lesions co-expressed β1-integrin and is located in close apposition to deposited fibronectin. These data suggest an important role for TG2 in the adhesion and migration of infiltrating monocytes during white matter lesion formation. Moreover, in grey matter lesions, TG2 is mainly present in microglial cells together with some β1-integrin, whereas fibronectin is absent in these lesions. These data imply an alternative role for microglial-derived TG2 in grey matter lesions, e.g. cell proliferation. Further research should clarify the functional role of TG2 in monocytes or microglial cells in MS lesion formation.

  16. Tissue transglutaminase in marmoset experimental multiple sclerosis: discrepancy between white and grey matter.

    Science.gov (United States)

    Espitia Pinzon, Nathaly; Stroo, Esther; 't Hart, Bert A; Bol, John G J M; Drukarch, Benjamin; Bauer, Jan; van Dam, Anne-Marie

    2014-01-01

    Infiltration of leukocytes is a major pathological event in white matter lesion formation in the brain of multiple sclerosis (MS) patients. In grey matter lesions, less infiltration of these cells occur, but microglial activation is present. Thus far, the interaction of β-integrins with extracellular matrix proteins, e.g. fibronectin, is considered to be of importance for the influx of immune cells. Recent in vitro studies indicate a possible role for the enzyme tissue Transglutaminase (TG2) in mediating cell adhesion and migration. In the present study we questioned whether TG2 is present in white and grey matter lesions observed in the marmoset model for MS. To this end, immunohistochemical studies were performed. We observed that TG2, expressed by infiltrating monocytes in white matter lesions co-expressed β1-integrin and is located in close apposition to deposited fibronectin. These data suggest an important role for TG2 in the adhesion and migration of infiltrating monocytes during white matter lesion formation. Moreover, in grey matter lesions, TG2 is mainly present in microglial cells together with some β1-integrin, whereas fibronectin is absent in these lesions. These data imply an alternative role for microglial-derived TG2 in grey matter lesions, e.g. cell proliferation. Further research should clarify the functional role of TG2 in monocytes or microglial cells in MS lesion formation.

  17. White matter correlates of neuropsychological dysfunction in systemic lupus erythematosus.

    Directory of Open Access Journals (Sweden)

    Rex E Jung

    Full Text Available Patients diagnosed with Systemic Lupus Erythematosus have similar levels of neuropsychological dysfunction (i.e., 20-50% as those with Neuropsychiatric Systemic Lupus Erythematosus (NPSLE. We hypothesized a gradient between cognition and white matter integrity, such that strongest brain-behavior relationships would emerge in NPSLE, intermediate in non-NPSLE, and minimal in controls. We studied thirty-one patients (16 non-NPSLE; 15 NPSLE, ranging in age from 18 to 59 years old (100% female, and eighteen age and gender matched healthy controls. DTI examinations were performed on a 1.5T scanner. A broad neuropsychological battery was administered, tapping attention, memory, processing speed, and executive functioning. The Total z-score consisted of the combined sum of all neuropsychological measures. In control subjects, we found no significant FA-Total z-score correlations. NPSLE, non-NPSLE, and control subjects differed significantly in terms of Total z-score (NPSLE = -2.25+/-1.77, non-NPSLE = -1.22+/-1.03, Controls = -0.10+/-.57; F = 13.2, p<.001. In non-NPSLE subjects, FA within the right external capsule was significantly correlated with Total z-score. In NPSLE subjects, the largest FA-Total z-score clusters were observed within the left anterior thalamic radiation and right superior longitudinal fasciculus. In subsequent analyses the largest number of significant voxels linked FA with the Processing Speed z-score in NPSLE. The current results reflect objective white matter correlates of neuropsychological dysfunction in both NPSLE and (to a lesser degree in non-NPSLE. non-NPSLE and NPSLE subjects did not differ significantly in terms of depression, as measured by the GDI; thus, previous hypotheses suggesting moderating effects of depression upon neuropsychological performance do not impact the current FA results.

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

    Energy Technology Data Exchange (ETDEWEB)

    Tjeerdema, Nathanja; Schinkel, Linda D. van [Leiden University Medical Center, Department of Endocrinology and General Internal Medicine (C7-Q), Albinusdreef 2, PO Box 9600, Leiden (Netherlands); Westenberg, Jos J.; Elderen, Saskia G. van; Buchem, Mark A. van; Grond, Jeroen van der; Roos, Albert de [Leiden University Medical Center, Department of Radiology, Leiden (Netherlands); Smit, Johannes W. [Leiden University Medical Center, Department of Endocrinology and General Internal Medicine (C7-Q), Albinusdreef 2, PO Box 9600, Leiden (Netherlands); University Medical Center Nijmegen, Department of General Internal Medicine, Nijmegen (Netherlands)

    2014-09-15

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

  19. Differential prefrontal white matter development in chimpanzees and humans.

    Science.gov (United States)

    Sakai, Tomoko; Mikami, Akichika; Tomonaga, Masaki; Matsui, Mie; Suzuki, Juri; Hamada, Yuzuru; Tanaka, Masayuki; Miyabe-Nishiwaki, Takako; Makishima, Haruyuki; Nakatsukasa, Masato; Matsuzawa, Tetsuro

    2011-08-23

    A comparison of developmental patterns of white matter (WM) within the prefrontal region between humans and nonhuman primates is key to understanding human brain evolution. WM mediates complex cognitive processes and has reciprocal connections with posterior processing regions [1, 2]. Although the developmental pattern of prefrontal WM in macaques differs markedly from that in humans [3], this has not been explored in our closest evolutionary relative, the chimpanzee. The present longitudinal study of magnetic resonance imaging scans demonstrated that the prefrontal WM volume in chimpanzees was immature and had not reached the adult value during prepuberty, as observed in humans but not in macaques. However, the rate of prefrontal WM volume increase during infancy was slower in chimpanzees than in humans. These results suggest that a less mature and more protracted elaboration of neuronal connections in the prefrontal portion of the developing brain existed in the last common ancestor of chimpanzees and humans, and that this served to enhance the impact of postnatal experiences on neuronal connectivity. Furthermore, the rapid development of the human prefrontal WM during infancy may help the development of complex social interactions, as well as the acquisition of experience-dependent knowledge and skills to shape neuronal connectivity.

  20. Constrained by our connections: white matter's key role in interindividual variability in visual working memory capacity.

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

    2014-11-05

    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 (f(axon)), an index of axonal density and caliber. Our results show that 59% of individual variability in VWM capacity may be explained by variations in f(axon) within a widely distributed network of white matter tracts. Increased f(axon) 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.

  1. White and grey matter relations to simple, choice, and cognitive reaction time in spina bifida.

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    Dennis, Maureen; Cirino, Paul T; Simic, Nevena; Juranek, Jenifer; Taylor, W Pat; Fletcher, Jack M

    2016-03-01

    Elevated reaction time (RT) is common in brain disorders. We studied three forms of RT in a neurodevelopmental disorder, spina bifida myelomeningocele (SBM), characterized by regional alterations of both white and grey matter, and typically developing individuals aged 8 to 48 years, in order to establish the nature of the lifespan-relations of RT and brain variables. Cognitive accuracy and RT speed and variability were all impaired in SBM relative to the typically developing group, but the most important effects of SBM on RT are seen on tasks that require a cognitive decision rule. Individuals with SBM are impaired not only in speeded performance, but also in the consistency of their performance on tasks that extend over time, which may contribute to poor performance on a range of cognitive tasks. The group with SBM showed smaller corrected corpus callosum proportions, larger corrected cerebellar white matter proportions, and larger corrected proportions for grey matter in the Central Executive and Salience networks. There were clear negative relations between RT measures and corpus callosum, Central Executive, and Default Mode networks in the group with SBM; relations were not observed in typically developing age peers. Statistical mediation analyses indicated that corpus callosum and Central Executive Network were important mediators. While RT is known to rely heavily on white matter under conditions of typical development and in individuals with adult-onset brain injury, we add the new information that additional involvement of grey matter may be important for a key neuropsychological function in a common neurodevelopmental disorder.

  2. Gray and white matter correlates of the Big Five personality traits.

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    Privado, Jesús; Román, Francisco J; Saénz-Urturi, Carlota; Burgaleta, Miguel; Colom, Roberto

    2017-05-04

    Personality neuroscience defines the scientific study of the neurobiological basis of personality. This field assumes that individual differences in personality traits are related with structural and functional variations of the human brain. Gray and white matters are structural properties considered separately in previous research. Available findings in this regard are largely disparate. Here we analyze the relationships between gray matter (cortical thickness (CT), cortical surface area (CSA), and cortical volume) and integrity scores obtained after several white matter tracts connecting different brain regions, with individual differences in the personality traits comprised by the Five-Factor Model (extraversion, agreeableness, conscientiousness, neuroticism, and openness to experience). These psychological and biological data were obtained from young healthy women. The main findings showed statistically significant associations between occipital CSA variations and extraversion, as well as between parietal CT variations and neuroticism. Regarding white matter integrity, openness showed positive correlations with tracts connecting posterior and anterior brain regions. Therefore, variations in discrete gray matter clusters were associated with temperamental traits (extraversion and neuroticism), whereas long-distance structural connections were related with the dimension of personality that has been associated with high-level cognitive processes (openness).

  3. White matter asymmetry in healthy individuals: a diffusion tensor imaging study using tract-based spatial statistics.

    Science.gov (United States)

    Takao, H; Hayashi, N; Ohtomo, K

    2011-10-13

    The purpose of this study was to investigate white matter asymmetry across the whole brain and evaluate the effects of age and sex on white matter asymmetry in a large sample of healthy adults. A total of 857 normal subjects (310 females and 547 males, mean age=56.1±9.9 years, age range=24.9-84.8 years) were included in this study. With use of tract-based spatial statistics (TBSS), we investigated white matter fractional anisotropy (FA) asymmetry and evaluated the effects of age and sex on white matter FA asymmetry. The voxel-wise analysis showed a large number of white matter FA asymmetries including leftward asymmetry of the arcuate fasciculus and cingulum. The effects of age and sex on white matter FA asymmetry were minor compared to overall FA asymmetries. Small regions showed a significant effect of age or sex, due to the large sample, but this may not be relevant in practice. There was no significant interaction between age and sex. The results of our study demonstrate white matter asymmetry in healthy adults and suggest that white matter asymmetry is relatively stable during aging and not much different between males and females.

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

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    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.

  5. Linking white and grey matter in schizophrenia: oligodendrocyte and neuron pathology in the prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Malin Hoistad

    2009-07-01

    Full Text Available 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.

  6. Tract profiles of white matter properties: automating fiber-tract quantification.

    Directory of Open Access Journals (Sweden)

    Jason D Yeatman

    Full Text Available Tractography based on diffusion weighted imaging (DWI data is a method for identifying the major white matter fascicles (tracts in the living human brain. The health of these tracts is an important factor underlying many cognitive and neurological disorders. In vivo, tissue properties may vary systematically along each tract for several reasons: different populations of axons enter and exit the tract, and disease can strike at local positions within the tract. Hence quantifying and understanding diffusion measures along each fiber tract (Tract Profile may reveal new insights into white matter development, function, and disease that are not obvious from mean measures of that tract. We demonstrate several novel findings related to Tract Profiles in the brains of typically developing children and children at risk for white matter injury secondary to preterm birth. First, fractional anisotropy (FA values vary substantially within a tract but the Tract FA Profile is consistent across subjects. Thus, Tract Profiles contain far more information than mean diffusion measures. Second, developmental changes in FA occur at specific positions within the Tract Profile, rather than along the entire tract. Third, Tract Profiles can be used to compare white matter properties of individual patients to standardized Tract Profiles of a healthy population to elucidate unique features of that patient's clinical condition. Fourth, Tract Profiles can be used to evaluate the association between white matter properties and behavioral outcomes. Specifically, in the preterm group reading ability is positively correlated with FA measured at specific locations on the left arcuate and left superior longitudinal fasciculus and the magnitude of the correlation varies significantly along the Tract Profiles. We introduce open source software for automated fiber-tract quantification (AFQ that measures Tract Profiles of MRI parameters for 18 white matter tracts. With further

  7. Grey and white matter changes across the amyotrophic lateral sclerosis-frontotemporal dementia continuum.

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    Patricia Lillo

    Full Text Available There is increasing evidence that amyotrophic lateral sclerosis (ALS and frontotemporal dementia (FTD lie on a clinical, pathological and genetic continuum with patients of one disease exhibiting features of the other. Nevertheless, to date, the underlying grey matter and white matter changes across the ALS-FTD disease continuum have not been explored. In this study fifty-three participants with ALS (n = 10, ALS-FTD (n = 10 and behavioural variant FTD (bvFTD; n = 15 as well as controls (n = 18, underwent detailed clinical assessment plus structural imaging using voxel-based morphometry (VBM and diffusion tensor imaging (DTI analysis of magnetic resonance brain imaging to examine grey and white matter differences and commonalities across the continuum. Importantly, patient groups were matched for age, education, gender and disease duration. VBM and DTI results showed that changes in the ALS group were confined mainly to the motor cortex and anterior cingulate as well as their underlying white matter tracts. ALS-FTD and bvFTD showed widespread grey matter and white matter changes involving frontal and temporal lobes. Extensive prefrontal cortex changes emerged as a marker for bvFTD compared to other subtypes, while ALS-FTD could be distinguished from ALS by additional temporal lobe grey and white matter changes. Finally, ALS could be mainly distinguished from the other two groups by corticospinal tract degeneration. The present study shows for the first time that FTD and ALS overlap in anterior cingulate, motor cortex and related white matter tract changes across the whole continuum. Nevertheless, frontal and temporal atrophy as well as corticospinal tract degeneration emerged as marker for subtype classification, which will inform future diagnosis and target disease management across the continuum.

  8. Grey and White Matter Changes across the Amyotrophic Lateral Sclerosis-Frontotemporal Dementia Continuum

    Science.gov (United States)

    Lillo, Patricia; Mioshi, Eneida; Burrell, James R.; Kiernan, Matthew C.; Hodges, John R.; Hornberger, Michael

    2012-01-01

    There is increasing evidence that amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) lie on a clinical, pathological and genetic continuum with patients of one disease exhibiting features of the other. Nevertheless, to date, the underlying grey matter and white matter changes across the ALS-FTD disease continuum have not been explored. In this study fifty-three participants with ALS (n = 10), ALS-FTD (n = 10) and behavioural variant FTD (bvFTD; n = 15) as well as controls (n = 18), underwent detailed clinical assessment plus structural imaging using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) analysis of magnetic resonance brain imaging to examine grey and white matter differences and commonalities across the continuum. Importantly, patient groups were matched for age, education, gender and disease duration. VBM and DTI results showed that changes in the ALS group were confined mainly to the motor cortex and anterior cingulate as well as their underlying white matter tracts. ALS-FTD and bvFTD showed widespread grey matter and white matter changes involving frontal and temporal lobes. Extensive prefrontal cortex changes emerged as a marker for bvFTD compared to other subtypes, while ALS-FTD could be distinguished from ALS by additional temporal lobe grey and white matter changes. Finally, ALS could be mainly distinguished from the other two groups by corticospinal tract degeneration. The present study shows for the first time that FTD and ALS overlap in anterior cingulate, motor cortex and related white matter tract changes across the whole continuum. Nevertheless, frontal and temporal atrophy as well as corticospinal tract degeneration emerged as marker for subtype classification, which will inform future diagnosis and target disease management across the continuum. PMID:22952843

  9. Microstructural white matter changes, not hippocampal atrophy, detect early amnestic mild cognitive impairment.

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    Lin Zhuang

    Full Text Available BACKGROUND: Alzheimer's disease (AD is generally considered to be characterized by pathology in gray matter of the brain, but convergent evidence suggests that white matter degradation also plays a vital role in its pathogenesis. The evolution of white matter deterioration and its relationship with gray matter atrophy remains elusive in amnestic mild cognitive impairment (aMCI, a prodromal stage of AD. METHODS: We studied 155 cognitively normal (CN and 27 'late' aMCI individuals with stable diagnosis over 2 years, and 39 'early' aMCI individuals who had converted from CN to aMCI at 2-year follow up. Diffusion tensor imaging (DTI tractography was used to reconstruct six white matter tracts three limbic tracts critical for episodic memory function - the fornix, the parahippocampal cingulum, and the uncinate fasciculus; two cortico-cortical association fiber tracts - superior longitudinal fasciculus and inferior longitudinal fasciculus; and one projection fiber tract - corticospinal tract. Microstructural integrity as measured by fractional anisotropy (FA, mean diffusivity (MD, radial diffusivity (RD and axial diffusivity (AxD was assessed for these tracts. RESULTS: Compared with CN, late aMCI had lower white matter integrity in the fornix, the parahippocampal cingulum, and the uncinate fasciculus, while early aMCI showed white matter damage in the fornix. In addition, fornical measures were correlated with hippocampal atrophy in late aMCI, whereas abnormality of the fornix in early aMCI occurred in the absence of hippocampal atrophy and did not correlate with hippocampal volumes. CONCLUSIONS: Limbic white matter tracts are preferentially affected in the early stages of cognitive dysfunction. Microstructural degradation of the fornix preceding hippocampal atrophy may serve as a novel imaging marker for aMCI at an early stage.

  10. Developmental patterns of doublecortin expression and white matter neuron density in the postnatal primate prefrontal cortex and schizophrenia.

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    Samantha J Fung

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

  11. The visual white matter: The application of diffusion MRI and fiber tractography to vision science

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    Rokem, Ariel; Takemura, Hiromasa; Bock, Andrew S.; Scherf, K. Suzanne; Behrmann, Marlene; Wandell, Brian A.; Fine, Ione; Bridge, Holly; Pestilli, Franco

    2017-01-01

    Visual neuroscience has traditionally focused much of its attention on understanding the response properties of single neurons or neuronal ensembles. The visual white matter and the long-range neuronal connections it supports are fundamental in establishing such neuronal response properties and visual function. This review article provides an introduction to measurements and methods to study the human visual white matter using diffusion MRI. These methods allow us to measure the microstructural and macrostructural properties of the white matter in living human individuals; they allow us to trace long-range connections between neurons in different parts of the visual system and to measure the biophysical properties of these connections. We also review a range of findings from recent studies on connections between different visual field maps, the effects of visual impairment on the white matter, and the properties underlying networks that process visual information supporting visual face recognition. Finally, we discuss a few promising directions for future studies. These include new methods for analysis of MRI data, open datasets that are becoming available to study brain connectivity and white matter properties, and open source software for the analysis of these data. PMID:28196374

  12. White matter integrity in right hemisphere predicts pitch-related grammar learning.

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    Loui, Psyche; Li, H Charles; Schlaug, Gottfried

    2011-03-15

    White matter plays an important role in various domains of cognitive function. While disruptions in white matter are known to affect many domains of behavior and cognition, the ability to acquire grammatical regularities has been mostly linked to the left hemisphere, perhaps due to its dependence on linguistic stimuli. The role of white matter in the right hemisphere in grammar acquisition is yet unknown. Here we show for the first time that in the domain of pitch, intact white matter connectivity in right-hemisphere analogs of language areas is important for grammar learning. A pitch-based artificial grammar learning task was conducted on subjects who also underwent diffusion tensor imaging. Probabilistic tractography using seed regions of interest in the right inferior frontal gyrus and right middle temporal gyrus showed positive correlations between tract volume and learning performance. Furthermore, significant correlations were observed between learning performance and FA in white matter underlying the supramarginal gyrus, corresponding to the right temporal-parietal junction of the arcuate fasciculus. The control task of recognition did not correlate with tract volume or FA, and control tracts in the left hemisphere did not correlate with behavioral performance. Results show that the right ventral arcuate fasciculus is important in pitch-based artificial grammar learning, and that brain structures subserving learning may be tied to the hemisphere that processes the stimulus more generally.

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

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    Laura E. Downey

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  15. White matter hyperintensities segmentation: a new semi-automated method.

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    Iorio, Mariangela; Spalletta, Gianfranco; Chiapponi, Chiara; Luccichenti, Giacomo; Cacciari, Claudia; Orfei, Maria D; Caltagirone, Carlo; Piras, Fabrizio

    2013-01-01

    White matter hyperintensities (WMH) are brain areas of increased signal on T2-weighted or fluid-attenuated inverse recovery magnetic resonance imaging (MRI) scans. In this study we present a new semi-automated method to measure WMH load that is based on the segmentation of the intensity histogram of fluid-attenuated inversion recovery images. Thirty patients with mild cognitive impairment with variable WMH load were enrolled. The semi-automated WMH segmentation included removal of non-brain tissue, spatial normalization, removal of cerebellum and brain stem, spatial filtering, thresholding to segment probable WMH, manual editing for correction of false positives and negatives, generation of WMH map, and volumetric estimation of the WMH load. Accuracy was quantitatively evaluated by comparing semi-automated and manual WMH segmentations performed by two independent raters. Differences between the two procedures were assessed using Student's t-tests and similarity was evaluated using linear regression model and Dice similarity coefficient (DSC). The volumes of the manual and semi-automated segmentations did not statistically differ (t-value = -1.79, DF = 29, p = 0.839 for rater 1; t-value = 1.113, DF = 29, p = 0.2749 for rater 2), were highly correlated [R (2) = 0.921, F (1,29) = 155.54, p < 0.0001 for rater 1; R (2) = 0.935, F (1,29) = 402.709, p < 0.0001 for rater 2] and showed a very strong spatial similarity (mean DSC = 0.78, for rater 1 and 0.77 for rater 2). In conclusion, our semi-automated method to measure the load of WMH is highly reliable and could represent a good tool that could be easily implemented in routinely neuroimaging analyses to map clinical consequences of WMH.

  16. The betweenness centrality of the brain white matter networks in patients with bipolar depression%双相抑郁患者脑白质网络介数中心度属性研究

    Institute of Scientific and Technical Information of China (English)

    陈建淮; 姚志剑; 赵可; 阎锐; 花玲玲; 贾凤南; 韦秋香; 卢青

    2015-01-01

    Objective To explore the differences of the betweenness centrality of the brain white matter networks between the bipolar depression (BD) patients and healthy control (HC) subjects,and then analyze its correlation with the severity of the disease.Methods The diffusion tensor imaging data were obtained from 17 BD patients and 21 HC subjects.The whole cerebral cortex was divided into 90 regions by the automated anatomical labeling map.Fiber tracking was performed in the whole cerebral cortex of each subject to reconstruct white matter tracts using the fiber assignment by continuous tracking algorithm.And then the brain white matter networks were constructed using the complex network theory.The nodal betweenness centrality of two groups was examined by two sample t-test and then the correlation between the betweenness centrality of the significant node and the severity of the disease was analyzed by the Pearson correlation analysis.Results The betweenness centrality of BD was significantly decreased in the left superior frontal gyrus (dorsolateral) (0.69±0.40;t=-3.74,P=0.03),inferior frontal gyrus (orbital part) (0.27±0.19;t=-3.62,P=0.03) and anterior cingulate gyri (1.45±0.97;t=-3.53,P=0.03),however,that of the right caudate nucleus increased significantly (1.89±1.02;t=4.08,P=0.02) when compared with HC (1.15±0.35,0.49±0.19,2.69± 1.15,0.85±0.51).The distribution of hub regions in the left frontal and occipital lobes of BD was different from that of HC.Significant negative correlation was found between the betweenness centrality of the left superior frontal gyrus (dorsolateral) and the total scores of 17-item Hamilton Rating Scale for Depression (r=-0.52,P=0.03).Conclusion The importance of the left prefrontal cortex in the transmission of information activity across the whole brain is decreased,however,that of the right caudate nucleus increased.The reduced importance of the left superior frontal gyrus (dorsolateral) is associated with the severity of the

  17. Soluble amyloid beta levels are elevated in the white matter of Alzheimer's patients, independent of cortical plaque severity.

    Science.gov (United States)

    Collins-Praino, Lyndsey E; Francis, Yitshak I; Griffith, Erica Y; Wiegman, Anne F; Urbach, Jonathan; Lawton, Arlene; Honig, Lawrence S; Cortes, Etty; Vonsattel, Jean Paul G; Canoll, Peter D; Goldman, James E; Brickman, Adam M

    2014-08-17

    Alzheimer's disease (AD) is the most common neurodegenerative disease and the leading cause of dementia. In addition to grey matter pathology, white matter changes are now recognized as an important pathological feature in the emergence of the disease. Despite growing recognition of the importance of white matter abnormalities in the pathogenesis of AD, the causes of white matter degeneration are still unknown. While multiple studies propose Wallerian-like degeneration as the source of white matter change, others suggest that primary white matter pathology may be due, at least in part, to other mechanisms, including local effects of toxic Aβ peptides. In the current study, we investigated levels of soluble amyloid-beta (Aβ) in white matter of AD patients (n=12) compared with controls (n=10). Fresh frozen white matter samples were obtained from anterior (Brodmann area 9) and posterior (Brodmann area 1, 2 and 3) areas of post-mortem AD and control brains. ELISA was used to examine levels of soluble Aβ -42 and Aβ -40. Total cortical neuritic plaque severity rating was derived from individual ratings in the following areas of cortex: mid-frontal, superior temporal, pre-central, inferior parietal, hippocampus (CA1), subiculum, entorhinal cortex, transentorhinal cortex, inferior temporal, amygdala and basal forebrain. Compared with controls, AD samples had higher white matter levels of both soluble Aβ -42 and Aβ -40. While no regional white matter differences were found in Aβ -40, Aβ -42 levels were higher in anterior regions than in posterior regions across both groups. After statistically controlling for total cortical neuritic plaque severity, differences in both soluble Aβ -42 and Aβ -40 between the groups remained, suggesting that white matter Aβ peptides accumulate independent of overall grey matter fibrillar amyloid pathology and are not simply a reflection of overall amyloid burden. These results shed light on one potential mechanism through which

  18. Assessing white matter ischemic damage in dementia patients by measurement of myelin proteins.

    Science.gov (United States)

    Barker, Rachel; Wellington, Dannielle; Esiri, Margaret M; Love, Seth

    2013-07-01

    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.

  19. White matter development in adolescence: the influence of puberty and implications for affective disorders.

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2016-05-01

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

  1. Gray and white matter volume abnormalities in monozygotic and same-gender dizygotic twins discordant for schizophrenia

    DEFF Research Database (Denmark)

    Hilshoff, Hilleke E.; Brans, Rachel G. H.; van Haren, Neeltje E. M.;

    2004-01-01

    BACKGROUND: Whole brain tissue volume decreases in schizophrenia have been related to both genetic risk factors and disease-related (possibly nongenetic) factors; however, whether genetic and environmental risk factors in the brains of patients with schizophrenia are differentially reflected in g...... matter volume are related to environmental risk factors. Study of genes involved in the (maintenance) of white matter structures may be particularly fruitful in schizophrenia......BACKGROUND: Whole brain tissue volume decreases in schizophrenia have been related to both genetic risk factors and disease-related (possibly nongenetic) factors; however, whether genetic and environmental risk factors in the brains of patients with schizophrenia are differentially reflected...... in gray or white matter volume change is not known. METHODS: Magnetic resonance imaging (1.5 T) brain scans of 11 monozygotic and 11 same-gender dizygotic twin pairs discordant for schizophrenia were acquired and compared with 11 monozygotic and 11 same-gender dizygotic healthy control twin pairs. RESULTS...

  2. Striatal and white matter predictors of estimated diagnosis for Huntington disease

    Science.gov (United States)

    Paulsen, Jane S.; Nopoulos, Peggy C.; Aylward, Elizabeth; Ross, Christopher A.; Johnson, Hans; Magnotta, Vincent A.; Juhl, Andrew; Pierson, Ronald K.; Mills, James; Langbehn, Douglas; Nance, Martha

    2010-01-01

    Previous MRI studies with participants prior to manifest Huntington disease have been conducted in small single-site samples. The current study reports data from a systematic multi-national study during the prodromal period of Huntington disease and examines whether various brain structures make unique predictions about the proximity to manifest disease. MRI scans were acquired from 657 participants enrolled at one of 32 PREDICT-HD research sites. Only prodromal Huntington disease participants (those not meeting motor criteria for diagnosis) were included and subgrouped by estimated diagnosis proximity (Near, Mid, and Far) based upon a formula incorporating age and CAG repeat length. Results show volumes of all three subgroups differed significantly from Controls for total brain tissue, cerebral spinal fluid, white matter, cortical gray matter, thalamus, caudate, and putamen. Total striatal volume demonstrated the largest differences between Controls and all three prodromal subgroups. Cerebral white matter offered additional independent power in the prediction of estimated proximity to diagnosis. In conclusion, this large cross-sectional study shows that changes in brain volume are detectable years to decades prior to estimated motor diagnosis of Huntington disease. This suggests that a clinical trial of a putative neuroprotective agent could begin as much as 15 years prior to estimated motor diagnosis in a cohort of persons at risk for but not meeting clinical motor diagnostic criteria for Huntington disease, and that neuroimaging (striatal and white matter volumes) may be among the best predictors of diagnosis proximity. PMID:20385209

  3. Striatal and white matter predictors of estimated diagnosis for Huntington disease.

    Science.gov (United States)

    Paulsen, Jane S; Nopoulos, Peggy C; Aylward, Elizabeth; Ross, Christopher A; Johnson, Hans; Magnotta, Vincent A; Juhl, Andrew; Pierson, Ronald K; Mills, James; Langbehn, Douglas; Nance, Martha

    2010-05-31

    Previous MRI studies with participants prior to manifest Huntington disease have been conducted in small single-site samples. The current study reports data from a systematic multi-national study during the prodromal period of Huntington disease and examines whether various brain structures make unique predictions about the proximity to manifest disease. MRI scans were acquired from 657 participants enrolled at 1 of 32 PREDICT-HD research sites. Only prodromal Huntington disease participants (those not meeting motor criteria for diagnosis) were included and subgrouped by estimated diagnosis proximity (Near, Mid, and Far) based upon a formula incorporating age and CAG-repeat length. Results show volumes of all three subgroups differed significantly from Controls for total brain tissue, cerebral spinal fluid, white matter, cortical gray matter, thalamus, caudate, and putamen. Total striatal volume demonstrated the largest differences between Controls and all three prodromal subgroups. Cerebral white matter offered additional independent power in the prediction of estimated proximity to diagnosis. In conclusion, this large cross-sectional study shows that changes in brain volume are detectable years to decades prior to estimated motor diagnosis of Huntington disease. This suggests that a clinical trial of a putative neuroprotective agent could begin as much as 15 years prior to estimated motor diagnosis in a cohort of persons at risk for but not meeting clinical motor diagnostic criteria for Huntington disease, and that neuroimaging (striatal and white matter volumes) may be among the best predictors of diagnosis proximity.

  4. Hypertension-related alterations in white matter microstructure detectable in middle age.

    Science.gov (United States)

    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 ε4 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.

  5. HYPERTENSION-RELATED ALTERATIONS IN WHITE MATTER MICROSTRUCTURE DETECTABLE IN MIDDLE AGE

    Science.gov (United States)

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

    2015-01-01

    Most studies examining associations between hypertension and brain white matter microstructure have focused on older adults or on cohorts with a large age range. Since 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 nine tracts reported to be sensitive to hypertension in older adults. Relative to normotensive individuals, individuals with longstanding hypertension (> 5.6 years) showed reduced fractional anisotropy or increased diffusivity in most tracts. Effects were stronger among carriers than non-carriers of the apolipoprotein E ε4 allele for two 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

  6. Altered gray matter volume and white matter integrity in college students with mobile phone dependence

    Directory of Open Access Journals (Sweden)

    Yongming eWang

    2016-05-01

    Full Text Available Mobile phone dependence (MPD is a behavioral addiction that has become an increasing public mental health issue. While previous research has explored some of the factors that may predict MPD, the underlying neural mechanisms of MPD have not been investigated yet. The current study aimed to explore the microstructural variations associated with MPD as measured with functional Magnetic Resonance Imaging (fMRI. Gray matter volume (GMV and white matter (WM integrity (four indexes: fractional anisotropy, FA; mean diffusivity, MD; axial diffusivity, AD; and radial diffusivity, RD were calculated via voxel-based morphometry (VBM and tract-based spatial statistics (TBSS analysis, respectively. Sixty-eight college students (42 female were enrolled and separated into two groups (MPD group, N=34; control group, N=34 based on Mobile Phone Addiction Index (MPAI scale score. Trait impulsivity was also measured using the Barrett Impulsivity Scale (BIS-11. In light of underlying trait impulsivity, results revealed decreased GMV in the MPD group relative to controls in regions such as the right superior frontal gyrus (sFG, right inferior frontal gyrus (iFG, and bilateral thalamus (Thal. In the MPD group, GMV in the above mentioned regions was negatively correlated with scores on the MPAI. Results also showed significantly less FA and AD measures of white matter integrity in the MPD group relative to controls in bilateral hippocampal cingulum bundle fibers (CgH. Additionally, in the MPD group, FA of the CgH was also negatively correlated with scores on the MPAI. These findings provide the first morphological evidence of altered brain structure with phone-overuse, and may help to better understand the neural mechanisms of MPD in relation with other behavioral and substance addiction disorders.

  7. Astrocytes in oligodendrocyte lineage development and white matter pathology

    Directory of Open Access Journals (Sweden)

    Jiasi eLi

    2016-05-01

    Full Text Available White matter is primarily composed of myelin and myelinated axons. Structural and functional completeness of myelin is critical for the reliable and efficient transmission of information. White matter injury has been associated with the development of many demyelinating diseases. Despite a variety of scientific advances aimed at promoting re-myelination, their benefit has proven at best to be marginal. Research suggests that the failure of the re-myelination process may be the result of an unfavorable microenvironment. Astrocytes, are the most ample and diverse type of glial cells in central nervous system which display multiple functions for the cells of the oligodendrocytes lineage. As such, much attention has recently been drawn to astrocyte function in terms of white matter myelin repair. They are different in white matter from those in grey matter in specific regards to development, morphology, location, protein expression and other supportive functions. During the process of demyelination and re-myelination, the functions of astrocytes are dynamic in that they are able to change functions in accordance to different time points, triggers or reactive pathways resulting in vastly different biologic effects. They have pivotal effects on oligodendrocytes and other cell types in the oligodendrocyte lineage by serving as an energy supplier, a participant of immunological and inflammatory functions, a source of trophic factors and iron and a sustainer of homeostasis. Astrocytic impairment has been shown to be directly linked to the development of neuromyelities optica. In addition, astroctyes have also been implicated in other white matter conditions such as psychiatric disorders and neurodegenerative diseases such as Alzheimer’s disease, multiple sclerosis and amyotrophic lateral sclerosis. Inhibiting specifically detrimental signaling pathways in astrocytes while preserving their beneficial functions may be a promising approach for

  8. Astrocytes in Oligodendrocyte Lineage Development and White Matter Pathology

    Science.gov (United States)

    Li, Jiasi; Zhang, Lei; Chu, Yongxin; Namaka, Michael; Deng, Benqiang; Kong, Jiming; Bi, Xiaoying

    2016-01-01

    White matter is primarily composed of myelin and myelinated axons. Structural and functional completeness of myelin is critical for the reliable and efficient transmission of information. White matter injury has been associated with the development of many demyelinating diseases. Despite a variety of scientific advances aimed at promoting re-myelination, their benefit has proven at best to be marginal. Research suggests that the failure of the re-myelination process may be the result of an unfavorable microenvironment. Astrocytes, are the most ample and diverse type of glial cells in central nervous system (CNS) which display multiple functions for the cells of the oligodendrocytes lineage. As such, much attention has recently been drawn to astrocyte function in terms of white matter myelin repair. They are different in white matter from those in gray matter in specific regards to development, morphology, location, protein expression and other supportive functions. During the process of demyelination and re-myelination, the functions of astrocytes are dynamic in that they are able to change functions in accordance to different time points, triggers or reactive pathways resulting in vastly different biologic effects. They have pivotal effects on oligodendrocytes and other cell types in the oligodendrocyte lineage by serving as an energy supplier, a participant of immunological and inflammatory functions, a source of trophic factors and iron and a sustainer of homeostasis. Astrocytic impairment has been shown to be directly linked to the development of neuromyelities optica (NMO). In addition, astroctyes have also been implicated in other white matter conditions such as psychiatric disorders and neurodegenerative diseases such as Alzheimer’s disease (AD), multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). Inhibiting specifically detrimental signaling pathways in astrocytes while preserving their beneficial functions may be a promising approach for

  9. Anatomical likelihood estimation meta-analysis of grey and white matter anomalies in autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Thomas P. DeRamus

    2015-01-01

    Full Text Available Autism spectrum disorders (ASD are characterized by impairments in social communication and restrictive, repetitive behaviors. While behavioral symptoms are well-documented, investigations into the neurobiological underpinnings of ASD have not resulted in firm biomarkers. Variability in findings across structural neuroimaging studies has contributed to difficulty in reliably characterizing the brain morphology of individuals with ASD. These inconsistencies may also arise from the heterogeneity of ASD, and wider age-range of participants included in MRI studies and in previous meta-analyses. To address this, the current study used coordinate-based anatomical likelihood estimation (ALE analysis of 21 voxel-based morphometry (VBM studies examining high-functioning individuals with ASD, resulting in a meta-analysis of 1055 participants (506 ASD, and 549 typically developing individuals. Results consisted of grey, white, and global differences in cortical matter between the groups. Modeled anatomical maps consisting of concentration, thickness, and volume metrics of grey and white matter revealed clusters suggesting age-related decreases in grey and white matter in parietal and inferior temporal regions of the brain in ASD, and age-related increases in grey matter in frontal and anterior-temporal regions. White matter alterations included fiber tracts thought to play key roles in information processing and sensory integration. Many current theories of pathobiology ASD suggest that the brains of individuals with ASD may have less-functional long-range (anterior-to-posterior connections. Our findings of decreased cortical matter in parietal–temporal and occipital regions, and thickening in frontal cortices in older adults with ASD may entail altered cortical anatomy, and neurodevelopmental adaptations.

  10. Anatomical likelihood estimation meta-analysis of grey and white matter anomalies in autism spectrum disorders.

    Science.gov (United States)

    DeRamus, Thomas P; Kana, Rajesh K

    2015-01-01

    Autism spectrum disorders (ASD) are characterized by impairments in social communication and restrictive, repetitive behaviors. While behavioral symptoms are well-documented, investigations into the neurobiological underpinnings of ASD have not resulted in firm biomarkers. Variability in findings across structural neuroimaging studies has contributed to difficulty in reliably characterizing the brain morphology of individuals with ASD. These inconsistencies may also arise from the heterogeneity of ASD, and wider age-range of participants included in MRI studies and in previous meta-analyses. To address this, the current study used coordinate-based anatomical likelihood estimation (ALE) analysis of 21 voxel-based morphometry (VBM) studies examining high-functioning individuals with ASD, resulting in a meta-analysis of 1055 participants (506 ASD, and 549 typically developing individuals). Results consisted of grey, white, and global differences in cortical matter between the groups. Modeled anatomical maps consisting of concentration, thickness, and volume metrics of grey and white matter revealed clusters suggesting age-related decreases in grey and white matter in parietal and inferior temporal regions of the brain in ASD, and age-related increases in grey matter in frontal and anterior-temporal regions. White matter alterations included fiber tracts thought to play key roles in information processing and sensory integration. Many current theories of pathobiology ASD suggest that the brains of individuals with ASD may have less-functional long-range (anterior-to-posterior) connections. Our findings of decreased cortical matter in parietal-temporal and occipital regions, and thickening in frontal cortices in older adults with ASD may entail altered cortical anatomy, and neurodevelopmental adaptations.

  11. White matters : When, where, and how?

    NARCIS (Netherlands)

    McClure, Stephanie M.

    2007-01-01

    The author reflects on the qualitative research process as both a first-time researcher and as a white woman doing research on African American men. This includes reflections on the assumption that the primary motivation for the researcher is romantically motivated, a discussion of racist sexism, an

  12. White Matter Hyperintensities Improve Ischemic Stroke Recurrence Prediction

    DEFF Research Database (Denmark)

    Andersen, Søren Due; Larsen, Torben Bjerregaard; Gorst-Rasmussen, Anders;

    2017-01-01

    -based, observational cohort study, we included 832 patients (mean age 59.6 (SD 13.9); 42.0% females) with incident ischemic stroke and no AF. We assessed the severity of white matter hyperintensities using MRI. Hazard ratios stratified by the white matter hyperintensities score and adjusted for the components......BACKGROUND: Nearly one in 5 patients with ischemic stroke will invariably experience a second stroke within 5 years. Stroke risk stratification schemes based solely on clinical variables perform only modestly in non-atrial fibrillation (AF) patients and improvement of these schemes will enhance...... their clinical utility. Cerebral white matter hyperintensities are associated with an increased risk of incident ischemic stroke in the general population, whereas their association with the risk of ischemic stroke recurrence is more ambiguous. In a non-AF stroke cohort, we investigated the association between...

  13. Magnetic resonance imaging of normal and pathological white matter maturation

    Energy Technology Data Exchange (ETDEWEB)

    Baierl, P.; Naegele, M.; Fink, U.; Kenn, W.; Foerster, C.; Fendel, H.

    1988-04-01

    Fifty children between 3 months postnatal and 16 years of age were examined by means of a 1.5 T superconductive magnet, run at 0.35 and 1.0 T. The myelination was studied qualitatively and quantitatively (relaxation times, proton densities, image contrast). With increasing age, a decrease of T1 and proton density of white matter was found, which was complete at one year of age. In regions with a slow progression of myelination, gray/white matter contrast showed an increase up to the end of the first decade. Pathological white matter maturation was diagnosed either as an abnormal transformation of myelin (characterized by abnormal relaxation values), or as a deficient or delayed myelin formation (in comparison with age-matched controls).

  14. Preserved white matter in unmedicated pediatric bipolar disorder.

    Science.gov (United States)

    Teixeira, Ana Maria A; Kleinman, Ana; Zanetti, Marcus; Jackowski, Marcel; Duran, Fábio; Pereira, Fabrício; Lafer, Beny; Busatto, Geraldo F; Caetano, Sheila C

    2014-09-01

    White matter (WM) abnormalities have been reported in bipolar disorder (BD) patients, as well as in their non-BD relatives, both children and adults. Although it is considered an emerging vulnerability marker for BD, there are no studies investigating WM alterations in pediatric unmedicated patients and young healthy offspring. In this study, we evaluated the presence of WM alterations in 18 pediatric, non medicated BD patients, as well as in 18 healthy offspring of BD type I parents and 20 healthy controls. 3T DT-MRI data were acquired and scans were processed with tract-based spatial statistics to provide measures of fractional anisotropy and diffusivity. We found no significant differences in WM microstructure between BD patients, healthy offspring and healthy controls. Previous studies that reported WM alterations investigated older subjects, either on medication (BD patients) or with psychiatric diagnoses other than BD (unaffected offspring). Our findings highlight the importance of the understanding of disease ontogeny and brain development dynamics in the search for early vulnerability markers for psychiatric disorders.

  15. Cognitive Intraindividual Variability and White Matter Integrity in Aging

    Directory of Open Access Journals (Sweden)

    Nathalie Mella

    2013-01-01

    Full Text Available 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.

  16. Lifelong Bilingualism Maintains White Matter Integrity in Older Adults

    Science.gov (United States)

    Luk, Gigi; Bialystok, Ellen; Craik, Fergus I. M.; Grady, Cheryl L.

    2012-01-01

    Previous research has shown that bilingual speakers have higher levels of cognitive control than comparable monolinguals, especially at older ages. The present study investigates a possible neural correlate of this behavioral effect. Given that white matter (WM) integrity decreases with age in adulthood, we tested the hypothesis that bilingualism is associated with maintenance of WM in older people. Using diffusion tensor imaging, we found higher WM integrity in older people who were lifelong bilinguals than in monolinguals. This maintained integrity was measured by fractional anisotropy (FA) and was found in the corpus callosum extending to the superior and inferior longitudinal fasciculi. We also hypothesized that stronger WM connections would be associated with more widely distributed patterns of functional connectivity in bilinguals. We tested this by assessing the resting-state functional connectivity of frontal lobe regions adjacent to WM areas with group differences in FA. Bilinguals showed stronger anterior to posterior functional connectivity compared to monolinguals. These results are the first evidence that maintained WM integrity is related to lifelong naturally occurring experience; the resulting enhanced structural and functional connectivity may provide a neural basis for “brain reserve.” PMID:22090506

  17. Lifelong bilingualism maintains white matter integrity in older adults.

    Science.gov (United States)

    Luk, Gigi; Bialystok, Ellen; Craik, Fergus I M; Grady, Cheryl L

    2011-11-16

    Previous research has shown that bilingual speakers have higher levels of cognitive control than comparable monolinguals, especially at older ages. The present study investigates a possible neural correlate of this behavioral effect. Given that white matter (WM) integrity decreases with age in adulthood, we tested the hypothesis that bilingualism is associated with maintenance of WM in older people. Using diffusion tensor imaging, we found higher WM integrity in older people who were lifelong bilinguals than in monolinguals. This maintained integrity was measured by fractional anisotropy (FA) and was found in the corpus callosum extending to the superior and inferior longitudinal fasciculi. We also hypothesized that stronger WM connections would be associated with more widely distributed patterns of functional connectivity in bilinguals. We tested this by assessing the resting-state functional connectivity of frontal lobe regions adjacent to WM areas with group differences in FA. Bilinguals showed stronger anterior to posterior functional connectivity compared to monolinguals. These results are the first evidence that maintained WM integrity is related to lifelong naturally occurring experience; the resulting enhanced structural and functional connectivity may provide a neural basis for "brain reserve."

  18. Tract-oriented statistical group comparison of diffusion in sheet-like white matter

    DEFF Research Database (Denmark)

    Lyksborg, Mark; Dyrby, T. B.; Sorensen, P. S.;

    2013-01-01

    Identifying specific structures of the brain where pathology differs between groups of subjects may aid to develop imaging-based markers for disease diagnosis. We propose a new technique for doing multivariate statistical analysis on white matter tracts with sheet like shapes. Previous works assume...... tube-like shapes, not always suitable for modelling the white matter tracts of the brain. The tract-oriented technique aimed at group studies, integrates the usage of multivariate features and outputs a single value of significance indicating tract-specific differences. This is in contrast to voxel...... based analysis techniques which outputs a significance per voxel basis, and requires multiple comparison correction. We demonstrate our technique by comparing a group of controls with a group of Multiple Sclerosis subjects obtaining significant differences on 11 different fascicle structures....

  19. Global and regional associations of smaller cerebral gray and white matter volumes with gait in older people.

    Directory of Open Access Journals (Sweden)

    Michele L Callisaya

    Full Text Available BACKGROUND: Gait impairments increase with advancing age and can lead to falls and loss of independence. Brain atrophy also occurs in older age and may contribute to gait decline. We aimed to investigate global and regional relationships of cerebral gray and white matter volumes with gait speed, and its determinants step length and cadence, in older people. METHODS: In a population-based study, participants aged >60 years without Parkinson's disease or brain infarcts underwent magnetic resonance imaging and gait measurements using a computerized walkway. Linear regression was used to study associations of total gray and white matter volumes with gait, adjusting for each other, age, sex, height and white matter hyperintensity volume. Other covariates considered in analyses included weight and vascular disease history. Voxel-based morphometry was used to study regional relationships of gray and white matter with gait. RESULTS: There were 305 participants, mean age 71.4 (6.9 years, 54% male, mean gait speed 1.16 (0.22 m/s. Smaller total gray matter volume was independently associated with poorer gait speed (p = 0.001 and step length (p<0.001, but not cadence. Smaller volumes of cortical and subcortical gray matter in bilateral regions important for motor control, vision, perception and memory were independently associated with slower gait speed and shorter steps. No global or regional associations were observed between white matter volume and gait independent of gray matter volume, white matter hyperintensity volume and other covariates. CONCLUSION: Smaller gray matter volume in bilaterally distributed brain networks serving motor control was associated with slower gait speed and step length, but not cadence.

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

    Energy Technology Data Exchange (ETDEWEB)

    Uh, Jinsoo, E-mail: jinsoo.uh@stjude.org [Department of Radiological Sciences, St Jude Children' s Research Hospital, Memphis, Tennessee (United States); Merchant, Thomas E. [Department of Radiological Sciences, St Jude Children' s Research Hospital, Memphis, Tennessee (United States); Li, Yimei; Li, Xingyu [Department of Biostatistics, St Jude Children' s Research Hospital, Memphis, Tennessee (United States); Sabin, Noah D. [Department of Radiological Sciences, St Jude Children' s Research Hospital, Memphis, Tennessee (United States); Indelicato, Daniel J. [Department of Radiation Oncology, University of Florida, Jacksonville, Florida (United States); Ogg, Robert J. [Department of Radiological Sciences, St Jude Children' s Research Hospital, Memphis, Tennessee (United States); Boop, Frederick A. [Semmes-Murphey Neurologic and Spine Institute, Memphis, Tennessee (United States); Jane, John A. [Department of Neurosurgery, University of Virginia, Charlottesville, Virginia (United States); Hua, Chiaho [Department of Radiological Sciences, St Jude Children' s Research Hospital, Memphis, Tennessee (United States)

    2015-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Brianne Magouirk Bettcher

    Full Text Available 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 [β=-.21; B=-.0024; 95% CI, -.0048 to -.0000; p=.05] and cingulate fibers [β=-.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.

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

    Science.gov (United States)

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

    2013-01-01

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

  3. CT hypodensity on cerebral white matter in Wilson's disease

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    Laura B. Jardim

    1991-06-01

    Full Text Available Wilson's disease in an autosomal recessive disorder of copper metabolism where systemic manifestations are secondary to thei accumulation of copper in hepatic, nervous and other tissues. In CNS, the structural lesions most commonly found by CT scan are ventricular dilatation, cortical atrophy, basal ganglia hyperdensities, and brainstem and cerebellar atrophy. Degenerative changes of cerebral white matter seen on early anatomo-pathologic studies, but were almost never found on CT scan from recently described patients. We report a case of Wilson's disease with an unusually rapid deterioration where asymmetric low-densities in the subcortical white matter were disclosed by CT scan.

  4. White matter hyperintensities among older adults are associated with futile increase in frontal activation and functional connectivity during spatial search.

    Directory of Open Access Journals (Sweden)

    Samuel N Lockhart

    Full Text Available 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.

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

    Science.gov (United States)

    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

  6. Unusual cerebral white matter change in a Chinese family with Spinocerebellar ataxia type 12.

    Science.gov (United States)

    Hu, Tao; Zhao, Bi; Wei, Qian-qian; Shang, Huifang

    2015-02-15

    In a Chinese family with Spinocerebellar ataxia type 12 (SCA12), presenting with action tremor, mild cerebellar dysfunction, and hyperreflexia, genetic testing revealed abnormal CAG repeat length in the brain-specific protein phosphatase 2, regulatory subunit B, beta isoform (PPP2R2B) gene. To our knowledge, this is the first report on patients with SCA12 presenting with prominent cerebral white matter change besides cerebral and/or cerebellar atrophy.

  7. Decreased plasma tryptophan associated with deep white matter lesions in elderly subjects

    OpenAIRE

    Yao, H; Yuzuriha, T; Koga, H; Fukuda, K.; ENDO, K.; Matsumoto, T.; Kato, A.; Uchino, A; Ezaki, T; Ibayashi, S; Uchimura, H; Fujishima, M.

    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 chemistry panel, and plasma amino acid measurements. Brain MRI ...

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

    OpenAIRE

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

    2015-01-01

    Impairments of social cognition are often leading features in frontotemporal lobar degeneration (FTLD) and likely to reflect large-scale brain network disintegration. However, the neuroanatomical basis of impaired social cognition in FTLD and the role of white matter connections have not been defined. Here we assessed social cognition in a cohort of patients representing two core syndromes of FTLD, behavioural variant frontotemporal dementia (bvFTD; n = 29) and semantic variant primary progre...

  9. Gray and White Matter Contributions to Cognitive Frontostriatal Deficits in Non-Demented Parkinson's Disease

    OpenAIRE

    Price, Catherine C.; Jared Tanner; Nguyen, Peter T.; Nadine A Schwab; Sandra Mitchell; Elizabeth Slonena; Babette Brumback; Okun, Michael S; Mareci, Thomas H.; Dawn Bowers

    2016-01-01

    Objective This prospective investigation examined: 1) processing speed and working memory relative to other cognitive domains in non-demented medically managed idiopathic Parkinson’s disease, and 2) the predictive role of cortical/subcortical gray thickness/volume and white matter fractional anisotropy on processing speed and working memory. Methods Participants completed a neuropsychological protocol, Unified Parkinson’s Disease Rating Scale, brain MRI, and fasting blood draw to rule out vas...

  10. High Resolution Diffusion Tensor Imaging of Cortical-Subcortical White Matter Tracts in TBI

    Science.gov (United States)

    2009-10-01

    of Trauma on Cerebral White Matter To assess the effects of trauma on DTI three analyses were applied. Gross measures of whole brain FA and thalamic...segmentation of the human thalamus. Cerebral Cortex 15, 31-39 (2005). 4 Magnotta, V., Gold, S., Andreasen , N., Ehrhardt, J. & Yuh, W. Visualization of sub...sensitive in acute severe trauma in predicting necrosis and outcome [42]. In summary, conventional structural MRI is an excellent tool for

  11. Longitudinal grey and white matter changes in frontotemporal dementia and Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Lars Frings

    Full Text Available 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.

  12. Association between baseline peri-infarct magnetic resonance spectroscopy and regional white matter atrophy after stroke

    Energy Technology Data Exchange (ETDEWEB)

    Yassi, Nawaf; Campbell, Bruce C.V.; Davis, Stephen M.; Bivard, Andrew [Melbourne Brain Centre rate at The Royal Melbourne Hospital, Departments of Medicine and Neurology, Parkville, Victoria (Australia); Moffat, Bradford A.; Steward, Christopher; Desmond, Patricia M. [The University of Melbourne, Department of Radiology, The Royal Melbourne Hospital, Parkville (Australia); Churilov, Leonid; Donnan, Geoffrey A. [The University of Melbourne, Florey Institute of Neuroscience and Mental Health, Parkville (Australia); Parsons, Mark W. [University of Newcastle and Hunter Medical Research Institute, Priority Research Centre for Translational Neuroscience and Mental Health, Newcastle (Australia)

    2016-01-15

    Cerebral atrophy after stroke is associated with poor functional outcome. The prediction and prevention of post-stroke brain atrophy could therefore represent a target for neurorestorative therapies. We investigated the associations between peri-infarct metabolite concentrations measured by quantitative MRS and brain volume change in the infarct hemisphere after stroke. Twenty patients with ischemic stroke were enrolled. Patients underwent 3T-MRI within 1 week of onset, and at 1 and 3 months. At the baseline scan, an MRS voxel was placed manually in the peri-infarct area and another in the corresponding contralateral region. Volumetric analysis of T1 images was performed using two automated processing packages. Changes in gray and white matter volume were assessed as percentage change between 1 and 3 months. Mean concentrations (institutional units) of N-acetylaspartic acid (NAA) (6.1 vs 7.0, p = 0.039), total creatine (Cr+PCr) (5.4 vs 5.8, p = 0.043), and inositol (4.5 vs 5.0, p = 0.014), were significantly lower in the peri-infarct region compared with the contralateral hemisphere. There was a significant correlation between baseline peri-infarct NAA and white matter volume change in the infarct hemisphere between 1 and 3 months, with lower NAA being associated with subsequent white matter atrophy (Spearman's rho = 0.66, p = 0.010). The baseline concentration of Cr+PCr was also significantly correlated with white matter atrophy in the infarct hemisphere (Spearman's rho = 0.59, p = 0.027). Both of these associations were significant after adjustment for the false discovery rate and were validated using the secondary volumetric method. MRS may be useful in the prediction of white matter atrophy post-stroke and in the testing of novel neurorestorative therapies. (orig.)

  13. Aerobic fitness is associated with greater white matter integrity in children

    Directory of Open Access Journals (Sweden)

    Laura eChaddock-Heyman

    2014-08-01

    Full Text Available Aerobic fitness has been found to play a positive role in brain and cognitive health of children. Yet, many of the neural biomarkers related to aerobic fitness remain unknown. Here, using diffusion tensor imaging (DTI, we demonstrated that higher aerobic fitness was related to greater estimates of white matter microstructure in children. Higher fit 9- and 10-year-old children showed greater fractional anisotropy (FA in sections of the corpus callosum, corona radiata, and superior longitudinal fasciculus, compared to lower fit children. The FA effects were primarily characterized by aerobic fitness differences in radial diffusivity (RD, thereby raising the possibility that estimates of myelination may vary as a function of individual differences in fitness during childhood. White matter structure may be another potential neural mechanism of aerobic fitness that assists in efficient communication between gray matter regions as well as the integration of regions into networks.

  14. Alterations of the Cerebral White Matter in a Middle-Aged Patient with Turner Syndrome: An MRI Study

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    Haruko Tanji

    2012-09-01

    Full Text Available A 52-year-old woman with intellectual disability was admitted to the hospital due to pneumonia. MRI of her brain showed diffuse hyperintensities on T2-weighted and fluid attenuated inversion recovery images in the bilateral cerebral white matter. Laboratory examination revealed sustained high levels of serum KL-6. Karyotyping revealed partial monosomy of the X chromosome. This is the first case showing diffuse white matter lesions in the brain, and sustained high levels of serum KL-6 in Turner syndrome.

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

    Science.gov (United States)

    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 accounting for vascular risk factors.

  16. The relation between white matter lesions of different parts of brain after acute cerebral infarction and depressive disorder%急性脑梗死后不同部位脑白质病变与抑郁的关系

    Institute of Scientific and Technical Information of China (English)

    姜丽杰; 于敏; 周莹; 侯宇; 娄伟

    2015-01-01

    目的 探讨急性脑梗死后不同部位的脑白质病变(WML)对抑郁发生的影响.方法 纳入大连市第三人民医院神经内科2012年3月至2013年4月住院的急性脑梗死患者97例,根据有无脑白质病变分为2组,比较2组间汉密尔顿焦虑量表(HAMA)评分及汉密尔顿抑郁量表(HAMD)评分有无差异.对有WML组行改良Scheltens评分,并将改良Scheltens评分与HAMD评分进行直线相关分析,了解额叶、颞叶、顶叶、枕叶、基底节、侧脑室旁及小脑、脑干等不同部位的白质损害程度与抑郁严重程度的相关性.结果 有WML组HAMD评分(10±6)分,HAMA评分(11±4)分,无WML组HAMD评分(6±4)分,HAMA评分(9±3)分,2组之间HAMD及HAMA评分比较差异均有统计学意义(均P<0.05);有WML组59例患者HAMD评分(10±6)分与改良Scheltens评分总分(4.39±0.49)分及额叶(2.76±0.43)分、枕叶白质(1.61±0.49)分、额部脑室旁白质(2.85±0.36)分,病变呈明显正相关(r=0.395,P=0.002;r=0.438,P =0.001;r =0.247,P=0.005;r =0.385,P=0.003).结论 急性脑梗死后不同部位的WML与抑郁障碍相关,主要以额部白质病变为主,额部白质病变越严重,抑郁程度越重.%Objective To evaluate the relationship between white matter lesions(WML) of different parts of brain after acute cerebral infarction and depressive disorder.Methods The clinical data of 97 patients with acute cerebral infarction were analyzed.All patients were divided into 2 groups according to with or without WML.The differences of Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) between 2 groups were analyzed.The WML group was scored using the semiquatitative rating scale of Scheltens Rating Scale(Scheltens).The correlation between the scheltens of lateral ventricle,frontal lobe,parietal lobe,temporal lobe,occipital lobe,basal ganglia,cerebella,brainstem and HAMD were observed.Results In WML group,the scale of HAMD was 10 ±6 and HAMA was 11 ±4.In without WML group

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

    Directory of Open Access Journals (Sweden)

    Christine Fennema-Notestine, PhD

    2016-01-01

    Full Text Available White matter disease in the brain increases with age and cardiovascular disease, emerging in midlife, and these associations may be influenced by both genetic and environmental factors. We examined the frequency, distribution, and heritability of abnormal white matter and its association with hypertension in 395 middle-aged male twins (61.9 ± 2.6 years from the Vietnam Era Twin Study of Aging, 67% of whom were hypertensive. A multi-channel segmentation approach estimated abnormal regions within the white matter. Using multivariable regression models, we characterized the frequency distribution of abnormal white matter in midlife and investigated associations with hypertension and Apolipoprotein E-ε4 status and the impact of duration and control of hypertension. Then, using the classical twin design, we estimated abnormal white matter heritability and the extent of shared genetic overlap with blood pressure. Abnormal white matter was predominantly located in periventricular and deep parietal and frontal regions; associated with age (t = 1.9, p = 0.05 and hypertension (t = 2.9, p = 0.004, but not Apolipoprotein ε4 status; and was greater in those with uncontrolled hypertension relative to controlled (t = 3.0, p = 0.003 and normotensive (t = 4.0, p = 0.0001 groups, suggesting that abnormal white matter may reflect currently active cerebrovascular effects. Abnormal white matter was highly heritable (a2 = 0.81 and shared some genetic influences with systolic blood pressure (rA = 0.26, although there was evidence for distinct genetic contributions and unique environmental influences. Future longitudinal research will shed light on factors impacting white matter disease presentation, progression, and potential recovery.

  18. Paradoxical embolisation and cerebral white matter lesions in dementia.

    NARCIS (Netherlands)

    Purandare, N.; Oude Voshaar, R.C.; McCollum, C.; Jackson, A.; Burns, A.

    2008-01-01

    The study aimed to examine the relationship between spontaneous cerebral emboli (SCE), patent foramen ovale (PFO) and white matter hyperintensities (WMH) on cerebral MRI in patients with Alzheimer's disease (AD) and vascular dementia (VaD). SCE were identified by transcranial Doppler of the middle c

  19. Anomalous White Matter Morphology in Adults Who Stutter

    Science.gov (United States)

    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,…

  20. Structural Angle and Power Images Reveal Interrelated Gray and White Matter Abnormalities in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Lai Xu

    2012-01-01

    Full Text Available We present a feature extraction method to emphasize the interrelationship between gray and white matter and identify tissue distribution abnormalities in schizophrenia. This approach utilizes novel features called structural phase and magnitude images. The phase image indicates the relative contribution of gray and white matter, and the magnitude image reflects the overall tissue concentration. Three different analyses are applied to the phase and magnitude images obtained from 120 healthy controls and 120 schizophrenia patients. First, a single-subject subtraction analysis is computed for an initial evaluation. Second, we analyze the extracted features using voxel based morphometry (VBM to detect voxelwise group differences. Third, source based morphometry (SBM analysis was used to determine abnormalities in structural networks that co-vary in a similar way. Six networks were identified showing significantly lower white-to-gray matter in schizophrenia, including thalamus, right precentral-postcentral, left pre/post-central, parietal, right cuneus-frontal, and left cuneus-frontal sources. Interestingly, some networks look similar to functional patterns, such as sensory-motor and vision. Our findings demonstrate that structural phase and magnitude images can naturally and efficiently summarize the associated relationship between gray and white matter. Our approach has wide applicability for studying tissue distribution differences in the healthy and diseased brain.

  1. Structural angle and power images reveal interrelated gray and white matter abnormalities in schizophrenia.

    Science.gov (United States)

    Xu, Lai; Adali, Tülay; Schretlen, David; Pearlson, Godfrey; Calhoun, Vince D

    2012-01-01

    We present a feature extraction method to emphasize the interrelationship between gray and white matter and identify tissue distribution abnormalities in schizophrenia. This approach utilizes novel features called structural phase and magnitude images. The phase image indicates the relative contribution of gray and white matter, and the magnitude image reflects the overall tissue concentration. Three different analyses are applied to the phase and magnitude images obtained from 120 healthy controls and 120 schizophrenia patients. First, a single-subject subtraction analysis is computed for an initial evaluation. Second, we analyze the extracted features using voxel based morphometry (VBM) to detect voxelwise group differences. Third, source based morphometry (SBM) analysis was used to determine abnormalities in structural networks that co-vary in a similar way. Six networks were identified showing significantly lower white-to-gray matter in schizophrenia, including thalamus, right precentral-postcentral, left pre/post-central, parietal, right cuneus-frontal, and left cuneus-frontal sources. Interestingly, some networks look similar to functional patterns, such as sensory-motor and vision. Our findings demonstrate that structural phase and magnitude images can naturally and efficiently summarize the associated relationship between gray and white matter. Our approach has wide applicability for studying tissue distribution differences in the healthy and diseased brain.

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

    Science.gov (United States)

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

    2012-10-10

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

  3. Transient asymptomatic white matter lesions following Epstein-Barr virus encephalitis

    Directory of Open Access Journals (Sweden)

    Yoo Young Jang

    2011-09-01

    Full Text Available We present the case of a patient with Epstein-Barr virus (EBV encephalitis who developed abnormal white matter lesions during the chronic phases of the infection. A 2-year-old-boy was admitted for a 2 day history of decreased activity with ataxic gait. The results of the physical examination were unremarkable except for generalized lethargy and enlarged tonsils with exudates. Brain magnetic resonance imaging (MRI at admission showed multiple high signal intensities in both basal ganglia and thalami. The result of EBV polymerase chain reaction (PCR of the cerebral spinal fluid was positive, and a serological test showed acute EBV infection. The patient was diagnosed with EBV encephalitis and recovered fully without any residual neurologic complications. Subsequently, follow-up MRI at 5 weeks revealed extensive periventricular white matter lesions. Since the patient remained clinically stable and asymptomatic during the follow-up period, no additional studies were performed and no additional treatments were provided. At the 1-year follow-up, cranial MRI showed complete disappearance of the abnormal high signal intensities previously seen in the white matter. The patient continued to remain healthy with no focal neurologic deficits on examination. This is the first case of asymptomatic self-limited white matter lesions seen in serial MRI studies in a Korean boy with EBV encephalitis.

  4. White matter integrity, creativity, and psychopathology: disentangling constructs with diffusion tensor imaging.

    Directory of Open Access Journals (Sweden)

    Rex E Jung

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

  5. Alterations of white matter integrity related to the season of birth in schizophrenia: a DTI study.

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    Stéphanie Giezendanner

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

  6. White matter fiber degradation attenuates hemispheric asymmetry when integrating visuomotor information.

    Science.gov (United States)

    Schulte, Tilman; Müller-Oehring, Eva M; Rohlfing, Torsten; Pfefferbaum, Adolf; Sullivan, Edith V

    2010-09-01

    Degradation of white matter fibers can affect the transmission of signals in brain circuits that normally enable integration of highly lateralized visual and motor processes. Here, we used diffusion tensor imaging tractography in combination with functional magnetic resonance imaging to examine the specific contributions of interhemispheric and intrahemispheric white matter fibers to functional measures of hemispheric transfer and parallel information processing using bilateral and unilateral left and right visual field stimulation in normal and compromised systems. In healthy adults, a greater degree of bilateral processing advantage with the left (nondominant) hand correlated with higher integrity of callosal fibers connecting occipital cortices, whereas less unilateral processing advantage with the right hand correlated with higher integrity of left-hemispheric posterior cingulate fibers. In contrast, alcoholics who have compromised callosal integrity showed less bilateral processing advantage than controls when responding with the left hand and greater unilateral processing advantage when responding with the right hand. We also found degraded left posterior cingulate and posterior callosal fibers in chronic alcoholics, which is consistent with functional imaging results of less left posterior cingulate and extrastriate cortex activation in alcoholics than controls when processing bilateral compared with unilateral visual field stimulation. Together, our results demonstrated that interhemispheric and intrahemispheric white matter fiber pathways mediate visuomotor integration asymmetrically and that subtle white matter fiber degradation in alcoholism attenuated the normal pattern of hemispheric asymmetry, which may have ramifications for the efficiency of visual information processing and fast response execution.

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

    Directory of Open Access Journals (Sweden)

    Efrat eSasson

    2013-03-01

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

  8. MRI markers for mild cognitive impairment: comparisons between white matter integrity and gray matter volume measurements.

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    Yu Zhang

    Full Text Available 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.

  9. Plasma NT-proBNP and White Matter Hyperintensities in Type 2 Diabetic Patients

    DEFF Research Database (Denmark)

    Reinhard, Henrik; Garde, Ellen; Skimminge, Arnold;

    2012-01-01

    Elevated plasma N-terminal (NT)-proBNP from the heart as well as white matter hyperintensities (WMH) in the brain predict cardiovascular (CV) mortality in the general population. The cause of poor prognosis associated with elevated P-NT-proBNP is not known but WMH precede strokes in high risk pop...... populations. We assessed the association between P-NT-proBNP and WMH or brain atrophy measured with magnetic resonance imaging (MRI) in type 2 diabetic patients, and age-matched controls....

  10. White matter correlates of cognitive inhibition during development: a diffusion tensor imaging study.

    Science.gov (United States)

    Treit, S; Chen, Z; Rasmussen, C; Beaulieu, C

    2014-09-12

    Inhibitory control and cognitive flexibility are two key executive functions that develop in childhood and adolescence, increasing one's capacity to respond dynamically to changing external demands and refrain from impulsive behaviors. These gains evolve in concert with significant brain development. Magnetic resonance imaging studies have identified numerous frontal and cingulate cortical areas associated with performance on inhibition tasks, but less is known about the involvement of the underlying anatomical connectivity, namely white matter. Here we used diffusion tensor imaging (DTI) to examine correlations between a DTI-derived parameter, fractional anisotropy (FA) of white matter, and performance on the NEPSY-II Inhibition test (Naming, Inhibition and Switching conditions) in 49 healthy children aged 5-16years (20 females; 29 males). First, whole brain voxel-based analysis revealed several clusters in the frontal projections of the corpus callosum, where higher FA was associated with worse inhibitory performance, as well as several clusters in posterior brain regions and one in the brainstem where higher FA was associated with better cognitive flexibility (in the Switching task), suggesting a dichotomous relationship between FA and these two aspects of cognitive control. Tractography through these clusters identified several white matter tracts, which were then manual traced in native space. Pearson's correlations confirmed associations between higher FA of frontal projections of the corpus callosum with poorer inhibitory performance (independent of age), though associations with Switching were not significant. Post-hoc evaluation suggested that FA of orbital and anterior frontal projections of the corpus callosum also mediated performance differences across conditions, which may reflect differences in self-monitoring or strategy use. These findings suggest a link between the development of inhibition and cognitive control with that of the underlying white

  11. Shared genetic variance between obesity and white matter integrity in Mexican Americans

    Science.gov (United States)

    Spieker, Elena A.; Kochunov, Peter; Rowland, Laura M.; Sprooten, Emma; Winkler, Anderson M.; Olvera, Rene L.; Almasy, Laura; Duggirala, Ravi; Fox, Peter T.; Blangero, John; Glahn, David C.; Curran, Joanne E.

    2015-01-01

    Obesity is a chronic metabolic disorder that may also lead to reduced white matter integrity, potentially due to shared genetic risk factors. Genetic correlation analyses were conducted in a large cohort of Mexican American families in San Antonio (N = 761, 58% females, ages 18–81 years; 41.3 ± 14.5) from the Genetics of Brain Structure and Function Study. Shared genetic variance was calculated between measures of adiposity [(body mass index (BMI; kg/m2) and waist circumference (WC; in)] and whole-brain and regional measurements of cerebral white matter integrity (fractional anisotropy). Whole-brain average and regional fractional anisotropy values for 10 major white matter tracts were calculated from high angular resolution diffusion tensor imaging data (DTI; 1.7 × 1.7 × 3 mm; 55 directions). Additive genetic factors explained intersubject variance in BMI (heritability, h2 = 0.58), WC (h2 = 0.57), and FA (h2 = 0.49). FA shared significant portions of genetic variance with BMI in the genu (ρG = −0.25), body (ρG = −0.30), and splenium (ρG = −0.26) of the corpus callosum, internal capsule (ρG = −0.29), and thalamic radiation (ρG = −0.31) (all p's = 0.043). The strongest evidence of shared variance was between BMI/WC and FA in the superior fronto-occipital fasciculus (ρG = −0.39, p = 0.020; ρG = −0.39, p = 0.030), which highlights region-specific variation in neural correlates of obesity. This may suggest that increase in obesity and reduced white matter integrity share common genetic risk factors. PMID:25763009

  12. Shared genetic variance between obesity and white matter integrity in Mexican-americans

    Directory of Open Access Journals (Sweden)

    Elena A Spieker

    2015-02-01

    Full Text Available Obesity is a chronic metabolic disorder that may also lead to reduced white matter integrity, potentially due to shared genetic risk factors. Genetic correlation analyses were conducted in a large cohort of Mexican American families in San Antonio (N=761, 58% females, ages 18-81y; 41.3±14.5 from the Genetics of Brain Structure and Function Study. Shared genetic variance was calculated between measures of adiposity ((body mass index (BMI; kg/m2 and waist circumference (WC; in and whole-brain and regional measurements of cerebral white matter integrity (fractional anisotropy. Whole-brain average and regional fractional anisotropy values for ten major white matter tracts were calculated from high angular resolution diffusion tensor imaging data (DTI; 1.7×1.7×3 mm; 55 directions. Additive genetic factors explained intersubject variance in BMI (heritability, h2=0.58, WC (h2=0.57, and FA (h2=0.49. FA shared significant portions of genetic variance with BMI in the genu (ρG = -0.25, body (ρG = -0.30, and splenium (ρG = -0.26 of the corpus callosum, internal capsule (ρG = -0.29, and thalamic radiation (ρG = -0.31 (all p’s = .043. The strongest evidence of shared variance was between BMI/WC and FA in the superior fronto-occipital fasciculus (ρG = -0.39, p = .020; ρG = -0.39, p = .030, which highlights region-specific variation in neural correlates of obesity. This may suggest that increase in obesity and reduced white matter integrity share common genetic risk factors.

  13. Convergent grey and white matter evidence of orbitofrontal cortex changes related to disinhibition in behavioural variant frontotemporal dementia.

    Science.gov (United States)

    Hornberger, Michael; Geng, John; Hodges, John R

    2011-09-01

    Disinhibition is a common behavioural symptom in frontotemporal dementia but its neural correlates are still debated. In the current study, we investigated the grey and white matter neural correlates of disinhibition in a sample of behavioural variant frontotemporal dementia (n = 14) and patients with Alzheimer's disease (n = 15). We employed an objective (Hayling Test of inhibitory functioning) and subjective/carer-based (Neuropsychiatric Inventory) measure of disinhibition to reveal convergent evidence of disinhibitory behaviour. Mean and overlap-based statistical analyses were conducted to investigate profiles of performance in patients with behavioural variant frontotemporal dementia, Alzheimer's disease and controls. Hayling Test and Neuropsychiatric Inventory scores were entered as covariates in a grey matter voxel-based morphometry, as well as in a white matter diffusion tensor imaging analysis to determine the underlying grey and white matter correlates. Patients with behavioural variant frontotemporal dementia showed more disinhibition on both behavioural measures in comparison to patients with Alzheimer's disease and controls. Voxel-based morphometry results revealed that atrophy in orbitofrontal/subgenual, medial prefrontal cortex and anterior temporal lobe areas covaried with total errors score of the Hayling Test. Similarly, the Neuropsychiatric Inventory disinhibition frequency score correlated with atrophy in orbitofrontal cortex and temporal pole brain regions. The orbitofrontal atrophy related to the objective (Hayling Test) and subjective (Neuropsychiatric Inventory) measures of disinhibition was partially overlapping. Diffusion tensor imaging analysis revealed that white matter integrity fractional anisotropy values of the white matter tracts connecting the identified grey matter regions, namely uncinate fasciculus, forceps minor and genu of the corpus callosum, correlated well with the total error score of the Hayling Test. Our results

  14. Association of white matter hyperintensities and gray matter volume with cognition in older individuals without cognitive impairment.

    Science.gov (United States)

    Arvanitakis, Zoe; Fleischman, Debra A; Arfanakis, Konstantinos; Leurgans, Sue E; Barnes, Lisa L; Bennett, David A

    2016-05-01

    Both presence of white matter hyperintensities (WMH) and smaller total gray matter volume on brain magnetic resonance imaging (MRI) are common findings in old age, and contribute to impaired cognition. We tested whether total WMH volume and gray matter volume had independent associations with cognition in community-dwelling individuals without dementia or mild cognitive impairment (MCI). We used data from participants of the Rush Memory and Aging Project. Brain MRI was available in 209 subjects without dementia or MCI (mean age 80; education = 15 years; 74 % women). WMH and gray matter were automatically segmented, and the total WMH and gray matter volumes were measured. Both MRI-derived measures were normalized by the intracranial volume. Cognitive data included composite measures of five different cognitive domains, based on 19 individual tests. Linear regression analyses, adjusted for age, sex, and education, were used to examine the relationship of logarithmically-transformed total WMH volume and of total gray matter volume to cognition. Larger total WMH volumes were associated with lower levels of perceptual speed (p  0.10). Smaller total gray matter volumes were associated with lower levels of perceptual speed (p = 0.013) and episodic memory (p = 0.001), but not with the other three cognitive domains (all p > 0.14). Larger total WMH volume was correlated with smaller total gray matter volume (p cognitive impairment suggests that the association of larger total WMH volume with lower perceptual speed is independent of total gray matter volume. These results help elucidate the pathological processes leading to lower cognitive function in aging.

  15. The effect of hypointense white matter lesions on automated gray matter segmentation in multiple sclerosis.

    Science.gov (United States)

    Gelineau-Morel, Rose; Tomassini, Valentina; Jenkinson, Mark; Johansen-Berg, Heidi; Matthews, Paul M; Palace, Jacqueline

    2012-12-01

    Previous imaging studies assessing the relationship between white matter (WM) damage and matter (GM) atrophy have raised the concern that Multiple Sclerosis (MS) WM lesions may affect measures of GM volume by inducing voxel misclassification during intensity-based tissue segmentation. Here, we quantified this misclassification error in simulated and real MS brains using a lesion-filling method. Using this method, we also corrected GM measures in patients before comparing them with controls in order to assess the impact of this lesion-induced misclassification error in clinical studies. We found that higher WM lesion volumes artificially reduced total GM volumes. In patients, this effect was about 72% of that predicted by simulation. Misclassified voxels were located at the GM/WM border and could be distant from lesions. Volume of individual deep gray matter (DGM) structures generally decreased with higher lesion volumes, consistent with results from total GM. While preserving differences in GM volumes between patients and controls, lesion-filling correction revealed more lateralised DGM shape changes in patients, which were not evident with the original images. Our results confirm that WM lesions can influence MRI measures of GM volume and shape in MS patients through their effect on intensity-based GM segmentation. The greater effect of lesions at increasing levels of damage supports the use of lesion-filling to correct for this problem and improve the interpretability of the results. Volumetric or morphometric imaging studies, where lesion amount and characteristics may vary between groups of patients or change over time, may especially benefit from this correction.

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

    Science.gov (United States)

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

    2016-03-01

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

  17. Altered topological organization of white matter structural networks in patients with neuromyelitis optica.

    Directory of Open Access Journals (Sweden)

    Yaou Liu

    Full Text Available 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.

  18. Cognitive impairment and associated loss in brain white microstructure in aircrew members exposed to engine oil fumes.

    Science.gov (United States)

    Reneman, Liesbeth; Schagen, Sanne B; Mulder, Michel; Mutsaerts, Henri J; Hageman, Gerard; de Ruiter, Michiel B

    2016-06-01

    Cabin air in airplanes can be contaminated with engine oil contaminants. These contaminations may contain organophosphates (OPs) which are known neurotoxins to brain white matter. However, it is currently unknown if brain white matter in aircrew is affected. We investigated whether we could objectify cognitive complaints in aircrew and whether we could find a neurobiological substrate for their complaints. After medical ethical approval from the local institutional review board, informed consent was obtained from 12 aircrew (2 females, on average aged 44.4 years, 8,130 flying hours) with cognitive complaints and 11 well matched control subjects (2 females, 43.4 years, 233 flying hours). Depressive symptoms and self-reported cognitive symptoms were assessed, in addition to a neuropsychological test battery. State of the art Magnetic Resonance Imaging (MRI) techniques were administered that assess structural and functional changes, with a focus on white matter integrity. In aircrew we found significantly more self-reported cognitive complaints and depressive symptoms, and a higher number of tests scored in the impaired range compared to the control group. We observed small clusters in the brain in which white matter microstructure was affected. Also, we observed higher cerebral perfusion values in the left occipital cortex, and reduced brain activation on a functional MRI executive function task. The extent of cognitive impairment was strongly associated with white matter integrity, but extent of estimated number of flight hours was not associated with cognitive impairment nor with reductions in white matter microstructure. Defects in brain white matter microstructure and cerebral perfusion are potential neurobiological substrates for cognitive impairments and mood deficits reported in aircrew.

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

    Science.gov (United States)

    Küper, Michael; Rabe, K; Esser, S; Gizewski, E R; Husstedt, I W; Maschke, M; Obermann, M

    2011-06-01

    In this cross-sectional study we used magnetic resonance imaging (MRI)-based voxel based morphometry (VBM) in a sample of 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 VBM analyses. Clinical testing in HIV patients included the HIV dementia scale (HDS), Unified Parkinson's Disease Rating Scale (UPDRS) and the grooved pegboard test. Comparing controls with HIV positive patients with cognitive dysfunction (n = 28) VBM showed gray matter decrease in the anterior cingulate and temporal cortices along with white matter reduction in the midbrain region. These changes were more prominent with increasing cognitive decline, when assigning HIV patients to three cognitive groups (not impaired, mildly impaired, overtly impaired) based on performance in the HIV dementia scale. Regression analysis including all HIV positive patients with available data revealed that prefrontal gray matter atrophy in HIV was associated with longer disease duration (n = 48), while motor dysfunction (n = 48) was associated with basal ganglia gray matter atrophy. Lower CD4 cell count (n = 47) correlated with decrease of occipital gray matter. Our results provide evidence for atrophy of nigro-striatal and fronto-striatal circuits in HIV. This pattern of atrophy is consistent with motor dysfunction and dysexecutive syndrome found in HIV patients with HIV-associated neurocognitive disorder.

  20. Prefrontal cortex white matter tracts in prodromal Huntington disease.

    Science.gov (United States)

    Matsui, Joy T; Vaidya, Jatin G; Wassermann, Demian; Kim, Regina Eunyoung; Magnotta, Vincent A; Johnson, Hans J; Paulsen, Jane S

    2015-10-01

    Huntington disease (HD) is most widely known for its selective degeneration of striatal neurons but there is also growing evidence for white matter (WM) deterioration. The primary objective of this research was to conduct a large-scale analysis using multisite diffusion-weighted imaging (DWI) tractography data to quantify diffusivity properties along major prefrontal cortex WM tracts in prodromal HD. Fifteen international sites participating in the PREDICT-HD study collected imaging and neuropsychological data on gene-positive HD participants without a clinical diagnosis (i.e., prodromal) and gene-negative control participants. The anatomical prefrontal WM tracts of the corpus callosum (PFCC), anterior thalamic radiations (ATRs), inferior fronto-occipital fasciculi (IFO), and uncinate fasciculi (UNC) were identified using streamline tractography of DWI. Within each of these tracts, tensor scalars for fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity coefficients were calculated. We divided prodromal HD subjects into three CAG-age product (CAP) groups having Low, Medium, or High probabilities of onset indexed by genetic exposure. We observed significant differences in WM properties for each of the four anatomical tracts for the High CAP group in comparison to controls. Additionally, the Medium CAP group presented differences in the ATR and IFO in comparison to controls. Furthermore, WM alterations in the PFCC, ATR, and IFO showed robust associations with neuropsychological measures of executive functioning. These results suggest long-range tracts essential for cross-region information transfer show early vulnerability in HD and may explain cognitive problems often present in the prodromal stage. Hum Brain Mapp 36:3717-3732, 2015. © 2015 Wiley Periodicals, Inc.

  1. Analysis of White Dwarfs with Strange-Matter Cores

    CERN Document Server

    Mathews, G J; O'Gorman, B; Lan, N Q; Zech, W; Otsuki, K; Weber, F

    2006-01-01

    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 ...

  2. Progressive volume loss and white matter degeneration in cstb-deficient mice: a diffusion tensor and longitudinal volumetry MRI study.

    Directory of Open Access Journals (Sweden)

    Otto Manninen

    Full Text Available Unverricht-Lundborg type progressive myoclonus epilepsy (EPM1, OMIM 254800 is an autosomal recessive disorder characterized by onset at the age of 6 to 16 years, incapacitating stimulus-sensitive myoclonus and tonic-clonic epileptic seizures. It is caused by mutations in the gene encoding cystatin B. Previously, widespread white matter changes and atrophy has been detected both in adult EPM1 patients and in 6-month-old cystatin B-deficient mice, a mouse model for the EPM1 disease. In order to elucidate the spatiotemporal dynamics of the brain atrophy and white matter changes in EPM1, we conducted longitudinal in vivo magnetic resonance imaging and ex vivo diffusion tensor imaging accompanied with tract-based spatial statistics analysis to compare volumetric changes and fractional anisotropy in the brains of 1 to 6 months of age cystatin B-deficient and control mice. The results reveal progressive but non-uniform volume loss of the cystatin B-deficient mouse brains, indicating that different neuronal populations possess distinct sensitivity to the damage caused by cystatin B deficiency. The diffusion tensor imaging data reveal early and progressive white matter alterations in cystatin B-deficient mice affecting all major tracts. The results also indicate that the white matter damage in the cystatin B-deficient brain is most likely secondary to glial activation and neurodegenerative events rather than a primary result of CSTB deficiency. The data also show that diffusion tensor imaging combined with TBSS analysis provides a feasible approach not only to follow white matter damage in neurodegenerative mouse models but also to detect fractional anisotropy changes related to normal white matter maturation and reorganisation.

  3. Melatonin promotes oligodendroglial maturation of injured white matter in neonatal rats.

    Directory of Open Access Journals (Sweden)

    Paul Olivier

    Full Text Available 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.

  4. Recreational marijuana use impacts white matter integrity and subcortical (but not cortical) morphometry.

    Science.gov (United States)

    Orr, Joseph M; Paschall, Courtnie J; Banich, Marie T

    2016-01-01

    A recent shift in legal and social attitudes toward marijuana use has also spawned a surge of interest in understanding the effects of marijuana use on the brain. There is considerable evidence that an adolescent onset of marijuana use negatively impacts white matter coherence. On the other hand, a recent well-controlled study demonstrated no effects of marijuana use on the morphometry of subcortical or cortical structures when users and non-users were matched for alcohol use. Regardless, most studies have involved small, carefully selected samples, so the ability to generalize to larger populations is limited. In an attempt to address this issue, we examined the effects of marijuana use on white matter integrity and cortical and subcortical morphometry using data from the Human Connectome Project (HCP) consortium. The HCP data consists of ultra-high resolution neuroimaging data from a large community sample, including 466 adults reporting recreational marijuana use. Rather than just contrasting two groups of individuals who vary significantly in marijuana usage as typifies prior studies, we leveraged the large sample size provided by the HCP data to examine parametric effects of recreational marijuana use. Our results indicate that the earlier the age of onset of marijuana use, the lower was white matter coherence. Age of onset also also affected the shape of the accumbens, while the number of lifetime uses impacted the shape of the amygdala and hippocampus. Marijuana use had no effect on cortical volumes. These findings suggest subtle but significant effects of recreational marijuana use on brain structure.

  5. White matter involvement after TBI: Clues to axon and myelin repair capacity.

    Science.gov (United States)

    Armstrong, Regina C; Mierzwa, Amanda J; Marion, Christina M; Sullivan, Genevieve M

    2016-01-01

    Impact-acceleration forces to the head cause traumatic brain injury (TBI) with damage in white matter tracts comprised of long axons traversing the brain. White matter injury after TBI involves both traumatic axonal injury (TAI) and myelin pathology that evolves throughout the post-injury time course. The axon response to initial mechanical forces and secondary insults follows the process of Wallerian degeneration, which initiates as a potentially reversible phase of intra-axonal damage and proceeds to an irreversible phase of axon fragmentation. Distal to sites of axon disconnection, myelin sheaths remain for prolonged periods, which may activate neuroinflammation and inhibit axon regeneration. In addition to TAI, TBI can cause demyelination of intact axons. These evolving features of axon and myelin pathology also represent opportunities for repair. In experimental TBI, demyelinated axons exhibit remyelination, which can serve to both protect axons and facilitate recovery of function. Myelin remodeling may also contribute to neuroplasticity. Efficient clearance of myelin debris is a potential target to attenuate the progression of chronic pathology. During the early phase of Wallerian degeneration, interventions that prevent the transition from reversible damage to axon disconnection warrant the highest priority, based on the poor regenerative capacity of axons in the CNS. Clinical evaluation of TBI will need to address the challenge of accurately detecting the extent and stage of axon damage. Distinguishing the complex white matter changes associated with axons and myelin is necessary for interpreting advanced neuroimaging approaches and for identifying a broader range of therapeutic opportunities to improve outcome after TBI.

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

    Science.gov (United States)

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

    2017-03-01

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

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

    Science.gov (United States)

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

    2011-12-30

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

  8. White Matter Integrity Pre- and Post Marijuana and Alcohol Initiation in Adolescence

    Directory of Open Access Journals (Sweden)

    Lindsay M. Squeglia

    2013-03-01

    Full Text Available Characterizing the effects of alcohol and marijuana use on adolescent brain development is important for understanding potential alterations in neurodevelopment. Several cross sectional studies have identified group differences in white matter integrity after initiation of heavy alcohol and marijuana use, however none have explored white matter trajectories in adolescents pre- and post initiation of use, particularly for marijuana users. This study followed 16 adolescents with minimal alcohol and marijuana use at ages 16–18 over three years. At follow-up, teens were 19–22 years old; half of the participants initiated heavy alcohol use and half initiated heavy alcohol and marijuana use. Repeated-measures ANOVA revealed 20 clusters in association and projection fibers tracts (p < 0.01 in which a group by time interaction was found. Most consistently, white matter integrity (i.e., fractional anisotropy decreased for those who initiated both heavy alcohol and marijuana use over the follow-up interval. No effect of time or change in white matter integrity was seen for those who initiated alcohol use only in the majority of clusters. In most regions, at the baseline time point, teens who would later initiate both alcohol and marijuana use demonstrated white matter integrity greater than or equal to teens that initiated alcohol use only. Findings suggest poorer tissue integrity associated with combined initiation of heavy alcohol and marijuana use in late adolescence. While pre-existing differences may also be related to likelihood of substance use, the present data suggest an effect on tissue integrity for these teens transitioning to combined alcohol and marijuana use in later adolescence.

  9. White matter development in early puberty: a longitudinal volumetric and diffusion tensor imaging twin study.

    Science.gov (United States)

    Brouwer, Rachel M; Mandl, René C W; Schnack, Hugo G; van Soelen, Inge L C; van Baal, G Caroline; Peper, Jiska S; Kahn, René S; Boomsma, Dorret I; Hulshoff Pol, H E

    2012-01-01

    White matter microstructure and volume show synchronous developmental patterns in children. White matter volume increases considerably during development. Fractional anisotropy, a measure for white matter microstructural directionality, also increases with age. Development of white matter volume and development of white matter microstructure seem to go hand in hand. The extent to which the same or different genetic and/or environmental factors drive these two aspects of white matter maturation is currently unknown. We mapped changes in white matter volume, surface area and diffusion parameters in mono- and dizygotic twins who were scanned at age 9 (203 individuals) and again at age 12 (126 individuals). Over the three-year interval, white matter volume (+6.0%) and surface area (+1.7%) increased, fiber bundles expanded (most pronounced in the left arcuate fasciculus and splenium), and fractional anisotropy increased (+3.0%). Genes influenced white matter volume (heritability ~85%), surface area (~85%), and fractional anisotropy (locally 7% to 50%) at both ages. Finally, volumetric white matter growth was negatively correlated with fractional anisotropy increase (r = -0.62) and this relationship was driven by environmental factors. In children who showed the most pronounced white matter growth, fractional anisotropy increased the least and vice-versa. Thus, white matter development in childhood may reflect a process of both expansion and fiber optimization.

  10. White matter development in early puberty: a longitudinal volumetric and diffusion tensor imaging twin study.

    Directory of Open Access Journals (Sweden)

    Rachel M Brouwer

    Full Text Available White matter microstructure and volume show synchronous developmental patterns in children. White matter volume increases considerably during development. Fractional anisotropy, a measure for white matter microstructural directionality, also increases with age. Development of white matter volume and development of white matter microstructure seem to go hand in hand. The extent to which the same or different genetic and/or environmental factors drive these two aspects of white matter maturation is currently unknown. We mapped changes in white matter volume, surface area and diffusion parameters in mono- and dizygotic twins who were scanned at age 9 (203 individuals and again at age 12 (126 individuals. Over the three-year interval, white matter volume (+6.0% and surface area (+1.7% increased, fiber bundles expanded (most pronounced in the left arcuate fasciculus and splenium, and fractional anisotropy increased (+3.0%. Genes influenced white matter volume (heritability ~85%, surface area (~85%, and fractional anisotropy (locally 7% to 50% at both ages. Finally, volumetric white matter growth was negatively correlated with fractional anisotropy increase (r = -0.62 and this relationship was driven by environmental factors. In children who showed the most pronounced white matter growth, fractional anisotropy increased the least and vice-versa. Thus, white matter development in childhood may reflect a process of both expansion and fiber optimization.

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

    Science.gov (United States)

    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.

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  20. Isolated acute non-cystic white matter injury in term infants presenting with neonatal encephalopathy.

    LENUS (Irish Health Repository)

    Barrett, Michael Joseph

    2013-03-01

    We discuss possible aetiological factors, MRI evolution of injury and neuro-developmental outcomes of neonatal encephalopathy (NE). Thirty-six consecutive infants diagnosed with NE were included. In this cohort, four infants (11%) were identified with injury predominantly in the deep white matter on MRI who were significantly of younger gestation, lower birthweight with higher Apgars at one and five minutes compared to controls. Placental high grade villitis of unknown aetiology (VUA) was identified in all four of these infants. Our hypothesis states VUA may induce white matter injury by causing a local inflammatory response and\\/or oxidative stress during the perinatal period. We underline the importance of continued close and systematic evaluation of all cases of NE, including examination of the placenta, in order to come to a better understanding of the clinical presentation, the patterns of brain injury and the underlying pathophysiological processes.

  1. Pharmacological Effects of Erythropoietin and its Derivative Carbamyl erythropoietin in Cerebral White Matter Injury

    Science.gov (United States)

    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

  2. Effects of prenatal alcohol exposure on the development of white matter volume and change in executive function

    Directory of Open Access Journals (Sweden)

    P. Gautam

    2014-01-01

    Full Text Available Prenatal alcohol exposure can cause a wide range of deficits in executive function that persist throughout life, but little is known about how changes in brain structure relate to cognition in affected individuals. In the current study, we predicted that the rate of white matter volumetric development would be atypical in children with fetal alcohol spectrum disorders (FASD when compared to typically developing children, and that the rate of change in cognitive function would relate to differential white matter development between groups. Data were available for 103 subjects [49 with FASD, 54 controls, age range 6–17, mean age = 11.83] with 153 total observations. Groups were age-matched. Participants underwent structural magnetic resonance imaging (MRI and an executive function (EF battery. Using white matter volumes measured bilaterally for frontal and parietal regions and the corpus callosum, change was predicted by modeling the effects of age, intracranial volume, sex, and interactions with exposure status and EF measures. While both groups showed regional increases in white matter volumes and improvement in cognitive performance over time, there were significant effects of exposure status on age-related relationships between white matter increases and EF measures. Specifically, individuals with FASD consistently showed a positive relationship between improved cognitive function and increased white matter volume over time, while no such relationships were seen in controls. These novel results relating improved cognitive function with increased white matter volume in FASD suggest that better cognitive outcomes could be possible for FASD subjects through interventions that enhance white matter plasticity.

  3. White matter apoptosis is increased by delayed hypothermia and rewarming in a neonatal piglet model of hypoxic ischemic encephalopathy.

    Science.gov (United States)

    Wang, B; Armstrong, J S; Reyes, M; Kulikowicz, E; Lee, J-H; Spicer, D; Bhalala, U; Yang, Z-J; Koehler, R C; Martin, L J; Lee, J K

    2016-03-01

    Therapeutic hypothermia is widely used to treat neonatal hypoxic ischemic (HI) brain injuries. However, potentially deleterious effects of delaying the induction of hypothermia and of rewarming on white matter injury remain unclear. We used a piglet model of HI to assess the effects of delayed hypothermia and rewarming on white matter apoptosis. Piglets underwent HI injury or sham surgery followed by normothermic or hypothermic recovery at 2h. Hypothermic groups were divided into those with no rewarming, slow rewarming at 0.5°C/h, or rapid rewarming at 4°C/h. Apoptotic cells in the subcortical white matter of the motor gyrus, corpus callosum, lateral olfactory tract, and internal capsule at 29h were identified morphologically and counted by hematoxylin & eosin staining. Cell death was verified by terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL) assay. White matter neurons were also counted, and apoptotic cells were immunophenotyped with the oligodendrocyte marker 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase). Hypothermia, slow rewarming, and rapid rewarming increased apoptosis in the subcortical white matter relative to normothermia (ppiglets had more apoptosis in the lateral olfactory tract than those that were rewarmed (ppiglets had more apoptosis than shams after normothermia, slow rewarming, and rapid rewarming (ppiglet model of HI; in some regions these temperature effects are independent of HI. Vulnerable cells include myelinating oligodendrocytes. This study identifies a deleterious effect of therapeutic hypothermia in the developing brain.

  4. Effects of ANK3 Variation on Gray and White Matter in Bipolar Disorder

    Science.gov (United States)

    Lippard, Elizabeth Thomas Cox; Jensen, Kevin Patrick; Wang, Fei; Johnston, Jennifer Ann Yadon; Spencer, Linda; Pittman, Brian; Gelernter, Joel; Blumberg, Hilary Patricia

    2016-01-01

    The single nucleotide polymorphism rs9804190 in the Ankyrin G (ANK3) gene has been reported in genome-wide association studies to be associated with bipolar disorder (BD). However, the neural system effects of rs9804190 in BD are not known. We investigated associations between rs9804190 with gray and white matter structure within a frontotemporal neural system implicated in BD. A total of 187 adolescent and adult European Americans were studied: a group homozygous for the C allele [52 individuals with BD and 56 controls] and a T-carrier group, carrying the high risk T allele (38 BD and 41 controls). Subjects participated in high-resolution structural magnetic resonance imaging and diffusion tensor imaging (DTI) scanning. Frontotemporal region of interest (ROI) and whole brain exploratory analyses were conducted. DTI ROI-based analysis revealed a significant diagnosis by genotype interaction within the uncinate fasciculus (p ≥ 0.05), with BD subjects carrying the T (risk) allele showing decreased fractional anisotropy compared to other subgroups, independent of age. Genotype effects were not observed in frontotemporal gray matter volume. These findings support effects of rs9804190 on frontotemporal white matter in adolescents and adults with BD and suggest a mechanism contributing to white matter pathology in BD. PMID:27240527

  5. White dwarf stars as strange quark matter detectors

    Energy Technology Data Exchange (ETDEWEB)

    Benvenuto, O G [Departamento de AstronomIa y AstroFisica, Pontificia Universidad Catolica, Vicuna Mackenna 4860, Casilla 306, Santiago (Chile); Facultad de Ciencias Astronomicas y GeoFisicas, Universidad Nacional de La Plata, Paseo del Bosque S/N, B1900FWA, La Plata (Argentina)

    2005-11-01

    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 WDs without any compact core. (letter to the editor)

  6. White matter hyperintensities and medial temporal lobe atrophy in clinical subtypes of mild cognitive impairment: the DESCRIPA study

    OpenAIRE

    Pol, van de, Jaco; Verhey, F.; Frisoni, G.B.; Tsolaki, M; Papapostolou, P.; Nobili, F.; Wahlund, L. O.; Minthon, L.; Frolich, L.; Hampel, H.; Soininen, H.; Knol, D.L.; Barkhof, F; Scheltens, P.; Visser, P.J.

    2009-01-01

    Abstract Clinical subtypes of mild cognitive impairment (MCI) may represent different underlying aetiologies. In a European, multi-center, memory-clinic based study (DESCRIPA) of non-demented subjects we investigated whether MCI subtypes have different brain correlates on MRI and whether the relation between subtypes and brain pathology is modified by age. Using visual rating scales medial temporal lobe atrophy (MTA) (0-4) and white matter hyperintensities (WMH) (0-30) were assesse...

  7. Altered Gray Matter Volume and White Matter Integrity in College Students with Mobile Phone Dependence.

    Science.gov (United States)

    Wang, Yongming; Zou, Zhiling; Song, Hongwen; Xu, Xiaodan; Wang, Huijun; d'Oleire Uquillas, Federico; Huang, Xiting

    2016-01-01

    Mobile phone dependence (MPD) is a behavioral addiction that has become an increasing public mental health issue. While previous research has explored some of the factors that may predict MPD, the underlying neural mechanisms of MPD have not been investigated yet. The current study aimed to explore the microstructural variations associated with MPD as measured with functional Magnetic Resonance Imaging (fMRI). Gray matter volume (GMV) and white matter (WM) integrity [four indices: fractional anisotropy (FA); mean diffusivity (MD); axial diffusivity (AD); and radial diffusivity (RD)] were calculated via voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) analysis, respectively. Sixty-eight college students (42 female) were enrolled and separated into two groups [MPD group, N = 34; control group (CG), N = 34] based on Mobile Phone Addiction Index (MPAI) scale score. Trait impulsivity was also measured using the Barratt Impulsiveness Scale (BIS-11). In light of underlying trait impulsivity, results revealed decreased GMV in the MPD group relative to controls in regions such as the right superior frontal gyrus (sFG), right inferior frontal gyrus (iFG), and bilateral thalamus (Thal). In the MPD group, GMV in the above mentioned regions was negatively correlated with scores on the MPAI. Results also showed significantly less FA and AD measures of WM integrity in the MPD group relative to controls in bilateral hippocampal cingulum bundle fibers (CgH). Additionally, in the MPD group, FA of the CgH was also negatively correlated with scores on the MPAI. These findings provide the first morphological evidence of altered brain structure with mobile phone overuse, and may help to better understand the neural mechanisms of MPD in relation to other behavioral and substance addiction disorders.

  8. Linking white matter tracts to associated cortical grey matter: a tract extension methodology.

    Science.gov (United States)

    Tozer, D J; Chard, D T; Bodini, B; Ciccarelli, O; Miller, D H; Thompson, A J; Wheeler-Kingshott, C A M

    2012-02-15

    Quantitative diffusion analysis of white matter (WM) tracts has been utilised in many diseases for determining damage to, and changes in, WM tracts throughout the brain. However, there are limited studies investigating associations between quantitative measures in WM tracts and anatomically linked grey matter (GM), due to the difficulty in determining GM regions connected with a given WM tract. This work describes a straightforward method for extending a WM tract through GM based on geometry. The tract is extended by following a straight line from each point on the tract boundary to the outer boundary of the cortex. A comparison between a multiplanar 2D approach and a 3D method was made. This study also tested an analysis pipeline from tracking WM tracts to quantifying magnetisation transfer ratios (MTR) in the associated cortical GM, and assessed the applicability of the method to healthy control subjects. Tract and associated cortical volumes and MTR values for the cortico-spinal tracts, genu and body of the corpus callosum were extracted; the between-subjects standard deviation was calculated. It was found that a multiplanar 2D approach produced a more anatomically plausible volume of GM than a 3D approach, at the expense of possible overestimation of the GM volume. The between-subjects standard deviation of the tract specific quantitative measurements (from both the WM and GM masks) ranged between 1.2 and 7.3% for the MTR measures, and between 10 and 45% for the absolute volume measures. The results show that the method can be used to produce anatomically plausible extensions of the WM tracts through the GM, and regions defined in this way yield reliable estimates of the MTR from the regions.

  9. Microstructural white matter alterations in preclinical Alzheimer’s disease detected using free water elimination diffusion tensor imaging

    Science.gov (United States)

    Ly, Martina; Carlsson, Cynthia M.; Okonkwo, Ozioma C.; Zetterberg, Henrik; Blennow, Kaj; Sager, Mark A.; Asthana, Sanjay; Johnson, Sterling C.; Alexander, Andrew L.; Bendlin, Barbara B.

    2017-01-01

    Brain changes associated with Alzheimer’s disease (AD) begin decades before disease diagnosis. While β-amyloid plaques and neurofibrillary tangles are defining features of AD, neuronal loss and synaptic pathology are closely related to the cognitive dysfunction. Brain imaging methods that are tuned to assess degeneration of myelinated nerve fibers in the brain (collectively called white matter) include diffusion tensor imaging (DTI) and related techniques, and are expected to shed light on disease-related loss of structural connectivity. Participants (N = 70, ages 47–76 years) from the Wisconsin Registry for Alzheimer’s Prevention study underwent DTI and hybrid diffusion imaging to determine a free-water elimination (FWE-DTI) model. The study assessed the extent to which preclinical AD pathology affects brain white matter. Preclinical AD pathology was determined using cerebrospinal fluid (CSF) biomarkers. The sample was enriched for AD risk (APOE ε4 and parental history of AD). AD pathology assessed by CSF analyses was significantly associated with altered microstructure on both DTI and FWE-DTI. Affected regions included frontal, parietal, and especially temporal white matter. The f-value derived from the FWE-DTI model appeared to be the most sensitive to the relationship between the CSF AD biomarkers and microstructural alterations in white matter. These findings suggest that white matter degeneration is an early pathological feature of AD that may have utility both for early disease detection and as outcome measures for clinical trials. More complex models of microstructural diffusion properties including FWE-DTI may provide increased sensitivity to early brain changes associated with AD over standard DTI. PMID:28291839

  10. Abnormal white matter integrity in adolescents with internet addiction disorder: a tract-based spatial statistics study.

    Directory of Open Access Journals (Sweden)

    Fuchun Lin

    Full Text Available BACKGROUND: Internet addiction disorder (IAD is currently becoming a serious mental health issue around the globe. Previous studies regarding IAD were mainly focused on associated psychological examinations. However, there are few studies on brain structure and function about IAD. In this study, we used diffusion tensor imaging (DTI to investigate white matter integrity in adolescents with IAD. METHODOLOGY/PRINCIPAL FINDINGS: Seventeen IAD subjects and sixteen healthy controls without IAD participated in this study. Whole brain voxel-wise analysis of fractional anisotropy (FA was performed by tract-based spatial statistics (TBSS to localize abnormal white matter regions between groups. TBSS demonstrated that IAD had significantly lower FA than controls throughout the brain, including the orbito-frontal white matter, corpus callosum, cingulum, inferior fronto-occipital fasciculus, and corona radiation, internal and external capsules, while exhibiting no areas of higher FA. Volume-of-interest (VOI analysis was used to detect changes of diffusivity indices in the regions showing FA abnormalities. In most VOIs, FA reductions were caused by an increase in radial diffusivity while no changes in axial diffusivity. Correlation analysis was performed to assess the relationship between FA and behavioral measures within the IAD group. Significantly negative correlations were found between FA values in the left genu of the corpus callosum and the Screen for Child Anxiety Related Emotional Disorders, and between FA values in the left external capsule and the Young's Internet addiction scale. CONCLUSIONS: Our findings suggest that IAD demonstrated widespread reductions of FA in major white matter pathways and such abnormal white matter structure may be linked to some behavioral impairments. In addition, white matter integrity may serve as a potential new treatment target and FA may be as a qualified biomarker to understand the underlying neural mechanisms of

  11. Research of Differential Expression between Grey Matter and White Matter in Rhesus Macaque Brain by Laser Capture Microdessection and Microarray%利用激光显微切割与microarray技术对恒河猴脑中白质与灰质基因表达的差异性的研究

    Institute of Scientific and Technical Information of China (English)

    梁洪雨; 张晓宇; 邵宁一; Philipp Khaitovich; 赵敏

    2012-01-01

    Objective: To investigate the different expression of the genes in the gray matter,white matter and cerebellar cortex. Methods: The white matter and gray matter were extracted from PFC and CBC via LCM technology. The expression differences between gray matter and white matter in the PFC and CBC were analyzed. Results: There were more highly expressed genes in the PFC than in the CBC whatever for grey matter or white matter. Conclusion: The LCM can extract a single cell population, which is vital for studies requiring a high level of precision.%目的:利用激光显微切割技术和microarray技术比较恒河猴脑组织中前额叶皮质(prefontal cortex,PFC)与小脑皮质(cerebellar cortex,CBC)的灰质与白质基因表达的差异.方法:利用激光显微切割技术(laser capture dissection,LCM)与microarray技术的有效结合,提取恒河猴PFC与CBC的白质与灰质,分别提取RNA,合成cDNA文库.最后利用GeneChip 1.0 ST芯片技术,分析得出大脑与小脑中灰质与白质的表达差异性.结果:无论是灰质还是白质,在PFC中的高表达基因都要远远多于在CBC中的高表达基因.结论:使用LCM可以提取单一的细胞群,从而用于要求更为精确的实验当中.

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

    Science.gov (United States)

    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

  13. Gray and White Matter Contributions to Cognitive Frontostriatal Deficits in Non-Demented Parkinson's Disease.

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    Catherine C Price

    Full Text Available This prospective investigation examined: 1 processing speed and working memory relative to other cognitive domains in non-demented medically managed idiopathic Parkinson's disease, and 2 the predictive role of cortical/subcortical gray thickness/volume and white matter fractional anisotropy on processing speed and working memory.Participants completed a neuropsychological protocol, Unified Parkinson's Disease Rating Scale, brain MRI, and fasting blood draw to rule out vascular contributors. Within group a priori anatomical contributors included bilateral frontal thickness, caudate nuclei volume, and prefrontal white matter fractional anisotropy.Idiopathic Parkinson's disease (n = 40; Hoehn & Yahr stages 1-3 and non-Parkinson's disease 'control' peers (n = 40 matched on demographics, general cognition, comorbidity, and imaging/blood vascular metrics. Cognitively, individuals with Parkinson's disease were significantly more impaired than controls on tests of processing speed, secondary deficits on working memory, with subtle impairments in memory, abstract reasoning, and visuoperceptual/spatial abilities. Anatomically, Parkinson's disease individuals were not statistically different in cortical gray thickness or subcortical gray volumes with the exception of the putamen. Tract Based Spatial Statistics showed reduced prefrontal fractional anisotropy for Parkinson's disease relative to controls. Within Parkinson's disease, prefrontal fractional anisotropy and caudate nucleus volume partially explained processing speed. For controls, only prefrontal white matter was a significant contributor to processing speed. There were no significant anatomical predictors of working memory for either group.Caudate nuclei volume and prefrontal fractional anisotropy, not frontal gray matter thickness, showed unique and combined significance for processing speed in Parkinson's disease. Findings underscore the relevance for examining gray-white matter interactions

  14. The strength of the nodes of the brain white matter weighted networks and its relationship with the course of disease in male schizophrenia%男性偏执型精神分裂症患者脑白质网络连接强度与病程相关性

    Institute of Scientific and Technical Information of China (English)

    陈建淮; 姚志剑; 秦姣龙; 赵可; 阎锐; 花玲玲; 卢青

    2014-01-01

    目的:探讨男性偏执型精神分裂症患者与男性正常对照者脑白质结构加权网络节点连接强度属性值的异同,分析患者不同脑区的连接纤维受损情况及其与病程的关系。方法对25例男性偏执型精神分裂症患者及26例男性对照者进行弥散张量成像扫描(diffusion tensor imaging,DTI),利用解剖学自动标记(auto⁃mated anatomical labeling,AAL)模板将大脑划分为90个区域,采用确定性纤维追踪(fiber assignment by continu⁃ous tracking,FACT)方法进行纤维追踪,构建脑白质结构加权网络。结果患者组右侧丘脑(P=0.03,校正后)、右侧颞横回(P=0.04,校正后)连接强度属性值较对照组下降。患者组右侧丘脑连接强度属性值与病程呈负相关(r=-0.45,P=0.03)。结论男性偏执型精神分裂症患者连接纤维受损的脑区主要位于丘脑和颞叶;同时,丘脑连接纤维的损害与病程有关。%Objective To explore the differences in the strength of the nodes in the brain white matter weighted networks between the male patients with paranoid schizophrenia and male healthy controls, and to analysis the integrity of the white matter fiber tracts that connected to the different brain regions and its relationship with the course of disease. Methods Diffusion tensor imaging (DTI) data were obtained from 25 male patients with paranoid schizophrenia and 26 male healthy controls. The whole brain was parcellated into 90 regions by using the anatomical label map. Tractography was performed in the whole brain of each subject to reconstruct white matter tracts using the FACT algorithm. The brain white matter weighted networks were then constructed using the complex network theory. Results The strength of the nodes in the networks of schizophrenia significantly decreased in the right thalamus (P=0.03, corrected) and the right hes⁃chl gyrus (P=0.04, corrected). Negative correlation was found

  15. Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL): Assessment of the involved white matter tracts by MRI

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    Kassem, Hassan [Department of Radiology, Benha University (Egypt); Wafaie, Ahmed, E-mail: a_wafaie@yahoo.com [Department of Radiology, Cairo University (Egypt); Abdelfattah, Sherif [Department of Radiology, Cairo University (Egypt); Farid, Tarek [Pediatric Department, Egyptian National Research Center (Egypt)

    2014-01-15

    Background and purpose: Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) is a recently identified autosomal recessive disorder with early onset of symptoms and slowly progressive pyramidal, cerebellar and dorsal column dysfunction. LBSL is characterized by distinct white matter abnormalities and selective involvement of brainstem and spinal cord tracts. The purpose of this study is to assess the imaging features of the involved white matter tracts in cases of LBSL by MRI. Patients and methods: We retrospectively reviewed the imaging features of the selectively involved white matter tracts in sixteen genetically proven cases of leukoencephalopathy with brainstem and spinal cord involvement and elevated brain lactate (LBSL). All patients presented with slowly progressive cerebellar sensory ataxia with spasticity and dorsal column dysfunction. MRI of the brain and spine using 1.5 T machine and proton magnetic resonance spectroscopy ({sup 1}H MRS) on the abnormal white matter were done to all patients. The MRI and MRS data sets were analyzed according to lesion location, extent, distribution and signal pattern as well as metabolite values and ratios in MRS. Laboratory examinations ruled out classic leukodystrophies. Results: In all cases, MRI showed high signal intensity in T2-weighted and FLAIR images within the cerebral subcortical, periventricular and deep white matter, posterior limbs of internal capsules, centrum semiovale, medulla oblongata, intraparenchymal trajectory of trigeminal nerves and deep cerebellar white matter. In the spine, the signal intensity of the dorsal column and lateral cortico-spinal tracts were altered in all patients. The subcortical U fibers, globi pallidi, thalami, midbrain and transverse pontine fibers were spared in all cases. In 11 cases (68.8%), the signal changes were inhomogeneous and confluent whereas in 5 patients (31.2%), the signal abnormalities were spotty. MRI also showed variable

  16. Meta-analytic investigations of structural grey matter, executive domain-related functional activations, and white matter diffusivity in obsessive compulsive disorder: an integrative review.

    Science.gov (United States)

    Eng, Goi Khia; Sim, Kang; Chen, Shen-Hsing Annabel

    2015-05-01

    Obsessive-compulsive disorder (OCD) is a debilitating disorder. However, existing neuroimaging findings involving executive function and structural abnormalities in OCD have been mixed. Here we conducted meta-analyses to investigate differences in OCD samples and controls in: Study 1 - grey matter structure; Study 2 - executive function task-related activations during (i) response inhibition, (ii) interference, and (iii) switching tasks; and Study 3 - white matter diffusivity. Results showed grey matter differences in the frontal, striatal, thalamus, parietal and cerebellar regions; task domain-specific neural differences in similar regions; and abnormal diffusivity in major white matter regions in OCD samples compared to controls. Our results reported concurrence of abnormal white matter diffusivity with corresponding abnormalities in grey matter and task-related functional activations. Our findings suggested the involvement of other brain regions not included in the cortico-striato-thalamo-cortical network, such as the cerebellum and parietal cortex, and questioned the involvement of the orbitofrontal region in OCD pathophysiology. Future research is needed to clarify the roles of these brain regions in the disorder.

  17. White-matter microstructure and gray-matter volumes in adolescents with subthreshold bipolar symptoms

    DEFF Research Database (Denmark)

    Paillère Martinot, M-L; Lemaitre, Henri Charles Francois; Artiges, E;

    2014-01-01

    Abnormalities in white-matter (WM) microstructure, as lower fractional anisotropy (FA), have been reported in adolescent-onset bipolar disorder and in youth at familial risk for bipolarity. We sought to determine whether healthy adolescents with subthreshold bipolar symptoms (SBP) would have earl...

  18. Short fused? associations between white matter connections, sex steroids, and aggression across adolescence.

    Science.gov (United States)

    Peper, Jiska S; de Reus, Marcel A; van den Heuvel, Martijn P; Schutter, Dennis J L G

    2015-03-01

    Functional neuroimaging studies in adults show that aggression involves reduced brain communication between subcortical and cortical areas dedicated to motivation and control, respectively. Prior research indicates that sex steroid hormone production during adolescence negatively influences the rapid development of white matter connectivity between subcortical and cortical areas during adolescence and may potentiate aggression. Here, we tested this hypothesis in 258 participants between 8 and 25 years of age by using Diffusion Weighted Imaging to examine the microstructure of white matter connections within the fronto-temporal-subcortical network. Trait aggression was measured using the Buss Perry Aggression Questionnaire and testosterone and estradiol levels were measured in saliva. Results indicated that higher levels of testosterone were associated with less white matter integrity within the fronto-temporal-subcortical network (i.e., higher mean diffusivity [MD] longitudinal [LD], and radial diffusivity [RD]). Furthermore, lower fractional anisotropy and higher MD, LD, and RD values within this network increased expressive forms of aggression and reduced inhibited forms of aggression (hostility). Our study indicates higher levels of testosterone relating to lower quality of structural cortical-subcortical connectivity, arguably resulting in a shift from inhibited towards expressive forms of aggression. Our data adds evidence to the idea that aggressive tendencies are subcortically driven, but individuals with relatively high testosterone might have lower structural connectivity within cortical control areas, resulting in a stronger tendency to act on these aggressive tendencies.

  19. Early life trauma is associated with altered white matter integrity and affective control.

    Science.gov (United States)

    Corbo, Vincent; Amick, Melissa A; Milberg, William P; McGlinchey, Regina E; Salat, David H

    2016-08-01

    Early life trauma (ELT) has been shown to impair affective control and attention well into adulthood. Neuroimaging studies have further shown that ELT was associated with decreased white matter integrity in the prefrontal areas in children and adults. However, no study to date has looked at the relationship between white matter integrity and affective control in individuals with and without a history of ELT. To examine this, we tested 240 Veterans with (ELT N = 80) and without (NoELT N = 160) a history of childhood sexual abuse, physical abuse or family violence. Affective control was measured with the Affective Go/No-Go (AGN) and attention was indexed with the Test of Variable Attention (TOVA). White matter integrity was measured using fractional anisotropy (FA). Results showed greater number of errors on the AGN in ELT compared to NoELT. There was no difference on the TOVA. While there were no mean differences in FA, there was an interaction between FA and reaction time to positive stimuli on the AGN where the ELT group showed a positive relationship between FA and reaction time in right frontal and prefrontal areas, whereas the NoELT group showed a negative or no association between FA and reaction time. This suggests that ELT may be associated with a distinct brain-behavior relationship that could be related to other determinants of FA than those present in healthy adults.

  20. Lessons from a Mouse Model Characterizing Features of Vascular Cognitive Impairment with White Matter Changes

    Directory of Open Access Journals (Sweden)

    Masafumi Ihara

    2011-01-01

    Full Text Available With the demographic shift in age in advanced countries inexorably set to progress in the 21st century, dementia will become one of the most important health problems worldwide. Vascular cognitive impairment is the second most common type of dementia after Alzheimer's disease and is frequently responsible for the cognitive decline of the elderly. It is characterized by cerebrovascular white matter changes; thus, in order to investigate the underlying mechanisms involved in white matter changes, a mouse model of chronic cerebral hypoperfusion has been developed, which involves the narrowing of the bilateral common carotid arteries with newly designed microcoils. The purpose of this paper is to provide a comprehensive summary of the achievements made with the model that shows good reproducibility of the white matter changes characterized by blood-brain barrier disruption, glial activation, oxidative stress, and oligodendrocyte loss following chronic cerebral hypoperfusion. Detailed characterization of this model may help to decipher the substrates associated with impaired memory and move toward a more integrated therapy of vascular cognitive impairment.

  1. Early-stage psychotherapy produces elevated frontal white matter integrity in adult major depressive disorder.

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    Tao Wang

    Full Text Available BACKGROUND: Psychotherapy has demonstrated comparable efficacy to antidepressant medication in the treatment of major depressive disorder. Metabolic alterations in the MDD state and in response to treatment have been detected by functional imaging methods, but the underlying white matter microstructural changes remain unknown. The goal of this study is to apply diffusion tensor imaging techniques to investigate psychotherapy-specific responses in the white matter. METHODS: Twenty-one of forty-five outpatients diagnosed with major depression underwent diffusion tensor imaging before and after a four-week course of guided imagery psychotherapy. We compared fractional anisotropy in depressed patients (n = 21 with healthy controls (n = 22, and before-after treatment, using whole brain voxel-wise analysis. RESULTS: Post-treatment, depressed subjects showed a significant reduction in the 17-item Hamilton Depression Rating Scale. As compared to healthy controls, depressed subjects demonstrated significantly increased fractional anisotropy in the right thalamus. Psychopathological changes did not recover post-treatment, but a novel region of increased fractional anisotropy was discovered in the frontal lobe. CONCLUSIONS: At an early stage of psychotherapy, higher fractional anisotropy was detected in the frontal emotional regulation-associated region. This finding reveals that psychotherapy may induce white matter changes in the frontal lobe. This remodeling of frontal connections within mood regulation networks positively contributes to the "top-down" mechanism of psychotherapy.

  2. White matter integrity in the vicinity of Broca's area predicts grammar learning success.

    Science.gov (United States)

    Flöel, Agnes; de Vries, Meinou H; Scholz, Jan; Breitenstein, Caterina; Johansen-Berg, Heidi

    2009-10-01

    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 involved in both natural and artificial language processing. Twelve young, right-handed individuals completed an artificial grammar learning task, and DTI of their brains were acquired. Inter-individual variability in performance correlated with white matter integrity (increasing fractional anisotropy (FA)) in fibres arising from Broca's area (left BA 44/45), but not from its right-hemispheric homologue. Variability in performance based on superficial familiarity did not show this association. Moreover, when Broca's area was used as a seed mask for probabilistic tractography, we found that mean FA values within the generated tracts was higher in subjects with better grammar learning. Our findings provide the first evidence that integrity of white matter fibre tracts arising from Broca's area is intimately linked with the ability to extract grammatical rules. The relevance of these findings for acquisition of a natural language has to be established in future studies.

  3. White matter volume mediates the relationship between self-efficacy and mobility in older women

    Science.gov (United States)

    Nagamatsu, Lindsay S.; Hsu, Chun Liang; Davis, Jennifer C.; Best, John R.; Liu-Ambrose, Teresa

    2017-01-01

    Background With our aging population, understanding determinants of healthy aging is a priority. One essential component of healthy aging is mobility. While self-efficacy can directly impact mobility in older adults, it is unknown what role brain health may play in this relationship. Methods We conducted a cross-sectional pilot analysis of community-dwelling women (n = 80, mean age = 69 years) to examine whether brain volume mediates the relationship between falls-related self-efficacy, as measured by the Activities-specific Balance Confidence (ABC) scale, and mobility, as measured by the Timed Up and Go (TUG) test. Age, depression, education, functional comorbidities, and Montreal Cognitive Assessment (MoCA) were included in the model as covariates. Results We report that total white matter volume, specifically, significantly mediates the relationship between self-efficacy and mobility, where higher self-efficacy was associated with greater white matter volume (r=0.28), which in turn, was associated with better mobility (r=−0.30). Conclusions Our pilot study extends our understanding of the psychosocial and neurological factors that contribute to mobility, and provides insight into effective strategies that may be used to improve functional independence among older adults. Future prospective and intervention studies are required to further elucidate the nature of the relationship between self-efficacy, mobility, and brain health. PMID:27749206

  4. White matter changes in 80 mild cognitive impairment patients using magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    Hyun Cho; Jee-Hyun Kwon; Sun-Young Kim

    2009-01-01

    BACKGROUND: Many studies have suggested that one possible etiology of mild cognitive impairment is small vessel cerebrovascular disease, which is associated with small subcortical infarcts and white matter abnormalities. These white matter changes have been detected as white matter hyperintensity (WMH) using magnetic resonance imaging. WMH may be associated with frontal lobe dysfunction. OBJECTIVE: To examine white matter changes in mild cognitive impairment patients of different subtypes, and to evaluate the correlation between white matter changes and neuropsychological characteristics, demographic information, vascular risk factors, and mild cognitive impairment subtypes. DESIGN, TIME AND SETTING: The neurophysiological, comparison study was performed at the Department of Neurology Memory Clinic, Ulsan University Hospital, South Korea, between March 2007 and March 2008.PARTICIPANTS: Out of a total of 83 subjects with clinically diagnosed mild cognitive impairment at the out-patient clinic, 3 subjects with severe WMH were excluded. A total of 80 subjects were included in this study. No patients suffered from cognitive impairment induced by neurological diseases, mental disorders, or somatic diseases. In accordance with magnetic resonance imaging results, the patients were assigned to two subtypes: 56 subjects without WMH and 24 subjects with WMH. METHODS: All patients were subjected to a standard neuropsychological battery using the Korean version of the Mini-Mental State Examination, Clinical Dementia Rating, and comprehensive Seoul Neuropsychological Screening Battery. The Clinical Dementia Rating reflected general cognitive function of patients. Results from the Seoul Neuropsychological Screening Battery reflected attention, language function, visuospatial function, verbal memory, nonverbal memory, long-term memory, and frontal/executive function. Magnetic resonance imaging was used to map changes in the brain. MAIN OUTCOME MEASURES: The association between

  5. Cerebral white matter in early puberty is associated with luteinizing hormone concentrations.

    Science.gov (United States)

    Peper, Jiska S; Brouwer, Rachel M; Schnack, Hugo G; van Baal, G Caroline M; van Leeuwen, Marieke; van den Berg, Stéphanie M; Delemarre-Van de Waal, Henriëtte A; Janke, Andrew L; Collins, D Louis; Evans, Alan C; Boomsma, Dorret I; Kahn, René S; Hulshoff Pol, Hilleke E

    2008-08-01

    Puberty is a period in which cerebral white matter grows considerably, whereas gray matter decreases. The first endocrinological marker of puberty in both boys and girls is an increased secretion of luteinizing hormone (LH). Here we investigated the phenotypic association between LH, global and focal gray and white matter in 104 healthy nine-year-old monozygotic and dizygotic twins. Volumetric MRI and voxel-based morphometry were applied to measure global gray and white matter and to estimate relative concentrations of regional cerebral gray and white matter, respectively. A possible common genetic origin of this association (genetic correlation) was examined. Results showed that higher LH levels are associated with a larger global white matter proportion and with higher regional white matter density. Areas of increased white matter density included the cingulum, middle temporal gyrus and splenium of the corpus callosum. No association between LH and global gray matter proportion or regional gray matter density was found. Our data indicate that a common genetic factor underlies the association between LH level and regional white matter density. We suggest that the increase of white matter growth during puberty reported earlier might be directly or indirectly mediated by LH production. In addition, genes involved in LH production may be promising candidate genes in neuropsychiatric illnesses with an onset in early adolescence.

  6. Ontogeny of AMPA and NMDA receptor gene expression in the developing sheep white matter and cerebral cortex.

    Science.gov (United States)

    Dean, Justin M; Fraser, Mhoyra; Shelling, Andrew N; Bennet, Laura; George, Sherly; Shaikh, Shamim; Scheepens, Arjan; Gunn, Alistair J

    2005-10-03

    This study examined the hypothesis that the high prevalence of white matter injury in premature infants is associated with increased expression of calcium-permeable forms of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype of glutamate receptors in pre-myelinating white matter. We characterized expression of subunits of the AMPA, and for reference, the N-methyl-d-aspartate (NMDA), glutamate receptors at 0.5, 0.65, 0.85, and term gestation in the ovine fetal white matter and cerebral cortex. There was a low expression of the critical calcium-impermeable AMPA receptor GluR2 subunit in subcortical white matter both absolutely and relative to other AMPA subunits throughout gestation. In contrast, GluR2 subunit mRNA expression fell in the cerebral cortex with increasing gestation whereas protein expression increased. These findings suggest a vulnerability of subcortical white matter to AMPA receptor-mediated calcium toxicity throughout the second half of gestation. Thus, the hypothesis that AMPA receptor-mediated glutamate toxicity contributes to brain damage in premature infants needs to be revised.

  7. Development of superficial white matter and its structural interplay with cortical gray matter in children and adolescents.

    Science.gov (United States)

    Wu, Minjie; Lu, Lisa H; Lowes, Allison; Yang, Shaolin; Passarotti, Alessandra M; Zhou, Xiaohong J; Pavuluri, Mani N

    2014-06-01

    Healthy human brain undergoes significant changes during development. The developmental trajectory of superficial white matter (SWM) is less understood relative to cortical gray matter (GM) and deep white matter. In this study, a multimodal imaging strategy was applied to vertexwise map SWM microstructure and cortical thickness to characterize their developmental pattern and elucidate SWM-GM associations in children and adolescents. Microscopic changes in SWM were evaluated with water diffusion parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in 133 healthy subjects aged 10-18 years. Results demonstrated distinct maturational patterns in SWM and GM. SWM showed increasing FA and decreasing MD and RD underneath bilateral motor sensory cortices and superior temporal auditory cortex, suggesting increasing myelination. A second developmental pattern in SWM was increasing FA and AD in bilateral orbitofrontal regions and insula, suggesting improved axonal coherence. These SWM patterns diverge from the more widespread GM maturation, suggesting that cortical thickness changes in adolescence are not explained by the encroachment of SWM myelin into the GM-WM boundary. Interestingly, age-independent intrinsic association between SWM and cortical GM seems to follow functional organization of polymodal and unimodal brain regions. Unimodal sensory areas showed positive correlation between GM thickness and FA whereas polymodal regions showed negative correlation. Axonal coherence and differences in interstitial neuron composition between unimodal and polymodal regions may account for these SWM-GM association patterns. Intrinsic SWM-GM relationships unveiled by neuroimaging in vivo can be useful for examining psychiatric disorders with known WM/GM disturbances.

  8. Cryptococcal meningitis accompanying lymphocytic inflammation predominantly in cerebral deep white matter: a possible manifestation of immune reconstitution inflammatory syndrome.

    Science.gov (United States)

    Kuwahara, Hiroya; Tsuchiya, Kuniaki; Kobayashi, Zen; Inaba, Akira; Akiyama, Haruhiko; Mizusawa, Hidehiro

    2014-02-01

    Cryptococcal meningitis is rarely complicated by immune-mediated leukoencephalopathy, but the precise pathomechanism is uncertain. A 72-year-old Japanese man treated with prednisolone for Sweet disease developed a subacute progression of meningitis, which was considered as neuro-Sweet disease. A treatment by methylprednisolone rapidly improved CSF findings with a remarkable decrease in lymphocyte numbers in the blood, but the patient's consciousness still worsened after the cessation of the treatment. The patient developed cryptococcal meningitis and MRI showed abnormal intensities predominantly in the cerebral deep white matter along with the recovery of lymphocyte numbers in the blood, which resulted in death. A postmortem examination of the brain revealed degenerative lesions, especially at the cerebral white matter and cortex adjacent to the leptomeninges abundantly infiltrated by Cryptococcus neoformans. In the affected cerebral deep white matter, perivascular infiltration of lymphocytes was prominent in coexistence with reactive astrocytes and vascular proliferation, but these findings were not observed in the subcortical and cortical lesions. Cryptococcus neoformans was not present within the brain parenchyma. This is the first report of a case suggesting that cryptococcal meningitis can accompany lymphocytic inflammation predominantly in cerebral deep white matter as a possible manifestation of immune reconstitution inflammatory syndrome.

  9. Recreational marijuana use impacts white matter integrity and subcortical (but not cortical morphometry

    Directory of Open Access Journals (Sweden)

    Joseph M. Orr

    2016-01-01

    Full Text Available A recent shift in legal and social attitudes toward marijuana use has also spawned a surge of interest in understanding the effects of marijuana use on the brain. There is considerable evidence that an adolescent onset of marijuana use negatively impacts white matter coherence. On the other hand, a recent well-controlled study demonstrated no effects of marijuana use on the morphometry of subcortical or cortical structures when users and non-users were matched for alcohol use. Regardless, most studies have involved small, carefully selected samples, so the ability to generalize to larger populations is limited. In an attempt to address this issue, we examined the effects of marijuana use on white matter integrity and cortical and subcortical morphometry using data from the Human Connectome Project (HCP consortium. The HCP data consists of ultra-high resolution neuroimaging data from a large community sample, including 466 adults reporting recreational marijuana use. Rather than just contrasting two groups of individuals who vary significantly in marijuana usage as typifies prior studies, we leveraged the large sample size provided by the HCP data to examine parametric effects of recreational marijuana use. Our results indicate that the earlier the age of onset of marijuana use, the lower was white matter coherence. Age of onset also also affected the shape of the accumbens, while the number of lifetime uses impacted the shape of the amygdala and hippocampus. Marijuana use had no effect on cortical volumes. These findings suggest subtle but significant effects of recreational marijuana use on brain structure.

  10. Increased white matter neuron density in a rat model of maternal immune activation - Implications for schizophrenia.

    Science.gov (United States)

    Duchatel, Ryan J; Jobling, Phillip; Graham, Brett A; Harms, Lauren R; Michie, Patricia T; Hodgson, Deborah M; Tooney, Paul A

    2016-02-01

    Interstitial neurons are located among white matter tracts of the human and rodent brain. Post-mortem studies have identified increased interstitial white matter neuron (IWMN) density in the fibre tracts below the cortex in people with schizophrenia. The current study assesses IWMN pathology in a model of maternal immune activation (MIA); a risk factor for schizophrenia. Experimental MIA was produced by an injection of polyinosinic:polycytidylic acid (PolyI:C) into pregnant rats on gestational day (GD) 10 or GD19. A separate control group received saline injections. The density of neuronal nuclear antigen (NeuN(+)) and somatostatin (SST(+)) IWMNs was determined in the white matter of the corpus callosum in two rostrocaudally adjacent areas in the 12week old offspring of GD10 (n=10) or GD19 polyI:C dams (n=18) compared to controls (n=20). NeuN(+) IWMN density trended to be higher in offspring from dams exposed to polyI:C at GD19, but not GD10. A subpopulation of these NeuN(+) IWMNs was shown to express SST. PolyI:C treatment of dams induced a significant increase in the density of SST(+) IWMNs in the offspring when delivered at both gestational stages with more regionally widespread effects observed at GD19. A positive correlation was observed between NeuN(+) and SST(+) IWMN density in animals exposed to polyI:C at GD19, but not controls. This is the first study to show that MIA increases IWMN density in adult offspring in a similar manner to that seen in the brain in schizophrenia. This suggests the MIA model will be useful in future studies aimed at probing the relationship between IWMNs and schizophrenia.

  11. Statistical estimation of white matter microstructure from conventional MRI

    Directory of Open Access Journals (Sweden)

    Leah H Suttner

    2016-01-01

    Full Text Available Diffusion tensor imaging (DTI has become the predominant modality for studying white matter integrity in multiple sclerosis (MS and other neurological disorders. Unfortunately, the use of DTI-based biomarkers in large multi-center studies is hindered by systematic biases that confound the study of disease-related changes. Furthermore, the site-to-site variability in multi-center studies is significantly higher for DTI than that for conventional MRI-based markers. In our study, we apply the Quantitative MR Estimation Employing Normalization (QuEEN model to estimate the four DTI measures: MD, FA, RD, and AD. QuEEN uses a voxel-wise generalized additive regression model to relate the normalized intensities of one or more conventional MRI modalities to a quantitative modality, such as DTI. We assess the accuracy of the models by comparing the prediction error of estimated DTI images to the scan-rescan error in subjects with two sets of scans. Across the four DTI measures, the performance of the models is not consistent: Both MD and RD estimations appear to be quite accurate, while AD estimation is less accurate than MD and RD; the accuracy of FA estimation is poor. Thus, in some cases when assessing white matter integrity, it may be sufficient to acquire conventional MRI sequences alone.

  12. White matter abnormalities revealed by DTI correlate with interictal grey matter FDG-PET metabolism in focal childhood epilepsies.

    Science.gov (United States)

    Lippé, Sarah; Poupon, Cyril; Cachia, Arnaud; Archambaud, Frédérique; Rodrigo, Sébastian; Dorfmuller, Georg; Chiron, Catherine; Hertz-Pannier, Lucie

    2012-12-01

    For patients with focal epilepsy scheduled for surgery, including MRI-negative cases, (18)FDG-PET was shown to disclose hypometabolism in the seizure onset zone. However, it is not clear whether grey matter hypometabolism is informative of the integrity of the surrounding white matter cerebral tissue. In order to study the relationship between metabolism of the seizure onset zone grey matter and the integrity of the surrounding white matter measured by diffusion tensor imaging (DTI), we performed a monocentric prospective study (from 2006 to 2009) in 15 children with pharmacoresistant focal epilepsy, suitable for interictal (18)FDG-PET, T1-, T2-, FLAIR sequence MRI and DTI. Children had either positive or negative MRI (eight with symptomatic and seven with cryptogenic epilepsies, respectively). Seven children subsequently underwent surgery. Standardised uptake values of grey matter PET metabolism were compared with DTI indices (fractional anisotropy [FA], apparent diffusion coefficient [ADC], parallel diffusion coefficient [PDC], and transverse diffusion coefficient [TDC]) in grey matter within the seizure onset zone and adjacent white matter, using regions of interest automatically drawn from individual sulcal and gyral parcellation. Hypometabolism correlated positively with white matter ADC, PDC, and TDC, and negatively with white matter FA. In the cryptogenic group of children, hypometabolism correlated positively with white matter ADC. Our results demonstrate a relationship between abnormalities of grey matter metabolism in the seizure onset zone and adjacent white matter structural alterations in childhood focal epilepsies, even in cryptogenic epilepsy. This relationship supports the hypothesis that microstructural alterations of the white matter are related to epileptic networks and has potential implications for the evaluation of children with MRI-negative epilepsy.

  13. Finite Element Modeling of CNS White Matter Kinematics: Use of a 3D-RVE to Determine Material Properties

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    Yi ePan

    2013-12-01

    Full Text Available Axonal injury represents a critical target area for the prevention and treatment of traumatic brain and spinal cord injuries. Finite element (FE models of the head and/or brain are often used to predict brain injury caused by external mechanical loadings, such as explosive waves and direct impact. The accuracy of these numerical models depends on correctly determining the material properties and on the precise depiction of the tissues’ microstructure (microscopic level. Moreover, since the axonal microstructure for specific regions of the brain white matter is locally oriented, the stress and strain fields are highly anisotropic and axon orientation dependent. Additionally, mechanical strain has been identified as the proximal cause of axonal injury, which further demonstrates the importance of this multi-scale relationship. In this study, our previously developed FE and kinematic axonal models are coupled and applied to a pseudo 3-dimensional representative volume element (RVE of central nervous system white matter to investigate the multi-scale mechanical behavior. An inverse FE procedure was developed to identify material parameters of spinal cord white matter by combining the results of uniaxial testing with FE modeling. A satisfactory balance between simulation and experiment was achieved via optimization by minimizing the squared error between the simulated and experimental force-stretch curve. The combination of experimental testing and FE analysis provides a useful analysis tool for soft biological tissues in general, and specifically enables evaluations of the axonal response to tissue-level loading and subsequent predictions of axonal damage.

  14. White dwarfs, red dwarfs and halo dark matter

    Energy Technology Data Exchange (ETDEWEB)

    GarcIa-Berro, E; Torres, S; Camacho, J [Departament de Fisica Aplicada, Escola Politecnica Superior de Castelldefels, Universitat Politecnica de Catalunya, Av. del Canal Olimpic, s/n, 08860 Castelldefels (Spain); Isern, J, E-mail: garcia@fa.upc.ed [Institut de Ciencies de l' Espai, CSIC, Campus UAB, Facultat de Ciencies, Torre C-5, 08193 Bellaterra (Spain)

    2009-06-01

    The nature of the microlensing events observed by the MACHO team towards the LMC still remains controversial. Low-mass substellar objects and stars with masses larger than approx 1M{sub o-dot} have been ruled out, while stars of approx 0.5 M{sub o-dot} are the most probable candidates. This means that the microlenses should be either red or white dwarfs. Consequently, we assess jointly the relative contributions of both types of stars to the mass budget of the Galactic halo. We use a Monte Carlo code that incorporates up-to-date evolutionary sequences of both red dwarfs and white dwarfs as well as detailed descriptions of both our Galaxy and the LMC and we compare the synthetic populations obtained with our simulator with the results obtained by the MACHO and EROS experiments. We find that the contribution of the red dwarf population is not enough to explain the number of events measured by the MACHO team. Even though, the optical depth obtained in our simulations almost doubles that obtained when taking into account the white dwarf population alone. Finally, we also find that the contribution to the halo dark matter of the entire population under study is smaller than 10%, at the 95% confidence level.

  15. Mapping topographic structure in white matter pathways with level set trees.

    Directory of Open Access Journals (Sweden)

    Brian P Kent

    Full Text Available Fiber tractography on diffusion imaging data offers rich potential for describing white matter pathways in the human brain, but characterizing the spatial organization in these large and complex data sets remains a challenge. We show that level set trees--which provide a concise representation of the hierarchical mode structure of probability density functions--offer a statistically-principled framework for visualizing and analyzing topography in fiber streamlines. Using diffusion spectrum imaging data collected on neurologically healthy controls (N = 30, we mapped white matter pathways from the cortex into the striatum using a deterministic tractography algorithm that estimates fiber bundles as dimensionless streamlines. Level set trees were used for interactive exploration of patterns in the endpoint distributions of the mapped fiber pathways and an efficient segmentation of the pathways that had empirical accuracy comparable to standard nonparametric clustering techniques. We show that level set trees can also be generalized to model pseudo-density functions in order to analyze a broader array of data types, including entire fiber streamlines. Finally, resampling methods show the reliability of the level set tree as a descriptive measure of topographic structure, illustrating its potential as a statistical descriptor in brain imaging analysis. These results highlight the broad applicability of level set trees for visualizing and analyzing high-dimensional data like fiber tractography output.

  16. Accelerated maturation of white matter in young children with autism: a high b value DWI study.

    Science.gov (United States)

    Ben Bashat, Dafna; Kronfeld-Duenias, Vered; Zachor, Ditza A; Ekstein, Perla M; Hendler, Talma; Tarrasch, Ricardo; Even, Ariela; Levy, Yonata; Ben Sira, Liat

    2007-08-01

    The goal of this work was to study white matter maturation in young children with autism following previous reports of increased cerebral volume during early development, as well as arguments for abnormal neural growth patterns and regulation at this critical developmental period. We applied diffusion tensor imaging (DTI) and high b value diffusion-weighted imaging (DWI) to young children diagnosed with autism and to a typically developing (TD) control group. Fractional anisotropy (FA), probability and displacement were measured in overall analysis as well as in regions of interest (ROI). Individual data points of children with autism were compared to the developmental curves obtained from typically developing children. Increased restriction, reflected in significantly increased FA and probability along with reduced displacement values, was detected in overall analysis as well as in several brain regions. Increased restriction, suggesting an early and accelerated abnormal maturation of white matter, was more dominant in the left hemisphere and was mainly detected in the frontal lobe. No changes were detected in the occipital lobes. These results support previous claims of abnormal brain overgrowth in young children with autism and are in contrast to the decreased restricted diffusion reported in previous studies in adolescent with autism.

  17. Progressive white matter changes following anterior temporal lobe resection for epilepsy ☆

    OpenAIRE

    Winston, Gavin P.; Jason Stretton; Sidhu, Meneka K; Symms, Mark R.; Duncan, John S.

    2013-01-01

    Anterior temporal lobe resection (ATLR) is an effective treatment for refractory temporal lobe epilepsy (TLE). Widespread abnormalities in diffusion parameters involving the ipsilateral temporal lobe white matter and extending into extratemporal white matter have been shown in cross-sectional studies in TLE. However longitudinal changes following surgery have been less well addressed. We systematically assess diffusion changes in white matter in patients with TLE in comparison to controls bef...

  18. White matter biomarkers from fast protocols using axially symmetric diffusion kurtosis imaging

    CERN Document Server

    Hansen, Brian; Shemesh, Noam; Lund, Torben E; Sangill, Ryan; Østergaard, Leif; Jespersen, Sune N

    2016-01-01

    White matter tract integrity (WMTI) can be used to characterize tissue microstructure in areas with axisymmetric fiber bundles. Several WMTI biomarkers have now been validated against microscopy and provided promising results in studies of brain development and aging, as well as in a number of brain disorders. In a clinical setting, however, the diffusion kurtosis imaging (DKI) protocol utilized as part of WMTI imaging may be prohibitively long. Consequently, the diagnostic value of the WMTI parameters is rarely explored outside of dedicated animal studies and clinical studies of slowly progressing diseases. Here, we evaluate WMTI based on recently introduced axially symmetric DKI which has lower data demand than conventional DKI. We compare WMTI parameters derived from conventional DKI to those from axially symmetric DKI and to parameters calculated analytically from the axially symmetric tensors. We also assess the effect of the imposed symmetry on the kurtosis fractional anisotropy (KFA). We employ numeric...

  19. Graph Theoretical Analysis of Developmental Patterns of the White Matter Network

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    Zhang eChen

    2013-11-01

    Full Text Available 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

  20. The axon-glia unit in white matter stroke: mechanisms of damage and recovery.

    Science.gov (United States)

    Rosenzweig, Shira; Carmichael, S Thomas

    2015-10-14

    Approximately one quarter of all strokes in humans occur in white matter, and the progressive nature of white matter lesions often results in severe physical and mental disability. Unlike cortical grey matter stroke, the pathology of white matter stroke revolves around disrupted connectivity and injured axons and glial cells, rather than neuronal cell bodies. Consequently, the mechanisms behind ischemic damage to white matter elements, the regenerative responses of glial cells and their signaling pathways, all differ significantly from those in grey matter. Development of effective therapies for white matter stroke would require an enhanced understanding of the complex cellular and molecular interactions within the white matter, leading to the identification of new therapeutic targets. This review will address the unique properties of the axon-glia unit during white matter stroke, describe the challenging process of promoting effective white matter repair, and discuss recently-identified signaling pathways which may hold potential targets for repair in this disease. This article is part of a Special Issue entitled SI: Cell Interactions In Stroke.

  1. Moderate Physical Activity Mediates the Association between White Matter Lesion Volume and Memory Recall in Breast Cancer Survivors.

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    Gillian E Cooke

    Full Text Available Increased survival rates among breast cancer patients have drawn significant attention to consequences of both the presence of cancer, and the subsequent treatment-related impact on the brain. The incidence of breast cancer and the effects of treatment often result in alterations in the microstructure of white matter and impaired cognitive functioning. However, physical activity is proving to be a successful modifiable lifestyle factor in many studies that could prove beneficial to breast cancer survivors. This study investigates the link between white matter lesion volume, moderate physical activity, and cognition in breast cancer survivors following treatment compared to non-cancer age-matched controls. Results revealed that brain structure significantly predicted cognitive function via mediation of physical activity in breast cancer survivors. Overall, the study provided preliminary evidence suggesting moderate physical activity may help reduce the treatment related risks associated with breast cancer, including changes to WM integrity and cognitive impairment.

  2. Multi-scale characterization of white matter tract geometry.

    Science.gov (United States)

    Savadjiev, Peter; Rathi, Yogesh; Bouix, Sylvain; Verma, Ragini; Westin, Carl-Fredrik

    2012-01-01

    The geometry of white matter tracts is of increased interest for a variety of neuroscientific investigations, as it is a feature reflective of normal neurodevelopment and disease factors that may affect it. In this paper, we introduce a novel method for computing multi-scale fibre tract shape and geometry based on the differential geometry of curve sets. By measuring the variation of a curve's tangent vector at a given point in all directions orthogonal to the curve, we obtain a 2D "dispersion distribution function" at that point. That is, we compute a function on the unit circle which describes fibre dispersion, or fanning, along each direction on the circle. Our formulation is then easily incorporated into a continuous scale-space framework. We illustrate our method on different fibre tracts and apply it to a population study on hemispheric lateralization in healthy controls. We conclude with directions for future work.

  3. Combination BMSC and Niaspan Treatment of Stroke Enhances White Matter Remodeling and Synaptic Protein Expression in Diabetic Rats

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    Cynthia Roberts

    2013-11-01

    Full Text Available Objective: White matter remodeling plays an important role in neurological recovery after stroke. Bone marrow stromal cells (BMSCs and Niaspan, an agent which increases high density lipoprotein (HDL, each induces neurorestorative effects and promotes white matter remodeling after stroke in non-diabetic rats. In this study, we test whether combination of BMSCs with Niaspan induces an enhanced white matter remodeling in the ischemic brain of diabetic rats. Research design and methods: Type-1 diabetes (T1DM rats were subjected to transient middle cerebral artery occlusion (MCAo and treated with or without BMSCs; Niaspan; and the combination of BMSCs + Niaspan daily for 14 days after MCAo. Immunostaining for white matter remodeling and synaptic protein expression including NG2; CNPase; BS (Bielschowsky silver; LFB (luxol fast blue; Synaptophysin and SMI-31 immunostaining were performed. Results: BMSC monotherapy did not regulate NG2 and CNPase expression compared to T1DM control rats. Both, combination of BMSCs + Niaspan treatment, and Niaspan monotherapy significantly increase NG2 and CNPase expression compared to T1DM control. While combination BMSC+Niaspan, BMSC monotherapy and Niaspan monotherapy groups all increase BS, LFB, synaptophysin, and SMI-31 expression in the ischemic brain compared to T1DM-MCAo control. In addition, the combination treatment significantly enhances LFB, SMI-31, and Synaptophysin expression compared to BMSC monotherapy. Conclusions: Combination treatment of stroke with BMSCs and Niaspan in T1DM rats increases white matter remodeling and additively increases BMSC monotherapy induced myelination and synaptic plasticity after stroke in T1DM rats.

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

    Directory of Open Access Journals (Sweden)

    Samuel Neal Lockhart

    2012-03-01

    Full Text Available Previous neuroimaging research indicates that white matter injury and integrity, measured respectively by white matter hyperintensities (WMH and fractional anisotropy (FA obtained from diffusion tensor imaging, differ with aging and cerebrovascular disease and are associated with episodic memory deficits in cognitively normal older adults. However, knowledge about tract-specific relationships between