WorldWideScience

Sample records for altered white matter

  1. 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.

  2. White matter alterations in neurodegenerative and vascular dementia; Marklagerveraenderungen bei neurodegenerativen und vaskulaeren Demenzerkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Supprian, T. [Arbeitsgruppe Gerontopsychiatrie, Universitaets-Nervenklinik Homburg (Germany); Arbeitsgruppe Gerontopsychiatrie, Universitaets-Nervenklinik, Psychiatrie und Psychotherapie, 66421, Homburg (Germany); Kessler, H.; Falkai, P. [Arbeitsgruppe Gerontopsychiatrie, Universitaets-Nervenklinik Homburg (Germany); Retz, W.; Roesler, M. [Arbeitsgruppe Gerontopsychiatrie, Universitaets-Nervenklinik Homburg (Germany); Institut fuer gerichtliche Psychologie und Psychiatrie, Universitaet des Saarlandes, Homburg (Germany); Grunwald, I.; Reith, W. [Abteilung fuer Neuroradiologie, Universitaetskliniken des Saarlandes, Homburg (Germany)

    2003-07-01

    Due to a significant overlap of the two syndromes, differentiation of degenerative dementia of the Alzheimer-type from vascular dementia may be difficult even when imaging studies are available. White matter changes occur in many patients suffering from Alzheimer's disease. Little is known about the impact of white matter changes on the course and clinical presentation of Alzheimer's disease. High sensitivity of MRI in the detection of white matter alterations may account for over-diagnosing vascular dementia. The clinical significance of white matter alterations in dementia is still a matter of debate. The article reviews current concepts about the role of white matter alterations in dementia. (orig.) [German] Die Zuordnung einer Demenzerkrankung zu einem neurodegenerativen Pathomechanismus, wie der Demenz vom Alzheimer-Typ (DAT) oder einem vaskulaeren Pathomechanismus, kann trotz der Verfuegbarkeit bildgebender Verfahren Probleme bereiten. Ueberlappungen neurodegenerativer und vaskulaerer Mechanismen sind haeufig. Mikroangiopathische Veraenderungen des Marklagers finden sich bei einem hohen Anteil von Patienten mit der klinischen Verlaufsform einer Demenz vom Alzheimer-Typ. Es ist unklar, ob es sich um eine Koinzidenz zweier Pathomechanismen handelt oder ob eine wechselseitige Beeinflussung stattfindet. Die hohe Sensitivitaet der Magnetresonanztomographie bei der Erfassung mikroangiopathischer Veraenderungen des Marklagers koennte dazu fuehren, dass zu vaskulaere Demenzerkrankungen haeufig diagnostiziert werden. Der Einfluss mikroangiopathischer Veraenderungen des Marklagers auf den Demenzverlauf wird kontrovers diskutiert. Die vorgelegte Arbeit gibt eine Uebersicht ueber die aktuellen Konzepte zum Stellenwert von Marklagerveraenderungen bei Demenzerkrankungen. (orig.)

  3. Experience-dependent plasticity in white matter microstructure: Reasoning training alters structural connectivity

    Directory of Open Access Journals (Sweden)

    Allyson P Mackey

    2012-08-01

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

  4. 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.

  5. 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

  6. 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

  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. Alterations of white matter integrity related to the season of birth in schizophrenia: a DTI study.

    Directory of Open Access Journals (Sweden)

    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.

  9. 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.

  10. 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

  11. 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.

  12. Extensive and interrelated subcortical white and gray matter alterations in preterm-born adults.

    Science.gov (United States)

    Meng, C; Bäuml, J G; Daamen, M; Jaekel, J; Neitzel, J; Scheef, L; Busch, B; Baumann, N; Boecker, H; Zimmer, C; Bartmann, P; Wolke, D; Wohlschläger, A M; Sorg, Christian

    2016-05-01

    Preterm birth is a leading cause for impaired neurocognitive development with an increased risk for persistent cognitive deficits in adulthood. In newborns, preterm birth is associated with interrelated white matter (WM) alterations and deep gray matter (GM) loss; however, little is known about the persistence and relevance of these subcortical brain changes. We tested the hypothesis that the pattern of correspondent subcortical WM and GM changes is present in preterm-born adults and has a brain-injury-like nature, i.e., it predicts lowered general cognitive performance. Eighty-five preterm-born and 69 matched term-born adults were assessed by diffusion- and T1-weighted MRI and cognitive testing. Main outcome measures were fractional anisotropy of water diffusion for WM property, GM volume for GM property, and full-scale IQ for cognitive performance. In preterm-born adults, reduced fractional anisotropy was widely distributed ranging from cerebellum to brainstem to hemispheres. GM volume was reduced in the thalamus, striatum, temporal cortices, and increased in the cingulate cortices. Fractional anisotropy reductions were specifically associated with GM loss in thalamus and striatum, with correlation patterns for both regions extensively overlapping in the WM of brainstem and hemispheres. For overlap regions, fractional anisotropy was positively related with both gestational age and full-scale IQ. Results provide evidence for extensive, interrelated, and adverse WM and GM subcortical changes in preterm-born adults. Data suggest persistent brain-injury-like changes of subcortical-cortical connectivity after preterm delivery.

  13. Schizophrenia Patients Demonstrate Both Inter-Voxel Level and Intra-Voxel Level White Matter Alterations.

    Science.gov (United States)

    Zhuo, Chuanjun; Ma, Xiaolei; Qu, Hongru; Wang, Lina; Jia, Feng; Wang, Chunli

    2016-01-01

    Fractional anisotropy (FA) and mean diffusivity (MD) are the most frequently used metrics to investigate white matter impairments in mental disorders. However, these two metrics are derived from intra-voxel analyses and only reflect the diffusion properties solely within the voxel unit. Local diffusion homogeneity (LDH) is a newly developed inter-voxel metric which quantifies the local coherence of water molecule diffusion in a model-free manner. In this study, 94 schizophrenia patients and 91 sex- and age-matched healthy controls underwent diffusion tensor imaging (DTI) examinations. White matter integrity was assessed by FA, MD and LDH. Group differences in these metrics were compared using tract-based spatial statistics (TBSS). Compared with healthy controls, schizophrenia patients exhibited reduced FA and increased MD in the corpus callosum, cingulum, internal capsule, fornix and widespread superficial white matter in the frontal, parietal, occipital and temporal lobes. We also found decreased LDH in the corpus callosum, cingulum, internal capsule and fornix in schizophrenia. Our findings suggest that both intra-voxel and inter-voxel diffusion metrics are able to detect impairments in the anisotropic white matter regions, and intra-voxel diffusion metrics could detect additional impairments in the widespread isotropic white matter regions in schizophrenia.

  14. White matter alterations associated with suicide in patients with schizophrenia or schizophreniform disorder.

    Science.gov (United States)

    Lee, Sung-Jae; Kim, Borah; Oh, Daeyoung; Kim, Min-Kyoung; Kim, Keun-Hyang; Bang, Seong Yun; Choi, Tai Kiu; Lee, Sang-Hyuk

    2016-02-28

    The risk of suicide is disproportionately high among people diagnosed with schizophrenia or schizophreniform disorder. Brain imaging studies have shown a few relationships between neuroanatomy and suicide. This study examines the relationship between alterations in brain white matter (WM) and suicidal behavior in people with schizophrenia or schizophreniform disorder. The study participants were 56 patients with schizophrenia or schizophreniform disorder, with (n=15) and without (n=41) a history of suicide attempts. Fractional anisotropy (FA) values were compared between suicide attempters and non-attempters using Tract-Based Spatial Statistics (TBSS). Attempters showed significantly higher FA values than non-attempters in the left corona radiata, the superior longitudinal fasciculus, the posterior limb and retrolenticular part of the internal capsule, the external capsule, the insula, the posterior thalamic radiation, the cerebral peduncle, the sagittal stratum, and temporal lobe WM. Scores of the picture arrangement test showed a significant positive correlation with FA values of the right corona radiata, the right superior longitudinal fasciculus, the body of the corpus callosum, and the left corona radiata in attempters but not in non-attempters. These findings suggest that fronto-temporo-limbic circuits can be associated mainly with suicidal behavior in people with schizophrenia or schizophreniform disorder.

  15. 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

  16. 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.

  17. Altered functional connectivity related to white matter changes inside the working memory network at the very early stage of MS.

    Science.gov (United States)

    Au Duong, My-Van; Audoin, Bertrand; Boulanouar, Kader; Ibarrola, Daniella; Malikova, Irina; Confort-Gouny, Sylrane; Celsis, Pierre; Pelletier, Jean; Cozzone, Patrick J; Ranjeva, Jean-Philippe

    2005-10-01

    Functional magnetic resonance imaging (fMRI) using paced auditory serial addition test (PASAT) as paradigm was used to study the functional connectivity in 18 patients at the very early stage of multiple sclerosis (MS) compared with 18 controls, to determine the existence of circuitry disturbance inside the working memory network and its relationship with white matter abnormalities assessed by conventional MRI and magnetization transfer ratio (MTR) imaging. The left BA 45/46 was selected as the seed region to compute correlation maps with other brain regions. After obtaining the correlation map for each subject, between-group comparisons were performed using random effect procedure. Compared with controls, patients did not show any greater functional connectivity between left BA 45/46 and other regions during PASAT. In contrast, decrease in functional connectivity was observed in patients between left BA 45/46 and left BA 9, right BA 3, and the anterior cingulate cortex (BA 24). In patients, no correlations were found between altered functional connectivity and clinical data. However, functional connectivity observed between left BA 45/46 and BA 24 in patients was correlated with the MTR of normal appearing white matter, and with brain T(2) lesion load. Altered functional connectivity is present inside the working memory network of patients at the very early stage of MS and is related to the extent of diffuse white matter changes.

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

    Directory of Open Access Journals (Sweden)

    Maria eJalbrzikowski

    2014-11-01

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

  19. Altered white matter and cortical structure in neonates with antenatally diagnosed isolated ventriculomegaly

    Directory of Open Access Journals (Sweden)

    G. Lockwood Estrin

    2016-01-01

    WM alterations in isolated VM cases may be consistent with abnormal development of WM tracts involved in language and cognition. Alterations in WM FA and MD may represent neural correlates for later neurodevelopmental deficits.

  20. 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

  1. Frontal white matter alterations in short-term medicated panic disorder patients without comorbid conditions: a diffusion tensor imaging study.

    Directory of Open Access Journals (Sweden)

    Borah Kim

    Full Text Available The frontal cortex might play an important role in the fear network, and white matter (WM integrity could be related to the pathophysiology of panic disorder (PD. A few studies have investigated alterations of WM integrity in PD. The aim of this study was to determine frontal WM integrity differences between patients with PD without comorbid conditions and healthy control (HC subjects by using diffusion tensor imaging. Thirty-six patients with PD who had used medication within 1 week and 27 age- and sex-matched HC subjects participated in this study. Structural brain magnetic resonance imaging was performed on all participants. Panic Disorder Severity Scale and Beck Anxiety Inventory (BAI scores were assessed. Tract-based spatial statistics (TBSS was used for image analysis. TBSS analysis showed decreased fractional anisotropy (FA in frontal WM and WM around the frontal lobe, including the corpus callosum of both hemispheres, in patients with PD compared to HC subjects. Moreover, voxel-wise correlation analysis revealed that the BAI scores for patients with PD were positively correlated with their FA values for regions showing group differences in the FA of frontal WM of both hemispheres. Altered integrity in frontal WM of patients with PD without comorbid conditions might represent the structural pathophysiology in these patients, and these changes could be related to clinical symptoms of PD.

  2. 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

  3. 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.

  4. 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...

  5. Alterations of the Cerebral White Matter in a Middle-Aged Patient with Turner Syndrome: An MRI Study

    Directory of Open Access Journals (Sweden)

    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.

  6. Alterations in white matter volume and its correlation with clinical characteristics in patients with generalized anxiety disorder

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Chung-Man [Chonnam National University Hospital, Research Institute for Medical Imaging, Gwangju (Korea, Republic of); Jeong, Gwang-Woo [Chonnam National University Hospital, Research Institute for Medical Imaging, Gwangju (Korea, Republic of); Chonnam National University Medical School, Department of Radiology, Chonnam National University Hospital, Gwangju (Korea, Republic of)

    2015-11-15

    Only a few morphological studies have focused on changes in white matter (WM) volume in patients with generalized anxiety disorder (GAD). We evaluated alterations in WM volume and its correlation with symptom severity and duration of illness in adults with GAD. The 44 subjects were comprised of 22 patients with GAD (13 males and nine females) diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) and 22 age-matched healthy controls (13 males and nine females). High-resolution magnetic resonance imaging (MRI) data were processed by voxel-based morphometry (VBM) analysis based on diffeomorphic anatomical registration using the exponentiated Lie algebra (DARTEL) algorithm in SPM8. Patients with GAD showed significantly reduced WM volume, particularly in the dorsolateral prefrontal cortex (DLPFC), anterior limb of the internal capsule (ALIC), and midbrain. In addition, DLPFC volume was negatively correlated with GAD-7 score and illness duration. ALIC volume was negatively correlated with GAD-7 score. Female patients had significantly less orbitofrontal cortex volume compared to that in male patients. The findings demonstrate localized changes in WM volume associated with cognitive and emotional dysfunction in patients with GAD. The finding will be helpful for understanding the neuropathology in patients with GAD. (orig.)

  7. 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.

  8. 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

  9. 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

  10. White matter alterations related to attention-deficit hyperactivity disorder and COMT val158met polymorphism: children with valine homozygote attention-deficit hyperactivity disorder have altered white matter connectivity in the right cingulum (cingulate gyrus

    Directory of Open Access Journals (Sweden)

    Kabukcu Basay B

    2016-04-01

    Full Text Available Burge Kabukcu Basay,1 Ahmet Buber,1 Omer Basay,1 Huseyin Alacam,2 Onder Ozturk,1 Serkan Suren,3 Ozlem Izci Ay,4 Cengizhan Acikel,5 Kadir Agladioglu,6 Mehmet Emin Erdal,4 Eyup Sabri Ercan,7 Hasan Herken21Child and Adolescent Psychiatry Department, Pamukkale University Medical Faculty, Denizli, 2Psychiatry Department, Pamukkale University Medical Faculty, Denizli, 3Medical Park Samsun Hospital, Samsun, 4Medical Biology and Genetics Department, Mersin University Medical Faculty, Mersin, 5Biostatistics Department, GATA (GMMA, Ankara, 6Radiology Department, Pamukkale University Medical Faculty, Denizli, 7Child and Adolescent Psychiatry Department, Ege University Medical Faculty, Izmir, TurkeyIntroduction: In this article, the COMT gene val158met polymorphism and attention-deficit hyperactivity disorder (ADHD-related differences in diffusion-tensor-imaging-measured white matter (WM structure in children with ADHD and controls were investigated.Patients and methods: A total of 71 children diagnosed with ADHD and 24 controls aged 8–15 years were recruited. Using diffusion tensor imaging, COMT polymorphism and ADHD-related WM alterations were investigated, and any interaction effect between the COMT polymorphism and ADHD was also examined. The effects of age, sex, and estimated total IQ were controlled by multivariate analysis of covariance (MANCOVA.Results: First, an interaction between the COMT val158met polymorphism and ADHD in the right (R cingulum (cingulate gyrus (CGC was found. According to this, valine (val homozygote ADHD-diagnosed children had significantly lower fractional anisotropy (FA and higher radial diffusivity (RD in the R-CGC than ADHD-diagnosed methionine (met carriers, and val homozygote controls had higher FA and lower RD in the R-CGC than val homozygote ADHD patients. Second, met carriers had higher FA and axial diffusivity in the left (L-uncinate fasciculus and lower RD in the L-posterior corona radiata and L

  11. White matter and behavioral neurology.

    Science.gov (United States)

    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.

  12. Diffuse alterations in grey and white matter associated with cognitive impairment in Shwachman–Diamond syndrome: Evidence from a multimodal approach

    Directory of Open Access Journals (Sweden)

    Sandra Perobelli

    2015-01-01

    Cognitive impairment in Shwachman–Diamond syndrome subjects is associated with diffuse brain anomalies in the grey matter (verbal skills with BA44 and BA20 in the right hemisphere; perceptual skills with BA5, 37, 20, 21, 42 in the left hemisphere and white matter connectivity (verbal skills with alterations in the fronto-occipital fasciculus and with the inferior-longitudinal fasciculus; perceptual skills with the arcuate fasciculus, limbic and ponto-cerebellar fasciculus; memory skills with the arcuate fasciculus; executive functions with the anterior cingulated and arcuate fasciculus.

  13. 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...

  14. Mild developmental foreign accent syndrome and psychiatric comorbidity: Altered white matter integrity in speech and emotion regulation networks

    Directory of Open Access Journals (Sweden)

    Marcelo L Berthier

    2016-08-01

    Full Text Available Foreign accent syndrome (FAS is a speech disorder that is defined by the emergence of a peculiar manner of articulation and intonation which is perceived as foreign. In most cases of acquired FAS (AFAS the new accent is secondary to small focal lesions involving components of the bilaterally distributed neural network for speech production. In the past few years FAS has also been described in different psychiatric conditions (conversion disorder, bipolar disorder, schizophrenia as well as in developmental disorders (specific language impairment, apraxia of speech. In the present study, two adult males, one with atypical phonetic production and the other one with cluttering, reported having developmental FAS (DFAS since their adolescence. Perceptual analysis by naïve judges could not confirm the presence of foreign accent, possibly due to the mildness of the speech disorder. However, detailed linguistic analysis provided evidence of prosodic and segmental errors previously reported in AFAS cases. Cognitive testing showed reduced communication in activities of daily living and mild deficits related to psychiatric disorders. Psychiatric evaluation revealed long-lasting internalizing disorders (neuroticism, anxiety, obsessive-compulsive disorder, social phobia, depression, alexithymia, hopelessness, and apathy in both subjects. Diffusion tensor imaging (DTI data from each subject with DFAS were compared with data from a group of 21 age- and gender-matched healthy control subjects. Diffusion parameters (MD, AD, and RD in predefined regions of interest showed changes of white matter microstructure in regions previously related with AFAS and psychiatric disorders. In conclusion, the present findings militate against the possibility that these two subjects have FAS of psychogenic origin. Rather, our findings provide evidence that mild DFAS occurring in the context of subtle, yet persistent, developmental speech disorders may be associated with

  15. Mild Developmental Foreign Accent Syndrome and Psychiatric Comorbidity: Altered White Matter Integrity in Speech and Emotion Regulation Networks

    Science.gov (United States)

    Berthier, Marcelo L.; Roé-Vellvé, Núria; Moreno-Torres, Ignacio; Falcon, Carles; Thurnhofer-Hemsi, Karl; Paredes-Pacheco, José; Torres-Prioris, María J.; De-Torres, Irene; Alfaro, Francisco; Gutiérrez-Cardo, Antonio L.; Baquero, Miquel; Ruiz-Cruces, Rafael; Dávila, Guadalupe

    2016-01-01

    Foreign accent syndrome (FAS) is a speech disorder that is defined by the emergence of a peculiar manner of articulation and intonation which is perceived as foreign. In most cases of acquired FAS (AFAS) the new accent is secondary to small focal lesions involving components of the bilaterally distributed neural network for speech production. In the past few years FAS has also been described in different psychiatric conditions (conversion disorder, bipolar disorder, and schizophrenia) as well as in developmental disorders (specific language impairment, apraxia of speech). In the present study, two adult males, one with atypical phonetic production and the other one with cluttering, reported having developmental FAS (DFAS) since their adolescence. Perceptual analysis by naïve judges could not confirm the presence of foreign accent, possibly due to the mildness of the speech disorder. However, detailed linguistic analysis provided evidence of prosodic and segmental errors previously reported in AFAS cases. Cognitive testing showed reduced communication in activities of daily living and mild deficits related to psychiatric disorders. Psychiatric evaluation revealed long-lasting internalizing disorders (neuroticism, anxiety, obsessive-compulsive disorder, social phobia, depression, alexithymia, hopelessness, and apathy) in both subjects. Diffusion tensor imaging (DTI) data from each subject with DFAS were compared with data from a group of 21 age- and gender-matched healthy control subjects. Diffusion parameters (MD, AD, and RD) in predefined regions of interest showed changes of white matter microstructure in regions previously related with AFAS and psychiatric disorders. In conclusion, the present findings militate against the possibility that these two subjects have FAS of psychogenic origin. Rather, our findings provide evidence that mild DFAS occurring in the context of subtle, yet persistent, developmental speech disorders may be associated with structural brain

  16. Mild Developmental Foreign Accent Syndrome and Psychiatric Comorbidity: Altered White Matter Integrity in Speech and Emotion Regulation Networks.

    Science.gov (United States)

    Berthier, Marcelo L; Roé-Vellvé, Núria; Moreno-Torres, Ignacio; Falcon, Carles; Thurnhofer-Hemsi, Karl; Paredes-Pacheco, José; Torres-Prioris, María J; De-Torres, Irene; Alfaro, Francisco; Gutiérrez-Cardo, Antonio L; Baquero, Miquel; Ruiz-Cruces, Rafael; Dávila, Guadalupe

    2016-01-01

    Foreign accent syndrome (FAS) is a speech disorder that is defined by the emergence of a peculiar manner of articulation and intonation which is perceived as foreign. In most cases of acquired FAS (AFAS) the new accent is secondary to small focal lesions involving components of the bilaterally distributed neural network for speech production. In the past few years FAS has also been described in different psychiatric conditions (conversion disorder, bipolar disorder, and schizophrenia) as well as in developmental disorders (specific language impairment, apraxia of speech). In the present study, two adult males, one with atypical phonetic production and the other one with cluttering, reported having developmental FAS (DFAS) since their adolescence. Perceptual analysis by naïve judges could not confirm the presence of foreign accent, possibly due to the mildness of the speech disorder. However, detailed linguistic analysis provided evidence of prosodic and segmental errors previously reported in AFAS cases. Cognitive testing showed reduced communication in activities of daily living and mild deficits related to psychiatric disorders. Psychiatric evaluation revealed long-lasting internalizing disorders (neuroticism, anxiety, obsessive-compulsive disorder, social phobia, depression, alexithymia, hopelessness, and apathy) in both subjects. Diffusion tensor imaging (DTI) data from each subject with DFAS were compared with data from a group of 21 age- and gender-matched healthy control subjects. Diffusion parameters (MD, AD, and RD) in predefined regions of interest showed changes of white matter microstructure in regions previously related with AFAS and psychiatric disorders. In conclusion, the present findings militate against the possibility that these two subjects have FAS of psychogenic origin. Rather, our findings provide evidence that mild DFAS occurring in the context of subtle, yet persistent, developmental speech disorders may be associated with structural brain

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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

  19. Age at First Exposure to Football Is Associated with Altered Corpus Callosum White Matter Microstructure in Former Professional Football Players.

    Science.gov (United States)

    Stamm, Julie M; Koerte, Inga K; Muehlmann, Marc; Pasternak, Ofer; Bourlas, Alexandra P; Baugh, Christine M; Giwerc, Michelle Y; Zhu, Anni; Coleman, Michael J; Bouix, Sylvain; Fritts, Nathan G; Martin, Brett M; Chaisson, Christine; McClean, Michael D; Lin, Alexander P; Cantu, Robert C; Tripodis, Yorghos; Stern, Robert A; Shenton, Martha E

    2015-11-15

    Youth football players may incur hundreds of repetitive head impacts (RHI) in one season. Our recent research suggests that exposure to RHI during a critical neurodevelopmental period prior to age 12 may lead to greater later-life mood, behavioral, and cognitive impairments. Here, we examine the relationship between age of first exposure (AFE) to RHI through tackle football and later-life corpus callosum (CC) microstructure using magnetic resonance diffusion tensor imaging (DTI). Forty retired National Football League (NFL) players, ages 40-65, were matched by age and divided into two groups based on their AFE to tackle football: before age 12 or at age 12 or older. Participants underwent DTI on a 3 Tesla Siemens (TIM-Verio) magnet. The whole CC and five subregions were defined and seeded using deterministic tractography. Dependent measures were fractional anisotropy (FA), trace, axial diffusivity, and radial diffusivity. Results showed that former NFL players in the AFE <12 group had significantly lower FA in anterior three CC regions and higher radial diffusivity in the most anterior CC region than those in the AFE ≥12 group. This is the first study to find a relationship between AFE to RHI and later-life CC microstructure. These results suggest that incurring RHI during critical periods of CC development may disrupt neurodevelopmental processes, including myelination, resulting in altered CC microstructure.

  20. 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.

  1. 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.

  2. Comparison of regional gray matter atrophy, white matter alteration, and glucose metabolism as a predictor of the conversion to Alzheimer's disease in mild cognitive impairment.

    Science.gov (United States)

    Sohn, Bo Kyung; Yi, Dahyun; Seo, Eun Hyun; Choe, Young Min; Kim, Jee Wook; Kim, Shin Gyeom; Choi, Hyo Jung; Byun, Min Soo; Jhoo, Jin Hyeong; Woo, Jong Inn; Lee, Dong Young

    2015-06-01

    We compared the predictive ability of the various neuroimaging tools and determined the most cost-effective, non-invasive Alzheimer's disease (AD) prediction model in mild cognitive impairment (MCI) individuals. Thirty-two MCI subjects were evaluated at baseline with [(18)F]-fluorodeoxyglucose positron emission tomography (FDG-PET), MRI, diffusion tensor imaging (DTI), and neuropsychological tests, and then followed up for 2 yr. After a follow up period, 12 MCI subjects converted to AD (MCIc) and 20 did not (MCInc). Of the voxel-based statistical comparisons of baseline neuroimaging data, the MCIc showed reduced cerebral glucose metabolism (CMgl) in the temporo-parietal, posterior cingulate, precuneus, and frontal regions, and gray matter (GM) density in multiple cortical areas including the frontal, temporal and parietal regions compared to the MCInc, whereas regional fractional anisotropy derived from DTI were not significantly different between the two groups. The MCIc also had lower Mini-Mental State Examination (MMSE) score than the MCInc. Through a series of model selection steps, the MMSE combined with CMgl model was selected as a final model (classification accuracy 93.8%). In conclusion, the combination of MMSE with regional CMgl measurement based on FDG-PET is probably the most efficient, non-invasive method to predict AD in MCI individuals after a two-year follow-up period.

  3. 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.

  4. 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.

  5. White matter abnormalities in major depression: a tract-based spatial statistics and rumination study.

    Directory of Open Access Journals (Sweden)

    Nianming Zuo

    Full Text Available Increasing evidence indicates that major depressive disorder (MDD is usually accompanied by altered white matter in the prefrontal cortex, the parietal lobe and the limbic system. As a behavioral abnormity of MDD, rumination has been believed to be a substantial indicator of the mental state of the depressive state. So far, however, no report that we are aware of has evaluated the relationship between white matter alterations and the ruminative state. In this study, we first explored the altered white matter using a tract-based spatial statistics (TBSS method based on diffusion tensor imaging of 19 healthy and 16 depressive subjects. We then investigated correlations between the altered white matter microstructure in the identified altered regions and the severity of ruminations measured by the ruminative response scale. Our results demonstrated altered white matter microstructure in circuits connecting the prefrontal lobe, the parietal lobe and the limbic system (p<0.005, uncorrected, findings which support previous research. More importantly, the result also indicated that a greater alteration in the white matter is associated with a more ruminative state (p<0.05, Bonferroni corrected. The detected abnormalities in the white matter should be interpreted cautiously because of the small sample size in this study. This finding supports the psychometric significance of white matter deficits in MDD.

  6. 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.

  7. The value of diffusion tensor imaging in the differential diagnosis of subcortical ischemic vascular dementia and Alzheimer's disease in patients with only mild white matter alterations on T2-weighted images

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Jian-Liang; Zhang, Ting (Dept. of Neurology, Shanghai Jiaotong Univ. Affiliated Sixth People' s Hospital, Shanghai (China)); Chang, Cheng; Zhang, Yu-Zhen; Li, Wen-Bin (Inst. of Diagnostic and Interventional Radiology, Shanghai Jiaotong Univ. Affiliated Sixth People' s Hospital, Shanghai (China)), Email: liwenbin@sh163.net

    2012-04-15

    Background: Diffusion tensor imaging (DTI) is a form of functional magnetic resonance imaging (MRI) that allows examination of the microstructural integrity of white matter in the brain. Dementia is a neurodegenerative disease, and DTI can provide indirect insights of the microstructural characteristics of brains in individuals with different forms of dementia. Purpose: To evaluate the value of DTI in the diagnosis and differential diagnosis of patients with subcortical ischemic vascular dementia (SIVD) and Alzheimer's disease (AD). Material and Methods: The study included 40 patients (20 AD patients and 20 SIVD patients) and 20 normal controls (NC). After routine MRI and DTI, fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were measured and compared in regions of interest (ROI). Results: Compared to NC and AD patients, SIVD patients had lower FA values and higher ADC values in the inferior-fronto-occipital fascicles (IFOF), genu of the corpus callosum (GCC), splenium of the corpus callosum (SCC), and superior longitudinal fasciculus (SLF). Compared to controls and SIVD patients, AD patients had lower FA values in the anterior frontal lobe, temporal lobe, hippocampus, IFOF, GCC, and CF; and higher ADC values in the temporal lobe and hippocampus. Conclusion: DTI can be used to estimate the white matter impairment in dementia patients. There were significant regional reductions of FA values and heightened ADC values in multiple regions in SIVD patients compared to AD patients. When compared with conventional MRI, DTI may provide a more objective method for the differential diagnosis of SIVD and AD disease patients who have only mild white matter alterations on T2-weighted imaging

  8. 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.

  9. 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.…

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

    Science.gov (United States)

    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.

  11. Assessment of the structural brain network reveals altered connectivity in children with unilateral cerebral palsy due to periventricular white matter lesions

    Directory of Open Access Journals (Sweden)

    Kerstin Pannek

    2014-01-01

    Conclusion: This study shows that network-based analysis of structural connectivity can identify alterations in FA in unilateral CP, and that these alterations in FA are related to clinical function. Application of this connectome-based analysis to investigate alterations in connectivity following treatment may elucidate the neurological correlates of improved functioning due to intervention.

  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. 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

  14. 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.

  15. Relationship of white and gray matter abnormalities to clinical and genetic features in myotonic dystrophy type 1

    Directory of Open Access Journals (Sweden)

    Stefano Zanigni

    2016-01-01

    Conclusion: In patients with DM1, the combined smaller overall gray matter volume and white matter alterations seem to be the main morpho-structural substrates of CNS involvement in this condition. The correlation of white matter differences with both clinical and genetic findings lends support to this notion.

  16. 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.

  17. 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.

  18. 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.

  19. CSF markers of Alzheimer’s pathology and microglial activation are associated with altered white matter microstructure in asymptomatic adults at risk for Alzheimer’s disease

    Science.gov (United States)

    Melah, Kelsey E; Lu, Sharon Yuan-Fu; Hoscheidt, Siobhan M; Alexander, Andrew L; Adluru, Nagesh; Destiche, Daniel J; Carlsson, Cynthia M; Zetterberg, Henrik; Blennow, Kaj; Okonkwo, Ozioma C; Gleason, Carey E; Dowling, N Maritza; Bratzke, Lisa C; Rowley, Howard A; Sager, Mark A; Asthana, Sanjay; Johnson, Sterling C; Bendlin, Barbara B

    2015-01-01

    Background The immune response in Alzheimer’s disease (AD) involves activation of microglia which may remove β-amyloid. However, overproduction of inflammatory compounds may exacerbate neural damage in Alzheimer’s disease. AD pathology accumulates years before diagnosis, yet the extent to which neuroinflammation is involved in the earliest disease stages is unknown. Objective To determine whether neuroinflammation exacerbates neural damage in preclinical AD. Methods We utilized cerebrospinal fluid (CSF) and magnetic resonance imaging collected in 192 asymptomatic late-middle-aged adults (mean age=60.98 years). Neuroinflammatory markers chitinase-3-like protein 1 (YKL-40) and monocyte chemoattractant protein-1 (MCP-1) in CSF were utilized as markers of neuroinflammation. Neural cell damage was assessed using CSF neurofilament light chain protein (NFL), CSF total tau (T-Tau), and neural microstructure assessed with diffusion tensor imaging (DTI). With regard to AD pathology, CSF Aβ42 and tau phosphorylated at threonine 181 (P-Tau181) were used as markers of amyloid and tau pathology, respectively. We hypothesized that higher YKL-40 and MCP-1 in the presence of AD pathology would be associated with higher NFL, T-Tau, and altered microstructure on DTI. Results Neuroinflammation was associated with markers of neural damage. Higher CSF YKL-40 was associated with both higher CSF NFL and T-Tau. Inflammation interacted with AD pathology, such that greater MCP-1 and lower Aβ42 was associated with altered microstructure in bilateral frontal and right temporal lobe and that greater MCP-1 and greater P-Tau181 was associated with altered microstructure in precuneus. Conclusion Inflammation may play a role in neural damage in preclinical AD. PMID:26836182

  20. 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.

  1. 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.

  2. 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.

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

    Science.gov (United States)

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

    2015-01-01

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

  5. 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.

  6. 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

  7. 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.

  8. 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...

  9. Susceptibility-weighted imaging provides insight into white matter damage in amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Tino Prell

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

  10. 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.

  11. 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.

  12. 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…

  13. 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…

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. Reduced thalamic volume in preterm infants is associated with abnormal white matter metabolism independent of injury

    Energy Technology Data Exchange (ETDEWEB)

    Wisnowski, Jessica L. [Children' s Hospital Los Angeles, Department of Radiology, Los Angeles, CA (United States); University of Pittsburgh, Department of Pediatric Radiology, Children' s Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States); University of Southern California, Brain and Creativity Institute, Los Angeles, CA (United States); Ceschin, Rafael C. [University of Pittsburgh, Department of Pediatric Radiology, Children' s Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States); University of Pittsburgh, Department of Biomedical Informatics, Pittsburgh, PA (United States); Choi, So Young [University of Southern California, Brain and Creativity Institute, Los Angeles, CA (United States); Schmithorst, Vincent J. [University of Pittsburgh, Department of Pediatric Radiology, Children' s Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States); Painter, Michael J. [University of Pittsburgh, Department of Pediatrics, Division of Neurology, Childrens Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States); Nelson, Marvin D. [Children' s Hospital Los Angeles, Department of Radiology, Los Angeles, CA (United States); Blueml, Stefan [Children' s Hospital Los Angeles, Department of Radiology, Los Angeles, CA (United States); Rudi Schulte Research Institute, Santa Barbara, CA (United States); Panigrahy, Ashok [Children' s Hospital Los Angeles, Department of Radiology, Los Angeles, CA (United States); University of Pittsburgh, Department of Pediatric Radiology, Children' s Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States)

    2015-05-01

    Altered thalamocortical development is hypothesized to be a key substrate underlying neurodevelopmental disabilities in preterm infants. However, the pathogenesis of this abnormality is not well-understood. We combined magnetic resonance spectroscopy of the parietal white matter and morphometric analyses of the thalamus to investigate the association between white matter metabolism and thalamic volume and tested the hypothesis that thalamic volume would be associated with diminished N-acetyl-aspartate (NAA), a measure of neuronal/axonal maturation, independent of white matter injury. Data from 106 preterm infants (mean gestational age at birth: 31.0 weeks ± 4.3; range 23-36 weeks) who underwent MR examinations under clinical indications were included in this study. Linear regression analyses demonstrated a significant association between parietal white matter NAA concentration and thalamic volume. This effect was above and beyond the effect of white matter injury and age at MRI and remained significant even when preterm infants with punctate white matter lesions (pWMLs) were excluded from the analysis. Furthermore, choline, and among the preterm infants without pWMLs, lactate concentrations were also associated with thalamic volume. Of note, the associations between NAA and choline concentration and thalamic volume remained significant even when the sample was restricted to neonates who were term-equivalent age or older. These observations provide convergent evidence of a neuroimaging phenotype characterized by widespread abnormal thalamocortical development and suggest that the pathogenesis may involve impaired axonal maturation. (orig.)

  2. White matter deficits in psychopathic offenders and correlation with factor structure.

    Directory of Open Access Journals (Sweden)

    Sylco S Hoppenbrouwers

    Full Text Available Psychopathic offenders show a persistent pattern of emotional unresponsivity to the often horrendous crimes they perpetrate. Recent studies have related psychopathy to alterations in white matter. Therefore, diffusion tensor imaging followed by tract-based spatial statistics (TBSS analysis in 11 psychopathic offenders matched to 11 healthy controls was completed. Fractional anisotropy was calculated within each voxel and comparisons were made between groups using a permutation test. Any clusters of white matter voxels different between groups were submitted to probabilistic tractography. Significant differences in fractional anisotropy were found between psychopathic offenders and healthy controls in three main white matter clusters. These three clusters represented two major networks: an amygdalo-prefrontal network, and a striato-thalamo-frontal network. The interpersonal/affective component of the PCL-R correlated with white matter deficits in the orbitofrontal cortex and frontal pole whereas the antisocial component correlated with deficits in the striato-thalamo-frontal network. In addition to replicating earlier work concerning disruption of an amygdala-prefrontal network, we show for the first time that white matter integrity in a striato-thalamo-frontal network is disrupted in psychopathic offenders. The novelty of our findings lies in the two dissociable white matter networks that map directly onto the two major factors of psychopathy.

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

    Directory of Open Access Journals (Sweden)

    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

  4. 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.

  5. 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

  6. 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.

  7. White Matter Deficits in Psychopathic Offenders and Correlation with Factor Structure

    NARCIS (Netherlands)

    Hoppenbrouwers, S.S.; Nazeri, A.; Jesus, D.R. de; Stirpe, T.; Felsky, D.; Schutter, D.J.L.G.; Daskalakis, Z.J.; Voineskos, A.N.

    2013-01-01

    Psychopathic offenders show a persistent pattern of emotional unresponsivity to the often horrendous crimes they perpetrate. Recent studies have related psychopathy to alterations in white matter. Therefore, diffusion tensor imaging followed by tract-based spatial statistics (TBSS) analysis in 11 ps

  8. 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

  9. 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.

  10. 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...

  11. 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.).

  12. 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.)

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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

  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. 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...

  2. 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).

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

    Directory of Open Access Journals (Sweden)

    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 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.

  5. 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.

  6. Pyrogenic organic matter can alter microbial communication

    Science.gov (United States)

    Masiello, Caroline; Gao, Xiaodong; Cheng, Hsiao-Ying; Silberg, Jonathan

    2016-04-01

    Soil microbes communicate with each other to manage a large range of processes that occur more efficiently when microbes are able to act simultaneously. This coordination occurs through the continuous production of signaling compounds that are easily diffused into and out of cells. As the number of microbes in a localized environment increases, the internal cellular concentration of these signaling compounds increases, and when a threshold concentration is reached, gene expression shifts, leading to altered (and coordinated) microbial behaviors. Many of these coordinated behaviors have biogeochemically important outcomes. For example, methanogenesis, denitrification, biofilm formation, and the development of plant-rhizobial symbioses are all regulated by a simple class of cell-cell signaling molecules known as acyl homoserine lactones (AHLs). Pyrogenic organic matter in soils can act to disrupt microbial communication through multiple pathways. In the case of AHLs, charcoal's very high surface area can sorb these signaling compounds, preventing microbes from detecting each others' presence (Masiello et al., 2014). In addition, the lactone ring in AHLs is vulnerable to pH increases accompanying PyOM inputs, with soil pH values higher than 7-8 leading to ring opening and compound destabilization. Different microbes use different classes of signaling compounds, and not all microbial signaling compounds are pH-vulnerable. This implies that PyOM-driven pH increases may trigger differential outcomes for Gram negative bacteria vs fungi, for example. A charcoal-driven reduction in microbes' ability to detect cell-cell communication compounds may lead to a shift in the ability of microbes to participate in key steps of C and N cycling. For example, an increase in an archaeon-specific AHL has been shown to lead to a cascade of metabolic processes that eventually results in the upregulation of CH4 production (Zhang et al., 2012). Alterations in similar AHL compounds leads to

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

  9. 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.

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

    Science.gov (United States)

    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…

  11. 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

  12. 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,…

  13. 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.

  14. 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.

  15. 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.

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  18. 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.

  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. 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.

  1. Correlation between white matter alterations and cognitive function decline in early Alzheimer's disease%早期阿尔茨海默病脑白质改变和认知功能损伤的相关性

    Institute of Scientific and Technical Information of China (English)

    倪红艳; 王明时; 祁吉

    2008-01-01

    Objective To investigate the effects of early stage Alzheimer's disease(AD)on white matter(WM)integrity using diffusion tensor imaging(DTI)and its relationship with cognitive function decline.Methods DTI was performed in 32 subjects,including 14 early AD patients and 18 elder controls(ON)with a 1.5 T MR scanner. Fractional anisotropy(FA)and mean diffusivity(-D)values were computed and compared for 9 regions of interest(ROI).Eight standard neuropsychological tests were performed and compared between AD and ON to evaluate basic cognitive capacities of AD.Correlation analysis was applied between FA,(-D) values and scores of neuropsychological tests for all subjects.Results FA significantly decreased in splenium of the corpus callosum and the posterior parietal-temporal region(S2),and D significantly increased in the splenium in AD patients(P<0.05).AD patients showed lower scores compared with ON in all neuropsychological tests(P<0.05).FA of the splenium and S2 positively correlated with several tests scores,while (-D) of multiple ROIs negatively correlated with several tests scores (P<0.05).Conclusions In the early stage of AD,neuropathology has effect not only on cognitive function,but also on white matter structure,and they have strong relationship.AD patients show white matter changes in specific regions,which reflect loss in cortico-cortical connections.%目的 探讨早期阿尔茨海默病(AD)脑白质变化与认知功能改变的关系.方法 对14例早期AD患者(AD组)和18名健康老年人(ON组)在1.5 T MR扫描仪上进行扩散张量成像(DTI)扫描.在9个感兴趣区测量并比较各向异性分数(FA)和平均扩散系数((-D)).对2组研究对象进行8个标准的神经心理测试,以评价其基本认知能力状态,并对测试结果 进行比较.分析所有研究对象DTI的FA和(-D)测量结果 与神经心理测试评分的相关性.结果 与ON组相比,AD患者在胼胝体压部(分别为0.25±0.03和0.49±0.03)

  2. 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

  3. 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.

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

    Science.gov (United States)

    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.

  5. 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....

  6. 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 ...

  7. 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

  8. 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.

    2015-01-01

    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 (ATR), 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. PMID:26179962

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. File list: ALL.Neu.05.AllAg.White_Matter [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.05.AllAg.White_Matter hg19 All antigens Neural White Matter SRX998282,SRX99...8280,SRX1096828,SRX1096827 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Neu.05.AllAg.White_Matter.bed ...

  14. File list: ALL.Neu.10.AllAg.White_Matter [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.10.AllAg.White_Matter hg19 All antigens Neural White Matter SRX998282,SRX10...96828,SRX998280,SRX1096827 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Neu.10.AllAg.White_Matter.bed ...

  15. File list: ALL.Neu.50.AllAg.White_Matter [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.50.AllAg.White_Matter hg19 All antigens Neural White Matter SRX998282,SRX10...96828,SRX998280,SRX1096827 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Neu.50.AllAg.White_Matter.bed ...

  16. File list: ALL.Neu.20.AllAg.White_Matter [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.20.AllAg.White_Matter hg19 All antigens Neural White Matter SRX998282,SRX10...96828,SRX998280,SRX1096827 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Neu.20.AllAg.White_Matter.bed ...

  17. 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.

  18. File list: His.Neu.20.AllAg.White_Matter [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.20.AllAg.White_Matter hg19 Histone Neural White Matter SRX998282,SRX1096828...,SRX998280,SRX1096827 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Neu.20.AllAg.White_Matter.bed ...

  19. File list: His.Neu.10.AllAg.White_Matter [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.10.AllAg.White_Matter hg19 Histone Neural White Matter SRX998282,SRX1096828...,SRX998280,SRX1096827 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Neu.10.AllAg.White_Matter.bed ...

  20. File list: His.Neu.05.AllAg.White_Matter [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.05.AllAg.White_Matter hg19 Histone Neural White Matter SRX998282,SRX998280,...SRX1096828,SRX1096827 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Neu.05.AllAg.White_Matter.bed ...

  1. File list: His.Neu.50.AllAg.White_Matter [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.50.AllAg.White_Matter hg19 Histone Neural White Matter SRX998282,SRX1096828...,SRX998280,SRX1096827 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Neu.50.AllAg.White_Matter.bed ...

  2. 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.

  3. 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.

  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. 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.

  7. 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.

  8. 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

  9. 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)

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Diffuse white matter tract abnormalities in clinically normal ageing retired athletes with a history of sports-related concussions.

    Science.gov (United States)

    Tremblay, Sebastien; Henry, Luke C; Bedetti, Christophe; Larson-Dupuis, Camille; Gagnon, Jean-François; Evans, Alan C; Théoret, Hugo; Lassonde, Maryse; De Beaumont, Louis

    2014-11-01

    Sports-related concussions have been shown to lead to persistent subclinical anomalies of the motor and cognitive systems in young asymptomatic athletes. In advancing age, these latent alterations correlate with detectable motor and cognitive function decline. Until now, the interacting effects of concussions and the normal ageing process on white matter tract integrity remain unknown. Here we used a tract-based spatial statistical method to uncover potential white matter tissue damage in 15 retired athletes with a history of concussions, free of comorbid medical conditions. We also investigated potential associations between white matter integrity and declines in cognitive and motor functions. Compared to an age- and education-matched control group of 15 retired athletes without concussions, former athletes with concussions exhibited widespread white matter anomalies along many major association, interhemispheric, and projection tracts. Group contrasts revealed decreases in fractional anisotropy, as well as increases in mean and radial diffusivity measures in the concussed group. These differences were primarily apparent in fronto-parietal networks as well as in the frontal aspect of the corpus callosum. The white matter anomalies uncovered in concussed athletes were significantly associated with a decline in episodic memory and lateral ventricle expansion. Finally, the expected association between frontal white matter integrity and motor learning found in former non-concussed athletes was absent in concussed participants. Together, these results show that advancing age in retired athletes presenting with a history of sports-related concussions is linked to diffuse white matter abnormalities that are consistent with the effects of traumatic axonal injury and exacerbated demyelination. These changes in white matter integrity might explain the cognitive and motor function declines documented in this population.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  13. 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.

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

    Science.gov (United States)

    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.

  15. 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.

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

    Science.gov (United States)

    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.

  17. 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

  18. The influence of comorbid oppositional defiant disorder on white matter microstructure in attention-deficit/hyperactivity disorder

    NARCIS (Netherlands)

    van Ewijk, Hanneke; Noordermeer, Siri D. S.; Heslenfeld, Dirk J.; Luman, Marjolein; Hartman, Catharina A.; Hoekstra, Pieter J.; Faraone, Stephen V.; Franke, Barbara; Buitelaar, Jan K.; Oosterlaan, J.

    2016-01-01

    Attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) are highly comorbid disorders. ADHD has been associated with altered white matter (WM) microstructure, though the literature is inconsistent, which may be due to differences in the in- or exclusion of participant

  19. MRI markers for mild cognitive impairment: comparisons between white matter integrity and gray matter volume measurements.

    Directory of Open Access Journals (Sweden)

    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.

  20. 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...

  1. 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

    with axonal disruption, where lower FA was associated with greater axonal disruption in white matter directly adjacent to hyperphosphorylated tau positive sulci. In summary, our findings indicate that axonal disruption and tau pathology are closely associated, and high spatial resolution ex vivo diffusion MRI has the potential to detect microstructural alterations observed in CTE tissue. Future studies will be required to determine whether this approach can be applied to living people.

  2. 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...

  3. 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.

  4. Magnetic resonance spectroscopy features of normal-appearing white matter in patients with acute brucellosis

    Energy Technology Data Exchange (ETDEWEB)

    Kayabas, Uner [Department of Infectious Disease and Clinical Microbiology, Inonu University, Medical Faculty, TR-44280 Malatya (Turkey)], E-mail: ukayabas@inonu.edu.tr; Alkan, Alpay; Firat, Ahmet Kemal; Karakas, Hakki Muammer [Department of Radiology, Inonu University, Medical Faculty, TR-44280 Malatya (Turkey); Bayindir, Yasar; Yetkin, Funda [Department of Infectious Disease and Clinical Microbiology, Inonu University, Medical Faculty, TR-44280 Malatya (Turkey)

    2008-03-15

    We aimed to evaluate whether the subtle metabolic cerebral changes are present in normal-appearing white matter on conventional MRI, in patients with acute brucellosis, by using MR spectroscopy (MRS). Sixteen patients with acute brucellosis and 13 healthy control subjects were investigated with conventional MRI and single-voxel MRS. Voxels were placed in normal-appearing parietal white matter (NAPWM). N-Acetyl aspartate (NAA)/creatine (Cr) and choline (Cho)/Cr ratios were calculated. There was no significant difference between the study subjects and the control group in NAA/Cr ratios obtained from NAPWM. However, the Cho/Cr ratios were significantly higher in patients with acute brucellosis compared to controls (p = 0.01). MRS revealed metabolic changes in normal-appearing white matter of patients with brucellosis. Brucellosis may cause subtle cerebral alterations, which may only be discernible with MRS. Increased Cho/Cr ratio possibly represents an initial phase of inflammation and/or demyelination process of brucellosis.

  5. Early-stage psychotherapy produces elevated frontal white matter integrity in adult major depressive disorder.

    Directory of Open Access Journals (Sweden)

    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.

  6. 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

  7. Investigation of spatial correlation in MR images of human cerebral white matter using geostatistical methods

    Energy Technology Data Exchange (ETDEWEB)

    Keil, Fabian

    2014-03-20

    Investigating the structure of human cerebral white matter is gaining interest in the neurological as well as in the neuroscientific community. It has been demonstrated in many studies that white matter is a very dynamic structure, rather than a static construct which does not change for a lifetime. That means, structural changes within white matter can be observed even on short timescales, e.g. in the course of normal ageing, neurodegenerative diseases or even during learning processes. To investigate these changes, one method of choice is the texture analysis of images obtained from white matter. In this regard, MRI plays a distinguished role as it provides a completely non-invasive way of acquiring in vivo images of human white matter. This thesis adapted a statistical texture analysis method, known as variography, to quantify the spatial correlation of human cerebral white matter based on MR images. This method, originally introduced in geoscience, relies on the idea of spatial correlation in geological phenomena: in naturally grown structures near things are correlated stronger to each other than distant things. This work reveals that the geological principle of spatial correlation can be applied to MR images of human cerebral white matter and proves that variography is an adequate method to quantify alterations therein. Since the process of MRI data acquisition is completely different to the measuring process used to quantify geological phenomena, the variographic analysis had to be adapted carefully to MR methods in order to provide a correctly working methodology. Therefore, theoretical considerations were evaluated with numerical samples in a first, and validated with real measurements in a second step. It was shown that MR variography facilitates to reduce the information stored in the texture of a white matter image to a few highly significant parameters, thereby quantifying heterogeneity and spatial correlation distance with an accuracy better than 5

  8. White Matter Abnormalities in Post-traumatic Stress Disorder Following a Specific Traumatic Event

    Directory of Open Access Journals (Sweden)

    Lei Li

    2016-02-01

    Full Text Available Studies of posttraumatic stress disorder (PTSD are complicated by wide variability in the intensity and duration of prior stressors in patient participants, secondary effects of chronic psychiatric illness, and a variable history of treatment with psychiatric medications. In magnetic resonance imaging (MRI studies, patient samples have often been small, and they were not often compared to similarly stressed patients without PTSD in order to control for general stress effects. Findings from these studies have been inconsistent. The present study investigated whole-brain microstructural alterations of white matter in a large drug-naive population who survived a specific, severe traumatic event (a major 8.0-magnitude earthquake. Using diffusion tensor imaging (DTI, we explored group differences between 88 PTSD patients and 91 matched traumatized non-PTSD controls in fractional anisotropy (FA, as well as its component elements axial diffusivity (AD and radial diffusivity (RD, and examined these findings in relation to findings from deterministic DTI tractography. Relations between white matter alterations and psychiatric symptom severity were examined. PTSD patients, relative to similarly stressed controls, showed an FA increase as well as AD and RD changes in the white matter beneath left dorsolateral prefrontal cortex and forceps major. The observation of increased FA in the PTSD group suggests that the pathophysiology of PTSD after a specific acute traumatic event is distinct from what has been reported in patients with several years duration of illness. Alterations in dorsolateral prefrontal cortex may be an important aspect of illness pathophysiology, possibly via the region's established role in fear extinction circuitry. Use-dependent myelination or other secondary compensatory changes in response to heightened demands for threat appraisal and emotion regulation may be involved.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  11. A preliminary study of white matter in adolescent depression: relationships with illness severity, anhedonia, and irritability

    Directory of Open Access Journals (Sweden)

    Sarah E Henderson

    2013-11-01

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

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

    Science.gov (United States)

    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.

  13. White matter damage in primary progressive aphasias: a diffusion tensor tractography study.

    Science.gov (United States)

    Galantucci, Sebastiano; Tartaglia, Maria Carmela; Wilson, Stephen M; Henry, Maya L; Filippi, Massimo; Agosta, Federica; Dronkers, Nina F; Henry, Roland G; Ogar, Jennifer M; Miller, Bruce L; Gorno-Tempini, Maria Luisa

    2011-10-01

    Primary progressive aphasia is a clinical syndrome that encompasses three major phenotypes: non-fluent/agrammatic, semantic and logopenic. These clinical entities have been associated with characteristic patterns of focal grey matter atrophy in left posterior frontoinsular, anterior temporal and left temporoparietal regions, respectively. Recently, network-level dysfunction has been hypothesized but research to date has focused largely on studying grey matter damage. The aim of this study was to assess the integrity of white matter tracts in the different primary progressive aphasia subtypes. We used diffusion tensor imaging in 48 individuals: nine non-fluent, nine semantic, nine logopenic and 21 age-matched controls. Probabilistic tractography was used to identify bilateral inferior longitudinal (anterior, middle, posterior) and uncinate fasciculi (referred to as the ventral pathway); and the superior longitudinal fasciculus segmented into its frontosupramarginal, frontoangular, frontotemporal and temporoparietal components, (referred to as the dorsal pathway). We compared the tracts' mean fractional anisotropy, axial, radial and mean diffusivities for each tract in the different diagnostic categories. The most prominent white matter changes were found in the dorsal pathways in non-fluent patients, in the two ventral pathways and the temporal components of the dorsal pathways in semantic variant, and in the temporoparietal component of the dorsal bundles in logopenic patients. Each of the primary progressive aphasia variants showed different patterns of diffusion tensor metrics alterations: non-fluent patients showed the greatest changes in fractional anisotropy and radial and mean diffusivities; semantic variant patients had severe changes in all metrics; and logopenic patients had the least white matter damage, mainly involving diffusivity, with fractional anisotropy altered only in the temporoparietal component of the dorsal pathway. This study demonstrates

  14. 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...

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.)

  3. 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.

  4. 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...

  5. 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.

  6. Macro- and micro-structural white matter differences correlate with cognitive performance in healthy aging.

    Science.gov (United States)

    Marques, Paulo César Gonçalves; Soares, José Miguel Montenegro; Magalhães, Ricardo José da Silva; Santos, Nadine Correia; Sousa, Nuno Jorge Carvalho

    2016-03-01

    Studies have shown that white matter (WM) volumetric reductions and overall degradation occur with aging. Nonetheless little is known about the WM alterations that may underlie different cognitive status in older individuals. The main goal of the present work was to identify and characterize possible macro and microstructural WM alterations that could distinguish between older healthy individuals with contrasting cognitive profiles (i.e., "poor" vs "good" cognitive performers). Structural and diffusion magnetic resonance imaging was performed in order to quantify local WM volumes, white matter signal abnormalities (WMSA) volume (a measure of lesion burden) and diffusion tensor imaging scalar maps known to probe WM microstructure. A battery of neurocognitive/psychological tests was administered to assess the cognitive performance. Poor performers showed a higher slope for the positive association between WMSA volume and age compared to good performers. Even when controlling for WMSA volume, poor performers also evidenced lower fractional anisotropy, as well as positive associations with age with higher slopes of regression parameters in radial and axial diffusivity. Altogether results suggest that cognitive performance is related to differences in WM, with poor cognitive performers displaying signs of faster aging in WM.

  7. White matter disruption at the prodromal stage of Alzheimer's disease: Relationships with hippocampal atrophy and episodic memory performance

    Directory of Open Access Journals (Sweden)

    Florence Rémy

    2015-01-01

    Full Text Available White matter tract alterations have been consistently described in Alzheimer's disease (AD. In particular, limbic fronto-temporal connections, which are critical to episodic memory function, may degenerate early in the course of the disease. However the relation between white matter tract degeneration, hippocampal atrophy and episodic memory impairment at the earliest stages of AD is still unclear. In this magnetic resonance imaging study, white matter integrity and hippocampal volumes were evaluated in patients with amnestic mild cognitive impairment due to AD (Albert et al., 2011 (n = 22 and healthy controls (n = 15. Performance in various episodic memory tasks was also evaluated in each participant. Relative to controls, patients showed a significant reduction of white matter fractional anisotropy (FA and increase of radial diffusivity (RD in the bilateral uncinate fasciculus, parahippocampal cingulum and fornix. Within the patient group, significant intra-hemispheric correlations were notably found between hippocampal grey matter volume and FA in the uncinate fasciculus, suggesting a relationship between atrophy and disconnection of the hippocampus. Moreover, episodic recognition scores were related with uncinate fasciculus FA across patients. These results indicate that fronto-hippocampal connectivity is reduced from the earliest pre-demential stages of AD. Disruption of fronto-hippocampal connections may occur progressively, in parallel with hippocampal atrophy, and may specifically contribute to early initial impairment in episodic memory.

  8. 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.

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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 WMH, FA, and episodic memory in aging remains limited. We hypothesized that white matter connections between frontal cortex and subcortical structures as well as connections between frontal and temporo-parietal cortex would be most affected. In the current study, we examined relationships between WMH, FA and episodic memory in 15 young adults, 13 elders with minimal WMH and 15 elders with extensive WMH, using an episodic recognition memory test for object-color associations. Voxel-based statistics were used to identify voxel clusters where white matter measures were specifically associated with variations in episodic memory performance, and white matter tracts intersecting these clusters were analyzed to examine white matter-memory relationships. White matter injury and integrity measures were significantly associated with episodic memory in extensive regions of white matter, located predominantly in frontal, parietal, and subcortical regions. Template based tractography indicated that white matter injury, as measured by WMH, in the uncinate and inferior longitudinal fasciculi were significantly negatively associated with episodic memory performance. Other tracts such as thalamo-frontal projections, superior longitudinal fasciculus, and dorsal cingulum bundle demonstrated strong negative associations as well. The results suggest that white matter injury to multiple pathways, including connections of frontal and temporal cortex and frontal-subcortical white matter tracts, plays a critical role in memory differences seen in older individuals.

  12. 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.

  13. Assessing prenatal white matter connectivity in commissural agenesis.

    Science.gov (United States)

    Kasprian, Gregor; Brugger, Peter C; Schöpf, Veronika; Mitter, Christian; Weber, Michael; Hainfellner, Johannes A; Prayer, Daniela

    2013-01-01

    Complete or partial agenesis of the corpus callosum are rather common developmental abnormalities, resulting in a wide spectrum of clinical neurodevelopmental deficits. Currently, a significant number of these cases are detected by prenatal sonography during second trimester screening examinations. However, major uncertainties about a detailed morphological diagnosis and the clinical significance do not allow accurate prenatal counselling. Here, we were able to demonstrate the 3D connectivity of aberrant commissural tracts in 16 cases with complete and four cases with partial callosal agenesis using the foetal magnetic resonance imaging techniques of diffusion tensor imaging and tractography in utero and in vivo between gestational weeks 20 and 37. The 'misguided' pre-myelinated callosal axons that represent the bundle of Probst were non-invasively visualized, and they showed a degree of structural integrity similar to that of the callosal pathways of age-matched foetuses without cerebral pathologies. In two foetuses, we were able to prove, by post-mortem histology, that diffusion tensor imaging allows the depiction of the bundle of Probst, even during early stages of pre-myelination at 20 and 22 gestational weeks. In cases with partial callosal agenesis, an aberrant sigmoid-shaped bundle was prenatally depicted, confirming the findings of heterotopic interhemispheric connectivity in adults with partial callosal agenesis. In addition to the corpus callosum, other white matter pathways were also involved, including somatosensory and motor pathways that showed significantly higher fractional anisotropy values in cases with callosal agenesis compared with control subjects. A detailed prenatal assessment of abnormal white matter connectivity in cases of midline anomalies will help to explain and understand the clinical heterogeneity in these cases, taking future foetal neurological counselling strategies to a new level.

  14. 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.

  15. 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.

  16. Pathological differences between white and grey matter multiple sclerosis lesions.

    Science.gov (United States)

    Prins, Marloes; Schul, Emma; Geurts, Jeroen; van der Valk, Paul; Drukarch, Benjamin; van Dam, Anne-Marie

    2015-09-01

    Multiple sclerosis (MS) is a debilitating disease characterized by demyelination of the central nervous system (CNS), resulting in widespread formation of white matter lesions (WMLs) and grey matter lesions (GMLs). WMLs are pathologically characterized by the presence of immune cells that infiltrate the CNS, whereas these immune cells are barely present in GMLs. This striking pathological difference between WMLs and GMLs raises questions about the underlying mechanism. It is known that infiltrating leukocytes contribute to the generation of WMLs; however, since GMLs show a paucity of infiltrating immune cells, their importance in GML formation remains to be determined. Here, we review pathological characteristics of WMLs and GMLs, and suggest some possible explanations for the observed pathological differences. In our view, cellular and molecular characteristics of WM and GM, and local differences within WMLs and GMLs (in particular, in glial cell populations and the molecules they express), determine the pathway to demyelination. Further understanding of GML pathogenesis, considered to contribute to chronic MS, may have a direct impact on the development of novel therapeutic targets to counteract this progressive neurological disorder.

  17. Lowered electroencephalographic spectral edge frequency predicts the presence of cerebral white matter injury in premature infants

    NARCIS (Netherlands)

    Inder, TE; Buckland, L; Williams, CE; Spencer, C; Gunning, MI; Darlow, BA; Volpe, JJ; Gluckman, PD

    2003-01-01

    Objective. Current methods for early identification of cerebral white matter injury in the premature infant at the bedside are inadequate. This study investigated the utility of advanced spectral analysis of the neonatal electroencephalogram (EEG) in the early diagnosis of white matter injury in the

  18. 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...

  19. 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…

  20. 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.

  1. White matter changes and diabetes predict cognitive decline in the elderly: the LADIS study

    DEFF Research Database (Denmark)

    Verdelho, A; Madureira, S; Moleiro, C;

    2010-01-01

    We aimed to study if age-related white matter changes (WMC) and vascular risk factors were predictors of cognitive decline in elderly subjects with WMC living independently.......We aimed to study if age-related white matter changes (WMC) and vascular risk factors were predictors of cognitive decline in elderly subjects with WMC living independently....

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

    Science.gov (United States)

    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…

  3. Disrupted white matter in language and motor tracts in developmental stuttering.

    Science.gov (United States)

    Connally, Emily L; Ward, David; Howell, Peter; Watkins, Kate E

    2014-04-01

    White matter tracts connecting areas involved in speech and motor control were examined using diffusion-tensor imaging in a sample of people who stutter (n=29) who were heterogeneous with respect to age, sex, handedness and stuttering severity. The goals were to replicate previous findings in developmental stuttering and to extend our knowledge by evaluating the relationship between white matter differences in people who stutter and factors such as age, sex, handedness and stuttering severity. We replicated previous findings that showed reduced integrity in white matter underlying ventral premotor cortex, cerebral peduncles and posterior corpus callosum in people who stutter relative to controls. Tractography analysis additionally revealed significantly reduced white matter integrity in the arcuate fasciculus bilaterally and the left corticospinal tract and significantly reduced connectivity within the left corticobulbar tract in people who stutter. Region-of-interest analyses revealed reduced white matter integrity in people who stutter in the three pairs of cerebellar peduncles that carry the afferent and efferent fibers of the cerebellum. Within the group of people who stutter, the higher the stuttering severity index, the lower the white matter integrity in the left angular gyrus, but the greater the white matter connectivity in the left corticobulbar tract. Also, in people who stutter, handedness and age predicted the integrity of the corticospinal tract and peduncles, respectively. Further studies are needed to determine which of these white matter differences relate to the neural basis of stuttering and which reflect experience-dependent plasticity.

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

    Science.gov (United States)

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

    2010-01-01

    The current study investigated the neurobiological role of white matter in visuospatial versus linguistic processing abilities in autism using diffusion tensor imaging. We examined differences in white matter integrity between high-functioning children with autism (HFA) and typically developing controls (CTRL), in relation to the groups' response…

  5. Cerebral White Matter Integrity Mediates Adult Age Differences in Cognitive Performance

    Science.gov (United States)

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

    2009-01-01

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

  6. 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

  7. Quantifying Cerebellum Grey Matter and White Matter Perfusion Using Pulsed Arterial Spin Labeling

    Directory of Open Access Journals (Sweden)

    Xiufeng Li

    2014-01-01

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

  8. 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

  9. Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL): Assessment of the involved white matter tracts by MRI

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  11. Reduced white matter integrity and its correlation with clinical symptom in first-episode, treatment-naive generalized anxiety disorder.

    Science.gov (United States)

    Wang, Wei; Qian, Shaowen; Liu, Kai; Li, Bo; Li, Min; Xin, Kuolin; Sun, Gang

    2016-11-01

    The purpose of this study was to explore white matter microstructural alterations in the patients with generalized anxiety disorder (GAD) using diffusion tensor imaging (DTI) technique, and to assess neural associations with the symptom severity. Twenty-eight first-episode, treatment-naive GAD patients without co-morbidities and 28 matched healthy controls underwent DTI acquisition and clinical symptom assessments. Tract-based spatial statistics (TBSS) was used to analyze white matter microstructural abnormalities in patients with GAD, as well as their associations with clinical symptom scores in a voxel-wise manner. Compared to controls, patients showed decreased fractional anisotropy (FA) values in 7 clusters of white matter in bilateral uncinate fasciculus, body of corpus callosum, left middle cingulum (cingulate gyrus), bilateral anterior thalamic radiation and corona radiate, right anterior limb of internal capsule, bilateral inferior frontal-occipital fasciculus, bilateral superior and inferior longitudinal fasciculus, and increased mean diffusivity and radial diffusivity in widespread white matter regions. Reduced FA values in right uncinate fasciculus, left cingulum bundle showed significantly negative correlations with clinical symptom severity for Hamilton anxiety Rating Scale scores. Our findings suggest microstructural abnormalities in uncinate fasciculus and cingulum bundle play key roles in the underlying neural basis of GAD.

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

    Directory of Open Access Journals (Sweden)

    C Joakim Ek

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

  13. Expert cognitive control and individual differences associated with frontal and parietal white matter microstructure.

    Science.gov (United States)

    Roberts, R Edward; Anderson, Elaine J; Husain, Masud

    2010-12-15

    Although many functional imaging studies have reported frontal activity associated with "cognitive control" tasks, little is understood about factors underlying individual differences in performance. Here we compared the behavior and brain structure of healthy controls with fighter pilots, an expert group trained to make precision choices at speed in the presence of conflicting cues. Two different behavioral paradigms--Eriksen Flanker and change of plan tasks--were used to assess the influence of distractors and the ability to update ongoing action plans. Fighter pilots demonstrated superior cognitive control as indexed by accuracy and postconflict adaptation on the Flanker task, but also showed increased sensitivity to irrelevant, distracting choices. By contrast, when pilots were examined on their ability to inhibit a current action plan in favor of an alternative response, their performance was no better than the control group. Diffusion weighted imaging revealed differences in white matter radial diffusivity between pilots and controls not only in the right dorsomedial frontal region but also in the right parietal lobe. Moreover, analysis of individual differences in reaction time costs for conflict trials on the Flanker task demonstrated significant correlations with radial diffusivity at these locations, but in different directions. Postconflict adaptation effects, however, were confined to the dorsomedial frontal locus. The findings demonstrate that in humans expert cognitive control may surprisingly be mediated by enhanced response gain to both relevant and irrelevant stimuli, and is accompanied by structural alterations in the white matter of the frontal and parietal lobe.

  14. 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

  15. 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

  16. 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...

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

    Science.gov (United States)

    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.

  18. 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.

  19. White matter structures associated with loneliness in young adults.

    Science.gov (United States)

    Nakagawa, Seishu; Takeuchi, Hikaru; Taki, Yasuyuki; Nouchi, Rui; Sekiguchi, Atsushi; Kotozaki, Yuka; Miyauchi, Carlos Makoto; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Kunitoki, Keiko; Sassa, Yuko; Kawashima, Ryuta

    2015-11-20

    Lonely individuals may exhibit dysfunction, particularly with respect to social empathy and self-efficacy. White matter (WM) structures related to loneliness have not yet been identified. We investigated the association between regional WM density (rWMD) using the UCLA Loneliness Scale in 776 healthy young students aged 18-27 years old. Loneliness scores were negatively correlated with rWMD in eight clusters: the bilateral inferior parietal lobule (IPL), right anterior insula (AI), posterior temporoparietal junction (pTPJ), left posterior superior temporal sulcus (pSTS), dorsomedial prefrontal cortex (dmPFC), and rostrolateral prefrontal cortex (RLPFC). The bilateral IPL, right AI, left pSTS, pTPJ, and RLPFC were strongly associated with Empathy Quotient (EQ), whereas the bilateral IPL, right AI, left pTPJ, and dmPFC were associated with General Self-Efficacy Scale (GSES) score. The neural correlates of loneliness comprise widespread reduction in WMD in areas related to self- and social cognition as well as areas associated with empathy and self-efficacy.

  20. 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

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

    Science.gov (United States)

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

    2010-03-01

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

  2. Profiles of aberrant white matter microstructure in fragile X syndrome.

    Science.gov (United States)

    Hall, Scott S; Dougherty, Robert F; Reiss, Allan L

    2016-01-01

    Previous studies attempting to quantify white matter (WM) microstructure in individuals with fragile X syndrome (FXS) have produced inconsistent findings, most likely due to the various control groups employed, differing analysis methods, and failure to examine for potential motion artifact. In addition, analyses have heretofore lacked sufficient specificity to provide regional information. In this study, we used Automated Fiber-tract Quantification (AFQ) to identify specific regions of aberrant WM microstructure along WM tracts in patients with FXS that differed from controls who were matched on age, IQ and degree of autistic symptoms. Participants were 20 patients with FXS, aged 10 to 23 years, and 20 matched controls. Using Automated Fiber-tract Quantification (AFQ), we created Tract Profiles of fractional anisotropy and mean diffusivity along 18 major WM fascicles. We found that fractional anisotropy was significantly increased in the left and right inferior longitudinal fasciculus (ILF), right uncinate fasciculus, and left cingulum hippocampus in individuals with FXS compared to controls. Conversely, mean diffusivity was significantly decreased in the right ILF in patients with FXS compared to controls. Age was significantly negatively associated with MD values across both groups in 11 tracts. Taken together, these findings indicate that FXS results in abnormal WM microstructure in specific regions of the ILF and uncinate fasciculus, most likely caused by inefficient synaptic pruning as a result of decreased or absent Fragile X Mental Retardation Protein (FMRP). Longitudinal studies are needed to confirm these findings.

  3. Profiles of aberrant white matter microstructure in fragile X syndrome

    Directory of Open Access Journals (Sweden)

    Scott S. Hall

    2016-01-01

    Full Text Available Previous studies attempting to quantify white matter (WM microstructure in individuals with fragile X syndrome (FXS have produced inconsistent findings, most likely due to the various control groups employed, differing analysis methods, and failure to examine for potential motion artifact. In addition, analyses have heretofore lacked sufficient specificity to provide regional information. In this study, we used Automated Fiber-tract Quantification (AFQ to identify specific regions of aberrant WM microstructure along WM tracts in patients with FXS that differed from controls who were matched on age, IQ and degree of autistic symptoms. Participants were 20 patients with FXS, aged 10 to 23 years, and 20 matched controls. Using Automated Fiber-tract Quantification (AFQ, we created Tract Profiles of fractional anisotropy and mean diffusivity along 18 major WM fascicles. We found that fractional anisotropy was significantly increased in the left and right inferior longitudinal fasciculus (ILF, right uncinate fasciculus, and left cingulum hippocampus in individuals with FXS compared to controls. Conversely, mean diffusivity was significantly decreased in the right ILF in patients with FXS compared to controls. Age was significantly negatively associated with MD values across both groups in 11 tracts. Taken together, these findings indicate that FXS results in abnormal WM microstructure in specific regions of the ILF and uncinate fasciculus, most likely caused by inefficient synaptic pruning as a result of decreased or absent Fragile X Mental Retardation Protein (FMRP. Longitudinal studies are needed to confirm these findings.

  4. Optimization of white matter fiber tractography with diffusional kurtosis imaging.

    Science.gov (United States)

    Glenn, G Russell; Helpern, Joseph A; Tabesh, Ali; Jensen, Jens H

    2015-10-01

    Diffusional kurtosis imaging (DKI) is a clinically feasible diffusion MRI technique for white matter (WM) fiber tractography (FT) with the ability to directly resolve intra-voxel crossing fibers by means of the kurtosis diffusion orientation distribution function (dODF). Here we expand on previous work by exploring properties of the kurtosis dODF and their subsequent effects on WM FT for in vivo human data. For comparison, the results are contrasted with fiber bundle orientation estimates provided by the diffusion tensor, which is the primary quantity obtained from diffusion tensor imaging. We also outline an efficient method for performing DKI-based WM FT that can substantially decrease the computational requirements. The recommended method for implementing the kurtosis ODF is demonstrated to optimize the reproducibility and sensitivity of DKI for detecting crossing fibers while reducing the occurrence of non-physically-meaningful, negative values in the kurtosis dODF approximation. In addition, DKI-based WM FT is illustrated for different protocols differing in image acquisition times from 48 to 5.3 min.

  5. 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

  6. 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.

  7. 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."

  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. White matter abnormalities in schizophrenia and schizotypal personality disorder.

    Science.gov (United States)

    Lener, Marc S; Wong, Edmund; Tang, Cheuk Y; Byne, William; Goldstein, Kim E; Blair, Nicholas J; Haznedar, M Mehmet; New, Antonia S; Chemerinski, Eran; Chu, King-Wai; Rimsky, Liza S; Siever, Larry J; Koenigsberg, Harold W; Hazlett, Erin A

    2015-01-01

    Prior diffusion tensor imaging (DTI) studies examining schizotypal personality disorder (SPD) and schizophrenia, separately have shown that compared with healthy controls (HCs), patients show frontotemporal white matter (WM) abnormalities. This is the first DTI study to directly compare WM tract coherence with tractography and fractional anisotropy (FA) across the schizophrenia spectrum in a large sample of demographically matched HCs (n = 55), medication-naive SPD patients (n = 49), and unmedicated/never-medicated schizophrenia patients (n = 22) to determine whether (a) frontal-striatal-temporal WM tract abnormalities in schizophrenia are similar to, or distinct from those observed in SPD; and (b) WM tract abnormalities are associated with clinical symptom severity indicating a common underlying pathology across the spectrum. Compared with both the HC and SPD groups, schizophrenia patients showed WM abnormalities, as indexed by lower FA in the temporal lobe (inferior longitudinal fasciculus) and cingulum regions. SPD patients showed lower FA in the corpus callosum genu compared with the HC group, but this regional abnormality was more widespread in schizophrenia patients. Across the schizophrenia spectrum, greater WM disruptions were associated with greater symptom severity. Overall, frontal-striatal-temporal WM dysconnectivity is attenuated in SPD compared with schizophrenia patients and may mitigate the emergence of psychosis.

  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. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. 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

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

    Science.gov (United States)

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

    2017-01-01

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

  17. Diffusion tensor imaging and white matter abnormalities in patients with disorders of consciousness

    Directory of Open Access Journals (Sweden)

    Carlo eCavaliere

    2015-01-01

    Full Text Available Progress in neuroimaging has yielded new powerful tools which, potentially, can be applied to clinical populations, improve the diagnosis of neurological disorders and predict outcome. At present, the diagnosis of consciousness disorders is limited to subjective assessment and objective measurements of behaviour, with an emerging role for neuroimaging techniques.In this review we focus on white matter alterations measured using Diffusion Tensor Imaging on patients with consciousness disorders, examining the most common diffusion imaging acquisition protocols and considering the main issues related to diffusion imaging analyses.We conclude by considering some of the remaining challenges to overcome, the existing knowledge gaps and the potential role of neuroimaging in understanding the pathogenesis and clinical features of disorders of consciousness.

  18. Children with Poor Reading Skills at the Word Level Show Reduced Fractional Anisotropy in White Matter Tracts of Both Hemispheres.

    Science.gov (United States)

    de Moura, Luciana Monteiro; Cogo-Moreira, Hugo; de Ávila, Clara Regina Brandão; Pan, Pedro Mario; Gadelha, Ary; Moriyama, Tais; Del Aquilla, Marco Antonio; Hoexter, Marcelo; Salum, Giovanni Abrahão; Picon, Felipe Almeida; Anés, Mauricio; Mercadante, Marcos Tomanik; Lacerda, Acioly; Amaro, Edson; Miguel, Euripedes Constantino; Rohde, Luis Augusto; Bressan, Rodrigo Affonseca; McGuire, Philip; Sato, João Ricardo; de Jesus Mari, Jair; Jackowski, Andrea Parolin

    2016-09-01

    Diffusion tensor imaging (DTI) studies showed that microstructural alterations are correlated to reading skills. In this study, we aim to investigate white matter microstructure of a group of Portuguese speakers with poor reading level, using different parameters of DTI. To perform this analysis, we selected children ranging from 8 to 12 years of age, poor readers (n = 17) and good readers (n = 23), evaluated in the word-level ability based on a Latent Class Analysis (LCA) of Academic Performance Test (TDE). Poor readers exhibited significant fractional anisotropy (FA) reductions in many tracts of both hemispheres, but small and restricted clusters of increased radial diffusivity (RD) in the left hemisphere. Spatial coherence of fibers might be the main source of differences, as changes in FA were not similarly accompanied in terms of extension by changes in RD. Widespread structural alterations in the white matter could prevent good reading ability at word level, which is consistent with recent studies demonstrating the involvement of multiple cortical regions and white matter tracts in reading disabilities.

  19. White matter of the cerebellum demonstrated by computed tomography: normal anatomy and physical principles.

    Science.gov (United States)

    Maravilla, K R; Pastel, M S; Kirkpatrick, J B

    1978-04-01

    Although computed tomography (CT) delineation of normal white matter of the cerebral hemispheres has been well documented, there has been no description of white matter within the cerebellum. Through the use of phantom studies, CT number correlations between cerebellum and cerebral hemispheres, and anatomic correlation with in vitro specimens, the ability to visualize cerebellar white matter is demonstrated. Thin sections decrease volume averaging and enable consistent imaging of these structures. Size and shape of the corpus medullaris on CT scan may vary with the scan angle and level of section. Representative examples of various normal appearances are illustrated.

  20. 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

  1. 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.

  2. Early microstructural white matter changes in patients with HIV: A diffusion tensor imaging study

    Directory of Open Access Journals (Sweden)

    Stubbe-Drger Bianca

    2012-05-01

    Full Text Available Abstract Background Previous studies have reported white matter (WM brain alterations in asymptomatic patients with human immunodeficiency virus (HIV. Methods We compared diffusion tensor imaging (DTI derived WM fractional anisotropy (FA between HIV-patients with and without mild macroscopic brain lesions determined using standard magnetic resonance imaging (MRI. We furthermore investigated whether WM alterations co-occurred with neurocognitive deficits and depression. We performed structural MRI and DTI for 19 patients and 19 age-matched healthy controls. Regionally-specific WM integrity was investigated using voxel-based statistics of whole-brain FA maps and region-of-interest analysis. Each patient underwent laboratory and neuropsychological tests. Results Structural MRI revealed no lesions in twelve (HIV-MRN and unspecific mild macrostructural lesions in seven patients (HIV-MRL. Both analyses revealed widespread FA-alterations in all patients. Patients with HIV-MRL had FA-alterations primarily adjacent to the observed lesions and, whilst reduced in extent, patients with HIV-MRN also exhibited FA-alterations in similar regions. Patients with evidence of depression showed FA-increase in the ventral tegmental area, pallidum and nucleus accumbens in both hemispheres, and patients with evidence of HIV-associated neurocognitive disorder showed widespread FA-reduction. Conclusion These results show that patients with HIV-MRN have evidence of FA-alterations in similar regions that are lesioned in HIV-MRL patients, suggesting common neuropathological processes. Furthermore, they suggest a biological rather than a reactive origin of depression in HIV-patients.

  3. 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

  4. Moderate Physical Activity Mediates the Association between White Matter Lesion Volume and Memory Recall in Breast Cancer Survivors.

    Directory of Open Access Journals (Sweden)

    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.

  5. Differential language expertise related to white matter architecture in regions subserving sensory-motor coupling, articulation, and interhemispheric transfer.

    Science.gov (United States)

    Elmer, Stefan; Hänggi, Jürgen; Meyer, Martin; Jäncke, Lutz

    2011-12-01

    The technique of diffusion tensor imaging (DTI) has been used to investigate alterations in white matter architecture following long-term training and expertise. Professional simultaneous interpreters (SI) provide an ideal model for the investigation of training-induced plasticity due to the high demands placed on sound to motor mapping mechanisms, which are vital for executing fast interpretations. In line with our hypothesis, we found clusters with decreased fractional anisotropy (FA) in the SI group in brain regions previously shown to support sensory-motor coupling mechanisms and speech articulation (cluster extent family-wise error corrected, P language expertise is accompanied by plastic adaptations in regions strongly involved in motor aspects of speech and in interhemispheric information transfer. These results have implications for our understanding of language expertise in relation to white matter adaptations.

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

    Science.gov (United States)

    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.

  7. Initial Incidence of White Matter Hyperintensities on MRI in Astronauts

    Science.gov (United States)

    Norcross, Jason; Sherman, Paul; McGuire, Steve; Kochunov, Peter

    2016-01-01

    Introduction: Previous literature has described the increase in white matter hyperintensity (WMH) burden associated with hypobaric exposure in the U-2 and altitude chamber operating personnel. Although astronauts have similar hypobaric exposure pressures to the U2 pilot population, astronauts have far fewer exposures and each exposure would be associated with a much lower level of decompression stress due to rigorous countermeasures to prevent decompression sickness. Therefore, we postulated that the WMH burden in the astronaut population would be less than in U2 pilots. Methods: Twenty-one post-flight de-identified astronaut MRIs (5 mm slice thickness FLAIR sequences) were evaluated for WMH count and volume. The only additional data provided was an age range of the astronauts (43-57) and if they had ever performed an EVA (13 yes, 8 no). Results: WMH count in these 21 astronaut MRI was 21.0 +/- 24.8 (mean+/- SD) and volume was 0.382 +/- 0.602 ml, which was significantly higher than previously published results for the U2 pilots. No significant differences between EVA and no EVA groups existed. Age range of astronaut population is not directly comparable to the U2 population. Discussion: With significantly less frequent (sometimes none) and less stressful hypobaric exposures, yet a much higher incidence of increased WMH, this indicates the possibility of additional mechanisms beyond hypobaric exposure. This increase unlikely to be attributable just to the differences in age between astronauts and U2 pilots. Forward work includes continuing review of post-flight MRI and evaluation of pre to post flight MRI changes if available. Data mining for potential WMH risk factors includes collection of age, sex, spaceflight experience, EVA hours, other hypobaric exposures, hyperoxic exposures, radiation, high performance aircraft experience and past medical history. Finally, neurocognitive and vision/eye results will be evaluated for any evidence of impairment linked to

  8. Discrimination and psychological distress: does Whiteness matter for Arab Americans?

    Science.gov (United States)

    Abdulrahim, Sawsan; James, Sherman A; Yamout, Rouham; Baker, Wayne

    2012-12-01

    The white racial category in the U.S. encompasses persons who have Arab ancestry. Arab Americans, however, have always occupied a precarious position in relationship to Whiteness. This study examined differences in reporting racial/ethnic discrimination among Arab Americans. It also investigated whether and how the association between discrimination and psychological distress varies by characteristics that capture an Arab American's proximity to/distance from Whiteness. We used data from the Detroit Arab American Study (2003; n = 1016), which includes measures of discrimination and the Kessler-10 scale of psychological distress. A series of logistic regression models were specified to test the discrimination-psychological distress association, stratified by five measures that capture Whiteness--subjective racial identification, religion, skin color, ethnic centrality, and residence in the ethnic enclave. Discrimination was more frequently reported by Muslim Arab Americans, those who racially identify as non-white, and who live in the ethnic enclave. Conversely, the association between discrimination and psychological distress was stronger for Christian Arab Americans, those who racially identify as white, who have dark skin color, and who live outside the ethnic enclave. Even though Arab Americans who occupy an identity location close to Whiteness are less subjected to discrimination, they are more negatively affected by it. The findings illuminate the complex pathways through which discrimination associates with psychological distress among 'white' immigrants. Further research on discrimination and health among Arab Americans can help unpack the white racial category and deconstruct Whiteness.

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

    Energy Technology Data Exchange (ETDEWEB)

    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 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

  11. MRI of white matter changes in the Sjoegren-Larsson syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Hussain, M.Z. [Dept. of Radiology, Yamanashi Medical Coll., Yamanashi (Japan); Oba, H. [Dept. of Radiology, Yamanashi Medical Coll., Yamanashi (Japan); Ohtomo, K. [Dept. of Radiology, Yamanashi Medical Coll., Yamanashi (Japan); Aihara, M. [Dept. of Paediatrics, Yamanashi Medical Coll., Tamahocho, Yamanashi (Japan); Hayashibe, H. [Dept. of Paediatrics, Yamanashi Medical Coll., Tamahocho, Yamanashi (Japan); Nakazawa, S. [Dept. of Paediatrics, Yamanashi Medical Coll., Tamahocho, Yamanashi (Japan); Uchiyama, G. [Dept. of Radiology, Yamanashi Medical Coll., Yamanashi (Japan)

    1995-10-01

    We report a case of Sjoegren-Larsson syndrome with spastic diplegia and conduction aphasia. MRI demonstrated the white matter changes deep in the cerebral hemispheres. We analyse the MRI findings and compare the results with neuropsychological signs. (orig.)

  12. Mapping white matter diffusion and cerebrovascular reactivity in carotid occlusive disease

    NARCIS (Netherlands)

    Conklin, J.; Fierstra, J.; Crawley, A. P.; Han, J. S.; Poublanc, J.; Silver, F. L.; Tymianski, M.; Fisher, J. A.; Mandell, D. M.; Mikulis, D. J.

    2011-01-01

    Objective: To characterize the relationship between cerebrovascular reactivity (CVR) and white matter (WM) diffusion in patients with internal carotid artery (ICA) occlusive disease. Methods: In this exploratory observational study, 41 patients with severe stenosis or occlusion of the extracranial I

  13. Cortical Lesions as Determinants of White Matter Lesion Formation and Cognitive Abnormalities in MS

    Science.gov (United States)

    2015-05-01

    AWARD NUMBER: W81XWH-13-1-0098 TITLE: Cortical Lesions as Determinants of White Matter Lesion Formation and Cognitive Abnormalities in MS...2015 4. TITLE AND SUBTITLE Cortical Lesions as Determinants of White Matter Lesion Formation and Cognitive Abnormalities in MS 5a. CONTRACT NUMBER...software developed for these maps will also be used to enhance tract-based FA and mean-diffusivity measurements in FSL, as originally proposed. The

  14. Depressive symptoms predict cognitive decline and dementia in older people independently of cerebral white matter changes

    DEFF Research Database (Denmark)

    Verdelho, Ana; Madureira, Sofia; Moleiro, Carla

    2013-01-01

    Depressive symptoms (DS) have been associated with increased risk of cognitive decline. Our aim was to evaluate the longitudinal influence of DS on cognition in independent older people, accounting for the severity of white matter changes (WMC).......Depressive symptoms (DS) have been associated with increased risk of cognitive decline. Our aim was to evaluate the longitudinal influence of DS on cognition in independent older people, accounting for the severity of white matter changes (WMC)....

  15. 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.)

  16. Neonatal white matter abnormalities an important predictor of neurocognitive outcome for very preterm children.

    Directory of Open Access Journals (Sweden)

    Lianne J Woodward

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

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

    Science.gov (United States)

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

    2009-01-01

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

  18. Recovery of behavioral changes and compromised white matter in C57BL/6 mice exposed to cuprizone: Effects of antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Haiyun eXu

    2011-07-01

    Full Text Available Recent animal and human studies have suggested that the cuprizone (CPZ, a copper chelator-feeding C57BL/6 mouse may be used as an animal model of schizophrenia. The goals of this study were to see the recovery processes of CPZ-induced behavioral changes and damaged white matter and to examine possible effects of antipsychotic drugs on the recovery processes. Mice were fed a CPZ-containing diet for five weeks then returned to normal food for three weeks, during which period mice were treated with different antipsychotic drugs. Various behaviors were measured at the end of CPZ-feeding phase as well as on the 14th and 21st days after CPZ-withdrawal. The damage to and recovery status of white matter in the brains of mice were examined. Dietary CPZ resulted in white matter damage and behavioral abnormalities in the elevated plus-maze, social interaction and Y-maze test. Elevated plus-maze performance recovered to normal range within two weeks after CPZ withdrawal. But, alterations in social interaction showed no recovery. Antipsychotics did not alter animals’ behavior in either of these tests during the recovery period. Altered performance in the Y-maze showed some recovery in the vehicle group; atypical antipsychotics, but not haloperidol, significantly promoted this recovery process. The recovery of damaged white matter was incomplete during the recovery period. None of the drugs significantly promoted the recovery of damaged white matter. These results suggest that CPZ-induced white matter damage and social interaction deficit may be resistant to the antipsychotic treatment employed in this study. They are in good accordance with the clinical observations that positive symptoms in schizophrenic patients respond well to antipsychotic drugs while social dysfunction is usually intractable.

  19. Hyperintense White Matter Lesions in 50 High-Altitude Pilots with Neurologic Decompression Sickness

    Science.gov (United States)

    2012-12-01

    1996 ; 67 : 199 – 206 . 9. Ding K, Marquez de la Plata C, Wang JY, Mumphrey M, Moore C, et al. Cerebral atrophy after traumatic white...coronary heart disease . Chest 2005 ; 127 : 1498 – 506 . 30. Pantoni L, Garcia JH . The signifi cance of cerebral white matter abnormalities 100

  20. 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.

  1. Vestibular loss and balance training cause similar changes in human cerebral white matter fractional anisotropy.

    Science.gov (United States)

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

    2014-01-01

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

  2. Mapping joint grey and white matter reductions in Alzheimer's disease using joint independent component analysis.

    Science.gov (United States)

    Guo, Xiaojuan; Han, Yuan; Chen, Kewei; Wang, Yan; Yao, Li

    2012-12-07

    Alzheimer's disease (AD) is a neurodegenerative disease concomitant with grey and white matter damages. However, the interrelationship of volumetric changes between grey and white matter remains poorly understood in AD. Using joint independent component analysis, this study identified joint grey and white matter volume reductions based on structural magnetic resonance imaging data to construct the covariant networks in twelve AD patients and fourteen normal controls (NC). We found that three networks showed significant volume reductions in joint grey-white matter sources in AD patients, including (1) frontal/parietal/temporal-superior longitudinal fasciculus/corpus callosum, (2) temporal/parietal/occipital-frontal/occipital, and (3) temporal-precentral/postcentral. The corresponding expression scores distinguished AD patients from NC with 85.7%, 100% and 85.7% sensitivity for joint sources 1, 2 and 3, respectively; 75.0%, 66.7% and 75.0% specificity for joint sources 1, 2 and 3, respectively. Furthermore, the combined source of three significant joint sources best predicted the AD/NC group membership with 92.9% sensitivity and 83.3% specificity. Our findings revealed joint grey and white matter loss in AD patients, and these results can help elucidate the mechanism of grey and white matter reductions in the development of AD.

  3. Fractional anisotropy in white matter tracts of very-low-birth-weight infants

    Energy Technology Data Exchange (ETDEWEB)

    Dudink, Jeroen; Conneman, Nikk; Goudoever, Johannes van; Govaert, Paul [Erasmus MC-Sophia Children' s Hospital, Division of Neonatology, Department of Paediatrics, P.O. Box 2060, Rotterdam (Netherlands); Lequin, Maarten [Erasmus MC-Sophia Children' s Hospital, Division of Paediatrics, Department of Radiology, Rotterdam (Netherlands); Pul, Carola van [Maxima Medical Center, Department of Clinical Physics, Veldhoven (Netherlands); Buijs, Jan [Maxima Medical Center, Division of Neonatology, Department of Paediatrics, Veldhoven (Netherlands)

    2007-12-15

    Advances in neonatal intensive care have not yet reduced the high incidence of neurodevelopmental disability among very-low-birth-weight (VLBW) infants. As neurological deficits are related to white-matter injury, early detection is important. Diffusion tensor imaging (DTI) could be an excellent tool for assessment of white-matter injury. To provide DTI fractional anisotropy (FA) reference values for white-matter tracts of VLBW infants for clinical use. We retrospectively analysed DTI images of 28 VLBW infants (26-32 weeks gestational age) without evidence of white-matter abnormalities on conventional MRI sequences, and normal developmental outcome (assessed at age 1-3 years). For DTI an echoplanar sequence with diffusion gradient (b = 1,000 s/mm{sup 2}) applied in 25 non-collinear directions was used. We measured FA and apparent diffusion coefficient (ADC) of different white-matter tracts in the first 4 days of life. A statistically significant correlation was found between gestational age and FA of the posterior limb of the internal capsule in VLBW infants (r = 0.495, P<0.01). Values of FA and ADC were measured in white-matter tracts of VLBW infants. FA of the pyramidal tracts measured in the first few days after birth is related to gestational age. (orig.)

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

    Science.gov (United States)

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

    2014-10-22

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

  5. 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.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  7. 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.

  8. 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.

  9. 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.

  10. Atypical functional connectivity in autism spectrum disorder is associated with disrupted white matter microstructural organisation

    Directory of Open Access Journals (Sweden)

    Jane eMcGrath

    2013-09-01

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

  11. Microstructural white matter correlates of emotion recognition impairment in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Crespi, Chiara; Cerami, Chiara; Dodich, Alessandra; Canessa, Nicola; Arpone, Marta; Iannaccone, Sandro; Corbo, Massimo; Lunetta, Christian; Scola, Elisa; Falini, Andrea; Cappa, Stefano F

    2014-04-01

    Amyotrophic Lateral Sclerosis (ALS) is associated in about half of the cases with behavioral and cognitive disorders, including impairments in socio-emotional processing, considered as key-features for the diagnosis of the behavioral variant of frontotemporal dementia (bv-FTD). The neurostructural bases of emotional deficits in ALS, however, still remain largely unexplored. Here we aim to assess emotion recognition in non-demented sporadic ALS patients compared with healthy controls, and to explore for the first time its microstructural white-matter correlates. Twenty-two subjects with either probable or definite diagnosis of ALS and 55 age-, gender-, and education-matched healthy controls were recruited in the study. All participants performed the Ekman 60-Faces Test, assessing the recognition of six basic emotions (i.e., anger, disgust, fear, sadness, surprise and happiness). A subgroup of subjects, comprising 19 patients and 20 healthy controls, also underwent a Diffusion Tensor Imaging scanning. Behavioral analysis highlighted a significant decline of emotion recognition skills in patients compared to controls, particularly affecting the identification of negative emotions. Moreover, the Diffusion Tensor Imaging analyses revealed a correlation between this impairment and the alteration of white-matter integrity along the right inferior longitudinal fasciculus and inferior fronto-occipital fasciculus. Our findings indicate the presence of an early emotion recognition deficit in non-demented sporadic ALS patients, associated with microstructural changes in ventral associative bundles connecting occipital, temporo-limbic and orbitofrontal regions in the right hemisphere. These changes may represent a frontotemporal-limbic microstructural marker of socio-emotional impairment in ALS.

  12. Indirect Probes of Dark Matter and Globular Cluster Properties From Dark Matter Annihilation within the Coolest White Dwarfs

    CERN Document Server

    Hurst, Travis J; Natarajan, Aravind; Badenes, Carles

    2014-01-01

    White Dwarfs (WD) capture Dark Matter (DM) as they orbit within their host halos. These captured particles may subsequently annihilate, heating the stellar core and preventing the WD from cooling. The potential wells of WDs are considerably deeper and core temperatures significantly cooler than those of main sequence stars. Consequently, DM evaporation is less important in WDs and DM with masses $M_{\\chi} \\gtrsim 100\\, \\kev$ and annihilation cross-sections orders of magnitude below the canonical thermal cross-section ($\\sigmav \\gtrsim 10^{-46}\\, \\cm^3$/s) can significantly alter WD cooling in particular astrophysical environments. We consider WDs in globular clusters (GCs) and dwarf galaxies. If the parameters of the DM particle are known, then the temperature of the coolest WD in a GC can be used to constrain the DM density of the cluster's halo (potentially even ruling out the presence of a halo if the inferred density is of order the ambient Galactic density). Recently several direct detection experiments ...

  13. 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

  14. 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

  15. 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

  16. 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.

  17. Increased density of DISC1-immunoreactive oligodendroglial cells in fronto-parietal white matter of patients with paranoid schizophrenia.

    Science.gov (United States)

    Bernstein, Hans-Gert; Jauch, Esther; Dobrowolny, Henrik; Mawrin, Christian; Steiner, Johann; Bogerts, Bernhard

    2016-09-01

    Profound white matter abnormalities have repeatedly been described in schizophrenia, which involve the altered expression of numerous oligodendrocyte-associated genes. Transcripts of the disrupted-in-schizophrenia 1 (DISC1) gene, a key susceptibility factor in schizophrenia, have recently been shown to be expressed by oligodendroglial cells and to negatively regulate oligodendrocyte differentiation and maturation. To learn more about the putative role(s) of oligodendroglia-associated DISC1 in schizophrenia, we analyzed the density of DISC1-immunoreactive oligodendrocytes in the fronto-parietal white matter in postmortem brains of patients with schizophrenia. Compared with controls (N = 12) and cases with undifferentiated/residual schizophrenia (N = 6), there was a significantly increased density of DISC1-expressing glial cells in paranoid schizophrenia (N = 12), which unlikely resulted from neuroleptic treatment. Pathophysiologically, over-expression of DISC1 protein(s) in white matter oligodendrocytes might add to the reduced levels of two myelin markers, 2',3'-cyclic-nucleotide 3'-phosphodiesterase and myelin basic protein in schizophrenia. Moreover, it might significantly contribute to cell cycle abnormalities as well as to deficits in oligodendroglial cell differentiation and maturation found in schizophrenia.

  18. White matter integrity predicts delay discounting behavior in 9- to 23-year-olds: a diffusion tensor imaging study.

    Science.gov (United States)

    Olson, Elizabeth A; Collins, Paul F; Hooper, Catalina J; Muetzel, Ryan; Lim, Kelvin O; Luciana, Monica

    2009-07-01

    Healthy participants (n = 79), ages 9-23, completed a delay discounting task assessing the extent to which the value of a monetary reward declines as the delay to its receipt increases. Diffusion tensor imaging (DTI) was used to evaluate how individual differences in delay discounting relate to variation in fractional anisotropy (FA) and mean diffusivity (MD) within whole-brain white matter using voxel-based regressions. Given that rapid prefrontal lobe development is occurring during this age range and that functional imaging studies have implicated the prefrontal cortex in discounting behavior, we hypothesized that differences in FA and MD would be associated with alterations in the discounting rate. The analyses revealed a number of clusters where less impulsive performance on the delay discounting task was associated with higher FA and lower MD. The clusters were located primarily in bilateral frontal and temporal lobes and were localized within white matter tracts, including portions of the inferior and superior longitudinal fasciculi, anterior thalamic radiation, uncinate fasciculus, inferior fronto-occipital fasciculus, corticospinal tract, and splenium of the corpus callosum. FA increased and MD decreased with age in the majority of these regions. Some, but not all, of the discounting/DTI associations remained significant after controlling for age. Findings are discussed in terms of both developmental and age-independent effects of white matter organization on discounting behavior.

  19. White Matter Changes Associated with Resting Sympathetic Tone in Frontotemporal Dementia vs. Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Mario F Mendez

    Full Text Available Resting sympathetic tone, a measure of physiological arousal, is decreased in patients with apathy and inertia, such as those with behavioral variant frontotemporal dementia (bvFTD and other frontally-predominant disorders.To identify the neuroanatomical correlates of skin conductance levels (SCLs, an index of resting sympathetic tone and apathy, among patients with bvFTD, where SCLs is decreased, compared to those with Alzheimer's disease (AD, where it is not.This study analyzed bvFTD (n = 14 patients and a comparison group with early-onset AD (n = 19. We compared their resting SCLs with gray matter and white matter regions of interest and white matter measures of fiber integrity on magnetic resonance imaging and diffusion tensor imaging.As expected, bvFTD patients, compared to AD patients, had lower SCLs, which correlated with an apathy measure, and more gray matter loss and abnormalities of fiber integrity (fractional anisotropy and mean diffusivity in frontal-anterior temporal regions. After controlling for group membership, the SCLs were significantly correlated with white matter volumes in the cingulum and inferior parietal region in the right hemisphere.Among dementia patients, SCLs, and resting sympathetic tone, may correlate with quantity of white matter, rather than with gray matter or with white matter fiber integrity. Loss of white matter volumes, especially involving a right frontoparietal network, may reflect chronic loss of cortical axons that mediate frontal control of resting sympathetic tone, changes that could contribute to the apathy and inertia of bvFTD and related disorders.

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

    Science.gov (United States)

    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

    , less than 1% of neuroblasts in the white matter were born in the 2 days following injury. These data show that the SVZ in the piglet shares many anatomical similarities with the SVZ in the human infant, and that TBI had only modest effects on the SVZ and the number of neuroblasts in the white matter. Piglets at an equivalent developmental stage to human infants were equipped with the largest SVZ and a tremendous number of neuroblasts in the white matter, which may be sufficient in lesion repair without the dramatic stimulation of neurogenic machinery. It has yet to be determined whether neurogenesis and migrating neuroblasts play a role in repair after TBI and/or whether an alteration of normal migration during active postnatal population of brain regions is beneficial in species with gyrencephalic brains.

  1. 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.

  2. Gray and white matter volume abnormalities in generalized anxiety disorder by categorical and dimensional characterization.

    Science.gov (United States)

    Hilbert, Kevin; Pine, Daniel S; Muehlhan, Markus; Lueken, Ulrike; Steudte-Schmiedgen, Susann; Beesdo-Baum, Katja

    2015-12-30

    Increasing efforts have been made to investigate the underlying pathophysiology of generalized anxiety disorder (GAD), but only limited consistent information is available on gray (GM) and white matter (WM) volume changes in affected adults. Additionally, few studies employed dimensional approaches to GAD pathology. This study compares structural brain imaging data from n=19 GAD subjects and n=24 healthy comparison (HC) subjects, all medication-free and matched on age, sex and education. Separate categorical and dimensional models were employed using voxel-based morphometry for GM and WM. Significantly higher GM volumes were found in GAD subjects mainly in basal ganglia structures and less consistently in the superior temporal pole. For WM, GAD subjects showed significantly lower volumes in the dlPFC. Largely consistent findings in dimensional and categorical models point toward these structural alterations being reliable and of importance for GAD. While lower volume in the dlPFC could reflect impaired emotional processing and control over worry in GAD, basal ganglia alterations may be linked to disturbed gain and loss anticipation as implicated in previous functional GAD studies. As perturbations in anticipation processes are central to GAD, these areas may warrant greater attention in future studies.

  3. 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...

  4. Voxel-based MRI intensitometry reveals extent of cerebral white matter pathology in amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Viktor Hartung

    Full Text Available Amyotrophic lateral sclerosis (ALS is characterized by progressive loss of upper and lower motor neurons. Advanced MRI techniques such as diffusion tensor imaging have shown great potential in capturing a common white matter pathology. However the sensitivity is variable and diffusion tensor imaging is not yet applicable to the routine clinical environment. Voxel-based morphometry (VBM has revealed grey matter changes in ALS, but the bias-reducing algorithms inherent to traditional VBM are not optimized for the assessment of the white matter changes. We have developed a novel approach to white matter analysis, namely voxel-based intensitometry (VBI. High resolution T1-weighted MRI was acquired at 1.5 Tesla in 30 ALS patients and 37 age-matched healthy controls. VBI analysis at the group level revealed widespread white matter intensity increases in the corticospinal tracts, corpus callosum, sub-central, frontal and occipital white matter tracts and cerebellum. VBI results correlated with disease severity (ALSFRS-R and patterns of cerebral involvement differed between bulbar- and limb-onset. VBI would be easily translatable to the routine clinical environment, and once optimized for individual analysis offers significant biomarker potential in ALS.

  5. 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

  6. 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.

  7. Cognitive state following stroke: the predominant role of preexisting white matter lesions.

    Directory of Open Access Journals (Sweden)

    Efrat Kliper

    Full Text Available Stroke is a major cause of cognitive impairment and dementia in adults, however the role of the ischemic lesions themselves, on top of other risk factors known in the elderly, remains controversial. This study used structural equation modeling to determine the respective impact of the new ischemic lesions' volume, preexisting white matter lesions and white matter integrity on post stroke cognitive state.Consecutive first ever mild to moderate stroke or transient ischemic attack patients recruited into the ongoing prospective TABASCO study underwent magnetic resonance imaging scans within seven days of stroke onset and were cognitively assessed one year after the event using a computerized neuropsychological battery. The volumes of both ischemic lesions and preexisting white matter lesions and the integrity of the normal appearing white matter tissue were measured and their contribution to cognitive state was assessed using structural equation modeling path analysis taking into account demographic parameters. Two models were hypothesized, differing by the role of ischemic lesions' volume.Structural equation modeling analysis of 142 patients confirmed the predominant role of white matter lesion volume (standardized path coefficient β =  -0.231 and normal appearing white matter integrity (β =  -0.176 on the global cognitive score, while ischemic lesions' volume showed no such effect (β = 0.038. The model excluding the ischemic lesion presented better fit to the data (comparative fit index 0.9 versus 0.092.Mild to moderate stroke patients with preexisting white matter lesions are more vulnerable to cognitive impairment regardless of their new ischemic lesions. Thus, these patients can serve as a target group for studies on cognitive rehabilitation and neuro-protective therapies which may, in turn, slow their cognitive deterioration.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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.

  13. 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.

  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. 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

  16. 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.

  17. 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.

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

    Science.gov (United States)

    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

  19. 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.

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

    Science.gov (United States)

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

    2014-03-01

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

  1. Cognitive processing speed in older adults: relationship with white matter integrity.

    Directory of Open Access Journals (Sweden)

    Geoffrey A Kerchner

    Full Text Available Cognitive processing slows with age. We sought to determine the importance of white matter integrity, assessed by diffusion tensor imaging (DTI, at influencing cognitive processing speed among normal older adults, assessed using a novel battery of computerized, non-verbal, choice reaction time tasks. We studied 131 cognitively normal adults aged 55-87 using a cross-sectional design. Each participant underwent our test battery, as well as MRI with DTI. We carried out cross-subject comparisons using tract-based spatial statistics. As expected, reaction time slowed significantly with age. In diffuse areas of frontal and parietal white matter, especially the anterior corpus callosum, fractional anisotropy values correlated negatively with reaction time. The genu and body of the corpus callosum, superior longitudinal fasciculus, and inferior fronto-occipital fasciculus were among the areas most involved. This relationship was not explained by gray or white matter atrophy or by white matter lesion volume. In a statistical mediation analysis, loss of white matter integrity mediated the relationship between age and cognitive processing speed.

  2. 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.

  3. White matter microstructure pathology in classic galactosemia revealed by neurite orientation dispersion and density imaging.

    Science.gov (United States)

    Timmers, Inge; Zhang, Hui; Bastiani, Matteo; Jansma, Bernadette M; Roebroeck, Alard; Rubio-Gozalbo, M Estela

    2015-03-01

    White matter abnormalities have been observed in patients with classic galactosemia, an inborn error of galactose metabolism. However, magnetic resonance imaging (MRI) data collected in the past were generally qualitative in nature. Our objective was to investigate white matter microstructure pathology and examine correlations with outcome and behaviour in this disease, by using multi-shell diffusion weighted imaging. In addition to standard diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI) was used to estimate density and orientation dispersion of neurites in a group of eight patients (aged 16-21 years) and eight healthy controls (aged 15-20 years). Extensive white matter abnormalities were found: neurite density index (NDI) was lower in the patient group in bilateral anterior areas, and orientation dispersion index (ODI) was increased mainly in the left hemisphere. These specific regional profiles are in agreement with the cognitive profile observed in galactosemia, showing higher order cognitive impairments, and language and motor impairments, respectively. Less favourable white matter properties correlated positively with age and age at onset of diet, and negatively with behavioural outcome (e.g. visual working memory). To conclude, this study provides evidence of white matter pathology regarding density and dispersion of neurites in these patients. The results are discussed in light of suggested pathophysiological mechanisms.

  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. Anterior temporal white matter lesions in myotonic dystrophy with intellectual impairment: an MRI and neuropathological study

    Energy Technology Data Exchange (ETDEWEB)

    Ogata, A.; Tashiro, K. [Department of Neurology, Hokkaido University School of Medicine, North-14, West-5, Kita-ku, Sapporo 060 (Japan); Terae, S. [Department of Radiology, Hokkaido University School of Medicine, Sapporo (Japan); Fujita, M. [Department of Pathology, Hokkaido University School of Medicine, Sapporo (Japan)

    1998-07-01

    We studied 12 patients with myotonic dystrophy using MRI and the Mini-mental state examination (MMSE), to see it specific MRI findings were associated with intellectual impairment. We also compared them with the neuropathological findings in an autopsy case of MD with intellectual impairment. Mild intellectual impairment was found in 8 of the 12 patients. On T 2-weighted and proton density-weighted images, high-intensity areas were seen in cerebral white matter in 10 of the 12 patients. In seven of these, anterior temporal white-matter lesions (ATWML) were found; all seven had mild intellectual impairment (MMSE 22-26), whereas none of the four patients with normal mentation had ATWML. In only one of the eight patients with intellectual impairment were white-matter lesions not found. Pathological findings were severe loss and disordered arrangement of myelin sheaths and axons in addition to heterotopic neurons within anterior temporal white matter. Bilateral ATWML might be a factor for intellectual impairment in MD. The retrospective pathological study raised the possibility that the ATWML are compatible with focal dysplasia of white matter. (orig.) With 4 figs., 1 tab., 21 refs.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  8. Comparison of grey matter volume and thickness for analysing cortical changes in chronic schizophrenia: a matter of surface area, grey/white matter intensity contrast, and curvature.

    Science.gov (United States)

    Kong, Li; Herold, Christina J; Zöllner, Frank; Salat, David H; Lässer, Marc M; Schmid, Lena A; Fellhauer, Iven; Thomann, Philipp A; Essig, Marco; Schad, Lothar R; Erickson, Kirk I; Schröder, Johannes

    2015-02-28

    Grey matter volume and cortical thickness are the two most widely used measures for detecting grey matter morphometric changes in various diseases such as schizophrenia. However, these two measures only share partial overlapping regions in identifying morphometric changes. Few studies have investigated the contributions of the potential factors to the differences of grey matter volume and cortical thickness. To investigate this question, 3T magnetic resonance images from 22 patients with schizophrenia and 20 well-matched healthy controls were chosen for analyses. Grey matter volume and cortical thickness were measured by VBM and Freesurfer. Grey matter volume results were then rendered onto the surface template of Freesurfer to compare the differences from cortical thickness in anatomical locations. Discrepancy regions of the grey matter volume and thickness where grey matter volume significantly decreased but without corresponding evidence of cortical thinning involved the rostral middle frontal, precentral, lateral occipital and superior frontal gyri. Subsequent region-of-interest analysis demonstrated that changes in surface area, grey/white matter intensity contrast and curvature accounted for the discrepancies. Our results suggest that the differences between grey matter volume and thickness could be jointly driven by surface area, grey/white matter intensity contrast and curvature.

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

    Science.gov (United States)

    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.

  10. Gray-white matter and cerebrospinal fluid volume differences in children with Specific Language Impairment and/or Reading Disability.

    Science.gov (United States)

    Girbau-Massana, Dolors; Garcia-Marti, Gracian; Marti-Bonmati, Luis; Schwartz, Richard G

    2014-04-01

    We studied gray-white matter and cerebrospinal fluid (CSF) alterations that may be critical for language, through an optimized voxel-based morphometry evaluation in children with Specific Language Impairment (SLI), compared to Typical Language Development (TLD). Ten children with SLI (8;5-10;9) and 14 children with TLD (8;2-11;8) participated. They received a comprehensive language and reading test battery. We also analyzed a subgroup of six children with SLI+RD (Reading Disability). Brain images from 3-Tesla MRIs were analyzed with intelligence, age, gender, and total intracranial volume as covariates. Children with SLI or SLI+RD exhibited a significant lower overall gray matter volume than children with TLD. Particularly, children with SLI showed a significantly lower volume of gray matter compared to children with TLD in the right postcentral parietal gyrus (BA4), and left and right medial occipital gyri (BA19). The group with SLI also exhibited a significantly greater volume of gray matter in the right superior occipital gyrus (BA19), which may reflect a brain reorganization to compensate for their lower volumes at medial occipital gyri. Children with SLI+RD, compared to children with TLD, showed a significantly lower volume of: (a) gray matter in the right postcentral parietal gyrus; and (b) white matter in the right inferior longitudinal fasciculus (RILF), which interconnects the temporal and occipital lobes. Children with TLD exhibited a significantly lower CSF volume than children with SLI and children with SLI+RD respectively, who had somewhat smaller volumes of gray matter allowing for more CSF volume. The significant lower gray matter volume at the right postcentral parietal gyrus and greater cerebrospinal fluid volume may prove to be unique markers for SLI. We discuss the association of poor knowledge/visual representations and language input to brain development. Our comorbid study showed that a significant lower volume of white matter in the right

  11. Field guide to hydrothermal alteration in the White River altered area and in the Osceola Mudflow, Washington

    Science.gov (United States)

    John, David A.; Rytuba, James J.; Ashley, Roger P.; Blakely, Richard J.; Vallance, James W.; Newport, Grant R.; Heinemeyer, Gary R.

    2003-01-01

    . The morning of the trip will examine the White River altered area, which includes high-level alteration related to a large, early Miocene magmatic-hydrothermal system exposed about 10 km east of Enumclaw, Washington. Here, vuggy silica alteration is being quarried for silica and advanced argillic alteration has been prospected for alunite. Clay-filled fractures and sulfide-rich, fine-grained sedimentary rocks of hydrothermal origin locally are enriched in precious metals. Many hydrothermal features common in high-sulfidation gold-silver deposits and in advanced argillic alteration zones overlying porphyry copper deposits (for example, Gustafson and Hunt, 1975; Hedenquist and others, 2000; Sillitoe, 2000) are exposed, although no economic base or precious metal mineralized rock has been discovered to date. The afternoon will be spent examining two exposures of the Osceola Mudflow along the White River. The Osceola Mudflow contains abundant clasts of altered Quaternary rocks from Mount Rainier that show various types of hydrothermal alteration and hydrothermal features. The mudflow matrix contains abundant hydrothermal clay minerals that added cohesiveness to the debris flow and helped allow it to travel much farther down valley than other, noncohesive debris flows from Mount Rainier (Crandell, 1971; Vallance and Scott, 1997). The White River altered area is the subject of ongoing studies by geoscientists from Weyerhaeuser Company and the U.S. Geological Survey (USGS). The generalized descriptions of the geology, geophysics, alteration, and mineralization presented here represent the preliminary results of this study (Ashley and others, 2003). Additional field, geochemical, geochronologic, and geophysical studies are underway. The Osceola Mudflow and other Holocene debris flows from Mount Rainier also are the subject of ongoing studies by the USGS (for example, Breit and others, 2003; John and others, 2003; Plumlee and others, 2003, Sisson and others, 2003; Vallance and

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

    Science.gov (United States)

    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.

  13. 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.

  14. Cerebral perfusion and cerebrovascular reactivity are reduced in white matter hyperintensities

    DEFF Research Database (Denmark)

    Marstrand, J.R.; Garde, E; Rostrup, Egill;

    2002-01-01

    BACKGROUND AND PURPOSE: There is growing evidence that white matter hyperintensities (WMH) should not be considered as benign age-dependent changes on MR images but indicate pathological changes with clinical consequences. Previous studies comparing subjects with WMH to normal controls have...... reported global reductions in cerebral blood flow (CBF) and cerebral vascular reactivity. In this study, we examined localized hemodynamic status to compare WMH to normal appearing white matter (NAWM). METHODS: A group of 21 normal 85-year-old subjects were studied using dynamic contrast-enhanced MRI...... together with administration of acetazolamide. From a combination of anatomic images with different signal weighting, regions of interest were generated corresponding to gray and white matter and WMH. Localized measurements of CBF and cerebral blood volume (CBV) and mean transit time were obtained directly...

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

    Science.gov (United States)

    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.

  16. 1H MR spectroscopy of gray and white matter in carbon monoxide poisoning

    DEFF Research Database (Denmark)

    Kondziella, D.; Danielsen, E.R.; Hansen, K.;

    2009-01-01

    -acetyl aspartate (NAA) ratios to creatine (Cr), predominantly in the white matter. Lactate peaks were detected in two patients during the early phase of high-dose CO poisoning. Two patients with chronic low-dose CO exposure and without loss of consciousness had normal MRI and MRS scans. On follow-up. five of our...... limited information is available to date on the use of this protocol in determining the neurological effects of CO poisoning. To further examine the short-term and long-term effects of CO on the central nervous system, we have studied seven patients with CO poisoning assessed by gray and white matter MRS......, magnetic resonance imaging (MRI) and neuropsychological testing. Five patients suffered from acute high-dose CO intoxication and were in coma for 1-6 days. In these patients, MRI revealed hyperintensities of the white matter and globus pallidus and also showed increased choline (Cho) and decreased N...

  17. Dyslexia and voxel-based morphometry: correlations between five behavioural measures of dyslexia and gray and white matter volumes.

    Science.gov (United States)

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

    2015-10-01

    In voxel-based morphometry studies of dyslexia, the relation between causal theories of dyslexia and gray matter (GM) and white matter (WM) volume alterations is still under debate. Some alterations are consistently reported, but others failed to reach significance. We investigated GM alterations in a large sample of Dutch students (37 dyslexics and 57 non-dyslexics) with two analyses: group differences in local GM and total GM and WM volume and correlations between GM and WM volumes and five behavioural measures. We found no significant group differences after corrections for multiple comparisons although total WM volume was lower in the group of dyslexics when age was partialled out. We presented an overview of uncorrected clusters of voxels (p  200) with reduced or increased GM volume. We found four significant correlations between factors of dyslexia representing various behavioural measures and the clusters found in the first analysis. In the whole sample, a factor related to performances in spelling correlated negatively with GM volume in the left posterior cerebellum. Within the group of dyslexics, a factor related to performances in Dutch-English rhyme words correlated positively with GM volume in the left and right caudate nucleus and negatively with increased total WM volume. Most of our findings were in accordance with previous reports. A relatively new finding was the involvement of the caudate nucleus. We confirmed the multiple cognitive nature of dyslexia and suggested that experience greatly influences anatomical alterations depending on various subtypes of dyslexia, especially in a student sample.

  18. 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

  19. Improved sensitivity to cerebral white matter abnormalities in Alzheimer's disease with spherical deconvolution based tractography.

    Directory of Open Access Journals (Sweden)

    Yael D Reijmer

    Full Text Available Diffusion tensor imaging (DTI based fiber tractography (FT is the most popular approach for investigating white matter tracts in vivo, despite its inability to reconstruct fiber pathways in regions with "crossing fibers." Recently, constrained spherical deconvolution (CSD has been developed to mitigate the adverse effects of "crossing fibers" on DTI based FT. Notwithstanding the methodological benefit, the clinical relevance of CSD based FT for the assessment of white matter abnormalities remains unclear. In this work, we evaluated the applicability of a hybrid framework, in which CSD based FT is combined with conventional DTI metrics to assess white matter abnormalities in 25 patients with early Alzheimer's disease. Both CSD and DTI based FT were used to reconstruct two white matter tracts: one with regions of "crossing fibers," i.e., the superior longitudinal fasciculus (SLF and one which contains only one fiber orientation, i.e. the midsagittal section of the corpus callosum (CC. The DTI metrics, fractional anisotropy (FA and mean diffusivity (MD, obtained from these tracts were related to memory function. Our results show that in the tract with "crossing fibers" the relation between FA/MD and memory was stronger with CSD than with DTI based FT. By contrast, in the fiber bundle where one fiber population predominates, the relation between FA/MD and memory was comparable between both tractography methods. Importantly, these associations were most pronounced after adjustment for the planar diffusion coefficient, a measure reflecting the degree of fiber organization complexity. These findings indicate that compared to conventionally applied DTI based FT, CSD based FT combined with DTI metrics can increase the sensitivity to detect functionally significant white matter abnormalities in tracts with complex white matter architecture.

  20. 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

  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. White matter growth as a mechanism of cognitive development in children.

    Science.gov (United States)

    Mabbott, Donald J; Noseworthy, Michael; Bouffet, Eric; Laughlin, Suzanne; Rockel, Conrad

    2006-11-15

    We examined the functional role of white matter growth in cognitive development. Specifically, we used hierarchical regression analyses to test the unique contributions of age versus white matter integrity in accounting for the development of information processing speed. Diffusion tensor imaging was acquired for 17 children and adolescents (age range 6-17 years), with apparent diffusion coefficient (ADC) and fractional anisotropy (FA) calculated for 10 anatomically defined fiber pathways and 12 regions of hemispheric white matter. Measures of speeded visual-spatial searching, rapid picture naming, reaction time in a sustained attention task, and intelligence were administered. Age-related increases were evident across tasks, as well as for white matter integrity in hemispheric white matter. ADC was related to few measures. FA within multiple hemispheric compartments predicted rapid picture naming and standard error of reaction time in sustained attention, though it did not contribute significantly to the models after controlling for age. Independent of intelligence, visual-spatial searching was related to FA in a number of hemispheric regions. A novel finding was that only right frontal-parietal regions contributed uniquely beyond the effect of age in accounting for performance: age did not contribute to visual-spatial searching when FA within these regions was first included in the models. Considering we found that both FA in right frontal-parietal regions and speed of visual-spatial searching increased with age, our findings are consistent with the growth of regional white matter organization as playing an important role in increased speed of visual searching with age.

  3. 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.

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

    Science.gov (United States)

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

    2016-01-01

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

  5. White matter magnetic resonance hyperintensities in dementia of the Alzheimer type

    DEFF Research Database (Denmark)

    Waldemar, G; Christiansen, P; Larsson, H B

    1994-01-01

    In a prospective MRI study the presence, appearance, volume, and regional cerebral blood flow (rCBF) correlates of periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs) were examined in 18 patients with probable Alzheimer's disease and in 10 age matched healthy...... in the Alzheimer's disease group (p ... patients had extensive DWMH lesions in the central white matter. In the group of patients with Alzheimer's disease as a whole, the volume of DWMHs correlated well with rCBF in the hippocampal region ( r = -0.72; p

  6. Cerebral perfusion and cerebrovascular reactivity are reduced in white matter hyperintensities

    DEFF Research Database (Denmark)

    Marstrand, J.R.; Garde, E; Rostrup, Egill;

    2002-01-01

    reported global reductions in cerebral blood flow (CBF) and cerebral vascular reactivity. In this study, we examined localized hemodynamic status to compare WMH to normal appearing white matter (NAWM). METHODS: A group of 21 normal 85-year-old subjects were studied using dynamic contrast-enhanced MRI...... together with administration of acetazolamide. From a combination of anatomic images with different signal weighting, regions of interest were generated corresponding to gray and white matter and WMH. Localized measurements of CBF and cerebral blood volume (CBV) and mean transit time were obtained directly...

  7. 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.)

  8. Right lateralized white matter abnormalities in first-episode, drug-naive paranoid schizophrenia.

    Science.gov (United States)

    Guo, Wenbin; Liu, Feng; Liu, Zhening; Gao, Keming; Xiao, Changqing; Chen, Huafu; Zhao, Jingping

    2012-11-30

    Numerous studies in first-episode schizophrenia suggest the involvement of white matter (WM) abnormalities in multiple regions underlying the pathogenesis of this condition. However, there has never been a neuroimaging study in patients with first-episode, drug-naive paranoid schizophrenia by using tract-based spatial statistics (TBSS) method. Here, we used diffusion tensor imaging (DTI) with TBSS method to investigate the brain WM integrity in patients with first-episode, drug-naive paranoid schizophrenia. Twenty patients with first-episode, drug-naive paranoid schizophrenia and 26 healthy subjects matched with age, gender, and education level were scanned with DTI. An automated TBSS approach was employed to analyze the data. Voxel-wise statistics revealed that patients with paranoid schizophrenia had decreased fractional anisotropy (FA) values in the right superior longitudinal fasciculus (SLF) II, the right fornix, the right internal capsule, and the right external capsule compared to healthy subjects. Patients did not have increased FA values in any brain regions compared to healthy subjects. There was no correlation between the FA values in any brain regions and patient demographics and the severity of illness. Our findings suggest right-sided alterations of WM integrity in the WM tracts of cortical and subcortical regions may play an important role in the pathogenesis of paranoid schizophrenia.

  9. Magnetic resonance fiber density mapping of age-related white matter changes

    Energy Technology Data Exchange (ETDEWEB)

    Stadlbauer, Andreas, E-mail: andi@nmr.at [MR Physics Group, Department of Radiology, Landesklinikum St. Poelten, Propst Fuehrer Strasse 4, A-3100 St. Poelten (Austria); Department of Neurosurgery, University of Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen (Germany); Ganslandt, Oliver [Department of Neurosurgery, University of Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen (Germany); Salomonowitz, Erich [MR Physics Group, Department of Radiology, Landesklinikum St. Poelten, Propst Fuehrer Strasse 4, A-3100 St. Poelten (Austria); Buchfelder, Michael [Department of Neurosurgery, University of Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen (Germany); Hammen, Thilo [Department of Neurology, Epilepsy Center, University of Erlangen-Nuremberg, Schwabachanlage 6, D-90429 Erlangen (Germany); Bachmair, Johanna [MR Physics Group, Department of Radiology, Landesklinikum St. Poelten, Propst Fuehrer Strasse 4, A-3100 St. Poelten (Austria); Eberhardt, Knut [Krankenhaus Schloss Werneck, MRT-Kompetenzzentrum, Balthasar-Neumann-Platz 1, D-97440 Werneck (Germany)

    2012-12-15

    Objectives: To introduce fiber density mapping (FDM) for investigation of age-related white matter (WM) changes and to compare its capabilities with conventional diffusion tensor imaging (DTI) post-processing. Methods: DTI data with 1.9 mm{sup 3} isotropic voxels were acquired from 44 healthy volunteers (18–88 years) at 3 T. FDM is a 3-step approach which includes diagonalization of the diffusion tensor, fiber reconstruction for the whole brain, and calculation of fiber density (FD) values. Maps of fractional anisotropy (FA) and mean diffusivity (MD) were additionally calculated. Voxel-based analyses were performed to determine volume clusters of significant correlation with age. Bivariate linear regression models and Hotelling–Williams tests were used to detect significant differences between correlations. Results: FDM detected a larger WM volume affected by age-related changes concomitant with fewer significant clusters compared to FA and MD. This indicates that WM alterations due to normal aging occur rather globally than locally. FD values showed a significant stronger correlation with age in frontal lobes (prefrontal and precentral gyrus), limbic lobes (cingulate and parahippocampal gyrus), the corpus callosum (genu) and temporal lobes. Conclusions: FDM shows higher sensitivity for detection of age-related WM changes because it includes all surrounding fiber structures into the evaluation of each DTI data voxel.

  10. Abnormal organization of white matter networks in patients with subjective cognitive decline and mild cognitive impairment

    Science.gov (United States)

    Chen, Guan-Qun; Zhang, Yi-He; Li, Xuan-Yu; Hao, Xu-Yang; Yu, Yang; Zhang, Meng; Sheng, Can; Li, Yu-Xia; Sun, Yu; Li, Hong-Yan; Song, Yang; Li, Kun-Cheng; Yan, Tian-Yi; Tang, Xiao-Ying; Han, Ying

    2016-01-01

    Network analysis has been widely used in studying Alzheimer's disease (AD). However, how the white matter network changes in cognitive impaired patients with subjective cognitive decline (SCD) (a symptom emerging during early stage of AD) and amnestic mild cognitive impairment (aMCI) (a pre-dementia stage of AD) is still unclear. Here, structural networks were constructed respectively based on FA and FN for 36 normal controls, 21 SCD patients, and 33 aMCI patients by diffusion tensor imaging and graph theory. Significantly lower efficiency was found in aMCI patients than normal controls (NC). Though not significant, the values in those with SCD were intermediate between aMCI and NC. In addition, our results showed significantly altered betweenness centrality located in right precuneus, calcarine, putamen, and left anterior cingulate in aMCI patients. Furthermore, association was found between network metrics and cognitive impairment. Our study suggests that the structural network properties might be preserved in SCD stage and disrupted in aMCI stage, which may provide novel insights into pathological mechanisms of AD. PMID:27418146

  11. Failure to Modulate Attentional Control in Advanced Aging Linked to White Matter Pathology

    Science.gov (United States)

    Van Dijk, Koene R. A.; Shire, Emily H.; Sperling, Reisa A.; Johnson, Keith A.; Buckner, Randy L.

    2012-01-01

    Advanced aging is associated with reduced attentional control and less flexible information processing. Here, the origins of these cognitive effects were explored using a functional magnetic resonance imaging task that systematically varied demands to shift attention and inhibit irrelevant information across task blocks. Prefrontal and parietal regions previously implicated in attentional control were recruited by the task and most so for the most demanding task configurations. A subset of older individuals did not modulate activity in frontal and parietal regions in response to changing task requirements. Older adults who did not dynamically modulate activity underperformed their peers and scored more poorly on neuropsychological measures of executive function and speed of processing. Examining 2 markers of preclinical pathology in older adults revealed that white matter hyperintensities (WMHs), but not high amyloid burden, were associated with failure to modulate activity in response to changing task demands. In contrast, high amyloid burden was associated with alterations in default network activity. These results suggest failure to modulate frontal and parietal activity reflects a disruptive process in advanced aging associated with specific neuropathologic processes. PMID:21765181

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Clinical and functional outcome in a subject with bipolar disorder and severe white matter hyperintensities

    OpenAIRE

    Gianluca Serafini; Maurizio Pompili; Massimiliano Angelone; David Lester,; Paolo Girardi; Roberto Tatarelli

    2011-01-01

    Background and Objectives: Neuroimaging studies have found higher rates of white matter hyperintensities (WMHs) in patients with bipolar disorder (BD) of all ages, although whether BD is associated with increased rates of WMHs independently from age and cerebrovascular risk factors is still matter of debate. The outcome of BD associated with severe WMHs is generally poor, but several authors have suggested that some factors could have a protective role in BD. The aim of the present study was ...

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

    Science.gov (United States)

    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.

  15. White Matter Tracts Critical for Recognition of Sarcasm

    OpenAIRE

    Davis, Cameron; Oishi, Kenichi; Faria, Andreia; HSU, JOHN; Gomez, Yessenia; Mori, Susumu; Hillis, Argye E.

    2015-01-01

    Sarcasm is commonly used to express criticism in a non-aggressive or humorous way. Failure to understand that the speaker is being sarcastic can lead to important miscommunications. Although numerous studies have identified impaired sarcasm comprehension in neurological impaired patients, few have attempted to identify lesions that lead to impaired sarcasm. Several gray matter structures seem to be critical for processing sarcasm, including right prefrontal cortex, superior temporal cortex, t...

  16. White matter abnormalities correlating with memory and depression in heroin users under methadone maintenance treatment.

    Directory of Open Access Journals (Sweden)

    Wei-Che Lin

    Full Text Available Methadone maintenance treatment (MMT has elevated rates of co-morbid memory deficit and depression that are associated with higher relapse rates for substance abuse. White matter (WM disruption in MMT patients have been reported but their impact on these co-morbidities is unknown. This study aimed to investigate changes in WM integrity of MMT subjects using diffusion tensor image (DTI, and their relationship with history of heroin and methadone use in treated opiate-dependent individuals. The association between WM integrity changes from direct group comparisons and the severity of memory deficit and depression was also investigated. Differences in WM integrity between 35 MMT patients and 23 healthy controls were evaluated using DTI with tract-based spatial statistical analysis. Differences in DTI indices correlated with diminished memory function, Beck Depression Inventory, duration of heroin use and MMT, and dose of heroin and methadone administration. Changes in WM integrity were found in several WM regions, including the temporal and frontal lobes, pons, cerebellum, and cingulum bundles. The duration of MMT was associated with declining DTI indices in the superior longitudinal fasciculus and para-hippocampus. MMT patients had more memory and emotional deficits than healthy subjects. Worse scores in both depression and memory functions were associated with altered WM integrity in the superior longitudinal fasciculus, para-hippocampus, and middle cerebellar peduncle in MMT. Patients on MMT also had significant WM differences in the reward circuit and in depression- and memory-associated regions. Correlations among decreased DTI indices, disease severity, and accumulation effects of methadone suggest that WM alterations may be involved in the psychopathology and pathophysiology of co-morbidities in MMT.

  17. Abnormal organization of white matter network in patients with no dementia after ischemic stroke.

    Directory of Open Access Journals (Sweden)

    Lin Shi

    Full Text Available Structural changes after ischemic stroke could affect information communication extensively in the brain network. It is likely that the defects in the white matter (WM network play a key role in information interchange. In this study, we used graph theoretical analysis to examine potential organization alteration in the WM network architecture derived from diffusion tensor images from subjects with no dementia and experienced stroke in the past 5.4-14.8 months (N = 47, Mini-Mental Screening Examination, MMSE range 18-30, compared with a normal control group with 44 age and gender-matched healthy volunteers (MMSE range 26-30. Region-wise connectivity was derived from fiber connection density of 90 different cortical and subcortical parcellations across the whole brain. Both normal controls and patients with chronic stroke exhibited efficient small-world properties in their WM structural networks. Compared with normal controls, topological efficiency was basically unaltered in the patients with chronic stroke, as reflected by unchanged local and global clustering coefficient, characteristic path length, and regional efficiency. No significant difference in hub distribution was found between normal control and patient groups. Patients with chronic stroke, however, were found to have reduced betweenness centrality and predominantly located in the orbitofrontal cortex, whereas increased betweenness centrality and vulnerability were observed in parietal-occipital cortex. The National Institutes of Health Stroke Scale (NIHSS score of patient is correlated with the betweenness centrality of right pallidum and local clustering coefficient of left superior occipital gyrus. Our findings suggest that patients with chronic stroke still exhibit efficient small-world organization and unaltered topological efficiency, with altered topology at orbitofrontal cortex and parietal-occipital cortex in the overall structural network. Findings from this study could

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

    Science.gov (United States)

    da Silva Alves, Fabiana; Schmitz, Nicole; Bloemen, Oswald; van der Meer, Johan; Meijer, Julia; Boot, Erik; Nederveen, Aart; de Haan, Lieuwe; Linszen, Don; van Amelsvoort, Therese

    2011-10-01

    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 measured fractional anisotropy (FA) and WM volume in 27 adults with 22q11DS with schizophrenia (n=12, 22q11DS SCZ+) and without schizophrenia (n=15, 22q11DS SCZ-), 12 individuals with idiopathic schizophrenia and 31 age-matched healthy controls. We found widespread decreased WM volume in posterior and temporal brain areas and decreased FA in areas of the frontal cortex in the whole 22q11DS group compared to healthy controls. In 22q11DS SCZ+ compromised WM integrity included inferior frontal areas of parietal and occipital lobe. Idiopathic schizophrenia patients showed decreased FA in inferior frontal and insular regions compared to healthy controls. We found no WM alterations in 22q11DS SCZ+ vs. 22q11DS SCZ-. However, there was a negative correlation between FA and PANSS scores (Positive and Negative Symptom Scale) in the whole 22q11DS group in the inferior frontal, cingulate, insular and temporal areas. This is the first study to investigate WM integrity in adults with 22q11DS. Our results suggest that pervasive WM dysfunction is intrinsic to 22q11DS and that psychotic development in adults with 22q11DS involves similar brain areas as seen in schizophrenia in the general population.

  19. CSF T-Tau/Aβ42 predicts white matter microstructure in healthy adults at risk for Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Barbara B Bendlin

    Full Text Available Cerebrospinal fluid (CSF biomarkers T-Tau and Aβ(42 are linked with Alzheimer's disease (AD, yet little is known about the relationship between CSF biomarkers and structural brain alteration in healthy adults. In this study we examined the extent to which AD biomarkers measured in CSF predict brain microstructure indexed by diffusion tensor imaging (DTI and volume indexed by T1-weighted imaging. Forty-three middle-aged adults with parental family history of AD received baseline lumbar puncture and MRI approximately 3.5 years later. Voxel-wise image analysis methods were used to test whether baseline CSF Aβ(42, total tau (T-Tau, phosphorylated tau (P-Tau and neurofilament light protein predicted brain microstructure as indexed by DTI and gray matter volume indexed by T1-weighted imaging. T-Tau and T-Tau/Aβ(42 were widely correlated with indices of brain microstructure (mean, axial, and radial diffusivity, notably in white matter regions adjacent to gray matter structures affected in the earliest stages of AD. None of the CSF biomarkers were related to gray matter volume. Elevated P-Tau and P-Tau/Aβ(42 levels were associated with lower recognition performance on the Rey Auditory Verbal Learning Test. Overall, the results suggest that CSF biomarkers are related to brain microstructure in healthy adults with elevated risk of developing AD. Furthermore, the results clearly suggest that early pathological changes in AD can be detected with DTI and occur not only in cortex, but also in white matter.

  20. The Black-White achievement gap: Do state policies matter?

    Directory of Open Access Journals (Sweden)

    Henry I. Braun

    2006-03-01

    Full Text Available A longstanding issue in American education is the gap in academic achievement between majority and minority students. The goal of this study is to accumulate and evaluate evidence on the relationship between state education policies and changes in the Black-White achievement gap, while addressing some of the methodological issues that have led to differences in interpretations of earlier findings. To that end, we consider the experiences of ten states that together enroll more than forty percent of the nation's Black students. We estimate the trajectories of Black student and White student achievement on the NAEP 8th grade mathematics assessment over the period 1992 to 2000, and examine the achievement gap at three levels of aggregation: the state as a whole, groups of schools (strata within a state defined by the SES level of the student population, and within schools within a stratum within a state. From 1992 to 2000, at every level of aggregation, mean achievement rose for both Black students and White students. However, for most states the achievement gaps were large and changed very little at every level of aggregation. The gaps are pervasive, profound and persistent. There is substantial heterogeneity among states in the types of policies they pursued, as well as the coherence and consistency of those policies during the period 1988-1998. We find that states' overall policy rankings (based on our review of the data correlate moderately with their record in improving Black student achievement but are somewhat less useful in predicting their record with respect to reducing the achievement gaps. States' rankings on commitment to teacher quality correlate almost as well as did the overall policy ranking. Thus, state reform efforts are a blunt tool, but a tool nonetheless. Our findings are consistent with the following recommendations: states' reform efforts should be built on broad-based support and buffered as much as possible from changes in

  1. 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

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

    Directory of Open Access Journals (Sweden)

    K.A. Meijer

    2016-01-01

    Despite the presence of white matter damage, it was possible to reveal patterns of FA covariance across SPMS patients. This could indicate that white matter tracts belonging to the same cluster, and thus with similar characteristics, tend to follow similar trends during neurodegeneration. Furthermore, these underlying FA patterns might help to explain cognitive dysfunction in SPMS.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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…

  8. 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

  9. 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.

  10. 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.

  11. Unraveling pathology in juvenile Alexander disease: serial quantitative MR imaging and spectroscopy of white matter

    Energy Technology Data Exchange (ETDEWEB)

    Voorn, J.P. van der [VU University Medical Center, Department of Child Neurology, Amsterdam (Netherlands); VU University Medical Center, Department of Pathology, Amsterdam (Netherlands); Pouwels, Petra J.W. [VU University Medical Center, Department of Physics and Medical Technology, Amsterdam (Netherlands); Salomons, Gajja S. [VU University Medical Center, Department of Clinical Chemistry (Metabolic Unit), Amsterdam (Netherlands); Barkhof, Frederik [VU University Medical Center, Department of Radiology, Amsterdam (Netherlands); Knaap, Marjo S. van der [VU University Medical Center, Department of Child Neurology, Amsterdam (Netherlands)

    2009-10-15

    Alexander disease is a rare disorder of the central nervous system with characteristic symmetric white matter abnormalities with frontal predominance on magnetic resonance (MR) images. Histopathology shows a lack of myelin in the affected white matter, variably interpreted as hypomyelination or demyelination. To increase our insight into the nature of the pathology leading to the MR imaging findings in Alexander disease, we applied serial MR imaging, spectroscopy, magnetization transfer (MT) imaging (MTI), and diffusion tensor imaging (DTI) in six patients with juvenile Alexander disease. The MR imaging protocol comprised T1- and T2-weighted spin echo images and fluid-attenuated inversion recovery images. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), and MT ratio (MTR) maps were generated, and MR spectroscopy concentrations were quantified for several metabolites. MR imaging showed similar cerebral white matter abnormalities in all patients, with only minor increase on prolonged follow-up, despite sometimes serious clinical progression. MR spectroscopy showed highly elevated levels of myo-inositol, lactate, and choline-containing compounds and decreased total N-acetyl-aspartate and N-acetyl-aspartyl-glutamate levels in the abnormal white matter. High values of ADC were observed, and both FA and MTR were attenuated. The sequential MR imaging findings in Alexander disease provide strong evidence against active demyelination as sole explanation for the underlying pathology. An alternative explanation for our spectroscopic, DTI, and MTI findings - which would suggest demyelination - could be hyperplasia and hypertrophy of astrocytes, as seen in low grade gliomas. (orig.)

  12. 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.

  13. 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…

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

    Science.gov (United States)

    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.

  15. Cerebral white matter blood flow and energy metabolism in multiple sclerosis

    NARCIS (Netherlands)

    Steen, Christel; D'haeseleer, Miguel; Hoogduin, Johannes M.; Fierens, Yves; Cambron, Melissa; Mostert, Jop P.; Heersema, Dorothea J.; Koch, Marcus W.; De Keyser, Jacques

    2013-01-01

    Background: Cerebral blood flow (CBF) is reduced in normal-appearing white matter (NAWM) of subjects with multiple sclerosis (MS), but the underlying mechanism is unknown. Objective: The objective of this article is to assess the relationship between reduced NAWM CBF and both axonal mitochondrial me

  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. 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.

  18. In vivo evidence of cerebellar atrophy and cerebral white matter loss in Huntington disease

    DEFF Research Database (Denmark)

    Fennema-Notestine, C; Archibald, S.L.; Jacobsen, M.W.;

    2004-01-01

    OBJECTIVE: To investigate the regional pattern of white matter and cerebellar changes, as well as subcortical and cortical changes, in Huntington disease (HD) using morphometric analyses of structural MRI. METHODS: Fifteen individuals with HD and 22 controls were studied; groups were similar in a...

  19. 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.

  20. 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…

  1. 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.

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

    Science.gov (United States)

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

    2015-01-01

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

  3. 'White matter connectivity and Internet gaming disorder' and broader considerations in the field.

    Science.gov (United States)

    Tam, Philip G E

    2017-01-01

    This invited commentary on the paper 'White Matter Connectivity and Internet gaming disorder' by Jeong et al. (unpublished) looks at the implications and importance of the MRI findings in the present study-one of the largest to date-and also considers the broader developments of neuroimaging within the complex, emerging field of 'Internet psychology' and problematic Internet usage.

  4. 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…

  5. Myelination-related genes are associated with decreased white matter integrity in schizophrenia

    NARCIS (Netherlands)

    I. Chavarria-Siles (Ivan); T.J.H. White (Tonya); C. de Leeuw (Christiaan); A. Goudriaan (Andrea); E. Lips (Esther); S.M. Ehrlich (Stefan); J. Turner (Jessica); V.D. Calhoun Vince D. (V.); R.L. Gollub (Randy); V. Magnotta; E.-C. Ho (Eng-Choon); A.B. Smit (August B.); M.H.G. Verheijen (Mark H.); D. Posthuma (Danielle)

    2016-01-01

    textabstractDisruptions in white matter (WM) tract structures have been implicated consistently in the pathophysiology of schizophrenia. Global WM integrity - as measured by fractional anisotropy (FA) - is highly heritable and may provide a good endophenotype for genetic studies of schizophrenia. WM

  6. B-Cell Depletion Attenuates White and Gray Matter Pathology in Marmoset Experimental Autoimmune Encephalomyelitis

    NARCIS (Netherlands)

    Kap, Yolanda S.; Bauer, Jan; van Driel, Nikki; Bleeker, Wim K.; Parren, Paul W. H. I.; Kooi, Evert-Jan; Geurts, Jeroen J. G.; Laman, Jon D.; Craigen, Jenny L.; Blezer, Erwin; 't Hart, Bert A.

    2011-01-01

    This study investigated the effect of CD20-positive B-cell depletion on central nervous system (CNS) white and gray matter pathology in experimental autoimmune encephalomyelitis in common marmosets, a relevant preclinical model of multiple sclerosis. Experimental autoimmune encephalomyelitis was ind

  7. Age-related microvascular degeneration in the human cerebral periventricular white matter

    NARCIS (Netherlands)

    Farkas, E; de Vos, RAI; Donka, G; Steur, ENJ; Mihaly, A; Luiten, PGM; Vos, Rob A.I. de

    2006-01-01

    Clinical studies have identified white matter (WM) lesions as hyperintensive regions in the MRI images of elderly patients. Since a cerebrovascular origin was attributed to such lesions, the present analysis set out to define the microvascular histopathologic changes in the periventricular WM in the

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

    DEFF Research Database (Denmark)

    Plessen, Kerstin J; Grüner, Renate; Lundervold, Arvid

    2006-01-01

    , and these anatomical features have been understood to reflect neural plasticity that helps to attenuate the severity of tics. METHOD: CC white matter connectivity, as measured by the Fractional Anisotropy (FA) index from diffusion tensor images, was assessed in 20 clinically well-defined boys with Tourette syndrome...

  9. Peptidylarginine deiminase activity in postmortem white matter of patients with multiple sclerosis

    NARCIS (Netherlands)

    De Keyser, J; Schaaf, M; Teelken, A

    1999-01-01

    The myelin sheath in multiple sclerosis (MS) appears to contain a higher proportion of the citrullinated isoform of myelin basic protein MBP-C8. In vitro, MBP-associated arginine is deiminated to citrulline by the enzyme peptidylarginine deiminase (PAD). We investigated PAD activity in white matter

  10. 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...

  11. In vivo evidence of cerebellar atrophy and cerebral white matter loss in Huntington disease

    DEFF Research Database (Denmark)

    Fennema-Notestine, C; Archibald, S.L.; Jacobsen, M.W.;

    2004-01-01

    OBJECTIVE: To investigate the regional pattern of white matter and cerebellar changes, as well as subcortical and cortical changes, in Huntington disease (HD) using morphometric analyses of structural MRI. METHODS: Fifteen individuals with HD and 22 controls were studied; groups were similar in age...

  12. 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...

  13. 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.

  14. PGJ(2 provides prolonged CNS stroke protection by reducing white matter edema.

    Directory of Open Access Journals (Sweden)

    James D Nicholson

    Full Text Available Few clinically effective approaches reduce CNS-white matter injury. After early in-vivo white matter infarct, NFκB-driven pro-inflammatory signals can amplify a relatively small amount of vascular damage, resulting in progressive endothelial dysfunction to create a severe ischemic lesion. This process can be minimized by 15-deoxy-Δ(12,14-prostaglandin J2 (PGJ(2, an analog of the metabolically active PGD(2 metabolite. We evaluated PGJ(2's effects and mechanisms using rodent anterior ischemic optic neuropathy (rAION; an in vivo white matter ischemia model. PGJ(2 administration systemically administered either acutely or 5 hours post-insult results in significant neuroprotection, with stereologic evaluation showing improved neuronal survival 30 days post-infarct. Quantitative capillary vascular analysis reveals that PGJ(2 improves perfusion at 1 day post-infarct by reducing tissue edema. Our results suggest that PGJ(2 acts by reducing NFκB signaling through preventing p65 nuclear localization and inhibiting inflammatory gene expression. Importantly, PGJ(2 showed no in vivo toxicity structurally as measured by optic nerve (ON myelin thickness, functionally by ON-compound action potentials, on a cellular basis by oligodendrocyte precursor survival or changes in ON-myelin gene expression. PGJ(2 may be a clinically useful neuroprotective agent for ON and other CNS infarcts involving white matter, with mechanisms of action enabling effective treatment beyond the currently considered maximal time for intervention.

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

    Science.gov (United States)

    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...

  16. Diffusion tensor MR imaging of white matter integrity in HIV-positive patients with planning deficit

    Energy Technology Data Exchange (ETDEWEB)

    Correa, Diogo Goulart; Doring, Thomas M.; Wilner, Nina Ventura; Cabral, Rafael Ferracini; Gasparetto, Emerson Leandro [Hospital Universitario Clementino Fraga Filho, Rio de Janeiro, RJ (Brazil); Clinica de Diagnostico por Imagem (CDPI), Rio de Janeiro, RJ (Brazil); Zimmermann, Nicolle; Fonseca, Rochele Paz [Hospital Universitario Clementino Fraga Filho, Rio de Janeiro, RJ (Brazil); Pontifical Catholic University of Rio Grande do Sul, Department of Psychology, Rio Grande do Sul (Brazil); Leite, Sarah C.B.; Bahia, Paulo R.V. [Hospital Universitario Clementino Fraga Filho, Rio de Janeiro, RJ (Brazil)

    2015-05-01

    The aim of this study was to evaluate whether normal controls and human immunodeficiency virus (HIV) patients with and without planning deficits differ on white matter integrity. A total of 34 HIV-positive patients with planning deficits were compared with 13 HIV-positive patients without planning deficits and 19 gender-, age-, and education-matched control subjects. Diffusion tensor imaging (DTI) was performed along 30 noncolinear directions in a 1.5-T scanner. For tract-based spatial statistics analysis, a white matter skeleton was created, and a permutation-based inference with 5000 permutations with a threshold of p < 0.05 was used to identify abnormalities in fractional anisotropy (FA). The median, radial, and axial diffusivities were also projected onto the mean FA skeleton. Compared with controls, HIV-positive patients with planning deficits had decreased FA in bilateral anterior thalamic radiations, bilateral inferior fronto-occiptal fasciculi, genu and splenium of the corpus callosum, bilateral superior longitudinal fascicule, and bilateral uncinate fasciculi. Compared to HIV-positive patients without planning deficits, patients with planning deficits had decreased FA in bilateral anterior thalamic radiations, bilateral inferior fronto-occiptal fasciculi, genu of the corpus callosum, bilateral superior longitudinal fascicule, and right uncinate fascicule. DTI can detect extensive white matter abnormalities in the normal-appearing white matter of HIV-positive patients with planning deficits compared with controls and HIV-positive patients without planning deficits. (orig.)

  17. Cigarette smoking is associated with reduced microstructural integrity of cerebral white matter

    NARCIS (Netherlands)

    Gons, R.A.R.; Norden, A.G.W. van; Laat, K.F. de; Oudheusden, L.J. van; Uden, I.W.M. van; Zwiers, M.P.; Norris, D.G.; Leeuw, F.E. de

    2011-01-01

    Cigarette smoking doubles the risk of dementia and Alzheimer's disease. Various pathophysiological pathways have been proposed to cause such a cognitive decline, but the exact mechanisms remain unclear. Smoking may affect the microstructural integrity of cerebral white matter. Diffusion tensor imagi

  18. 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.

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

    NARCIS (Netherlands)

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

    2012-01-01

    In patients with multiple sclerosis (MS), a diffuse axonal degeneration occurring throughout the white matter of the central nervous system causes progressive neurologic disability. The underlying mechanism is unclear. This review describes a number of pathways by which dysfunctional astrocytes in M

  20. 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...

  1. The Structural Plasticity of White Matter Networks Following Anterior Temporal Lobe Resection

    Science.gov (United States)

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

    2010-01-01

    Anterior temporal lobe resection is an effective treatment for refractory temporal lobe epilepsy. The structural consequences of such surgery in the white matter, and how these relate to language function after surgery remain unknown. We carried out a longitudinal study with diffusion tensor imaging in 26 left and 20 right temporal lobe epilepsy…

  2. 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.

  3. 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…

  4. Clinical prediction of fall risk and white matter abnormalities: a diffusion tensor imaging study

    Science.gov (United States)

    The Tinetti scale is a simple clinical tool designed to predict risk of falling by focusing on gait and stance impairment in elderly persons. Gait impairment is also associated with white matter (WM) abnormalities. Objective: To test the hypothesis that elderly subjects at risk for falling, as deter...

  5. 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.)

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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).

  8. 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.)

  9. Differential white matter involvement associated with distinct visuospatial deficits after right hemisphere stroke.

    Science.gov (United States)

    Carter, Alex R; McAvoy, Mark P; Siegel, Joshua S; Hong, Xin; Astafiev, Serguei V; Rengachary, Jennifer; Zinn, Kristi; Metcalf, Nicholas V; Shulman, Gordon L; Corbetta, Maurizio

    2017-03-01

    Visuospatial attention depends on the integration of multiple processes, and people with right hemisphere lesions after a stroke may exhibit severe or no visuospatial deficits. The anatomy of core components of visuospatial attention is an area of intense interest. Here we examine the relationship between the disruption of core components of attention and lesion distribution in a heterogeneous group (N = 70) of patients with right hemisphere strokes regardless of the presence of clinical neglect. Deficits of lateralized spatial orienting, measured as the difference in reaction times for responding to visual targets in the contralesional or ipsilesional visual field, and deficits in re-orienting attention, as measured by the difference in reaction times for invalidly versus validly cued targets, were measured using a computerized spatial orienting task. Both measures were related through logistic regression and a novel ridge regression method to anatomical damage measured with magnetic resonance imaging. While many regions were common to both deficit maps, a deficit in lateralized spatial orienting was more associated with lesions in the white matter underlying the posterior parietal cortex, and middle and inferior frontal gyri. A deficit in re-orienting of attention toward unattended locations was associated with lesions in the white matter of the posterior parietal cortex, insular cortex and less so with white matter involvement of the anterior frontal lobe. An hodological analysis also supports this partial dissociation between the white matter tracts that are damaged in lateralized spatial biases versus impaired re-orienting. Our results underscore that the integrity of fronto-parietal white matter tracts is crucial for visuospatial attention and that different attention components are mediated by partially distinct neuronal substrates.

  10. White matter microstructure complements morphometry for predicting verbal memory in epilepsy.

    Science.gov (United States)

    McDonald, Carrie R; Leyden, Kelly M; Hagler, Donald J; Kucukboyaci, Nuri E; Kemmotsu, Nobuko; Tecoma, Evelyn S; Iragui, Vicente J

    2014-09-01

    Verbal memory is the most commonly impaired cognitive domain in patients with temporal lobe epilepsy (TLE). Although damage to the hippocampus and adjacent temporal lobe structures is known to contribute to memory impairment, little is known of the relative contributions of white versus gray matter structures, or whether microstructural versus morphometric measures of temporal lobe pathology are stronger predictors of impairment. We evaluate whether measures of temporal lobe pathology derived from diffusion tensor imaging (DTI; microstructural) versus structural MRI (sMRI; morphometric) contribute the most to memory performances in TLE, after controlling for hippocampal volume (HCV). DTI and sMRI were performed on 26 patients with TLE and 35 controls. Verbal memory was measured with the Logical Memory (LM) subtest of the Wechsler Memory Scale-III. Hierarchical regression analyses were performed to examine unique contributions of DTI and sMRI measures to verbal memory with HCV entered in block 1. In patients, impaired recall was associated with increased mean diffusivity (MD) of multiple fiber tracts that project through the temporal lobes. In addition, increased MD of the left cortical and bilateral pericortical white matter was associated with impaired recall. After controlling for left HCV, only microstructural measures of white matter pathology contributed to verbal recall. The best predictive model included left HCV and MD of the left inferior longitudinal fasciculus (ILF) and pericortical white matter beneath the left entorhinal cortex. This model explained 60% of the variance in delayed recall and revealed that MD of the left ILF was the strongest predictor. These data reveal that white matter microstructure within the temporal lobe can be used in conjunction with left HCV to enhance the prediction of verbal memory impairment, and speak to the complementary nature of DTI and sMRI for understanding cognitive dysfunction in epilepsy and possibly other memory

  11. Surface-based reconstruction and diffusion MRI in the assessment of gray and white matter damage in multiple sclerosis

    Science.gov (United States)

    Caffini, Matteo; Bergsland, Niels; LaganÃ, Marcella; Tavazzi, Eleonora; Tortorella, Paola; Rovaris, Marco; Baselli, Giuseppe

    2014-03-01

    Despite advances in the application of nonconventional MRI techniques in furthering the understanding of multiple sclerosis pathogenic mechanisms, there are still many unanswered questions, such as the relationship between gray and white matter damage. We applied a combination of advanced surface-based reconstruction and diffusion tensor imaging techniques to address this issue. We found significant relationships between white matter tract integrity indices and corresponding cortical structures. Our results suggest a direct link between damage in white and gray matter and contribute to the notion of gray matter loss relating to clinical disability.

  12. 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.

  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. 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.

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

    Science.gov (United States)

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

    2013-10-09

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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

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

    2016-08-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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

  20. 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.

  1. 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

  2. Gray and White Matter Contributions to Cognitive Frontostriatal Deficits in Non-Demented Parkinson's Disease.

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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.

  4. Seasonal variation of fluxes of dispersed sedimentary matter in the White Sea (Arctic ocean basin)

    Science.gov (United States)

    Lisitzin, A. P.; Novigatsky, A. N.; Klyuvitkin, A. A.

    2015-11-01

    The monthly and seasonal quantity estimates of vertical fluxes of sedimentary matter from the White Sea performed during studies are the basis for the direct calculations of incoming chemical components, minerals, and various pollutants to the surface layer of bottom sediments. The White Sea, one of six Russian Arctic seas, may be considered as a megapolygon for further modern research using the new regularities of arctic sedimentogenesis established. This study focuses on the development of new technologies for complex studies of marine water areas using underwater sedimentation observatories, regular observations onboard vessels, and satellite oceanological data. The first priority task is year-round monitoring along the Northern Sea Route.

  5. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Ruess, Lynne; Rusin, Jerome A. [Nationwide Children' s Hospital, Department of Radiology, Columbus, OH (United States); The Ohio State University College of Medicine and Public Health, Columbus, OH (United States); Dent, Carly M.; Tiarks, Hailey J.; Yoshida, Michelle A. [Nationwide Children' s Hospital, Department of Radiology, Columbus, OH (United States)

    2014-11-15

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

  7. Reduced frontal-subcortical white matter connectivity in association with suicidal ideation in major depressive disorder.

    Science.gov (United States)

    Myung, W; Han, C E; Fava, M; Mischoulon, D; Papakostas, G I; Heo, J-Y; Kim, K W; Kim, S T; Kim, D J H; Kim, D K; Seo, S W; Seong, J-K; Jeon, H J

    2016-06-07

    Major depressive disorder (MDD) and suicidal behavior have been associated with structural and functional changes in the brain. However, little is known regarding alterations of brain networks in MDD patients with suicidal ideation. We investigated whether or not MDD patients with suicidal ideation have different topological organizations of white matter networks compared with MDD patients without suicidal ideation. Participants consisted of 24 patients with MDD and suicidal ideation, 25 age- and gender-matched MDD patients without suicidal ideation and 31 healthy subjects. A network-based statistics (NBS) and a graph theoretical analysis were performed to assess differences in the inter-regional connectivity. Diffusion tensor imaging (DTI) was performed to assess topological changes according to suicidal ideation in MDD patients. The Scale for Suicide Ideation (SSI) and the Korean version of the Barrett Impulsiveness Scale (BIS) were used to assess the severity of suicidal ideation and impulsivity, respectively. Reduced structural connectivity in a characterized subnetwork was found in patients with MDD and suicidal ideation by utilizing NBS analysis. The subnetwork included the regions of the frontosubcortical circuits and the regions involved in executive function in the left hemisphere (rostral middle frontal, pallidum, superior parietal, frontal pole, caudate, putamen and thalamus). The graph theoretical analysis demonstrated that network measures of the left rostral middle frontal had a significant positive correlation with severity of SSI (r=0.59, P=0.02) and BIS (r=0.59, P=0.01). The total edge strength that was significantly associated with suicidal ideation did not differ between MDD patients without suicidal ideation and healthy subjects. Our findings suggest that the reduced frontosubcortical circuit of structural connectivity, which includes regions associated with executive function and impulsivity, appears to have a role in the emergence of suicidal

  8. Relationship between the suspended particulate matter and microorganisms in the White Sea waters

    Science.gov (United States)

    Kravchishina, M. D.; Mitzkevich, I. N.; Veslopolova, E. F.; Shevchenko, V. P.; Lisitzin, A. P.

    2008-12-01

    During the summer periods of 2003-2005, the spatial and vertical distributions of the suspended particulate matter and bacteria in stratified and homogeneous waters of the White Sea was studied. The results of the study of various quantitative characteristics of the suspended particulate matter (first of all, the area of the surface and the volumetric and mass concentrations) and the abundance of microorganisms in the water are discussed. A direct correlation between the value of the surface area of the suspended particulate matter and the total number of bacteria in the water is revealed. However, it was manifested only during the early summer period of the observations and was not expressed at the end of the summer. The enhanced surface area of the suspended particulate matter can indicate the higher biochemical activity of its particles. The influence of the pelitic fraction on the bacteria abundance in different parts of the sea during the summer is estimated.

  9. White matter cysts in patients with tuberous sclerosis; Quistes de sustancia blanca en pacientes con esclerosis tuberosa

    Energy Technology Data Exchange (ETDEWEB)

    Marti-Bonmati, L.; Dosda, R. [Hospital Universitario Dr. Peset. Servicio de Resonancia Magnetica ATQ-Quiron. Valencia (Spain); Menor, F. [Hospital Infantil La Fe. Valencia (Spain); Arana, E. [Hospital Casa de La Salud. Valencia (Spain); Poyatos, C. [Hospital Universitario Dr. Peset. Valencia (Spain)

    1999-07-01

    The presence of cysts in the white matter of the central nervous system of patients with tuberous sclerosis (TS) is an uncommon finding that has been reported only recently in neuroimaging studies. This article assesses the prevalence of these lesions in a large series of patients studied by magnetic resonance imaging (MRI) and their relationship to other epidemiological and imaging findings. MRI studies were performed in 46 patients (23 males and 23 females) with a mean age of 12.7 years, and the results were examined retrospectively in the search for cortical tubers, subependymal nodules and white matter nodules, lines and cysts. Nine patients (19.6%) presented cysts in white matter. Seven had only one cyst and the remaining two patients each had two. Multiple regression analysis relating the presence of the cysts with other neuroimaging findings in these patients revealed a statistically significant relationship only with white matter nodules (odds ratio: 7.5; p=0.006). White matter cysts are small, supratentorial lesions of deep location. There is a statistically relationship between the presence of these cysts and that of nodular lesions in the white matter. This finding supports the theory that the cyst originate from white matter nodules. (Author) 17 refs.

  10. Astroglial NF-kB contributes to white matter damage and cognitive impairment in a mouse model of vascular dementia.

    Science.gov (United States)

    Saggu, Raman; Schumacher, Toni; Gerich, Florian; Rakers, Cordula; Tai, Khalid; Delekate, Andrea; Petzold, Gabor C

    2016-08-04

    Vascular cognitive impairment is the second most common form of dementia. The pathogenic pathways leading to vascular cognitive impairment remain unclear but clinical and experimental data have shown that chronic reactive astrogliosis occurs within white matter lesions, indicating that a sustained pro-inflammatory environment affecting the white matter may contribute towards disease progression. To model vascular cognitive impairment, we induced prolonged mild cerebral hypoperfusion in mice by bilateral common carotid artery stenosis. This chronic hypoperfusion resulted in reactive gliosis of astrocytes and microglia within white matter tracts, demyelination and axonal degeneration, consecutive spatial memory deficits, and loss of white matter integrity, as measured by ultra high-field magnetic resonance diffusion tensor imaging. White matter astrogliosis was accompanied by activation of the pro-inflammatory transcription factor nuclear factor (NF)-kB in reactive astrocytes. Using mice expressing a dominant negative inhibitor of NF-kB under the control of the astrocyte-specific glial fibrillary acid protein (GFAP) promoter (GFAP-IkBα-dn), we found that transgenic inhibition of astroglial NF-kB signaling ameliorated gliosis and axonal loss, maintained white matter structural integrity, and preserved memory function. Collectively, our results imply that pro-inflammatory changes in white matter astrocytes may represent an important detrimental component in the pathogenesis of vascular cognitive impairment, and that targeting these pathways may lead to novel therapeutic strategies.

  11. 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.

  12. White matter microstructure in late middle-age: Effects of apolipoprotein E4 and parental family history of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Nagesh Adluru

    2014-01-01

    Conclusion: APOE4 genotype, parental family history of AD, age, and sex are all associated with microstructural white matter differences in late middle-aged adults. In participants at risk for AD, alterations in diffusion characteristics—both expected and unexpected—may represent cellular changes occurring at the earliest disease stages, but further work is needed. Higher mean, radial, and axial diffusivities were observed in participants who are more likely to be experiencing later stage preclinical pathology, including participants who were both older and carried APOE4, or who were positive for both APOE4 and parental family history of AD.

  13. Clinical significance of white matter hyperintensities in MRI in senile dementia of the Alzheimer type

    Energy Technology Data Exchange (ETDEWEB)

    Takita, Masashi [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1996-08-01

    To elucidate clinical significance of white matter hyperintensities (WMH) in MRI, fifty patients with senile dementia of the Alzheimer type (SDAT) and twenty normal controls were studied. Twenty nine patients with SDAT (58.0%) had periventricular hyperintensities (PVH) and twenty three patients with SDAT (46.0%) had deep white matter hyperintensities (DWMH). Eight controls (40.0%) had PVH and ten controls (50.0%) had DWMH. There were no significant differences in frequency of WMH between patients with SDAT and normal controls. Past history of hypertension was more frequent in patients with PVH or DWMH than in patients without them. Serum cholesterol level was higher in patients with DWMH than in patients without them. However there were no significant differences in the other clinical features between patients with WMH and patients without them. The results of present study suggest that DWMH in patients with SDAT is associated with cerebrovascular risk factors such as hypertension and hyperlipidemia. (author)

  14. [Interhemispheric disconnection, Balint's syndrome and persistent anarthria: Marchifava-Bignami disease with white matter hemorrhage].

    Science.gov (United States)

    Truffert, A; Dumas, J J; Dandelot, J B

    1996-03-01

    A 37-year-old alcoholic right-handed man developed a complex neuropsychological picture following a mild head injury and a severe confusional state. Prominent features were Balint's syndrome, signs of interhemispheric deconnection, and speech disorders with anarthria and dysprosody. Iterative CT scans showed pathognomonic hypodensities of the genu and splenium of corpus callosum, confirmative of Machiafava-Bignami disease. After a two years follow-up, a favourable outcome was observed despite haemmoragic transformation of bilateral necrotic lesions of the parietal white matter, an exceptional neuropathological fact. This case is demonstrative of the possibility of articulate speech impairment when lesions of both corpus callosum and subcortical white matter are present. It also raises several aetiopathogenic problems which are discussed.

  15. 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.

  16. Occipital deep white matter hyperintensity as seen by MRI, 1; Clinical significance

    Energy Technology Data Exchange (ETDEWEB)

    Miyazaki, Masahito; Hashimoto, Toshiaki; Tayama, Masanobu; Kuroda, Yasuhiro (Tokushima Univ. (Japan). School of Medicine)

    1992-05-01

    Magnetic resonance imaging was performed in 270 patients with various neurologic complaints (1-15Y) with a 0.5 tesla superconducting imaging system using a field echo T1-weighted sequence and spin echo T2-weighted and PD-weighted sequences. Twenty-seven of them had deep white matter hyperintensity (DWMH) in the occipital lobe on T2-weighted images. The frequency of mild DWMH differed in different age groups, suggesting that mild DWMH may result from delayed myelination in the central nervous system. However, the frequency of severe DWMH, which was revealed as isointense relative to cerebrospinal fluid, did not differ in different age groups and it was significantly more common in severely retarded patients. Classification of DWMH based on the signal intensity is valuable to distinguish white matter abnormalities in the occipital lobe from delayed myelination in the same site. (author).

  17. 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....

  18. A correlative study between white matter lesions of migraine and patent foramen ovale

    Directory of Open Access Journals (Sweden)

    Qiang ZHANG

    2014-09-01

    Full Text Available Migraine is a kind of common primary headache, which seriously damages human health and quality of life. Recent studies show there is a high incidence of white matter lesions (WML in migraineurs, which is independent of other risk factors for cerebrovascular diseases. The patent foramen ovale (PFO in migraineurs, especially in migraineurs with aura, is more common than in general population. There is a close relationship between them, but it is controversial whether it is a causal link. Patent foramen ovale can cause paradoxical embolism, but its role in the pathogenesis of migraine is still unknown. It is worth exploring whether there is difference in white matter lesions between the migraineurs with and without patent foramen ovale. doi: 10.3969/j.issn.1672-6731.2014.09.015

  19. 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.

  20. 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

  1. Age-related slowing of memory retrieval: Contributions of perceptual speed and cerebral white matter integrity

    Science.gov (United States)

    Bucur, Barbara; Madden, David J.; Spaniol, Julia; Provenzale, James M.; Cabeza, Roberto; White, Leonard E.; Huettel, Scott A.

    2007-01-01

    Previous research suggests that, in reaction time (RT) measures of episodic memory retrieval, the unique effects of adult age are relatively small compared to the effects aging shares with more elementary abilities such as perceptual speed. Little is known, however, regarding the mechanisms of perceptual speed. We used diffusion tensor imaging (DTI) to test the hypothesis that white matter integrity, as indexed by fractional anisotropy (FA), serves as one mechanism of perceptual slowing in episodic memory retrieval. Results indicated that declines in FA in the pericallosal frontal region and in the genu of the corpus callosum, but not in other regions, mediated the relationship between perceptual speed and episodic retrieval RT. This relation held, though to a different degree, for both hits and correct rejections. These findings suggest that white matter integrity in prefrontal regions is one mechanism underlying the relation between individual differences in perceptual speed and episodic retrieval. PMID:17383774

  2. Dimensions of Attention Associated With the Microstructure of Corona Radiata White Matter.

    Science.gov (United States)

    Stave, Elise A; De Bellis, Michael D; Hooper, Steven R; Woolley, Donald P; Chang, Suk Ki; Chen, Steven D

    2017-01-01

    Mirsky proposed a model of attention that included these dimensions: focus/execute, sustain, stabilize, encode, and shift. The neural correlates of these dimensions were investigated within corona radiata subregions in healthy youth. Diffusion tensor imaging and neuropsychological assessments were conducted in 79 healthy, right-handed youth aged 4-17 years. Diffusion tensor imaging maps were analyzed using standardized parcellation methods. Partial Pearson correlations between neuropsychological standardized scores, representing these attention dimensions, and diffusion tensor imaging measures of corona radiata subregions were calculated after adjusting for gender and IQ. Significant correlations were found between the focus/execute, sustain, stabilize, and shift dimensions and imaging metrics in hypothesized corona radiata subregions. Results suggest that greater microstructural white matter integrity of the corona radiata is partly associated with attention across 4 attention dimensions. Findings suggest that white matter microstructure of the corona radiata is a neural correlate of several, but not all, attention dimensions.

  3. 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.

  4. 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.

  5. 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 ...

  6. 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

  7. 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

  8. In vivo parahippocampal white matter pathology as a biomarker of disease progression to Alzheimer's disease.

    Science.gov (United States)

    Solodkin, Ana; Chen, E Elinor; Van Hoesen, Gary W; Heimer, Lennart; Shereen, Ahmed; Kruggel, Frithjof; Mastrianni, James

    2013-12-15

    Noninvasive diagnostic tests for Alzheimer's disease (AD) are limited. Postmortem diagnosis is based on density and distribution of neurofibrillary tangles (NFTs) and amyloid-rich neuritic plaques. In preclinical stages of AD, the cells of origin for the perforant pathway within the entorhinal cortex are among the first to display NFTs, indicating its compromise in early stages of AD. We used diffusion tensor imaging (DTI) to assess the integrity of the parahippocampal white matter in mild cognitive impairment (MCI) and AD, as a first step in developing a noninvasive tool for early diagnosis. Subjects with AD (N = 9), MCI (N = 8), or no cognitive impairment (NCI; N = 20) underwent DTI-MRI. Fractional anisotropy (FA) and mean (MD) and radial (RD) diffusivity measured from the parahippocampal white matter in AD and NCI subjects differed greatly. Discriminant analysis in the MCI cases assigned statistical membership of 38% of MCI subjects to the AD group. Preliminary data 1 year later showed that all MCI cases assigned to the AD group either met the diagnostic criteria for probable AD or showed significant cognitive decline. Voxelwise analysis in the parahippocampal white matter revealed a progressive change in the DTI patterns in MCI and AD subjects: whereas converted MCI cases showed structural changes restricted to the anterior portions of this region, in AD the pathology was generalized along the entire anterior-posterior axis. The use of DTI for in vivo assessment of the parahippocampal white matter may be useful for identifying individuals with MCI at highest risk for conversion to AD and for assessing disease progression.

  9. 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...

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

    Directory of Open Access Journals (Sweden)

    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

  11. 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.

  12. 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...

  13. 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

  14. Diffuse Cerebral White Matter T2-Weighted Hyperintensity: A New Finding of General Paresis

    Energy Technology Data Exchange (ETDEWEB)

    Alam, F.; Yasutomi, H.; Fukuda, H.; Horiguchi, J.; Murakami, Y.; Ohshita, T.; Inoue, K.; Ito, K. [Graduate School of Biomedical Sciences, Hiroshima Univ. (Japan). Depts. of Radiology, and Clinical Neurosciences and Therapeutics

    2006-07-15

    General paresis (parenchymatous neurosyphilis) is a rare disease, and in recent years the number of papers published on the magnetic resonance imaging findings has been limited. The findings are as follows: cerebral atrophy; mesiotemporal T2 hyperintensity; ventriculomegaly; pathological T2 hypointensity of the globus pallidus, putamen, the head of the caudate nucleus and thalamus. We present a new finding, diffuse cerebral white matter T2 hyperintensity, observed in a patient with general paresis with a 5-year history of progressive dementia.

  15. Ion channel expression by white matter glia: I. Type 2 astrocytes and oligodendrocytes.

    Science.gov (United States)

    Barres, B A; Chun, L L; Corey, D P

    1988-01-01

    White matter is a compact structure consisting primarily of neuronal axons and glial cells. As in other parts of the nervous system, the function of glial cells in white matter is poorly understood. We have explored the electrophysiological properties of two types of glial cells found predominantly in white matter: type 2 astrocytes and oligodendrocytes. Whole-cells and single-channel patch-clamp techniques were used to study these cell types in postnatal rat optic nerve cultures prepared according to the procedures of Raff et al. (Nature, 303:390-396, 1983b). Type 2 astrocytes in culture exhibit a "neuronal" channel phenotype, expressing at least six distinct ion channel types. With whole-cell recording we observed three inward currents: a voltage-sensitive sodium current qualitatively similar to that found in neurons and both transient and sustained calcium currents. In addition, type 2 astrocytes had two components of outward current: a delayed potassium current which activated at 0 mV and an inactivating calcium-dependent potassium current which activated at -30 mV. Type 2 astrocytes in culture could be induced to fire single regenerative potentials in response to injections of depolarizing current. Single-channel recording demonstrated the presence of an outwardly rectifying chloride channel in both type 2 astrocytes and oligodendrocytes, but this channel could only be observed in excised patches. Oligodendrocytes expressed only one other current: an inwardly rectifying potassium current that is mediated by 30- and 120-pS channels. Because these channels preferentially conduct potassium from outside to inside the cell, and because they are open at the resting potential of the cell, they would be appropriate for removing potassium from the extracellular space; thus it is proposed that oligodendrocytes, besides myelinating axons, play an important role in potassium regulation in white matter. The conductances present in oligodendrocytes suggest a "modulated

  16. 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

  17. Cerebellar hypoplasia and brainstem thinning associated with severe white matter and basal ganglia abnormalities in a child with an mtDNA deletion.

    Science.gov (United States)

    Biancheri, Roberta; Bruno, Claudio; Cassandrini, Denise; Bertini, Enrico; Santorelli, Filippo M; Rossi, Andrea

    2011-12-01

    Cerebellar and brainstem hypoplasia may occur in different conditions, including those disorders designated as pontocerebellar hypoplasia (PCH). In particular, when PCH is combined with severe supratentorial white matter involvement and cerebral atrophy, mutations in the mitochondrial arginyl-tRNA synthethase (RARS2) gene causing PCH6 are possible. We describe a patient with a lethal mitochondrial encephalomyopathy due to a mtDNA deletion and no alterations in RARS2, whose magnetic resonance (MR) findings mimicked PCH6. A thorough diagnostic work-up for mitochondrial disorders should be carried out when facing with a PCH-like and severe white matter and basal ganglia involvement on brain MR imaging in children, even if clinical and laboratory mitochondrial "stigmata" are scant or nonspecific.

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

    Science.gov (United States)

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

    2013-04-01

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

  19. Unusual progression of herpes simplex encephalitis with basal ganglia and extensive white matter involvement

    Directory of Open Access Journals (Sweden)

    Yasuhiro Manabe

    2009-08-01

    Full Text Available We report a 51-year old male with herpes simplex encephalitis (HSE showing unusual progression and magnetic resonance (MR findings. The initial neurological manifestation of intractable focal seizure with low-grade fever persisted for three days, and rapidly coma, myoclonic status, and respiratory failure with high-grade fever emerged thereafter. The polymerase chain reaction (PCR result of cerebrospinal fluid (CSF was positive for HSV-1 DNA. In the early stage, MR images (MRI were normal. On subsequent MR diffusion-weighted (DW and fluid-attenuated inversion recovery (FLAIR images, high-intensity areas first appeared in the left frontal cortex, which was purely extra-temporal involvement, and extended into the basal ganglia, then the white matter, which are relatively spared in HSE. Antiviral therapy and immunosuppressive therapy did not suppress the progression of HSE, and finally severe cerebral edema developed into cerebral herniation, which required emergency decompressive craniectomy. Histological examination of a biopsy specimen of the white matter detected perivascular infiltration and destruction of basic structure, which confirmed non specific inflammatory change without obvious edema or demyelination. The present case shows both MR and pathological findings in the white matter in the acute stage of HSE.

  20. 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.

  1. 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.

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

    Science.gov (United States)

    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.

  3. 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.

  4. Relations between the geometry of cortical gyrification and white-matter network architecture.

    Science.gov (United States)

    Henderson, James A; Robinson, Peter A

    2014-03-01

    A geometrically based network model of cortico-cortical white-matter connectivity is used in combination with diffusion spectrum MRI (DSI) data to show that white-matter cortical network architecture is founded on a homogeneous, isotropic geometric connection principle. No other special information about single connections or groups of connections is required to generate networks very similar to experimental ones. This model provides excellent agreement with experimental DSI frequency distributions of network measures-degree, clustering coefficient, path length, and betweenness centrality. In the model, these distributions are a result of geometrically induced spatial variations in the values of these measures with deep nodes having more hublike properties than superficial nodes. This leads to experimentally testable predictions of corresponding variations in real cortexes. The convoluted geometry of the cortex is also found to introduce weak modularity, similar to the lobe structure of the cortex, with the boundaries between modules having hublike properties. These findings mean that some putative discoveries regarding the structure of white-matter cortical networks are simply artifacts and/or consequences of geometry. This model may help provide insight into diseases associated with differences in gyrification as well as evolutionary development of the cortex.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Grey and White Matter Clinico-Anatomical Correlates of Disinhibition in Neurodegenerative Disease

    Science.gov (United States)

    Santillo, Alexander Frizell; Lundblad, Karl; Nilsson, Markus; Landqvist Waldö, Maria; van Westen, Danielle; Lätt, Jimmy; Blennow Nordström, Erik; Vestberg, Susanna; Lindberg, Olof; Nilsson, Christer

    2016-01-01

    Disinhibition is an important symptom in neurodegenerative diseases. However, the clinico-anatomical underpinnings remain controversial. We explored the anatomical correlates of disinhibition in neurodegenerative disease using the perspective of grey and white matter imaging. Disinhibition was assessed with a neuropsychological test and a caregiver information-based clinical rating scale in 21 patients with prefrontal syndromes due to behavioural variant frontotemporal dementia (n = 12) or progressive supranuclear palsy (n = 9), and healthy controls (n = 25). Cortical thickness was assessed using the Freesurfer software on 3T MRI data. The integrity of selected white matter tracts was determined by the fractional anisotropy (FA) from Diffusion Tensor Imaging. Disinhibition correlated with the cortical thickness of the right parahippocampal gyrus, right orbitofrontal cortex and right insula and the FA of the right uncinate fasciculus and right anterior cingulum. Notably, no relationship was seen with the thickness of ventromedial prefrontal cortex. Our results support an associative model of inhibitory control, distributed in a medial temporal lobe-insular-orbitofrontal network, connected by the intercommunicating white matter tracts. This reconciles some of the divergences among previous studies, but also questions the current conceptualisation of the “prefrontal” syndrome and the central role attributed to the ventromedial prefrontal