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Sample records for white matter region

  1. Brain region white matter associations with visual selective attention.

    PubMed

    Seiler, Christie Burger; Jones, Kelly E; Shera, David; Armstrong, Carol L

    2011-12-01

    To understand how normal variations in white matter relate to cognition, magnetization transfer imaging ratios (MTR) of a hypothesized neural network were associated with a test of visual selective attention (VST). Healthy adults (N?=?16) without abnormal signal on brain scans viewed a version of DeSchepper and Treisman's test of VST (1996) with two levels of processing (novel shape matching with and without distractors, contingency feedback). A hypothesized neural network and component regions was significantly associated with accuracy and response times when distractors were present, with betas predicting 55% of variance in accuracy, and 59% of response times. MTR for anterior and posterior cingulate, prefrontal region, and thalami comprised a model predicting 55% of accuracy when distractors were present, and the anterior cingulate accounted for the majority of this effect. Prefrontal MTR predicted longer response times which was associated with increased accuracy. Distal neural areas involved in complex, processing-driven tasks (error processing, response selection, and variable response competition and processing load) may be dependent on white matter fibers to connect distal brain regions/nuclei of a macronetwork, including prefrontal executive functions. PMID:21720733

  2. Regional white matter volumes correlate with delay discounting.

    PubMed

    Yu, Rongjun

    2012-01-01

    A preference for immediate gratification is a central feature in addictive processes. However, the neural structures underlying reward delay tolerance are still unclear. Healthy participants (n?=?121) completed a delay discounting questionnaire assessing the extent to which they prefer smaller immediate rewards to larger delayed reward after undergoing magnetic resonance imaging (MRI) scanning. Whole brain voxel-based morphometric analysis shows that delay discounting severity was negatively correlated with right prefrontal subgyral white matter volume and positively correlated with white matter volume in parahippocampus/hippocampus, after whole brain correction. This study might better our understanding of the neural basis of impulsivity and addiction. PMID:22393420

  3. Vanishing White Matter Disease

    MedlinePLUS

    ... Vanishing White Matter Disease What is Vanishing White Matter Disease? Vanishing White Matter Disease (VWM) is inherited ... about this). Other Clinical Names for Vanishing White Matter Disease Other clinical names of Vanishing White Matter ...

  4. Regional White Matter Damage Predicts Speech Fluency in Chronic Post-Stroke Aphasia

    PubMed Central

    Basilakos, Alexandra; Fillmore, Paul T.; Rorden, Chris; Guo, Dazhou; Bonilha, Leonardo; Fridriksson, Julius

    2014-01-01

    Recently, two different white matter regions that support speech fluency have been identified: the aslant tract and the anterior segment of the arcuate fasciculus (ASAF). The role of the ASAF was demonstrated in patients with post-stroke aphasia, while the role of the aslant tract shown in primary progressive aphasia. Regional white matter integrity appears to be crucial for speech production; however, the degree that each region exerts an independent influence on speech fluency is unclear. Furthermore, it is not yet defined if damage to both white matter regions influences speech in the context of the same neural mechanism (stroke-induced aphasia). This study assessed the relationship between speech fluency and quantitative integrity of the aslant region and the ASAF. It also explored the relationship between speech fluency and other white matter regions underlying classic cortical language areas such as the uncinate fasciculus and the inferior longitudinal fasciculus (ILF). Damage to these regions, except the ILF, was associated with speech fluency, suggesting synergistic association of these regions with speech fluency in post-stroke aphasia. These observations support the theory that speech fluency requires the complex, orchestrated activity between a network of pre-motor, secondary, and tertiary associative cortices, supported in turn by regional white matter integrity. PMID:25368572

  5. Aging White Matter and Cognition: Differential Effects of Regional Variations in Diffusion Properties on Memory, Executive Functions, and Speed

    ERIC Educational Resources Information Center

    Kennedy, Kristen M.; Raz, Naftali

    2009-01-01

    Disruption of cerebral white matter has been proposed as an explanation for age-related cognitive declines. However, the role of specific regions in specific cognitive declines remains unclear. We used diffusion tensor imaging to examine the associations between regional microstructural integrity of the white matter and performance on…

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

    PubMed

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

    2015-06-15

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

  7. The Relationship between Processing Speed and Regional White Matter Volume in Healthy Young People.

    PubMed

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

    2015-01-01

    Processing speed is considered a key cognitive resource and it has a crucial role in all types of cognitive performance. Some researchers have hypothesised the importance of white matter integrity in the brain for processing speed; however, the relationship at the whole-brain level between white matter volume (WMV) and processing speed relevant to the modality or problem used in the task has never been clearly evaluated in healthy people. In this study, we used various tests of processing speed and Voxel-Based Morphometry (VBM) analyses, it is involves a voxel-wise comparison of the local volume of gray and white, to assess the relationship between processing speed and regional WMV (rWMV). We examined the association between processing speed and WMV in 887 healthy young adults (504 men and 383 women; mean age, 20.7 years, SD, 1.85). We performed three different multiple regression analyses: we evaluated rWMV associated with individual differences in the simple processing speed task, word-colour and colour-word tasks (processing speed tasks with words) and the simple arithmetic task, after adjusting for age and sex. The results showed a positive relationship at the whole-brain level between rWMV and processing speed performance. In contrast, the processing speed performance did not correlate with rWMV in any of the regions examined. Our results support the idea that WMV is associated globally with processing speed performance regardless of the type of processing speed task. PMID:26397946

  8. The Relationship between Processing Speed and Regional White Matter Volume in Healthy Young People

    PubMed Central

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

    2015-01-01

    Processing speed is considered a key cognitive resource and it has a crucial role in all types of cognitive performance. Some researchers have hypothesised the importance of white matter integrity in the brain for processing speed; however, the relationship at the whole-brain level between white matter volume (WMV) and processing speed relevant to the modality or problem used in the task has never been clearly evaluated in healthy people. In this study, we used various tests of processing speed and Voxel-Based Morphometry (VBM) analyses, it is involves a voxel-wise comparison of the local volume of gray and white, to assess the relationship between processing speed and regional WMV (rWMV). We examined the association between processing speed and WMV in 887 healthy young adults (504 men and 383 women; mean age, 20.7 years, SD, 1.85). We performed three different multiple regression analyses: we evaluated rWMV associated with individual differences in the simple processing speed task, word–colour and colour–word tasks (processing speed tasks with words) and the simple arithmetic task, after adjusting for age and sex. The results showed a positive relationship at the whole-brain level between rWMV and processing speed performance. In contrast, the processing speed performance did not correlate with rWMV in any of the regions examined. Our results support the idea that WMV is associated globally with processing speed performance regardless of the type of processing speed task. PMID:26397946

  9. White matter dementia

    PubMed Central

    2012-01-01

    White matter dementia (WMD) is a syndrome introduced in 1988 to highlight the potential of cerebral white matter disorders to produce cognitive loss of sufficient severity to qualify as dementia. Neurologists have long understood that such a syndrome can occur, but the dominance of gray matter as the locus of higher function has strongly directed neurobehavioral inquiry to the cerebral cortex while white matter has received less attention. Contemporary neuroimaging has been crucial in enabling the recognition of white matter abnormalities in a host of disorders, and the correlation of these changes with cognitive performance. Comprising about half the brain, white matter is prominently or exclusively involved in well over 100 disorders, in each of which white matter dysfunction can potentially cause or contribute to dementia. Neuropsychological findings from ten categories of white matter disorder lead to a convergence of findings that document remarkable neurobehavioral commonality among the dementias produced. More recently, the syndrome of mild cognitive dysfunction (MCD) has been introduced to expand the concept of WMD by proposing a precursor syndrome related to early white matter neuropathology. WMD and MCD inform the understanding of how white matter contributes to normal and abnormal cognition, and the specific neuroanatomic focus of these syndromes may enhance the diagnosis and treatment of many disabling disorders that do not primarily implicate the cerebral cortex. Forming essential connections within widely distributed neural networks, white matter is critical for rapid and efficient information transfer that complements the information processing of gray matter. As neuroimaging continues to advance, further information on white matter structure can be expected, and behavioral neurology will play a central role in elucidating the functional significance of these emerging data. By emphasizing the contribution of myelinated systems to higher function, the study of white matter and cognition represents investigation of the basic neuroscience of human behavior. PMID:22973423

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

    PubMed

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

    2012-12-01

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

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

    ERIC Educational Resources Information Center

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

    2011-01-01

    Working memory is the limited capacity storage system involved in the maintenance and manipulation of information over short periods of time. Previous imaging studies have suggested that the frontoparietal regions are activated during working memory tasks; a putative association between the structure of the frontoparietal regions and working…

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

    PubMed Central

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

    2013-01-01

    The human brain undergoes rapid and dynamic development early in life. Assessment of brain growth patterns relevant to neurological disorders and disease requires a normative population model of growth and variability in order to evaluate deviation from typical development. In this paper, we focus on maturation of brain white matter as shown in diffusion tensor MRI (DT-MRI), measured by fractional anisotropy (FA), mean diffusivity (MD), as well as axial and radial diffusivities (AD, RD). We present a novel methodology to model temporal changes of white matter diffusion from longitudinal DT-MRI data taken at discrete time points. Our proposed framework combines nonlinear modeling of trajectories of individual subjects, population analysis, and testing for regional differences in growth pattern. We first perform deformable mapping of longitudinal DT-MRI of healthy infants imaged at birth, 1 year, and 2 years of age, into a common unbiased atlas. An existing template of labeled white matter regions is registered to this atlas to define anatomical regions of interest. Diffusivity properties of these regions, presented over time, serve as input to the longitudinal characterization of changes. We use non-linear mixed effect (NLME) modeling where temporal change is described by the Gompertz function. The Gompertz growth function uses intuitive parameters related to delay, rate of change, and expected asymptotic value; all descriptive measures which can answer clinical questions related to quantitative analysis of growth patterns. Results suggest that our proposed framework provides descriptive and quantitative information on growth trajectories that can be interpreted by clinicians using natural language terms that describe growth. Statistical analysis of regional differences between anatomical regions which are known to mature differently demonstrates the potential of the proposed method for quantitative assessment of brain growth and differences thereof. This will eventually lead to a prediction of white matter diffusion properties and associated cognitive development at later stages given imaging data at early stages. PMID:23235270

  13. White matter of the brain

    MedlinePLUS

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

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

    PubMed

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

    2014-01-01

    Self-disclosure is an important performance in human social communication. Generally, an individual is likely to have a good physical and mental health if he is prone to self-disclosure under stressful life events. However, as for now, little is known about the neural structure associated with self-disclosure. Therefore, in this study, we used voxel-based morphometry to explore regional gray matter volume (rGMV) and white matter volume (rWMV) associated with self-disclosure measured by the Jourard Self-disclosure Questionnaire in a large sample of college students. Results showed that individual self-disclosure was significantly and positively associated with rGMV of the left postcentral gyrus, which might be related to strengthen individual's ability of body feeling; while self-disclosure was significantly and negatively associated with rGMV of the right orbitofrontal cortex (OFC), which might be involved in increased positive emotion experience seeking (intrinsically rewarding). In addition, individual self-disclosure was also associated with smaller rWMV in the right inferior parietal lobule (IPL). These findings suggested a biological basis for individual self-disclosure, distributed across different gray and white matter areas of the brain. PMID:24899238

  15. White Space Regions

    NASA Astrophysics Data System (ADS)

    Ehsani, Shayan; Fazli, Mohammadamin; Ghodsi, Mohammad; Safari, Mohammadali; Saghafian, Morteza; Tavakkoli, Mohammad

    We study a classical problem in communication and wireless networks called Finding White Space Regions. In this problem, we are given a set of antennas (points) some of which are noisy (black) and the rest are working fine (white). The goal is to find a set of convex hulls with maximum total area that cover all white points and exclude all black points. In other words, these convex hulls make it safe for white antennas to communicate with each other without any interference with black antennas. We study the problem on three different settings (based on overlapping between different convex hulls) and find hardness results and good approximation algorithms.

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

    PubMed

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

    2015-11-01

    In neurosurgical applications, a tool capable of distinguishing grey matter, white matter, and areas of tumor and/or necrosis in near-real time could greatly aid in tumor resection decision making. Raman spectroscopy is a non-destructive spectroscopic technique which provides molecular information about the tissue under examination based on the vibrational properties of the constituent molecules. With careful measurement and data processing, a spatial step and repeat acquisition of Raman spectra can be used to create Raman images. Forty frozen brain tissue sections were imaged in their entirety using a 300-µm-square measurement grid, and two or more regions of interest within each tissue were also imaged using a 25 µm-square step size. Molecular correlates for histologic features of interest were identified within the Raman spectra, and novel imaging algorithms were developed to compare molecular features across multiple tissues. In previous work, the relative concentration of individual biomolecules was imaged. Here, the relative concentrations of 1004, 1300:1344, and 1660 cm(-1), which correspond primarily to protein and lipid content, were simultaneously imaged across all tissues. This provided simple interpretation of boundaries between grey matter, white matter, and diseased tissue, and corresponded with findings from adjacent hematoxylin and eosin-stained sections. This novel, yet simple, multi-channel imaging technique allows clinically-relevant resolution with straightforward molecular interpretation of Raman images not possible by imaging any single peak. This method can be applied to either surgical or laboratory tools for rapid, non-destructive imaging of grey and white matter. PMID:26359131

  17. White matter injury detection in neonatal MRI

    NASA Astrophysics Data System (ADS)

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

    2013-02-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2003-05-01

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

  19. Bootstrapping white matter segmentation, Eve++

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  20. APOE-?4 and risk for Alzheimer’s disease: Do regionally distributed white matter hyperintensities play a role?

    PubMed Central

    Brickman, Adam M.; Schupf, Nicole; Manly, Jennifer J.; Stern, Yaakov; Luchsinger, José A.; Provenzano, Frank A.; Narkhede, Atul; Razlighi, Qolamreza; Collins-Praino, Lyndsey; Artero, Sylvaine; Akbaraly, Tasnime N.; Ritchie, Karen; Mayeux, Richard; Portet, Florence

    2014-01-01

    Background We previously demonstrated that parietal lobe white matter hyperintensities (WMH) increase risk for Alzheimer’s disease (AD). Here, we examined whether individuals with APOE*4have increased parietal WMH volume. Methods Participants were from the Washington Heights-Inwood Columbia Aging Project (WHICAP; n=694, 47 with dementia) in northern Manhattan and the Etude Santé Psychologique Prévalence Risques et Traitement study (ESPRIT; n=539, 8 with dementia) in Montpellier. The association between regional WMH and APOE*4 was examined separately in each group and then in a combined analysis. Results In WHICAP, ?4 carriers had higher WMH volume particularly in parietal and occipital lobes. In ESPRIT, ?4 carriers had elevated WMH particularly in parietal and temporal lobes. In the combined analysis, ?4 carriers had higher WMH in parietal and occipital lobes. Increased WMH volume was associated with increased frequency of dementia irrespective of APOE*4 status; those with the ?4 were more likely to have dementia if they also had increased parietal WMH. Conclusions APOE*4 is associated with increased parietal lobe WMH. PMID:25304991

  1. Canavan Disease: A White Matter Disorder

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  2. White matter disintegration in cluster headache

    PubMed Central

    2013-01-01

    Background Previous studies in primary headache disorders showed microstructural alterations in the white matter as measured by diffusion imaging. However these investigations are not in full agreement and some of those, especially in cluster headache, restricted the analysis to only a limited number of diffusion parameters. Therefore, in the current study we examined white matter microstructure in cluster headache patients. Methods Diffusion weighted MRI images with 60 directions were acquired from thirteen patients with cluster headache and sixteen age-matched healthy controls. Tract based spatial statistics were used to compare white matter integrity in the core of the fibre bundles. Correlation of the diffusion parameters with cumulative number of headache days was examined. Results There was a significant increment of the mean, axial and perpendicular diffusivity in widespread white matter regions in the frontal, parietal, temporal and occipital lobes. Reduced fractional anisotropy was found in the corpus callosum and some frontal and parietal white matter tracts mainly in the contralateral side of the pain. Axial diffusivity showed negative correlation to the number of the headache attacks. Conclusions The in vivo analysis of microstructural alterations in cluster headache provides important features of the disease, which might offer a deeper insight into the pathomechanism of the disease. PMID:23883140

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

    PubMed Central

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

    2015-01-01

    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. PMID:25560665

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

    PubMed

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

    2015-12-01

    White matter abnormalities in schizophrenia have been revealed by many imaging techniques and analysis methods. One of the findings by diffusion tensor imaging is a decrease in fractional anisotropy (FA), which is an indicator of white matter integrity. On the other hand, elevation of metabolic rate in white matter was observed from positron emission tomography (PET) studies. In this report, we aim to compare the two structural and functional effects on the same subjects. Our comparison is based on the hypothesis that signal fluctuation in white matter is associated with white matter functional activity. We examined the variance of the signal in resting state fMRI and found significant differences between individuals with schizophrenia and non-psychiatric controls specifically in white matter tissue. Controls showed higher temporal signal-to-noise ratios clustered in regions including temporal, frontal, and parietal lobes, cerebellum, corpus callosum, superior longitudinal fasciculus, and other major white matter tracts. These regions with higher temporal signal-to-noise ratio agree well with those showing higher metabolic activity reported by studies using PET. The results suggest that individuals with schizophrenia tend to have higher functional activity in white matter in certain brain regions relative to healthy controls. Despite some overlaps, the distinct regions for physiological noise are different from those for FA derived from diffusion tensor imaging, and therefore provide a unique angle to explore potential mechanisms to white matter abnormality. PMID:25560665

  5. ORIGINAL ARTICLE Individual differences in regional prefrontal gray matter

    E-print Network

    Banich, Marie T.

    and subcortical regions. Keywords MRI Á Anatomy Á PFC Á Executive function Á Grey matter Á White matter determined the association between regional PFC grey matter (GM) morphometry and white matter tract examining the associations between grey matter (GM) morphometry and EF have yielded variable results

  6. White matter involvement in sporadic Creutzfeldt-Jakob disease.

    PubMed

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

    2014-12-01

    Sporadic Creutzfeldt-Jakob disease is considered primarily a disease of grey matter, although the extent of white matter involvement has not been well described. We used diffusion tensor imaging to study the white matter in sporadic Creutzfeldt-Jakob disease compared to healthy control subjects and to correlated magnetic resonance imaging findings with histopathology. Twenty-six patients with sporadic Creutzfeldt-Jakob disease and nine age- and gender-matched healthy control subjects underwent volumetric T1-weighted and diffusion tensor imaging. Six patients had post-mortem brain analysis available for assessment of neuropathological findings associated with prion disease. Parcellation of the subcortical white matter was performed on 3D T1-weighted volumes using Freesurfer. Diffusion tensor imaging maps were calculated and transformed to the 3D-T1 space; the average value for each diffusion metric was calculated in the total white matter and in regional volumes of interest. Tract-based spatial statistics analysis was also performed to investigate the deeper white matter tracts. There was a significant reduction of mean (P=0.002), axial (P=0.0003) and radial (P=0.0134) diffusivities in the total white matter in sporadic Creutzfeldt-Jakob disease. Mean diffusivity was significantly lower in most white matter volumes of interest (P<0.05, corrected for multiple comparisons), with a generally symmetric pattern of involvement in sporadic Creutzfeldt-Jakob disease. Mean diffusivity reduction reflected concomitant decrease of both axial and radial diffusivity, without appreciable changes in white matter anisotropy. Tract-based spatial statistics analysis showed significant reductions of mean diffusivity within the white matter of patients with sporadic Creutzfeldt-Jakob disease, mainly in the left hemisphere, with a strong trend (P=0.06) towards reduced mean diffusivity in most of the white matter bilaterally. In contrast, by visual assessment there was no white matter abnormality either on T2-weighted or diffusion-weighted images. Widespread reduction in white matter mean diffusivity, however, was apparent visibly on the quantitative attenuation coefficient maps compared to healthy control subjects. Neuropathological analysis showed diffuse astrocytic gliosis and activated microglia in the white matter, rare prion deposition and subtle subcortical microvacuolization, and patchy foci of demyelination with no evident white matter axonal degeneration. Decreased mean diffusivity on attenuation coefficient maps might be associated with astrocytic gliosis. We show for the first time significant global reduced mean diffusivity within the white matter in sporadic Creutzfeldt-Jakob disease, suggesting possible primary involvement of the white matter, rather than changes secondary to neuronal degeneration/loss. PMID:25367029

  7. Quantifying the Effects of Normal Ageing on White Matter Structure using Unsupervised Tract Shape Modelling 

    E-print Network

    Bastin, Mark; Munoz Maniega, Susana; Ferguson, Karen J; Brown, Laura J; Wardlaw, Joanna M; MacLullich, Alasdair M; Clayden, Jonathan D

    Quantitative tractography may provide insights into regional heterogeneity of changes in white matter structure in normal ageing. Here we examine how brain atrophy and white matter lesions affect correlations between ...

  8. A probabilistic atlas of the cerebellar white matter.

    PubMed

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

    2016-01-01

    Imaging of the cerebellar cortex, deep cerebellar nuclei and their connectivity are gaining attraction, due to the important role the cerebellum plays in cognition and motor control. Atlases of the cerebellar cortex and nuclei are used to locate regions of interest in clinical and neuroscience studies. However, the white matter that connects these relay stations is of at least similar functional importance. Damage to these cerebellar white matter tracts may lead to serious language, cognitive and emotional disturbances, although the pathophysiological mechanism behind it is still debated. Differences in white matter integrity between patients and controls might shed light on structure-function correlations. A probabilistic parcellation atlas of the cerebellar white matter would help these studies by facilitating automatic segmentation of the cerebellar peduncles, the localization of lesions and the comparison of white matter integrity between patients and controls. In this work a digital three-dimensional probabilistic atlas of the cerebellar white matter is presented, based on high quality 3T, 1.25mm resolution diffusion MRI data from 90 subjects participating in the Human Connectome Project. The white matter tracts were estimated using probabilistic tractography. Results over 90 subjects were symmetrical and trajectories of superior, middle and inferior cerebellar peduncles resembled the anatomy as known from anatomical studies. This atlas will contribute to a better understanding of cerebellar white matter architecture. It may eventually aid in defining structure-function correlations in patients with cerebellar disorders. PMID:26385011

  9. Maturation of normal primate white matter: computed tomographic correlation

    SciTech Connect

    Quencer, R.M.

    1982-09-01

    Five infant baboons were examined with computed tomography (CT) during the first year of their lives to determine the rate and degree of normal white matter maturation in frontal, occipital, and parietal areas. The increase in CT numbers with age was correlated with gross and histologic specimens. Two phases of maturation were identified: a rapid phase (first 8-12 weeks) and a gradual phase (after 12 weeks). Frontal white matter was the most immature in the immediate postnatal period but it became equal in attenuation to the other regions by 4 weeks of age. Knowledge of white matter maturation rates may be particularly useful in cases of neonatal hypoxia/ischemia where zones of periventricular hypodensity are identified. The failure of such regions to follow a normal rate of maturation may indicate damage to the white matter and have significant prognostic implications.

  10. Modeling White Matter MRI Scan Parameters

    E-print Network

    Leahy, Richard M.

    Modeling White Matter MRI Scan Parameters http://resource.loni.usc.edu Mapping Changes in White Matter Microstructure throughout Development K. Lynch & K. Clark Introduction Methods Results Discussion References · Imaging and behavioral data comes from the C-MIND (Cincinnati MRI Imaging of Neurodevelopment

  11. Astrocytes and Developmental White Matter Disorders

    ERIC Educational Resources Information Center

    Sen, Ellora; Levison, Steven W.

    2006-01-01

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

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

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

    PubMed Central

    Bouix, Sylvain; Kubicki, Marek

    2014-01-01

    The medial orbitofrontal cortex (mOFC) and rostral anterior cingulate cortex (rACC) are part of a wider neural network that plays an important role in general intelligence and executive function. We used structural brain imaging to quantify magnetic resonance gray matter volume and diffusion tensor white matter integrity of the mOFC-rACC network in 26 healthy participants who also completed neuropsychological tests of intellectual abilities and executive function. Stochastic tractography, the most effective Diffusion Tensor Imaging method for examining white matter connections between adjacent gray matter regions, was employed to assess the integrity of mOFC-rACC pathways. Fractional anisotropy (FA), which reflects the integrity of white matter connections, was calculated. Results indicated that higher intelligence correlated with greater gray matter volumes for both mOFC and rACC, as well as with increased FA for left posterior mOFC-rACC connectivity. Hierarchical regression analyses revealed that DTI-derived FA of left posterior mOFC-rACC uniquely accounted for 29%–34% of the variance in IQ, in comparison to 11%–16% uniquely explained by gray matter volume of the left rACC. Together, left rACC gray matter volume and white matter connectivity between left posterior mOFC and rACC accounted for up to 50% of the variance in general intelligence. This study is to our knowledge the first to examine white matter connectivity between OFC and ACC, two gray matter regions of interests that are very close in physical proximity, and underscores the important independent contributions of variations in rACC gray matter volume and mOFC-rACC white matter connectivity to individual differences in general intelligence. PMID:25551572

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

    NASA Astrophysics Data System (ADS)

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

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

  15. Dark-matter admixed white dwarfs

    NASA Astrophysics Data System (ADS)

    Leung, Shing Chi; Chu, Ming Chung; Lin, Lap Ming; Wong, Ka Wing

    2014-03-01

    We study the equilibrium structures of white dwarfs (WD) with dark matter cores formed by non-self-annihilating dark matter (DM) particles with masses ranging from 1 GeV to 100 GeV, assuming in form of an ideal degenerate Fermi gas inside the stars. For DM particles of mass 10 GeV and 100 GeV, we find that stable stellar models exist only if the mass of the DM core inside the star is less than O and -3)Msun , respectively. The global properties of these stars, and the corresponding Chandrasekhar mass (CM) limits, are essentially the same as those of traditional WD models without DM. Nevertheless, in the 10 GeV case, the gravitational attraction of the DM core is strong enough to squeeze the normal matter in the core region to densities above neutron drip. For the 1 GeV case, the DM core inside the star can be as massive as O and affects the global structure of the star significantly. The radius of a stellar model with DM can be about two times smaller than that of a traditional WD. Furthermore, the CM limit can be decreased by as much as 40%. Our results may have implications on the extent to which type Ia supernovae can be regarded as standard candles. This work is partially supported by a grant from the Research Grant Council of the Hong Kong Special Administrative Region, China (Project No. 400910).

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

    PubMed Central

    2013-01-01

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

  17. Gender Differences in White Matter Microstructure

    PubMed Central

    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

  18. Cerebral white matter analysis using diffusion imaging

    E-print Network

    O'Donnell, Lauren Jean

    2006-01-01

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

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

    PubMed Central

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

    2015-01-01

    Objective Aging is associated with reduced neural integrity, yet there are remarkable individual differences in brain health among older adults (OA). One factor that may attenuate age-related neural decline is cardiorespiratory fitness (CRF). The primary aim of this study was to link CRF to neural white matter microstructure using diffusion tensor imaging in OA. Methods Young adults (YA; n = 32) and OA (n = 27) completed a graded maximal exercise test to evaluate CRF and diffusion tensor magnetic resonance imaging to examine neural white matter integrity. Results As expected, pervasive age-related declines in white matter integrity were observed when OA were compared to YA. Further, peak VO2 was positively associated with fractional anisotropy (FA), an indicator of white matter integrity, in multiple brain regions in OA, but not YA. In multiple posterior regions such as the splenium, sagittal stratum, posterior corona radiata, and superior parietal white matter, FA values were similar in YA and OA classified as higher fit, with both groups having greater FA than lower fit OA. However, age-related differences in FA values remained in other regions, including the body and genu of the corpus callosum, precuneus, and superior frontal gyrus. Interpretation CRF is positively associated with neural white matter microstructure in aging. The relationship between peak VO2 and FA appears to be tract-specific, as equivalent FA values were observed in higher fit OA and YA in some white matter tracts, but not others. Further, the association between peak VO2 and FA appears to be age-dependent. PMID:26125043

  20. A voxel-based morphometry (VBM) analysis of regional grey and white matter volume abnormalities within the speech production network of children who stutter

    PubMed Central

    Beal, Deryk S.; Gracco, Vincent L.; Brettschneider, Jane; Kroll, Robert M.; De Nil, Luc F.

    2012-01-01

    It is well documented that neuroanatomical differences exist between adults who stutter and their fluently speaking peers. Specifically, adults who stutter have been found to have more grey matter volume (GMV) in speech relevant regions including inferior frontal gyrus, insula and superior temporal gyrus (Beal et al., 2007; Song et al., 2007). Despite stuttering having its onset in childhood only one study has investigated the neuroanatomical differences between children who do and do not stutter. Chang et al. (2008) reported children who stutter had less GMV in the bilateral inferior frontal gyri and middle temporal gyrus relative to fluently speaking children. Thus it appears that children who stutter present with unique neuroanatomical abnormalities as compared to those of adults who stutter. In order to better understand the neuroanatomical correlates of stuttering earlier in its development, near the time of onset, we used voxel-based morphometry to examine volumetric differences between 11 children who stutter and 11 fluent children. Children who stutter had less GMV in the bilateral inferior frontal gyri and left putamen but more GMV in right Rolandic operculum and superior temporal gyrus relative to fluent children. Children who stutter also had less white matter volume bilaterally in the forceps minor of the corpus callosum. We discuss our findings of widespread anatomic abnormalities throughout the cortical network for speech motor control within the context of the speech motor skill limitations identified in people who stutter (Namasivayam and van Lieshout, 2008; Smits-Bandstra et al., 2006). PMID:23140891

  1. A voxel-based morphometry (VBM) analysis of regional grey and white matter volume abnormalities within the speech production network of children who stutter.

    PubMed

    Beal, Deryk S; Gracco, Vincent L; Brettschneider, Jane; Kroll, Robert M; De Nil, Luc F

    2013-09-01

    It is well documented that neuroanatomical differences exist between adults who stutter and their fluently speaking peers. Specifically, adults who stutter have been found to have more grey matter volume (GMV) in speech relevant regions including inferior frontal gyrus, insula and superior temporal gyrus (Beal et al., 2007; Song et al., 2007). Despite stuttering having its onset in childhood only one study has investigated the neuroanatomical differences between children who do and do not stutter. Chang et al. (2008) reported children who stutter had less GMV in the bilateral inferior frontal gyri and middle temporal gyrus relative to fluently speaking children. Thus it appears that children who stutter present with unique neuroanatomical abnormalities as compared to those of adults who stutter. In order to better understand the neuroanatomical correlates of stuttering earlier in its development, near the time of onset, we used voxel-based morphometry to examine volumetric differences between 11 children who stutter and 11 fluent children. Children who stutter had less GMV in the bilateral inferior frontal gyri and left putamen but more GMV in right Rolandic operculum and superior temporal gyrus relative to fluent children. Children who stutter also had less white matter volume bilaterally in the forceps minor of the corpus callosum. We discuss our findings of widespread anatomic abnormalities throughout the cortical network for speech motor control within the context of the speech motor skill limitations identified in people who stutter (Namasivayam and van Lieshout, 2008; Smits-Bandstra et al., 2006). PMID:23140891

  2. Developmental Differences in White Matter Architecture Between Boys and Girls

    PubMed Central

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

    2007-01-01

    Previous studies have found developmental differences between males and females in brain structure. During childhood and adolescence, relative white matter volume increases faster in boys than in girls. Sex differences in the development of white matter microstructure were investigated in a cohort of normal children ages 5-18 in a cross-sectional diffusion tensor imaging (DTI) study. Greater fractional anisotropy (FA) in boys was shown in associative white matter regions (including the frontal lobes), while greater FA in girls was shown in the splenium of the corpus callosum. Greater mean diffusivity (MD) in boys was shown in the corticospinal tract and in frontal white matter in the right hemisphere; greater MD in girls was shown in occipito-parietal regions and the most superior aspect of the corticospinal tract in the right hemisphere. Significant sex-age interactions on FA and MD were also shown. Girls displayed a greater rate of fiber density increase with age compared with boys in associative regions (reflected in MD values). However girls displayed a trend toward increased organization with age (reflected in FA values) only in the right hemisphere, while boys displayed this trend only in the left hemisphere. These results indicate differing developmental trajectories in white matter for boys and girls and the importance of taking sex into account in developmental DTI studies. The results also may have implications for the study of the relationship of brain architecture with intelligence. PMID:17598163

  3. The energetics of central nervous system white matter

    PubMed Central

    Harris, Julia J.; Attwell, David

    2012-01-01

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

  4. White matter predictors of cognitive functioning in older adults

    PubMed Central

    Meier, Irene B.; Manly, Jennifer J.; Provenzano, Frank A.; Louie, Karmen S.; Wasserman, Ben T.; Griffith, Erica Y.; Hector, Josina T.; Allocco, Elizabeth; Brickman, Adam M.

    2013-01-01

    Background Few studies have applied multiple imaging modalities to examine cognitive correlates of white matter. We examined the utility of T2-weighted MRI-derived white matter hyperintensities (WMH) and diffusion tensor imaging-derived fractional anisotropy (FA) to predict cognitive functioning among older adults. Methods Quantitative MRI and neuropsychological evaluations were performed in 112 older participants from an ongoing study of the genetics of Alzheimer’s disease (AD) in African Americans. Regional WMH volumes and FA were measured in multiple regions of interest. We examined the association of regional WMH and an FA summary score with cognitive test performance. Differences in WMH and FA were compared across diagnostic groups (i.e., normal controls, mild cognitive impairment, and probable AD). Results Increased WMH volume in frontal lobes was associated with poorer delayed memory performance. FA did not emerge as a significant predictor of cognition. White matter hyperintensity volume in the frontal and parietal lobes was increased in MCI participants and more so in AD patients relative to controls. Discussion These results highlight the importance of regionally-distributed small vessel cerebrovascular disease in memory performance and AD among African American older adults. White matter microstructural changes, quantified with DTI, appear to play a lesser role in our sample. PMID:22390883

  5. Age-related changes in the neurophysiology of language in adults: Relationship to regional cortical thinning and white matter microstructure

    PubMed Central

    Kemmotsu, Nobuko; Girard, Holly M.; Kucukboyaci, N. Erkut; McEvoy, Linda K.; Hagler, Donald J.; Dale, Anders M.; Halgren, Eric; McDonald, Carrie R.

    2012-01-01

    Although reading skill remains relatively stable with advancing age in humans, neurophysiological measures suggest potential reductions in efficiency of lexical information processing. It is unclear whether these age-related changes are secondary to decreases in regional cortical thickness and/or microstructure of fiber tracts essential to language. Magnetoencephalography, volumetric MRI, and diffusion tensor imaging were performed in 10 young (18–33 years) and 10 middle-aged (42–64 years) human individuals to evaluate the spatiotemporal dynamics and structural correlates of age-related changes in lexical-semantic processing. Increasing age was associated with reduced activity in left temporal lobe regions from 250–350ms and in left inferior prefrontal cortex from 350–450ms (i.e., N400). Hierarchical regression indicated that age no longer predicted left inferior prefrontal activity after cortical thickness and fractional anisotropy (FA) of the uncinate fasciculus (UF) were considered. Interestingly, FA of the UF was a stronger predictor of the N400 response than cortical thickness. Age-related reductions in left-lateralization of language responses were observed between 250–350ms, and were associated with left temporal thinning and frontotemporal FA reductions. N400 reductions were not associated with poorer task performance. Rather, increasing age was associated with reduction in the left prefrontal N400, which in turn was also associated with slower response time. These results reveal that changes in the neurophysiology of language occur by middle age and appear to be partially mediated by structural brain loss. These neurophysiological changes may reflect an adaptive process that ensues as communication between left perisylvian regions declines. PMID:22933802

  6. Specific white matter tissue microstructure changes associated with obesity.

    PubMed

    Kullmann, Stephanie; Callaghan, Martina F; Heni, Martin; Weiskopf, Nikolaus; Scheffler, Klaus; Häring, Hans-Ulrich; Fritsche, Andreas; Veit, Ralf; Preissl, Hubert

    2016-01-15

    Obesity-related structural brain alterations point to a consistent reduction in gray matter with increasing body mass index (BMI) but changes in white matter have proven to be more complex and less conclusive. Hence, more recently diffusion tensor imaging (DTI) has been employed to investigate microstructural changes in white matter structure. Altogether, these studies have mostly shown a loss of white matter integrity with obesity-related factors in several brain regions. However, the variety of these obesity-related factors, including inflammation and dyslipidemia, resulted in competing influences on the DTI indices. To increase the specificity of DTI results, we explored specific brain tissue properties by combining DTI with quantitative multi-parameter mapping in lean, overweight and obese young adults. By means of multi-parameter mapping, white matter structures showed differences in MRI parameters consistent with reduced myelin, increased water and altered iron content with increasing BMI in the superior longitudinal fasciculus, anterior thalamic radiation, internal capsule and corpus callosum. BMI-related changes in DTI parameters revealed mainly alterations in mean and axial diffusivity with increasing BMI in the corticospinal tract, anterior thalamic radiation and superior longitudinal fasciculus. These alterations, including mainly fiber tracts linking limbic structures with prefrontal regions, could potentially promote accelerated aging in obese individuals leading to an increased risk for cognitive decline. PMID:26458514

  7. White Matter Tractography Using Diffusion Tensor Deflection

    E-print Network

    Laidlaw, David

    , University of Utah, Salt Lake City, Utah 2 Department of Computer Science, University of Utah, Salt Lake City, Utah 3 Department of Radiology, University of Utah, Salt Lake City, Utah 4 Department of Medical for mapping the organizational patterns of white matter in the human brain as well as mapping the relationship

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

    PubMed

    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. PMID:24038774

  9. Genetics Home Reference: Leukoencephalopathy with vanishing white matter

    MedlinePLUS

    ... Additional NIH Resources - National Institutes of Health NINDS Leukodystrophy Information Page Educational resources - Information pages (2 links) ... diffusa vanishing white matter disease vanishing white matter leukodystrophy For more information about naming genetic conditions, see ...

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

    PubMed Central

    Xu, Haiyun; Li, Xin-Min

    2011-01-01

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

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

    PubMed Central

    Schmidt-Wilcke, Tobias; Cagnoli, Patricia; Wang, Page; Schultz, Thomas; Lotz, Anne; Mccune, William J.; Sundgren, Pia C.

    2014-01-01

    Purpose Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease that can affect the central nervous system. Neuropsychiatric symptoms are found in 25–70% of patients. Using diffusion tensor imaging (DTI) various studies have reported changes in white matter integrity in SLE patients with neuropsychiatric symptoms (NPSLE patients). The purpose of this study was to investigate, if regional changes in white matter integrity can also be detected in SLE patients without neuropsychiatric symptoms (non-NPSLE patients). Methods Applying DTI and tract based spatial statistics (TBSS) we investigated 19 NPSLE patients, 19 non-NPSLE and 18 healthy controls. Groups were matched for age and sex. Image pre-processing was performed using FSL, following the TBSS pipeline (eddy current correction, estimation of fractional anisotropy (FA), normalization, skeletonization of the group mean FA image). A general linear model with threshold-free cluster enhancement was used to assess significant differences between the three groups. Results Statistical analyses revealed several regions of decreased prefrontal white matter integrity (decreased FA) in both groups of SLE patients. The changes found in the non-NPSLE patients (as compared to healthy controls) overlapped with those in the NPSLE patients, but were not as pronounced. 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. PMID:25161895

  12. CLINICAL INVESTIGATION WHITE MATTER FRACTIONAL ANISOTROPY CORRELATES WITH SPEED

    E-print Network

    van Vliet, Lucas J.

    CLINICAL INVESTIGATION WHITE MATTER FRACTIONAL ANISOTROPY CORRELATES WITH SPEED OF PROCESSING medulloblastoma and acute lymphoblastic leukemia (ALL) survivors have decreased white matter fractional anisotropy the right IFO WMFA was related to motor speed (r = 0.49, p White matter tracts, using

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

    E-print Network

    Shi, Riyi

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

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

    E-print Network

    Wandell, Brian A.

    Frontoparietal white matter diffusion properties predict mental arithmetic skills in children oxygen level­dependent signals in the parietal and frontal regions. We tested whether white matter in the mind, is important for everyday tasks, from paying a bill to estimating the time before a bus arrives

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

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

    PubMed

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

    2013-10-01

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

  17. White matter abnormalities in dystonia normalize after botulinum toxin treatment

    PubMed Central

    Blood, Anne J.; Tuch, David S.; Makris, Nikos; Makhlouf, Miriam L.; Sudarsky, Lewis R.; Sharma, Nutan

    2011-01-01

    The pathophysiology of dystonia is still poorly understood. We used diffusion tensor imaging to screen for white matter abnormalities in regions between the basal ganglia and the thalamus in cervical and hand dystonia patients. All patients exhibited an abnormal hemispheric asymmetry in a focal region between the pallidum and the thalamus. This asymmetry was absent 4 weeks after the same patients were treated with intramuscular botulinum toxin injections. These findings represent a new systems-level abnormality in dystonia, which may lead to new insights about the pathophysiology of movement disorders. More generally, these findings demonstrate central nervous system changes following peripheral reductions in muscle activity. This raises the possibility that we have observed activity-dependent white matter plasticity in the adult human brain. PMID:16951564

  18. Stochastic process for white matter injury detection in preterm neonates?

    PubMed Central

    Cheng, Irene; Miller, Steven P.; Duerden, Emma G.; Sun, Kaiyu; Chau, Vann; Adams, Elysia; Poskitt, Kenneth J.; Branson, Helen M.; Basu, Anup

    2015-01-01

    Preterm births are rising in Canada and worldwide. As clinicians strive to identify preterm neonates at greatest risk of significant developmental or motor problems, accurate predictive tools are required. Infants at highest risk will be able to receive early developmental interventions, and will also enable clinicians to implement and evaluate new methods to improve outcomes. While severe white matter injury (WMI) is associated with adverse developmental outcome, more subtle injuries are difficult to identify and the association with later impairments remains unknown. Thus, our goal was to develop an automated method for detection and visualization of brain abnormalities in MR images acquired in very preterm born neonates. We have developed a technique to detect WMI in T1-weighted images acquired in 177 very preterm born infants (24–32 weeks gestation). Our approach uses a stochastic process that estimates the likelihood of intensity variations in nearby pixels; with small variations being more likely than large variations. We first detect the boundaries between normal and injured regions of the white matter. Following this we use a measure of pixel similarity to identify WMI regions. Our algorithm is able to detect WMI in all of the images in the ground truth dataset with some false positives in situations where the white matter region is not segmented accurately. PMID:25844316

  19. The effects of puberty on white matter development in boys

    PubMed Central

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

    2015-01-01

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

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

    E-print Network

    Piatkowski, Jakub Przemyslaw

    2014-06-27

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

  1. Sex Differences in White Matter Alterations Accompanying Obstructive Sleep Apnea

    PubMed Central

    Macey, Paul M.; Kumar, Rajesh; Yan-Go, Frisca L.; Woo, Mary A.; Harper, Ronald M.

    2012-01-01

    Study Objectives: Females with obstructive sleep apnea (OSA) show different psychological and physiological symptoms from males, which may be associated with sex-related variations in neural injury occurring with the disorder. To determine whether male- or female-specific brain injury is present in OSA, we assessed influences of sex on white matter changes in the condition. Design: Two-group factorial. Setting: University medical center. Patients or Participants: 80 subjects total, with newly diagnosed, untreated OSA groups of 10 female (age mean ± SE: 52.6 ± 2.4 years, AHI 22.5 ± 4.1 events/h) and 20 male (age 48.9 ± 1.7, AHI 25.5 ± 2.9) patients, and 20 female (age 50.3 ± 1.7) and 30 male (age 49.2 ± 1.4) healthy control subjects. Interventions: None. Measurements and Results: Brain fiber integrity was assessed with fractional anisotropy (FA), a diffusion tensor imaging-derived measure. Sleep quality, daytime sleepiness, depression, and anxiety were assessed with questionnaires. We identified regions of differing injury in male versus female OSA patients by assessing brain regions with significant interaction effects of OSA and sex on FA. Areas of sex-specific, OSA-related FA reductions appeared in females relative to males, including in the bilateral cingulum bundle adjacent to the mid hippocampus, right stria terminalis near the amygdala, prefrontal and posterior-parietal white matter, corpus callosum, and left superior cerebellar peduncle. Females with OSA showed higher daytime sleepiness, anxiety and depression levels, and reduced sleep quality. Conclusions: Sex differences in white matter structural integrity appeared in OSA patients, with females more affected than males. These female-specific structural changes may contribute to or derive from neuropsychological and physiological symptom differences between sexes. Citation: Macey PM; Kumar R; Yan-Go FL; Woo MA; Harper RM. Sex differences in white matter alterations accompanying obstructive sleep apnea. SLEEP 2012;35(12):1603-1613. PMID:23204603

  2. ORIGINAL CONTRIBUTION Mediterranean Diet and White Matter Hyperintensity

    E-print Network

    Neurol. 2012;69(2):251-256 W HITE MATTER HYPER- intensities (WMHs) visible on T2- weighted magneticORIGINAL CONTRIBUTION Mediterranean Diet and White Matter Hyperintensity Volume in the Northern magnetic resonance imaging white matter hyperintensity volume (WMHV). Design: A cross-sectional analysis

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

    PubMed

    Zuo, Nianming; Fang, Jiliang; Lv, Xueyu; Zhou, Yuan; Hong, Yang; Li, Tao; Tong, Haibing; Wang, Xiaoling; Wang, Weidong; Jiang, Tianzi

    2012-01-01

    Increasing evidence indicates that major depressive disorder (MDD) is usually accompanied by altered white matter in the prefrontal cortex, the parietal lobe and the limbic system. As a behavioral abnormity of MDD, rumination has been believed to be a substantial indicator of the mental state of the depressive state. So far, however, no report that we are aware of has 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. PMID:22666366

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

    PubMed

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

    2013-08-01

    Online game addiction (OGA) has attracted greater attention as a serious public mental health issue. However, there are only a few brain magnetic resonance imaging studies on brain structure about OGA. In the current study, we used voxel-based morphometry (VBM) analysis and tract-based spatial statistics (TBSS) to investigate the microstructural changes in OGA and assessed the relationship between these morphology changes and the Young's Internet Addiction Scale (YIAS) scores within the OGA group. Compared with healthy subjects, OGA individuals showed significant gray matter atrophy in the right orbitofrontal cortex, bilateral insula, and right supplementary motor area. According to TBSS analysis, OGA subjects had significantly reduced FA in the right genu of corpus callosum, bilateral frontal lobe white matter, and right external capsule. Gray matter volumes (GMV) of the right orbitofrontal cortex, bilateral insula and FA values of the right external capsule were significantly positively correlated with the YIAS scores in the OGA subjects. Our findings suggested that microstructure abnormalities of gray and white matter were present in OGA subjects. This finding may provide more insights into the understanding of the underlying neural mechanisms of OGA. PMID:23480966

  5. White matter changes in chronic alcoholic liver disease: Hypothesized association and putative biochemical mechanisms.

    PubMed

    Hathout, Leith; Huang, Jimmy; Zamani, Amir; Morioka, Craig; El-Saden, Suzie

    2015-12-01

    Advanced liver disease has long been associated with cerebral abnormalities. These abnormalities, termed acquired hepatocerebral degeneration, are typically visualized as T1 weighted hyperintensity on MRI in the deep gray matter of the basal ganglia. Recent reports, however, have demonstrated that a subset of patients with chronic alcoholic liver disease may also develop white matter abnormalities. Thus far, the morphology of these changes is not well characterized. Previous studies have described these changes as patchy, sporadic white matter abnormalities but have not posited localization of these changes to any particular white matter tracts. This paper hypothesizes that the white matter findings associated with advanced alcoholic liver disease localize to the corticocerebellar tracts. As an initial investigation of this hypothesis, 78 patients with a diagnosis of liver cirrhosis and an MRI showing clearly abnormal T1 weighted hyperintensity in the bilateral globus pallidus, characteristic of chronic liver disease, were examined for white matter signal abnormalities in the corticocerebellar tracts using FLAIR and T2 weighted images. The corticocerebellar tracts were subdivided into two regions: periventricular white matter (consisting of the sum of the centrum-semiovale and corona radiata), and lower white matter (consisting of the corona radiata, internal capsules, middle cerebral peduncles, middle cerebellar peduncles and cerebellum). As compared to matched controls, significantly greater signal abnormalities in both the periventricular white matter and lower white matter regions of the corticocerebellar tracts were observed in patients with known liver cirrhosis and abnormal T1W hyperintensity in the globi pallidi. This difference was most pronounced in the lower white matter region of the corticocerebellar tract, with statistical significance of p<0.0005. Furthermore, the pathophysiologic mechanism underlying these changes remains unknown. This paper hypothesizes that the etiology of white matter changes associated with advanced liver disease may resemble that of white matter findings in subacute combined degeneration secondary to vitamin B12 deficiency. Specifically, significant evidence suggests that dysfunctional methionine metabolism as well as dysregulated cytokine production secondary to B12 deficiency play a major role in the development of subacute combined degeneration. Similar dysfunction of methionine metabolism and cytokine regulation is seen in alcoholic liver disease and is hypothesized in this paper to, at least in part, lead to white matter findings associated with alcoholic liver disease. PMID:26474927

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

    PubMed

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

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

    PubMed

    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. PMID:26602958

  8. Examining the relationships between cortical maturation and white matter myelination throughout early childhood.

    PubMed

    Croteau-Chonka, Elise C; Dean, Douglas C; Remer, Justin; Dirks, Holly; O'Muircheartaigh, Jonathan; Deoni, Sean C L

    2016-01-15

    Cortical development and white matter myelination are hallmark processes of infant and child neurodevelopment, and play a central role in the evolution of cognitive and behavioral functioning. Non-invasive magnetic resonance imaging (MRI) has been used to independently track these microstructural and morphological changes in vivo, however few studies have investigated the relationship between them despite their concurrency in the developing brain. Further, because measures of cortical morphology rely on underlying gray-white matter tissue contrast, which itself is a function of white matter myelination, it is unclear if contrast-based measures of cortical development accurately reflect cortical architecture, or if they merely represent adjacent white matter maturation. This may be particularly true in young children, in whom brain structure is rapidly maturing. Here for the first time, we investigate the dynamic relationship between cortical and white matter development across early childhood, from 1 to 6years. We present measurements of cortical thickness with respect to cortical and adjacent myelin water fraction (MWF) in 33 bilateral cortical regions. Significant results in only 14 of 66 (21%) cortical regions suggest that cortical thickness measures are not heavily driven by changes in adjacent white matter, and that brain imaging studies of cortical and white matter maturation reflect distinct, but complimentary, neurodevelopmental processes. PMID:26499814

  9. White Matter Damage After Chronic Subclinical Inflammation in Newborn Mice

    PubMed Central

    Wang, Xiaoyang; Hellgren, Gunnel; Löfqvist, Chatarina; Li, Wenli; Hellström, Ann; Hagberg, Henrik; Mallard, Carina

    2013-01-01

    Preterm infants exposed to inflammation are at increased risk of white matter injury and/or cerebral palsy. To investigate the effect of chronic inflammation on developing white matter, we administered low-dose lipopolysaccharide once a day from postnatal day 3 to 11 examined white matter changes at postnatal day 12, and monitored serum levels of insulin-like growth factor 1 (IGF-1) and insulin-like factor binding protein-3 (IGFBP-3). A single injection of lipopolysaccharide decreased the serum IGF-1 level but not the IGFBP-3 level. At postnatal day 12, quantification of immunohistochemical staining for axonal, myelin, and oligodendrocyte markers revealed impaired myelination in subcortical white matter. In addition, brain grey matter volume decreased and spleen and liver weight increased at postnatal day 12. These data suggest chronic subclinical inflammation hampers development of white and grey matter in early life, which may be associated with IGF-1 deficiency. PMID:19745089

  10. Inflammation in White Matter: Clinical and Pathophysiological Aspects

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  11. BRAINA JOURNAL OF NEUROLOGY White matter structural connectivity underlying

    E-print Network

    Caramazza, Alfonso

    BRAINA JOURNAL OF NEUROLOGY White matter structural connectivity underlying semantic processing, Harvard University, Cambridge, MA 02138, USA 4 Centre of Mind/Brain Sciences (CIMeC), University of Trento the relationship between the integrity of major white matter tracts and the presence of semantic deficits

  12. RESEARCH Open Access Brain white matter microstructure alterations in

    E-print Network

    Maestripieri, Dario

    RESEARCH Open Access Brain white matter microstructure alterations in adolescent rhesus monkeys maltreatment to study the long-term effects of this early life stress on brain white matter integrity during adolescence, its behavioral correlates, and the relationship with early levels of stress hormones. Methods

  13. White matter fiber tractography based on a directional diffusion field in diffusion tensor MRI

    NASA Astrophysics Data System (ADS)

    Kumazawa, S.; Yoshiura, T.; Arimura, H.; Mihara, F.; Honda, H.; Higashida, Y.; Toyofuku, F.

    2006-03-01

    Diffusion tensor (DT) MRI provides the directional information of water molecular diffusion, which can be utilized to estimate the connectivity of white matter tract pathways in the human brain. Several white matter tractography methods have been developed to reconstruct the white matter fiber tracts using DT-MRI. With conventional methods (e.g., streamline techniques), however, it would be very difficult to trace the white matter tracts passing through the fiber crossing and branching regions due to the ambiguous directional information with the partial volume effect. The purpose of this study was to develop a new white matter tractography method which permits fiber tract branching and passing through crossing regions. Our tractography method is based on a three-dimensional (3D) directional diffusion function (DDF), which was defined by three eigenvalues and their corresponding eigenvectors of DT in each voxel. The DDF-based tractography (DDFT) consists of the segmentation of white matter tract region and fiber tracking process. The white matter tract regions were segmented by thresholding the 3D directional diffusion field, which was generated by the DDF. In fiber tracking, the DDFT method estimated the local tract direction based on overlap of the DDFs instead of the principal eigenvector, which has been used in conventional methods, and reconstructed tract branching by means of a one-to-many relation model. To investigate the feasibility and usefulness of the DDFT method, we applied it to DT-MRI data of five normal subjects and seven patients with a brain tumor. With the DDFT method, the detailed anatomy of white matter tracts was depicted more appropriately than the conventional methods.

  14. White matter changes with age utilizing quantitative diffusion MRI

    PubMed Central

    Laidlaw, David H.; Conturo, Thomas E.; Hogan, Joseph; Zhao, Yi; Luo, Xi; Correia, Stephen; Cabeen, Ryan; Lane, Elizabeth M.; Heaps, Jodi M.; Bolzenius, Jacob; Salminen, Lauren E.; Akbudak, Erbil; McMichael, Amanda R.; Usher, Christina; Behrman, Ashley; Paul, Robert H.

    2014-01-01

    Objective: To investigate the relationship between older age and mean cerebral white matter fiber bundle lengths (FBLs) in specific white matter tracts in the brain using quantified diffusion MRI. Methods: Sixty-three healthy adults older than 50 years underwent diffusion tensor imaging. Tractography tracings of cerebral white matter fiber bundles were derived from the diffusion tensor imaging data. Results: Results revealed significantly shorter FBLs in the anterior thalamic radiation for every 1-year increase over the age of 50 years. Conclusions: We investigated the effects of age on FBL in specific white matter tracts in the brains of healthy older individuals utilizing quantified diffusion MRI. The results revealed a significant inverse relationship between age and FBL. Longitudinal studies of FBL across a lifespan are needed to examine the specific changes to the integrity of white matter. PMID:24928121

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

    PubMed Central

    Bennett, Ilana J.; Madden, David J.

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    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.

    2015-01-01

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

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

    PubMed

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

    2013-11-15

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

  19. Anomalous White Matter Morphology in Adults Who Stutter

    PubMed Central

    Cieslak, Matthew; 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, diffusion spectrum imaging was used to reconstruct streamlines to examine white matter connections in people who stutter (PWS) and in people who do not stutter (PWNS). Method WM morphology of the entire brain was assayed in 8 right-handed male PWS and 8 similarly aged right-handed male PWNS. WM was exhaustively searched using a deterministic algorithm that identifies missing or largely misshapen tracts. To be abnormal, a tract (defined as all streamlines connecting a pair of gray matter regions) was required to be at least one 3rd missing, in 7 out of 8 subjects in one group and not in the other group. Results Large portions of bilateral arcuate fasciculi, a heavily researched speech pathway, were abnormal in PWS. Conversely, all PWS had a prominent connection in the left temporo-striatal tract connecting frontal and temporal cortex that was not observed in PWNS. Conclusion These previously unseen structural differences of WM morphology in classical speech-language circuits may underlie developmental stuttering. PMID:25635376

  20. White matter microstructure alterations: a study of alcoholics with and without post-traumatic stress disorder.

    PubMed

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

    2013-01-01

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

  1. Overlapping and Distinct Gray and White Matter Abnormalities in Schizophrenia and Bipolar I Disorder

    PubMed Central

    Anderson, Dana; Ardekani, Babak A.; Burdick, Katherine E.; Robinson, Delbert G.; John, Majnu; Malhotra, Anil K.; Szeszko, Philip R.

    2013-01-01

    Background Schizophrenia and bipolar disorder may share common neurobiological mechanisms, but few studies have directly compared gray and white matter structure in these disorders. We used diffusion-weighted magnetic resonance imaging and a region-of-interest based analysis to identify overlapping and distinct gray and white matter abnormalities in 35 patients with schizophrenia and 20 patients with bipolar I disorder in comparison to 56 healthy volunteers. Methods We examined fractional anisotropy within the white matter and mean diffusivity within the gray matter in 42 regions-of-interest defined on a probabilistic atlas following non-linear registration of the images to atlas space. Results Patients with schizophrenia had significantly lower fractional anisotropy in temporal (superior temporal and parahippocampal) and occipital (superior and middle occipital) white matter compared to patients with bipolar disorder and healthy volunteers. In contrast, both patient groups demonstrated significantly higher mean diffusivity in frontal (inferior frontal and lateral orbitofrontal) and temporal (superior temporal and parahippocampal) gray matter compared to healthy volunteers, but did not differ from each other. Discussion Our study implicates overlapping gray matter frontal and temporal lobe structural alterations in the neurobiology of schizophrenia and bipolar I disorder, but suggests that temporal and occipital lobe white matter deficits may be an additional risk factor for schizophrenia. Our findings may have relevance for future diagnostic classification systems and the identification of susceptibility genes for these disorders. PMID:23796123

  2. Widespread effects of alcohol on white matter microstructure

    PubMed Central

    Fortier, Catherine Brawn; Leritz, Elizabeth C.; Salat, David H.; Lindemer, Emily; Maksimovskiy, Arkadiy L.; Shepel, Juli; Williams, Victoria; Venne, Jonathan R.; Milberg, William P.; McGlinchey, Regina E.

    2014-01-01

    Background Evidence suggests that chronic misuse of alcohol may preferentially affect the integrity of frontal white matter tracts, which can impact executive functions important to achieve and maintain abstinence. Methods Global and regional white matter (WM) microstructure was assessed using diffusion magnetic resonance (MR) measures of fractional anisotropy (FA) for 31 abstinent alcoholics with an average of 25 years of abuse and approximately 5 years of sobriety and 20 nonalcoholic control participants. Data processing was conducted with FreeSurfer and FSL processing streams. Voxelwise processing of the FA data was carried out using TBSS (Tract-Based Spatial Statistics). Clusters of significance were created to provide a quantitative summary of highly significant regions within the voxel wise analysis. Results Widespread, bilateral reductions in FA were observed in abstinent alcoholics as compared to nonalcoholic control participants in multiple frontal, temporal, parietal, and cerebellar WM tracts. FA in the left inferior frontal gyrus was associated with drinking severity. Conclusions The present study found widespread reductions in WM integrity in a group of abstinent alcoholics compared to nonalcoholic control participants, with most pronounced effects in frontal and superior tracts. Decreased FA throughout the frontostriatal circuits that mediate inhibitory control may result in impulsive behavior and inability to maintain sobriety. PMID:25406797

  3. Intrauterine Endotoxin Administration Leads to White Matter Diffusivity Changes in Newborn Rabbits

    PubMed Central

    Saadani-Makki, Fadoua; Kannan, Sujatha; Makki, Malek; Muzik, Otto; Janisse, James; Romero, Roberto; Chugani, Diane

    2010-01-01

    Maternal intrauterine inflammation has been implicated in the development of periventricular leukomalacia and white matter injury in the neonate. We hypothesized that intrauterine endotoxin administration would lead to microstructural changes in the neonatal rabbit white matter in vivo that could be detected at birth using diffusion tensor magnetic resonance imaging (MRI). Term newborn rabbit kits (gestational age 31 days) born to dams exposed to saline or endotoxin in utero on gestational day 28 underwent diffusion tensor imaging, and brain sections were stained for microglia. Comparison between normal and endotoxin groups showed significant decreases in both fractional anisotropy and eigenvalue (e1) in all periventricular white matter regions that showed an increase in the number of activated microglial cells, indicating that after maternal inflammation, microglial infiltration may predominantly explain this change in diffusivity in the immediate neonatal period. Diffusion tensor imaging may be a clinically useful tool for detecting neuroinflammation induced by maternal infection in neonatal white matter. PMID:19745090

  4. Structural changes in white matter are uniquely related to children’s reading development

    PubMed Central

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

    2014-01-01

    This study examined whether variations in brain development between kindergarten and Grade 3 predicted individual differences in reading ability at the latter time point. Structural MRI measurements indicated that increases in volume of two left temporo-parietal white matter clusters are unique predictors of reading outcome at Grade 3. Using diffusion MRI, the larger of these two clusters was identified as a location where fibers of the long segment of arcuate fasciculus and superior corona radiata intersect, and the smaller cluster as the posterior arcuate fasciculus. Bias-free regression analyses using regions-of-interest from prior literature revealed white matter volume changes in temporo-parietal white matter, together with preliteracy measures, predicted 56% of the variance in reading outcomes. Our findings demonstrate the important contribution of developmental differences in areas of left dorsal white matter, often implicated in phonological processing, as a sensitive early biomarker for later reading abilities, and by extension, reading difficulties. PMID:25212581

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  7. A white matter stroke model in the mouse: Axonal damage, progenitor responses and MRI correlates

    PubMed Central

    Sozmen, Elif G.; Kolekar, Arunima; Havton, Leif A.; Carmichael, S. Thomas

    2015-01-01

    Subcortical white matter stroke is a common stroke subtype but has had limited pre-clinical modeling. Recapitulating this disease process in mice has been impeded by the relative inaccessibility of the sub-cortical white matter arterial supply to induce white matter ischemia in isolation. In this report, we detail a subcortical white matter stroke model developed in the mouse and its characterization with a comprehensive set of MRI, immunohistochemical, neuronal tract tracing and electron microscopic studies. Focal injection of the vasoconstrictor endothelin-1 into the subcortical white matter produces an infarct core that develops a maximal MRI signal by day 2, which is comparable in relative size and location to human subcortical stroke. Immunohistochemical studies indicate that oligodendrocyte apoptosis is maximal at day 1 and apoptotic cells extend away from the stroke core into the peri-infarct white matter. The amount of myelin loss exceeds axonal fiber loss in this peri-infarct region. Activation of microglia/macrophages takes place at 1 day after injection near injured axons. Neuronal tract tracing demonstrates that subcortical white matter stroke disconnects a large region of bilateral sensorimotor cortex. There is a robust glial response after stroke by BrdU pulse-labeling, and oligodendrocyte precursor cells are initiated to proliferate and differentiate within the first week of injury. These results demonstrate the utility of the endothelin-1 mediated subcortical stroke in the mouse to study post-stroke repair mechanisms, as the infarct core extends through the partially damaged peri-infarct white matter and induces an early glial progenitor response. PMID:19439360

  8. White Matter Damage and Systemic Inflammation in Obstructive Sleep Apnea

    PubMed Central

    Chen, Hsiu-Ling; Lu, Cheng-Hsien; Lin, Hsin-Ching; Chen, Pei-Chin; Chou, Kun-Hsien; Lin, Wei-Ming; Tsai, Nai-Wen; Su, Yu-Jih; Friedman, Michael; Lin, Ching-Po; Lin, Wei-Che

    2015-01-01

    Study Objectives: To evaluate white matter integrity in patients with obstructive sleep apnea (OSA) using diffusion tensor imaging (DTI) and to assess its relationship with systemic inflammation. Design: Cross-sectional study. Setting: One tertiary medical center research institute. Patients or Participants: Twenty patients with severe OSA (apnea-hypopnea index [AHI] > 30, 18 men and 2 women) and 14 healthy volunteers (AHI < 5, 11 men and 3 women). Interventions: N/A. Measurements and Results: Patients with severe OSA and healthy volunteers underwent polysomnography to determine the severity of sleep apnea, and DTI scanning to determine fiber integrity. Early or late phase changes in leukocyte apoptosis and its subsets were determined by flow cytometry. DTI-related indices (including fractional anisotropy [FA], axial diffusivity [AD], radial diffusivity [RD], and mean diffusivity [MD]) were derived from DTI. The FA maps were compared using voxel-based statistics to determine differences between the severe OSA and control groups. The differences in DTI indices, clinical severity, and leukocyte apoptosis were correlated after adjusting for age, sex, body mass index, and systolic blood pressure. Exploratory group-wise comparison between the two groups revealed that patients with OSA exhibited low FA accomplished by high RD in several brain locations, without any differences in AD and MD. The FA values were negatively correlated with clinical disease severity and leukocyte early apoptosis. Conclusions: Obstructive sleep apnea impairs white matter integrity in vulnerable regions, and this impairment is associated with increased disease severity. The possible interactions between systemic inflammation and central nervous system microstructural damage may represent variant hypoxic patterns and their consequent processes in obstructive sleep apnea. Citation: Chen HL, Lu CH, Lin HC, Chen PC, Chou KH, Lin WM, Tsai NW, Su YJ, Friedman M, Lin CP, Lin WC. White matter damage and systemic inflammation in obstructive sleep apnea. SLEEP 2015;38(3):361–370. PMID:25325459

  9. Pathophysiology of Glia in Perinatal White Matter Injury

    PubMed Central

    Back, Stephen A.; Rosenberg, Paul A.

    2014-01-01

    Injury to the preterm brain has a particular predilection for cerebral white matter. White matter injury (WMI) is the most common cause of brain injury in preterm infants and a major cause of chronic neurological morbidity including cerebral palsy. Factors that predispose to WMI include cerebral oxygenation disturbances and maternal-fetal infection. During the acute phase of WMI, pronounced oxidative damage occurs that targets late oligodendrocyte progenitors (preOLs). The developmental predilection for WMI to occur during prematurity appears to be related to both the timing of appearance and regional distribution of susceptible preOLs that are vulnerable to a variety of chemical mediators including reactive oxygen species, glutamate, cytokines, and adenosine. During the chronic phase of WMI, the white matter displays abberant regeneration and repair responses. Early OL progenitors responds to WMI with a rapid robust proliferative response that results in a several fold regeneration of preOLs that fail to terminally differentiate along their normal developmental time course. PreOL maturation arrest appears to be related in part to inhibitory factors that derive from reactive astrocytes in chronic lesions. Recent high field MRI data support that three distinct forms of chronic WMI exist, each of which displays unique MRI and histopathological features. These findings suggest the possibility that therapies directed at myelin regeneration and repair could be initiated early after WMI and monitored over time. These new mechanisms of acute and chronic WMI provide access to a variety of new strategies to prevent or promote repair of WMI in premature infants. PMID:24687630

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

    PubMed Central

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

    2015-01-01

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

  11. Synergistic Effects of Age on Patterns of White and Gray Matter Volume across Childhood and Adolescence(1,2,3).

    PubMed

    Bray, Signe; Krongold, Mark; Cooper, Cassandra; Lebel, Catherine

    2015-01-01

    The human brain develops with a nonlinear contraction of gray matter across late childhood and adolescence with a concomitant increase in white matter volume. Across the adult population, properties of cortical gray matter covary within networks that may represent organizational units for development and degeneration. Although gray matter covariance may be strongest within structurally connected networks, the relationship to volume changes in white matter remains poorly characterized. In the present study we examined age-related trends in white and gray matter volume using T1-weighted MR images from 360 human participants from the NIH MRI study of Normal Brain Development. Images were processed through a voxel-based morphometry pipeline. Linear effects of age on white and gray matter volume were modeled within four age bins, spanning 4-18 years, each including 90 participants (45 male). White and gray matter age-slope maps were separately entered into k-means clustering to identify regions with similar age-related variability across the four age bins. Four white matter clusters were identified, each with a dominant direction of underlying fibers: anterior-posterior, left-right, and two clusters with superior-inferior directions. Corresponding, spatially proximal, gray matter clusters encompassed largely cerebellar, fronto-insular, posterior, and sensorimotor regions, respectively. Pairs of gray and white matter clusters followed parallel slope trajectories, with white matter changes generally positive from 8 years onward (indicating volume increases) and gray matter negative (decreases). As developmental disorders likely target networks rather than individual regions, characterizing typical coordination of white and gray matter development can provide a normative benchmark for understanding atypical development. PMID:26464999

  12. White Matter Hyperintensities and Medication Adherence

    PubMed Central

    Insel, Kathleen C.; Reminger, Sheryl L.; Hsiao, Chao-Pin

    2015-01-01

    White matter hyperintensities (WMH) are associated with hypertension, age, and cognitive function, but the association between WMH and medication adherence has not been examined. The intent of this investigation was to consider the potential implications of hypertension-related brain morphological changes on medication adherence and thereby improve understanding of the self-management consequences of hypertension. The associations between WMH, blood pressure, age, cognitive function (specifically assessments of prefrontal function), and medication adherence were examined in 16 middle-aged and older adults self-managing at least one prescribed antihypertensive agent. Magnetic resonance imaging using an axial fluid attenuated inversion recovery (FLAIR) sequence was used to assess the presence of WMH. Cognitive assessments included measures of executive function, working memory, attention, and immediate recall. Adherence was monitored for 8 weeks using electronic medication monitoring. More WMH were associated with poorer adherence (rs = ?.25) and with higher systolic blood pressure (rs = .46), although these relationships were not statistically significant. WMH were associated with cognitive assessments in the expected direction including Digit Span Backward (rs = ?.53, p < .05). Adherence was associated with immediate memory (rs = .54, p < .05) and inversely associated with failure to maintain set on the Wisconsin Card Sorting Test (WCST; rs = ?.61, p < .05). These findings provide preliminary evidence for the association between WMH, assessments of prefrontal function, and medication adherence. PMID:18829595

  13. Deep White Matter in Huntington's Disease

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Mendez, Mario F.; Joshi, Aditi; Daianu, Madelaine; Jimenez, Elvira; Thompson, Paul

    2015-01-01

    Background 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. Objective 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. Methods 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. Results 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. Conclusion 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. PMID:26606247

  15. A study of brain white matter plasticity in early blinds using tract-based spatial statistics and tract statistical analysis.

    PubMed

    Lao, Yi; Kang, Yue; Collignon, Olivier; Brun, Caroline; Kheibai, Shadi B; Alary, Flamine; Gee, James; Nelson, Marvin D; Lepore, Franco; Lepore, Natasha

    2015-12-16

    Early blind individuals are known to exhibit structural brain reorganization. Particularly, early-onset blindness may trigger profound brain alterations that affect not only the visual system but also the remaining sensory systems. Diffusion tensor imaging (DTI) allows in-vivo visualization of brain white matter connectivity, and has been extensively used to study brain white matter structure. Among statistical approaches based on DTI, tract-based spatial statistics (TBSS) is widely used because of its ability to automatically perform whole brain white matter studies. Tract specific analysis (TSA) is a more recent method that localizes changes in specific white matter bundles. In the present study, we compare TBSS and TSA results of DTI scans from 12 early blind individuals and 13 age-matched sighted controls, with two aims: (a) to investigate white matter alterations associated with early visual deprivation; (b) to examine the relative sensitivity of TSA when compared with TBSS, for both deficit and hypertrophy of white matter microstructures. Both methods give consistent results for broad white matter regions of deficits. However, TBSS does not detect hypertrophy of white matter, whereas TSA shows a higher sensitivity in detecting subtle differences in white matter colocalized to the posterior parietal lobe. PMID:26559727

  16. Mechanical properties of gray and white matter brain tissue by indentation.

    PubMed

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

    2015-06-01

    The mammalian brain is composed of an outer layer of gray matter, consisting of cell bodies, dendrites, and unmyelinated axons, and an inner core of white matter, consisting primarily of myelinated axons. Recent evidence suggests that microstructural differences between gray and white matter play an important role during neurodevelopment. While brain tissue as a whole is rheologically well characterized, the individual features of gray and white matter remain poorly understood. Here we quantify the mechanical properties of gray and white matter using a robust, reliable, and repeatable method, flat-punch indentation. To systematically characterize gray and white matter moduli for varying indenter diameters, loading rates, holding times, post-mortem times, and locations we performed a series of n=192 indentation tests. We found that indenting thick, intact coronal slices eliminates the common challenges associated with small specimens: it naturally minimizes boundary effects, dehydration, swelling, and structural degradation. When kept intact and hydrated, brain slices maintained their mechanical characteristics with standard deviations as low as 5% throughout the entire testing period of five days post mortem. White matter, with an average modulus of 1.89 5kPa ± 0.592 kPa, was on average 39% stiffer than gray matter, p<0.01, with an average modulus of 1.389 kPa ± 0.289 kPa, and displayed larger regional variations. It was also more viscous than gray matter and responded less rapidly to mechanical loading. Understanding the rheological differences between gray and white matter may have direct implications on diagnosing and understanding the mechanical environment in neurodevelopment and neurological disorders. PMID:25819199

  17. Reproducibility of Quantitative Tractography Methods Applied to Cerebral White Matter

    PubMed Central

    Wakana, Setsu; Caprihan, Arvind; Panzenboeck, Martina M.; Fallon, James H.; Perry, Michele; Gollub, Randy L.; Hua, Kegang; Zhang, Jiangyang; Jiang, Hangyi; Dubey, Prachi; Blitz, Ari; van Zijl, Peter; Mori, Susumu

    2007-01-01

    Tractography based on diffusion tensor imaging (DTI) allows visualization of white matter tracts. In this study, protocols to reconstruct eleven major white matter tracts are described. The protocols were refined by several iterations of intra- and inter-rater measurements and identification of sources of variability. Reproducibility of the established protocols was then tested by raters who did not have previous experience in tractography. The protocols were applied to a DTI database of adult normal subjects to study size, fractional anisotropy (FA), and T2 of individual white matter tracts. Distinctive features in FA and T2 were found for the corticospinal tract and callosal fibers. Hemispheric asymmetry was observed for the size of white matter tracts projecting to the temporal lobe. This protocol provides guidelines for reproducible DTI-based tract-specific quantification. PMID:17481925

  18. ORIGINAL CONTRIBUTION Measuring Cerebral Atrophy and White Matter

    E-print Network

    marker for dis- ease staging in AD. Areas of increased intensity on T2- weighted MRI sequences, includingORIGINAL CONTRIBUTION Measuring Cerebral Atrophy and White Matter Hyperintensity Burden to Predict

  19. Genetic determinants of white matter integrity in bipolar disorder 

    E-print Network

    Sprooten, Emma

    2012-06-30

    Bipolar disorder is a heritable psychiatric disorder, and several of the genes associated with bipolar disorder and related psychotic disorders are involved in the development and maintenance of white matter in the brain. ...

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

    PubMed Central

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

    2012-01-01

    Background Cerebral white matter abnormalities on term MRI are a strong predictor of motor disability in children born very preterm. However, their contribution to cognitive impairment is less certain. Objective Examine relationships between the presence and severity of cerebral white matter abnormalities on neonatal MRI and a range of neurocognitive outcomes assessed at ages 4 and 6 years. Design/Methods The study sample consisted of a regionally representative cohort of 104 very preterm (?32 weeks gestation) infants born from 1998–2000 and a comparison group of 107 full-term infants. At term equivalent, all preterm infants underwent a structural MRI scan that was analyzed qualitatively for the presence and severity of cerebral white matter abnormalities, including cysts, signal abnormalities, loss of white matter volume, ventriculomegaly, and corpus callosal thinning/myelination. At corrected ages 4 and 6 years, all children underwent a comprehensive neurodevelopmental assessment that included measures of general intellectual ability, language development, and executive functioning. Results At 4 and 6 years, very preterm children without cerebral white matter abnormalities showed no apparent neurocognitive impairments relative to their full-term peers on any of the domain specific measures of intelligence, language, and executive functioning. In contrast, children born very preterm with mild and moderate-to-severe white matter abnormalities were characterized by performance impairments across all measures and time points, with more severe cerebral abnormalities being associated with increased risks of cognitive impairment. These associations persisted after adjustment for gender, neonatal medical risk factors, and family social risk. Conclusions Findings highlight the importance of cerebral white matter connectivity for later intact cognitive functioning amongst children born very preterm. Preterm born children without cerebral white matter abnormalities on their term MRI appear to be spared many of the cognitive impairments commonly associated with preterm birth. Further follow-up will be important to assess whether this finding persists into the school years. PMID:23284800

  1. Military blast exposure, ageing and white matter integrity.

    PubMed

    Trotter, Benjamin B; Robinson, Meghan E; Milberg, William P; McGlinchey, Regina E; Salat, David H

    2015-08-01

    Mild traumatic brain injury, or concussion, is associated with a range of neural changes including altered white matter structure. There is emerging evidence that blast exposure-one of the most pervasive causes of casualties in the recent overseas conflicts in Iraq and Afghanistan-is accompanied by a range of neurobiological events that may result in pathological changes to brain structure and function that occur independently of overt concussion symptoms. The potential effects of brain injury due to blast exposure are of great concern as a history of mild traumatic brain injury has been identified as a risk factor for age-associated neurodegenerative disease. The present study used diffusion tensor imaging to investigate whether military-associated blast exposure influences the association between age and white matter tissue structure integrity in a large sample of veterans of the recent conflicts (n = 190 blast-exposed; 59 without exposure) between the ages of 19 and 62 years. Tract-based spatial statistics revealed a significant blast exposure × age interaction on diffusion parameters with blast-exposed individuals exhibiting a more rapid cross-sectional age trajectory towards reduced tissue integrity. Both distinct and overlapping voxel clusters demonstrating the interaction were observed among the examined diffusion contrast measures (e.g. fractional anisotropy and radial diffusivity). The regions showing the effect on fractional anisotropy included voxels both within and beyond the boundaries of the regions exhibiting a significant negative association between fractional anisotropy and age in the entire cohort. The regional effect was sensitive to the degree of blast exposure, suggesting a 'dose-response' relationship between the number of blast exposures and white matter integrity. Additionally, there was an age-independent negative association between fractional anisotropy and years since most severe blast exposure in a subset of the blast-exposed group, suggesting a specific influence of time since exposure on tissue structure, and this effect was also independent of post-traumatic stress symptoms. Overall, these data suggest that blast exposure may negatively affect brain-ageing trajectories at the microstructural tissue level. Additional work examining longitudinal changes in brain tissue integrity in individuals exposed to military blast forces will be an important future direction to the initial findings presented here. PMID:26033970

  2. Abnormal gray matter and white matter volume in 'Internet gaming addicts'.

    PubMed

    Lin, Xiao; Dong, Guangheng; Wang, Qiandong; Du, Xiaoxia

    2015-01-01

    Internet gaming addiction (IGA) is usually defined as the inability of an individual to control his/her use of the Internet with serious negative consequences. It is becoming a prevalent mental health concern around the world. To understand whether Internet gaming addiction contributes to cerebral structural changes, the present study examined the brain gray matter density and white matter density changes in participants suffering IGA using voxel-based morphometric analysis. Compared with the healthy controls (N=36, 22.2 ± 3.13 years), IGA participants (N=35, 22.28 ± 2.54 years) showed significant lower gray matter density in the bilateral inferior frontal gyrus, left cingulate gyrus, insula, right precuneus, and right hippocampus (all p<0.05). IGA participants also showed significant lower white matter density in the inferior frontal gyrus, insula, amygdala, and anterior cingulate than healthy controls (all p<0.05). Previous studies suggest that these brain regions are involved in decision-making, behavioral inhibition and emotional regulation. Current findings might provide insight in understanding the biological underpinnings of IGA. PMID:25260201

  3. Regional Background Fine Particulate Matter

    EPA Science Inventory

    A modeling system composed of the global model GEOS-Chem providing hourly lateral boundary conditions to the regional model CMAQ was used to calculate the policy relevant background level of fine particulate: matter. Simulations were performed for the full year of 2004 over the d...

  4. Extensive White Matter Alterations and Its Correlations with Ataxia Severity in SCA 2 Patients

    PubMed Central

    Hernandez-Castillo, Carlos R.; Galvez, Victor; Mercadillo, Roberto; Diaz, Rosalinda; Campos-Romo, Aurelio; Fernandez-Ruiz, Juan

    2015-01-01

    Background Previous studies of SCA2 have revealed significant degeneration of white matter tracts in cerebellar and cerebral regions. The motor deficit in these patients may be attributable to the degradation of projection fibers associated with the underlying neurodegenerative process. However, this relationship remains unclear. Statistical analysis of diffusion tensor imaging enables an unbiased whole-brain quantitative comparison of the diffusion proprieties of white matter tracts in vivo. Methods Fourteen genetically confirmed SCA2 patients and aged-matched healthy controls participated in the study. Tract-based spatial statistics were performed to analyze structural white matter damage using two different measurements: fractional anisotropy (FA) and mean diffusivity (MD). Significant diffusion differences were correlated with the patient's ataxia impairment. Results Our analysis revealed decreased FA mainly in the inferior/middle/superior cerebellar peduncles, the bilateral posterior limb of the internal capsule and the bilateral superior corona radiata. Increases in MD were found mainly in cerebellar white matter, medial lemniscus, and middle cerebellar peduncle, among other regions. Clinical impairment measured with the SARA score correlated with FA in superior parietal white matter and bilateral anterior corona radiata. Correlations with MD were found in cerebellar white matter and the middle cerebellar peduncle. Conclusion Our findings show significant correlations between diffusion measurements in key areas affected in SCA2 and measures of motor impairment, suggesting a disruption of information flow between motor and sensory-integration areas. These findings result in a more comprehensive view of the clinical impact of the white matter degeneration in SCA2. PMID:26263162

  5. Variability of gray and white matter during normal development: a voxel-based MRI analysis

    PubMed Central

    Wilke, Marko; Holland, Scott K.

    2008-01-01

    This study was aimed at investigating regional and local variability of brain tissue during normal human brain development. We investigated high-resolution MR-imaging data using SPM99 (Wellcome Department, University College London, UK). A pixel-wise variation coefficient of gray and white matter was calculated to visualize local variability. Data from 200 normal children (5–18 years) was analyzed. We found a profound interaction between variability of brain structures and normal development in both gray and white matter. Variability in gray and white matter shows regionally specific, age-related variations, possibly offering a new tool for the assessment of subtle brain abnormalities. Our results emphasize the necessity to take this variability into account when planning pediatric neuroimaging studies. PMID:14561914

  6. Quantitative Tract-of-Interest Metrics for White Matter Integrity Based on Diffusion Tensor MRI Data Stephanie Y. Lee1

    E-print Network

    Laidlaw, David

    ) and patients with vascular cognitive impairment (VCI), disorder characterized by T2 white matter hyperintensities. Background: The majority of published clinical research studies using DTI have relied on region

  7. Contrasting gray and white matter changes in preclinical Huntington disease

    E-print Network

    Aron, Adam

    Contrasting gray and white matter changes in preclinical Huntington disease An MRI study DD ABSTRACT Background: In Huntington disease (HD), substantial striatal atrophy precedes clinical motor of view; GM gray matter; HD Huntington disease; MRI magnetic resonance imaging; pre-HD preclinical HD

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

    PubMed

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

    2013-03-30

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

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

    PubMed Central

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

    2015-01-01

    Multi-atlas labeling has come in wide spread use for whole brain labeling on magnetic resonance imaging. Recent challenges have shown that leading techniques are near (or at) human expert reproducibility for cortical gray matter labels. However, these approaches tend to treat white matter as essentially homogeneous (as white matter exhibits isointense signal on structural MRI). The state-of-the-art for white matter atlas is the single-subject Johns Hopkins Eve atlas. Numerous approaches have attempted to use tractography and/or orientation information to identify homologous white matter structures across subjects. Despite success with large tracts, these approaches have been plagued by difficulties in with subtle differences in course, low signal to noise, and complex structural relationships for smaller tracts. Here, we investigate use of atlas-based labeling to propagate the Eve atlas to unlabeled datasets. We evaluate single atlas labeling and multi-atlas labeling using synthetic atlases derived from the single manually labeled atlas. On 5 representative tracts for 10 subjects, we demonstrate that (1) single atlas labeling generally provides segmentations within 2mm mean surface distance, (2) morphologically constraining DTI labels within structural MRI white matter reduces variability, and (3) multi-atlas labeling did not improve accuracy. These efforts present a preliminary indication that single atlas labels with correction is reasonable, but caution should be applied. To purse multi-atlas labeling and more fully characterize overall performance, more labeled datasets would be necessary. PMID:25914503

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

    PubMed Central

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

    2014-01-01

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

  11. NMDA receptor antibodies associated with distinct white matter syndromes

    PubMed Central

    Hacohen, Yael; Absoud, Michael; Hemingway, Cheryl; Jacobson, Leslie; Lin, Jean-Pierre; Pike, Mike; Pullaperuma, Sunil; Siddiqui, Ata; Wassmer, Evangeline; Waters, Patrick; Irani, Sarosh R.; Buckley, Camilla

    2014-01-01

    Objective: To report the clinical and radiologic findings of children with NMDA receptor (NMDAR) antibodies and white matter disorders. Method: Ten children with significant white matter involvement, with or without anti-NMDAR encephalitis, were identified from 46 consecutive NMDAR antibody–positive pediatric patients. Clinical and neuroimaging features were reviewed and the treatment and outcomes of the neurologic syndromes evaluated. Results: Three distinct clinicoradiologic phenotypes were recognized: brainstem encephalitis (n = 3), leukoencephalopathy following herpes simplex virus encephalitis (HSVE) (n = 2), and acquired demyelination syndromes (ADS) (n = 5); 3 of the 5 with ADS had myelin oligodendrocyte glycoprotein as well as NMDAR antibodies. Typical NMDAR antibody encephalitis was seen in 3 patients remote from the first neurologic syndrome (2 brainstem, 1 post-HSVE). Six of the 7 patients (85%) who were treated acutely, during the original presentation with white matter involvement, improved following immunotherapy with steroids, IV immunoglobulin, and plasma exchange, either individually or in combination. Two patients had escalation of immunotherapy at relapse resulting in clinical improvement. The time course of clinical features, treatments, and recoveries correlated broadly with available serum antibody titers. Conclusion: Clinicoradiologic evidence of white matter involvement, often distinct, was identified in 22% of children with NMDAR antibodies and appears immunotherapy responsive, particularly when treated in the acute phase of neurologic presentation. When observed, this clinical improvement is often mirrored by reduction in NMDAR antibody levels, suggesting that these antibodies may mediate the white matter disease. PMID:25340058

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

    PubMed

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

    2014-05-01

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

  13. Greater Insula White Matter Fiber Connectivity in Women Recovered from Anorexia Nervosa.

    PubMed

    Shott, Megan E; Pryor, Tamara L; Yang, Tony T; Frank, Guido K W

    2016-01-01

    Anorexia nervosa is a severe psychiatric disorder associated with reduced drive to eat. Altered taste-reward circuit white matter fiber organization in anorexia nervosa after recovery could indicate a biological marker that alters the normal motivation to eat. Women recovered from restricting-type anorexia (Recovered AN, n=24, age=30.3±8.1 years) and healthy controls (n=24, age=27.4±6.3 years) underwent diffusion weighted imaging of the brain. Probabilistic tractography analyses calculated brain white matter connectivity (streamlines) as an estimate of fiber connections in taste-reward-related white matter tracts, and microstructural integrity (fractional anisotropy, FA) was assessed using tract-based spatial statistics. Recovered AN showed significantly (range P<0.05-0.001, Bonferroni corrected) greater white matter connectivity between bilateral insula regions and ventral striatum, left insula and middle orbitofrontal cortex (OFC), and right insula projecting to gyrus rectus and medial OFC. Duration of illness predicted connectivity of tracts projecting from the insula to ventral striatum and OFC. Microstructural integrity was lower in Recovered AN in most insula white matter tracts, as was whole-brain FA in parts of the anterior corona radiata, external capsule, and cerebellum (P<0.05, family-wise error-corrected). This study indicates higher structural white matter connectivity, an estimate of fibers connections, in anorexia after recovery in tracts that connect taste-reward processing regions. Greater connectivity together with less-fiber integrity could indicate altered neural activity between those regions, which could interfere with normal food-reward circuit function. Correlations between connectivity and illness duration suggest that connectivity could be a marker for illness severity. Whether greater connectivity can predict prognosis of the disorder requires further study. PMID:26076832

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  16. Clinical Contributors to Cerebral White Matter Integrity in HIV-infected Individuals

    PubMed Central

    Gongvatana, Assawin; Cohen, Ronald A.; Correia, Stephen; Devlin, Kathryn N.; Miles, Jadrian; Kang, Hakmook; Ombao, Hernando; Navia, Bradford; Laidlaw, David H.; Tashima, Karen T.

    2013-01-01

    HIV-infected people frequently exhibit brain dysfunction characterized by preferential damage to the cerebral white matter. Despite suppressed viral load and reconstituted immune function afforded by combination antiretroviral therapy (CART), brain dysfunction continues to be observed even in medically stable individuals. To provide insight into the etiology of HIV-associated brain dysfunction in the CART era, we examined the effects of HIV disease markers, antiretroviral treatment, hepatitis C (HCV) coinfection, and age on DTI measures of white matter integrity in a cohort of 85 individuals aged 23 to 65 with chronic HIV infection. Fractional anisotropy (FA) and mean diffusivity (MD) were derived from 29 cerebral white matter regions, which were segmented on each individual brain using a high-resolution T1-weighted image and registered to diffusion images. Significant effects of clinical variables were found on white matter abnormalities in nearly all brain regions examined. Most notably, HCV coinfection and older age were associated with decreased anisotropy or increased diffusivity in the majority of brain regions. Individuals with higher current CD4 levels exhibited higher anisotropy in parietal lobe regions, while those undergoing antiretroviral treatment exhibited higher anisotropy in temporal lobe regions. The observed diffuse pattern of white matter injury suggests that future neuroimaging studies should employ methodologies that are not limited to circumscribed regions of interest. The current findings underline the multifactorial nature of HIV-associated brain dysfunction in the CART era, and the importance of examining the effect of HIV disease in the context of other comorbidities, in particular HCV coinfection and aging. PMID:21965122

  17. COMT genotype affects prefrontal white matter pathways in children and adolescents

    PubMed Central

    Thomason, Moriah E.; Dougherty, Robert F.; Colich, Natalie L.; Perry, Lee M.; Rykhlevskaia, Elena I.; Louro, Hugo M.; Hallmayer, Joachim F.; Waugh, Christian E.; Bammer, Roland; Glover, Gary H.; Gotlib, Ian H.

    2010-01-01

    Diffusion tensor imaging is widely used to evaluate the development of white matter. Information about how alterations in major neurotransmitter systems, such as the dopamine (DA) system, influence this development in healthy children, however, is lacking. Catechol-O-metyltransferase (COMT) is the major enzyme responsible for DA degradation in prefrontal brain structures, for which there is a corresponding genetic polymorphism (val158met) that confers either a more or less efficient version of this enzyme. The result of this common genetic variation is that children may have more or less available synaptic DA in prefrontal brain regions. In the present study we examined the relation between diffusion properties of frontal white matter structures and the COMT val158met polymorphism in 40 children ages 9–15. We found that the val allele was associated with significantly elevated fractional anisotropy values and reduced axial and radial diffusivities. These results indicate that the development of white matter in healthy children is related to COMT genotype and that alterations in white matter may be related to the differential availability of prefrontal DA. This investigation paves the way for further studies of how common functional variants in the genome might influence the development of brain white matter. PMID:20083203

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

    PubMed

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

    2010-11-01

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

  19. Gray and white matter structural changes in corticobasal syndrome.

    PubMed

    Upadhyay, Neeraj; Suppa, Antonio; Piattella, Maria Cristina; Di Stasio, Flavio; Petsas, Nikolaos; Colonnese, Claudio; Colosimo, Carlo; Berardelli, Alfredo; Pantano, Patrizia

    2016-01-01

    We investigated gray matter and white matter (WM) changes in corticobasal syndrome (CBS). T1-weighted and diffusion tensor images (3T-magnet) were obtained in 11 patients and 11 healthy subjects (HS). Magnetic resonance imaging data were analyzed using FreeSurfer and Tracts Constrained by Underlying Anatomy to evaluate cortical thickness (CTh), surface area, and subcortical volumes as well as diffusion tensor image parameters along the major WM tracts. Compared with HS, the whole patient group showed decreased CTh in the prefrontal cortex, precentral gyrus, supplementary motor area, insula, and temporal pole bilaterally. When we divided patients into 2 subgroups (left: L-CBS, right: R-CBS) on the basis of the clinically more affected upper limb, the most prominent decrease in CTh occurred in the hemisphere contralateral to the more affected side. The whole patient group also had volume loss in the putamen, hippocampus, and accumbens bilaterally, in the corpus callosum and right amygdala. Finally, we found diffusion changes in several WM tracts with axial diffusivity being altered more than radial diffusivity. The upper limb motor severity negatively correlated with the contralateral CTh in the precentral and/or postcentral gyri and contralateral volumes of putamen and accumbens. The CTh asymmetry in postcentral and/or paracentral gyri also negatively correlated with disease duration. Cortical thinning, volume loss, and fiber tract degeneration in specific brain regions are important pathophysiological abnormalities in CBS. PMID:26545629

  20. Zinc Protoporphyrin Attenuates White Matter Injury after Intracerebral Hemorrhage.

    PubMed

    Gu, Yuxiang; Gong, Ye; Liu, Wen-Quan; Keep, Richard F; Xi, Guohua; Hua, Ya

    2016-01-01

    Intracerebral hemorrhage (ICH)-induced white matter injury has not been well studied. The objective of this study was to examine the effect of zinc protoporphyrin (ZnPP) on white matter injury induced by ICH. This study was divided into two parts. In the first part, rats received either a needle insertion (sham) or 100 ?l autologous blood into the right basal ganglia. The rats were euthanized at 1, 3, 7, 14, or 28 days later for myelin basic protein (MBP) measurement. In the second part, rats had intracerebral infusion of 100 ?l autologous blood, and an intraperitoneal osmotic mini-pump was implanted immediately after ICH to deliver vehicle or ZnPP (1 nmol/h), a heme oxygenase inhibitor, for up to 14 days. Rats were euthanized at day 28 for MBP staining. The number of MBP-labeled fiber bundles and their area were determined. The time-course showed that the white matter was lost in the ipsilateral basal ganglia from day 1 to day 28 after ICH. The number of MBP-labeled bundles and their area were significantly lower 2 weeks after ICH compared with sham-operated rats (p?white matter injury occurs after ICH. ZnPP reduces white matter injury, suggesting a role of heme degradation products in ICH-induced white matter damage. PMID:26463948

  1. Scalable brain network construction on white matter fibers

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

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

  2. White matter tracts critical for recognition of sarcasm.

    PubMed

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

    2016-02-01

    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. PMID:25805326

  3. A comprehensive assessment of gray and white matter volumes and their relationship to outcome and severity in schizophrenia

    PubMed Central

    Mitelman, Serge A.; Brickman, Adam M.; Shihabuddin, Lina; Newmark, Randall E.; Hazlett, Erin A.; Haznedar, M. Mehmet; Buchsbaum, Monte S.

    2007-01-01

    Preliminary data suggest an association of posterior cortical gray matter reduction with poor outcome in schizophrenia. We made a systematic MRI assessment of regional gray and white matter volumes, parcellated into 40 Brodmann’s areas, in 104 patients with schizophrenia (51 with good outcomes, 53 with poor outcomes) and 41 normal comparison subjects, and investigated correlations of regional morphometry with outcome and severity of the illness. Schizophrenia patients displayed differential reductions in frontal and to a lesser degree temporal gray matter volumes in both hemispheres, most pronounced in the frontal pole and lateral temporal cortex. White matter volumes in schizophrenia patients were bilaterally increased, primarily in the frontal, parietal, and isolated temporal regions, with volume reductions confined to anterior cingulate gyrus. In patients with schizophrenia as a group, higher illness severity was associated with reduced temporal gray matter volumes and expanded frontal white matter volumes in both hemispheres. In comparison to good-outcome group, patients with poor outcomes had lower temporal, occipital, and to a lesser degree parietal gray matter volumes in both hemispheres and temporal, parietal, occipital, and posterior cingulate white matter volumes in the right hemisphere. While gray matter deficits in the granular cortex were observed in all schizophrenia patients, agranular cortical deficits in the left hemisphere were peculiar to patients with poor outcomes. These results provide support for frontotemporal gray matter reduction and frontoparietal white matter expansion in schizophrenia. Poor outcome is associated with more posterior distribution (posteriorization) of both gray and white matter changes, and with preferential impairment in the unimodal visual and paralimbic cortical regions. PMID:17587598

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

    PubMed Central

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

    2015-01-01

    Blast-related traumatic brain injury (TBI) has been a common injury among returning troops due to the widespread use of improvised explosive devices in the Iraq and Afghanistan Wars. As most of the TBIs sustained are in the mild range, brain changes may not be detected by standard clinical imaging techniques such as CT. Furthermore, the functional significance of these types of injuries is currently being debated. However, accumulating evidence suggests that diffusion tensor imaging (DTI) is sensitive to subtle white matter abnormalities and may be especially useful in detecting mild TBI (mTBI). The primary aim of this study was to use DTI to characterize the nature of white matter abnormalities following blast-related mTBI, and in particular, examine the extent to which mTBI-related white matter abnormalities are region-specific or spatially heterogeneous. In addition, we examined whether mTBI with loss of consciousness (LOC) was associated with more extensive white matter abnormality than mTBI without LOC, as well as the potential moderating effect of number of blast exposures. A second aim was to examine the relationship between white matter integrity and neurocognitive function. Finally, a third aim was to examine the contribution of PTSD symptom severity to observed white matter alterations. One hundred fourteen OEF/OIF veterans underwent DTI and neuropsychological examination and were divided into three groups including a control group, blast-related mTBI without LOC (mTBI - LOC) group, and blast-related mTBI with LOC (mTBI + LOC) group. Hierarchical regression models were used to examine the extent to which mTBI and PTSD predicted white matter abnormalities using two approaches: 1) a region-specific analysis and 2) a measure of spatial heterogeneity. Neurocognitive composite scores were calculated for executive functions, attention, memory, and psychomotor speed. Results showed that blast-related mTBI + LOC was associated with greater odds of having spatially heterogeneous white matter abnormalities. Region-specific reduction in fractional anisotropy (FA) in the left retrolenticular part of the internal capsule was observed in the mTBI + LOC group as the number of blast exposures increased. A mediation analysis revealed that mTBI + LOC indirectly influenced verbal memory performance through its effect on white matter integrity. PTSD was not associated with spatially heterogeneous white matter abnormalities. However, there was a suggestion that at higher levels of PTSD symptom severity, LOC was associated with reduced FA in the left retrolenticular part of the internal capsule. These results support postmortem reports of diffuse axonal injury following mTBI and suggest that injuries with LOC involvement may be particularly detrimental to white matter integrity. Furthermore, these results suggest that LOC-associated white matter abnormalities in turn influence neurocognitive function. PMID:26106539

  5. White matter integrity, language, and childhood onset schizophrenia

    PubMed Central

    Clark, Kristi; Narr, Katherine L.; O’Neill, Joseph; Levitt, Jennifer; Siddarth, Prabha; Phillips, Owen; Toga, Arthur; Caplan, Rochelle

    2012-01-01

    Background The heterogeneity of symptoms and cognitive deficits in schizophrenia can be explained by abnormal connectivity between brain regions. Childhood-onset schizophrenia (COS) is a particularly severe form of schizophrenia, with an onset during a key time period for both cerebral pruning and myelination. Methods Diffusion tensor images were acquired from 18 children and adolescents with COS and 25 controls. The COS group was divided into two sub-groups--one with linguistic impairment (LI) and the other without (NLI). The fractional anisotropy (FA), axial (AD), and radial diffusivity (RD) data from the two COS sub-groups were compared to each other and to the controls using tract-based spatial statistics (TBSS) analyses, which is a voxel-based method used to identify regions of white matter abnormalities. Results TBSS identified several regions in the left hemisphere where the LI group had increased AD and RD relative to the NLI and the control groups. These areas primarily localized to linguistic tracts: left superior longitudinal fasciculus and left inferior longitudinal fasciculus/inferior fronto-occipital fasciculus. Regions of increased RD overlapped regions of increased AD, with the former showing more pronounced effects. Conclusions Studies of adult-onset schizophrenia typically identify areas of higher RD but unchanged AD; however, normal development studies have shown that while RD decreases are pronounced over this age range, smaller decreases in AD can also be detected. The observed increases in both RD and AD suggest that developmental disturbances affecting the structural connectivity of these pathways are more severe in COS accompanied by severe linguistic impairments. PMID:22405729

  6. Automatic segmentation of brain white matter and white matter lesions in normal aging: comparison of five multispectral techniques.

    PubMed

    Valdés Hernández, Maria Del C; Gallacher, Peter J; Bastin, Mark E; Royle, Natalie A; Maniega, Susana Muñoz; Deary, Ian J; Wardlaw, Joanna M

    2012-02-01

    White matter loss, ventricular enlargement and white matter lesions are common findings on brain scans of older subjects. Accurate assessment of these different features is therefore essential for normal aging research. Recently, we developed a novel unsupervised classification method, named 'Multispectral Coloring Modulation and Variance Identification' (MCMxxxVI), that fuses two different structural magnetic resonance imaging (MRI) sequences in red/green color space and uses Minimum Variance Quantization (MVQ) as the clustering technique to segment different tissue types. Here we investigate how this method performs compared with several commonly used supervised image classifiers in segmenting normal-appearing white matter, white matter lesions and cerebrospinal fluid in the brains of 20 older subjects with a wide range of white matter lesion load and brain atrophy. The three tissue classes were segmented from T(1)-, T(2)-, T(2)?- and fluid attenuation inversion recovery (FLAIR)-weighted structural MRI data using MCMxxxVI and the four supervised multispectral classifiers available in the Analyze package, namely, Back-Propagated Neural Networks, Gaussian classifier, Nearest Neighbor and Parzen Windows. Bland-Altman analysis and Jaccard index values indicated that, in general, MCMxxxVI performed better than the supervised multispectral classifiers in identifying the three tissue classes, although final manual editing was still required to deliver radiologically acceptable results. These analyses show that MVQ, as implemented in MCMxxxVI, has the potential to provide quick and accurate white matter segmentations in the aging brain, although further methodological developments are still required to automate fully this technique. PMID:22071410

  7. Edge density imaging: mapping the anatomic embedding of the structural connectome within the white matter of the human brain.

    PubMed

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

    2015-04-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  10. Anomalous White Matter Morphology in Adults Who Stutter

    ERIC Educational Resources Information Center

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

    2015-01-01

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

  11. Maternal adiposity negatively influences infant brain white matter development

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

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

    E-print Network

    is to assess the impact of early adolescent onset of regular cannabis use on brain white matter tissue with schizophrenia. The ultimate goal is to determine the liability of early adolescent use of cannabis on brain phase schizophrenia: the impact of early adolescent cannabis use Denise Bernier1* , Jacob Cookey1

  14. Different associations of white matter lesions with depression and cognition

    E-print Network

    2012-01-01

    life-onset geriatric depression. Neurology 1996, 46(6):1567–lesions with depression and cognition. BMC Neurology 2012Neurology 2012, 12:83 http://www.biomedcentral.com/1471-2377/12/83 RESEARCH ARTICLE Open Access Different associations of white matter lesions with depression and

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

  16. Decreased and Increased Anisotropy along Major Cerebral White Matter Tracts in Preterm Children and Adolescents

    PubMed Central

    Ben-Shachar, Michal; Feldman, Heidi M.

    2015-01-01

    Premature birth is highly prevalent and associated with neurodevelopmental delays and disorders. Adverse outcomes, particularly in children born before 32 weeks of gestation, have been attributed in large part to white matter injuries, often found in periventricular regions using conventional imaging. To date, tractography studies of white matter pathways in children and adolescents born preterm have evaluated only a limited number of tracts simultaneously. The current study compares diffusion properties along 18 major cerebral white matter pathways in children and adolescents born preterm (n = 27) and full term (n = 19), using diffusion magnetic resonance imaging and tractography. We found that compared to the full term group, the preterm group had significantly decreased FA in segments of the bilateral uncinate fasciculus and anterior segments of the right inferior fronto-occipital fasciculus. Additionally, the preterm group had significantly increased FA in segments of the right and left anterior thalamic radiations, posterior segments of the right inferior fronto-occipital fasciculus, and the right and left inferior longitudinal fasciculus. Increased FA in the preterm group was generally associated with decreased radial diffusivity. These findings indicate that prematurity-related white matter differences in later childhood and adolescence do not affect all tracts in the periventricular zone and can involve both decreased and increased FA. Differences in the patterns of radial diffusivity and axial diffusivity suggest that the tissue properties underlying group FA differences may vary within and across white matter tracts. Distinctive diffusion properties may relate to variations in the timing of injury in the neonatal period, extent of white matter dysmaturity and/or compensatory processes in childhood. PMID:26560745

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

    PubMed Central

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

    2014-01-01

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

  18. Shortened telomere length in white matter oligodendrocytes in major depression: potential role of oxidative stress.

    PubMed

    Szebeni, Attila; Szebeni, Katalin; DiPeri, Timothy; Chandley, Michelle J; Crawford, Jessica D; Stockmeier, Craig A; Ordway, Gregory A

    2014-10-01

    Telomere shortening is observed in peripheral mononuclear cells from patients with major depressive disorder (MDD). Whether this finding and its biological causes impact the health of the brain in MDD is unknown. Brain cells have differing vulnerabilities to biological mechanisms known to play a role in accelerating telomere shortening. Here, two glia cell populations (oligodendrocytes and astrocytes) known to have different vulnerabilities to a key mediator of telomere shortening, oxidative stress, were studied. The two cell populations were separately collected by laser capture micro-dissection of two white matter regions shown previously to demonstrate pathology in MDD patients. Cells were collected from brain donors with MDD at the time of death and age-matched psychiatrically normal control donors (N = 12 donor pairs). Relative telomere lengths in white matter oligodendrocytes, but not astrocytes, from both brain regions were significantly shorter for MDD donors as compared to matched control donors. Gene expression levels of telomerase reverse transcriptase were significantly lower in white matter oligodendrocytes from MDD as compared to control donors. Likewise, the gene expression of oxidative defence enzymes superoxide dismutases (SOD1 and SOD2), catalase (CAT) and glutathione peroxidase (GPX1) were significantly lower in oligodendrocytes from MDD as compared to control donors. No such gene expression changes were observed in astrocytes from MDD donors. These findings suggest that attenuated oxidative stress defence and deficient telomerase contribute to telomere shortening in oligodendrocytes in MDD, and suggest an aetiological link between telomere shortening and white matter abnormalities previously described in MDD. PMID:24967945

  19. Gender differences in the relationship between white matter organization and adolescent substance use disorders

    PubMed Central

    Thatcher, Dawn L.; Pajtek, Stefan; Chung, Tammy; Terwilliger, Robert A.; Clark, Duncan B.

    2011-01-01

    Few studies have focused on the neurobiological correlates of adolescent-onset substance use disorders (SUDs), particularly with respect to white matter development and organization. This study investigated microstructural white matter characteristics associated with SUDs during the adolescent developmental period. Twenty-four case adolescents (ages 14-18) entering treatment for SUDs and 12 sex- and age-matched control adolescents with no psychopathology were compared. Diffusion tensor imaging data were collected and analyzed using the whole brain, tract-based spatial statistics (TBSS) method. In order to comprehensively characterize diffusivity characteristics, we first studied fractional anisotropy (FA), and within regions that differed in FA, other indicators of microstructure, including the axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD). A large cluster of significantly lower FA values was found in cases compared to controls in the superior longitudinal fasciculus (SLF). Within this cluster, AD and RD were also significantly different between the groups, while MD was not significantly different. For FA, a significant group by sex interaction was found; females with SUD exhibited lower FA than males with SUD, while control females exhibited higher FA than control males. These results indicated significantly lower white matter integrity in the superior longitudinal fasciculus region of association cortex, and assessed using multiple indicators of diffusion. These findings suggest that the disruption of normal white matter development due to substance exposure may be more severe in females than in males. PMID:20392574

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

    PubMed

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

    2016-01-01

    While brain gray matter is primarily associated with sensorimotor processing and cognition, white matter modulates the distribution of action potentials, coordinates communication between different brain regions, and acts as a relay for input/output signals. Previous studies have described morphological changes in gray and white matter during childhood and adolescence, which are consistent with cellular genesis and maturation, but corresponding events in infants are poorly documented. In the present study, we estimated the total number of cells (neurons, oligodendrocytes, astrocytes, and microglia) in the cerebral white matter of 9 infants aged 0-33 months, using design-based stereological methods to obtain quantitative data about brain development. There were linear increases with age in the numbers of oligodendrocytes (7-28 billion) and astrocytes (1.5-6.7 billion) during the first 3 years of life, thus attaining two-thirds of the corresponding numbers in adults. The numbers of neurons (0.7 billion) and microglia (0.2 billion) in the white matter did not increase during the first 3 years of life, but showed large biological variation. PMID:25122465

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

    E-print Network

    Shmuel Balberg; Stuart L. Shapiro

    2000-04-24

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

  2. Edinburgh Research Explorer APOE/TOMM40 genetic loci, white matter hyperintensities and

    E-print Network

    Vijayakumar, Sethu

    Edinburgh Research Explorer APOE/TOMM40 genetic loci, white matter hyperintensities and cerebral, J 2015, 'APOE/TOMM40 genetic loci, white matter hyperintensities and cerebral microbleeds. 2015 #12;APOE/TOMM40 genetic loci, white matter hyperintensities, and cerebral microbleeds Donald M

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  4. White Matter Development in Early Puberty: A Longitudinal Volumetric and Diffusion Tensor Imaging Twin Study

    PubMed Central

    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.; Pol, H. E. Hulshoff

    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. PMID:22514599

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

    PubMed

    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. PMID:25844306

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

    PubMed Central

    DeRamus, Thomas P.; Kana, Rajesh K.

    2014-01-01

    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. PMID:25844306

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

    PubMed

    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

    2015-01-01

    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. PMID:26585372

  8. Probing dark matter crests with white dwarfs and IMBHs

    E-print Network

    Amaro-Seoane, Pau; Schödel, Rainer; Davidson, Emily; Cuadra, Jorge

    2015-01-01

    White dwarfs (WDs) are the most promising captors of dark matter (DM) particles in the crests that are expected to build up in the cores of dense stellar clusters. The DM particles could reach sufficient densities in WD cores to liberate energy through self-annihilation. The extinction associated with our Galactic Centre, the most promising region where to look for such effects, makes it impossible to detect the potential associated luminosity of the DM-burning WDs. However, in smaller stellar systems which are close enough to us and not heavily extincted, such as $\\omega-$Cen, we may be able to detect DM-burning WDs. We investigate the prospects of detection of DM-burning WDs in a stellar cluster harbouring an IMBH, which leads to higher densities of DM at the centre as compared with clusters without one. We calculate the capture rate of WIMPs by a WD around an IMBH and estimate the luminosity that a WD would emit depending on its distance to the center of the cluster. Direct-summation $N-$body simulations o...

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

    PubMed Central

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

    2015-01-01

    Each day, we make hundreds of decisions. In some instances, these decisions are guided by our innate needs; in other instances they are guided by memory. Probabilistic reversal learning tasks exemplify the close relationship between decision making and memory, as subjects are exposed to repeated pairings of a stimulus choice with a reward or punishment outcome. After stimulus–outcome associations have been learned, the associated reward contingencies are reversed, and participants are not immediately aware of this reversal. Individual differences in the tendency to choose the previously rewarded stimulus reveal differences in the tendency to make poorly considered, inflexible choices. Lesion studies have strongly linked reversal learning performance to the functioning of the orbitofrontal cortex, the hippocampus, and in some instances, the amygdala. Here, we asked whether individual differences in the microstructure of the uncinate fasciculus, a white matter tract that connects anterior and medial temporal lobe regions to the orbitofrontal cortex, predict reversal learning performance. Diffusion tensor imaging and behavioral paradigms were used to examine this relationship in 33 healthy young adults. The results of tractography revealed a significant negative relationship between reversal learning performance and uncinate axial diffusivity, but no such relationship was demonstrated in a control tract, the inferior longitudinal fasciculus. Our findings suggest that the uncinate might serve to integrate associations stored in the anterior and medial temporal lobes with expectations about expected value based on feedback history, computed in the orbitofrontal cortex. PMID:26150776

  10. Decreased frontal white-matter integrity in abstinent methamphetamine abusers.

    PubMed

    Chung, Ain; Lyoo, In Kyoon; Kim, Seog Ju; Hwang, Jaeuk; Bae, Soojeong C; Sung, Young Hoon; Sim, Minyoung E; Song, In Chan; Kim, Jihyun; Chang, Kee Hyun; Renshaw, Perry F

    2007-12-01

    This study explored differences in frontal white-matter (WM) integrity between methamphetamine (MA) abusers and healthy comparison subjects using diffusion tensor imaging (DTI). Fractional anisotropy (FA) values, which indicate WM integrity, were calculated for regions-of-interest in frontal WM on diffusion tensor images of 32 MA abusers and 30 healthy comparison subjects. Frontal executive functions were also assessed by the Wisconsin Card Sorting test (WCST). MA abusers had significantly lower FA values in bilateral frontal WM at the anterior commissure-posterior commissure (AC-PC) plane and the right frontal WM 5 mm above the AC-PC plane relative to healthy comparison subjects. MA abusers had more total, perseveration and non-perseveration errors in the WCST relative to healthy comparison subjects. FA values of the right frontal WM 5 mm above the AC-PC plane negatively correlated with the number of total and non-perseveration errors in the WCST in MA abusers. In the sub-analysis for gender differences, lower FA values in frontal WM and more errors in the WCST were found only in male MA abusers, not in female MA abusers, relative to comparison subjects of the respective gender. We report that frontal WM integrity of MA abusers is compromised. This finding may also be related to impairment in frontal executive function. In addition, the neurotoxic effect of MA on frontal WM may be less prominent in women than in men, possibly due to oestrogen's neuroprotective effect. PMID:17147837

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

    PubMed

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

    2015-01-01

    Each day, we make hundreds of decisions. In some instances, these decisions are guided by our innate needs; in other instances they are guided by memory. Probabilistic reversal learning tasks exemplify the close relationship between decision making and memory, as subjects are exposed to repeated pairings of a stimulus choice with a reward or punishment outcome. After stimulus-outcome associations have been learned, the associated reward contingencies are reversed, and participants are not immediately aware of this reversal. Individual differences in the tendency to choose the previously rewarded stimulus reveal differences in the tendency to make poorly considered, inflexible choices. Lesion studies have strongly linked reversal learning performance to the functioning of the orbitofrontal cortex, the hippocampus, and in some instances, the amygdala. Here, we asked whether individual differences in the microstructure of the uncinate fasciculus, a white matter tract that connects anterior and medial temporal lobe regions to the orbitofrontal cortex, predict reversal learning performance. Diffusion tensor imaging and behavioral paradigms were used to examine this relationship in 33 healthy young adults. The results of tractography revealed a significant negative relationship between reversal learning performance and uncinate axial diffusivity, but no such relationship was demonstrated in a control tract, the inferior longitudinal fasciculus. Our findings suggest that the uncinate might serve to integrate associations stored in the anterior and medial temporal lobes with expectations about expected value based on feedback history, computed in the orbitofrontal cortex. PMID:26150776

  12. White matter structures associated with loneliness in young adults

    PubMed Central

    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

    2015-01-01

    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. PMID:26585372

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

    PubMed Central

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

    2014-01-01

    Activity of the hypothalamic–pituitary–adrenal axis (measured via cortisol reactivity) may be a biological marker of risk for depression and anxiety, possibly even early in development. However, the structural neural correlates of early cortisol reactivity are not well known, although these would potentially inform broader models of mechanisms of risk, especially if the early environment further shapes these relationships. Therefore, we examined links between white matter architecture and young girls' cortisol reactivity and whether early caregiving moderated these links. We recruited 45 6-year-old girls based on whether they had previously shown high or low cortisol reactivity to a stress task at age 3. White matter integrity was assessed by calculating fractional anisotropy (FA) of diffusion-weighted magnetic resonance imaging scans. Parenting styles were measured via a standardized parent–child interaction task. Significant associations were found between FA in white matter regions adjacent to the left thalamus, the right anterior cingulate cortex, and the right superior frontal gyrus (all ps < .001). Further, positive early caregiving moderated the effect of high cortisol reactivity on white matter FA (all ps ? .05), with high stress reactive girls who received greater parent positive affect showing white matter structure more similar to that of low stress reactive girls. Results show associations between white matter integrity of various limbic regions of the brain and early cortisol reactivity to stress and provide preliminary support for the notion that parenting may moderate associations. PMID:25379418

  14. White matter alterations in first episode treatment-naïve patients with deficit schizophrenia: a combined VBM and DTI study

    PubMed Central

    Lei, Wei; Li, Na; Deng, Wei; Li, Mingli; Huang, Chaohua; Ma, Xiaohong; Wang, Qiang; Guo, Wanjun; Li, Yinfei; Jiang, Lijun; Zhou, Yi; Hu, Xun; Mary McAlonan, Grainne; Li, Tao

    2015-01-01

    Categorizing ‘deficit schizophrenia’ (DS) as distinct from ‘non-deficit’ schizophrenia (NDS) may help reduce heterogeneity within schizophrenia. However, it is unknown if DS has a discrete white matter signature. Here we used MRI to compare white matter volume (voxel-based morphometry) and microstructural integrity (fractional anisotropy, FA) in first-episode treatment-naïve patients with DS and NDS and their unaffected relatives to control groups of similar age. We found that white matter disruption was prominent in DS compared to controls; the DS group had lower volumes in the cerebellum, bilateral extra-nuclear and bilateral frontoparietal regions, and lower FA in the body of corpus callosum, posterior superior longitudinal fasciculus and uncinate fasciculus. The DS group also had lower volume in bilateral extra-nuclear regions compared to NDS, and the volume of these clusters was negatively correlated with deficit symptom ratings. NDS patients however, had no significant volume alterations and limited disruption of microstructural integrity compared to controls. Finally, first-degree relatives of those with DS shared volume abnormalities in right extra-nuclear white matter. Thus, white matter pathology in schizophrenia is most evident in the deficit condition, and lower extra-nuclear white matter volumes in both DS patients and their relatives may represent a brain structural ‘endophenotype’ for DS. PMID:26257373

  15. Effect of Simulated Microgravity on Human Brain Gray Matter and White Matter – Evidence from MRI

    PubMed Central

    Li, Ke; Guo, Xiaojuan; Jin, Zhen; Ouyang, Xin; Zeng, Yawei; Feng, Jinsheng; Wang, Yu; Yao, Li; Ma, Lin

    2015-01-01

    Background There is limited and inconclusive evidence that space environment, especially microgravity condition, may affect microstructure of human brain. This experiment hypothesized that there would be modifications in gray matter (GM) and white matter (WM) of the brain due to microgravity. Method Eighteen male volunteers were recruited and fourteen volunteers underwent -6° head-down bed rest (HDBR) for 30 days simulated microgravity. High-resolution brain anatomical imaging data and diffusion tensor imaging images were collected on a 3T MR system before and after HDBR. We applied voxel-based morphometry and tract-based spatial statistics analysis to investigate the structural changes in GM and WM of brain. Results We observed significant decreases of GM volume in the bilateral frontal lobes, temporal poles, parahippocampal gyrus, insula and right hippocampus, and increases of GM volume in the vermis, bilateral paracentral lobule, right precuneus gyrus, left precentral gyrus and left postcentral gyrus after HDBR. Fractional anisotropy (FA) changes were also observed in multiple WM tracts. Conclusion These regions showing GM changes are closely associated with the functional domains of performance, locomotion, learning, memory and coordination. Regional WM alterations may be related to brain function decline and adaption. Our findings provide the neuroanatomical evidence of brain dysfunction or plasticity in microgravity condition and a deeper insight into the cerebral mechanisms in microgravity condition. PMID:26270525

  16. DTI-measured white matter abnormalities in adolescents with Conduct Disorder

    PubMed Central

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

    2013-01-01

    Emerging research suggests that antisocial behavior in youth is linked to abnormal brain white matter microstructure, but the extent of such anatomical connectivity abnormalities remain largely untested because previous Conduct Disorder (CD) studies typically have selectively focused on specific frontotemporal tracts. This study aimed to replicate and extend previous frontotemporal diffusion tensor imaging (DTI) findings to determine whether noncomorbid CD adolescents have white matter microstructural abnormalities in major white matter tracts across the whole brain. Seventeen CD-diagnosed adolescents recruited from the community were compared to a group of 24 non-CD youth which did not differ in average age (12–18) or gender proportion. Tract-based spatial statistics (TBSS) fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) measurements were compared between groups using FSL nonparametric two-sample t test, clusterwise whole-brain corrected, p<.05. CD FA and AD deficits were widespread, but unrelated to gender, verbal ability, or CD age of onset. CD adolescents had significantly lower FA and AD values in frontal lobe and temporal lobe regions, including frontal lobe anterior/superior corona radiata, and inferior longitudinal and fronto-occpital fasciculi passing through the temporal lobe. The magnitude of several CD FA deficits was associated with number of CD symptoms. Because AD, but not RD, differed between study groups, abnormalities of axonal microstructure in CD rather than myelination are suggested. This study provides evidence that adolescent antisocial disorder is linked to abnormal white matter microstructure in more than just the uncinate fasciulcus as identified in previous DTI studies, or frontotemporal brain structures as suggested by functional neuroimaging studies. Instead, neurobiological risk specific to antisociality in adolescence is linked to microstructural abnormality in numerous long-range white matter connections among many diverse different brain regions. PMID:24139595

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

    PubMed Central

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

    2010-01-01

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

  18. Individual Differences in Expert Motor Coordination Associated with White Matter Microstructure in the Cerebellum

    PubMed Central

    Roberts, R.E.; Bain, P.G.; Day, B.L.; Husain, M.

    2013-01-01

    Recent investigations into the neural basis of elite sporting performance have focused on whether cortical activity might characterize individual differences in ability. However, very little is understood about how changes in brain structure might contribute to individual differences in expert motor control. We compared the behavior and brain structure of healthy controls with a group of karate black belts, an expert group who are able to perform rapid, complex movements that require years of training. Using 3D motion tracking, we investigated whether the ability to control ballistic arm movements was associated with differences in white matter microstructure. We found that karate experts are better able than novices to coordinate the timing of inter-segmental joint velocities. Diffusion tensor imaging revealed significant differences between the groups in the microstructure of white matter in the superior cerebellar peduncles (SCPs) and primary motor cortex—brain regions that are critical to the voluntary control of movement. Motor coordination, the amount of experience, and the age at which training began were all associated with individual differences in white matter integrity in the cerebellum within the karate groups. These findings suggest a role for the white matter pathways of the SCPs in motor expertise. PMID:22892425

  19. Neuroanatomy of intergroup bias: A white matter microstructure study of individual differences.

    PubMed

    Baumgartner, Thomas; Nash, Kyle; Hill, Christopher; Knoch, Daria

    2015-11-15

    Intergroup bias-the tendency to behave more positively toward an ingroup member than an outgroup member-is a powerful social force, for good and ill. Although it is widely demonstrated, intergroup bias is not universal, as it is characterized by significant individual differences. Recently, attention has begun to turn to whether neuroanatomy might explain these individual differences in intergroup bias. However, no research to date has examined whether white matter microstructure could help determine differences in behavior toward ingroup and outgroup members. In the current research, we examine intergroup bias with the third-party punishment paradigm and white matter integrity and connectivity strength as determined by diffusion tensor imaging (DTI). We found that both increased white matter integrity at the right temporal-parietal junction (TPJ) and connectivity strength between the right TPJ and the dorsomedial prefrontal cortex (DMPFC) were associated with increased impartiality in the third-party punishment paradigm, i.e., reduced intergroup bias. Further, consistent with the role that these brain regions play in the mentalizing network, we found that these effects were mediated by mentalizing processes. Participants with greater white matter integrity at the right TPJ and connectivity strength between the right TPJ and the DMPFC employed mentalizing processes more equally for ingroup and outgroup members, and this non-biased use of mentalizing was associated with increased impartiality. The current results help shed light on the mechanisms of bias and, potentially, on interventions that promote impartiality over intergroup bias. PMID:26275384

  20. Lifespan maturation and degeneration of human brain white matter

    PubMed Central

    Yeatman, Jason D.; Wandell, Brian A.; Mezer, Aviv A.

    2014-01-01

    Properties of human brain tissue change across the lifespan. Here we model these changes in the living human brain by combining quantitative MRI measurements of R1 (1/T1) with diffusion MRI and tractography (N=102, ages 7–85). The amount of R1 change during development differs between white matter fascicles, but in each fascicle the rate of development and decline are mirror symmetric; the rate of R1 development as the brain approaches maturity predicts the rate of R1 degeneration in aging. Quantitative measurements of macromolecule tissue volume (MTV) confirm that R1 is an accurate index of the growth of new brain tissue. In contrast to R1, diffusion development follows an asymmetric time-course with rapid childhood changes but a slow rate of decline in old age. Together, the time-courses of R1 and diffusion changes demonstrate that multiple biological processes drive changes in white matter tissue properties over the lifespan. PMID:25230200

  1. Characterizing longitudinal white matter development during early childhood.

    PubMed

    Dean, Douglas C; O'Muircheartaigh, Jonathan; Dirks, Holly; Waskiewicz, Nicole; Walker, Lindsay; Doernberg, Ellen; Piryatinsky, Irene; Deoni, Sean C L

    2015-07-01

    Post-mortem studies have shown the maturation of the brain's myelinated white matter, crucial for efficient and coordinated brain communication, follows a nonlinear spatio-temporal pattern that corresponds with the onset and refinement of cognitive functions and behaviors. Unfortunately, investigation of myelination in vivo is challenging and, thus, little is known about the normative pattern of myelination, or its association with functional development. Using a novel quantitative magnetic resonance imaging technique sensitive to myelin we examined longitudinal white matter development in 108 typically developing children ranging in age from 2.5 months to 5.5 years. Using nonlinear mixed effects modeling, we provide the first in vivo longitudinal description of myelin water fraction development. Moreover, we show distinct male and female developmental patterns, and demonstrate significant relationships between myelin content and measures of cognitive function. These findings advance a new understanding of healthy brain development and provide a foundation from which to assess atypical development. PMID:24710623

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-05-01

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

  4. Shaping of white matter composition by biophysical scaling constraints

    PubMed Central

    Wang, Samuel S.-H.; Shultz, Jennifer R.; Burish, Mark J.; Harrison, Kimberly H.; Hof, Patrick R.; Towns, Lex C.; Wagers, Matthew W.; Wyatt, Krysta D.

    2009-01-01

    The brains of large mammals have lower rates of metabolism than those of small mammals, but the functional consequences of this scaling are not well understood. An attractive target for analysis is axons, whose size, speed and energy consumption are straightforwardly related. Here we show that from shrews to whales, the composition of white matter shifts from compact, slow-conducting, and energetically expensive unmyelinated axons to large, fast-conducting, and energetically inexpensive myelinated axons. The fastest axons have conduction times of 1–5 milliseconds across the neocortex and less than 1 millisecond from the eye to the brain, suggesting that in select sets of communicating fibers, large brains reduce transmission delays and metabolic firing costs at the expense of increased volume. Delays and potential imprecision in cross-brain conduction times are especially great in unmyelinated axons, which may transmit information via firing rate rather than precise spike timing. In neocortex, axon size distributions can account for the scaling of per-volume metabolic rate and suggest a maximum supportable firing rate, averaged across all axons, of 7 ± 2 Hz. Axon size distributions also account for the scaling of white matter volume with respect to brain size. The heterogeneous white matter composition found in large brains thus reflects a metabolically constrained trade-off that reduces both volume and conduction time. PMID:18400904

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

    PubMed Central

    Jiang, Guangyao; Yin, Xuntao; Li, Chuanming; Li, Lei; Zhao, Lu; Evans, Alan C.; Jiang, Tianzi; Wu, Jixiang; Wang, Jian

    2015-01-01

    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. PMID:26587289

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

    PubMed Central

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

    2015-01-01

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

  7. Association between Perivascular Spaces and Progression of White Matter Hyperintensities in Lacunar Stroke Patients

    PubMed Central

    Loos, Caroline M. J.; Klarenbeek, Pim; van Oostenbrugge, Robert J.; Staals, Julie

    2015-01-01

    Objectives Perivascular spaces are associated with MRI markers of cerebral small vessel disease, including white matter hyperintensities. Although perivascular spaces are considered to be an early MRI marker of cerebral small vessel disease, it is unknown whether they are associated with further progression of MRI markers, especially white matter hyperintensities. We determined the association between perivascular spaces and progression of white matter hyperintensities after 2-year follow-up in lacunar stroke patients. Methods In 118 lacunar stroke patients we obtained brain MRI and 24-hour ambulatory blood pressure measurements at baseline, and a follow-up brain MRI 2 years later. We visually graded perivascular spaces and white matter hyperintensities at baseline. Progression of white matter hyperintensities was assessed using a visual white matter hyperintensity change scale. Associations with white matter hyperintensity progression were tested with binary logistic regression analysis. Results Extensive basal ganglia perivascular spaces were associated with progression of white matter hyperintensities (OR 4.29; 95% CI: 1.28–14.32; p<0.05), after adjustment for age, gender, 24-hour blood pressure and vascular risk factors. This association lost significance after additional adjustment for baseline white matter hyperintensities. Centrum semiovale perivascular spaces were not associated with progression of white matter hyperintensities. Conclusions Our study shows that extensive basal ganglia perivascular spaces are associated with progression of white matter hyperintensities in cerebral small vessel disease. However, this association was not independent of baseline white matter hyperintensities. Therefore, presence of white matter hyperintensities at baseline remains an important determinant of further progression of white matter hyperintensities in cerebral small vessel disease. PMID:26352265

  8. Mapping Magnetic Susceptibility Anisotropies of White Matter in vivo in the Human Brain at 7 Tesla

    PubMed Central

    Li, Xu; Vikram, Deepti S; Lim, Issel Anne L; Jones, Craig K; Farrell, Jonathan A.D.; van Zijl, Peter C. M.

    2012-01-01

    High-resolution magnetic resonance phase- or frequency- shift images acquired at high field show contrast related to magnetic susceptibility differences between tissues. Such contrast varies with the orientation of the organ in the field, but the development of quantitative susceptibility mapping (QSM) has made it possible to reproducibly image the intrinsic tissue susceptibility contrast. However, recent studies indicate that magnetic susceptibility is anisotropic in brain white matter and, as such, needs to be described by a symmetric second-rank tensor (?¯¯). To fully determine the elements of this tensor, it would be necessary to acquire frequency data at six or more orientations. Assuming cylindrical symmetry of the susceptibility tensor in myelinated white matter fibers, we propose a simplified method to reconstruct the susceptibility tensor in terms of a mean magnetic susceptibility, MMS = (?? + 2??)/3 and a magnetic susceptibility anisotropy, MSA = ?? ? ??, where ?? and ?? are susceptibility parallel and perpendicular to the white matter fiber direction, respectively. Computer simulations show that with a practical head rotation angle of around 20°–30°, four head orientations suffice to reproducibly reconstruct the tensor with good accuracy. We tested this approach on whole brain 1×1×1 mm3 frequency data acquired from five healthy subjects at 7 T. The frequency information from phase images collected at four head orientations was combined with the fiber direction information extracted from diffusion tensor imaging (DTI) to map the white matter susceptibility tensor. The MMS and MSA were quantified for regions in several large white matter fiber structures, including the corona radiata, posterior thalamic radiation and corpus callosum. MMS ranged from ?0.037 to ?0.053 ppm (referenced to CSF being about zero). MSA values could be quantified without the need for a reference and ranged between 0.004 and 0.029 ppm, in line with the expectation that the susceptibility perpendicular to the fiber is more diamagnetic than the one parallel to it. PMID:22561358

  9. Reduced blood flow in normal white matter predicts development of leukoaraiosis.

    PubMed

    Bernbaum, Manya; Menon, Bijoy K; Fick, Gordon; Smith, Eric E; Goyal, Mayank; Frayne, Richard; Coutts, Shelagh B

    2015-10-01

    The purpose of this study was to investigate whether low cerebral blood flow (CBF) is associated with subsequent development of white matter hyperintensities (WMH). Patients were included from a longitudinal magnetic resonance (MR) imaging study of minor stroke/transient ischemic attack patients. Images were co-registered and new WMH at 18 months were identified by comparing follow-up imaging with baseline fluid-attenuated inversion recovery (FLAIR). Regions-of-interest (ROIs) were placed on FLAIR images in one of three categories: (1) WMH seen at both baseline and follow-up imaging, (2) new WMH seen only on follow-up imaging, and (3) regions of normal-appearing white matter at both time points. Registered CBF maps at baseline were used to measure CBF in the ROIs. A multivariable model was developed using mixed-effects logistic regression to determine the effect of baseline CBF on the development on new WMH. Forty patients were included. Mean age was 61±11 years, 30% were female. Low baseline CBF, female sex, and presence of diabetes were independently associated with the presence of new WMH on follow-up imaging. The odds of having new WMH on follow-up imaging reduces by 0.61 (95% confidence interval=0.57 to 0.65) for each 1?mL/100?g per minute increase in baseline CBF. We conclude that regions of white matter with low CBF develop new WMH on follow-up imaging. PMID:25966951

  10. Similarities and differences of white matter connectivity and water diffusivity in bipolar I and II disorder.

    PubMed

    Ha, Tae Hyon; Her, Ju Young; Kim, Jae Hyoung; Chang, Jae Seung; Cho, Hyun Sang; Ha, Kyooseob

    2011-11-14

    Differences and similarities in microstructural white matter alterations between bipolar I and bipolar II disorder were investigated. Twelve patients with bipolar I disorder, 12 patients with bipolar II disorder and 22 healthy controls underwent diffusion tensor imaging. Fractional anisotropy (FA) and mean apparent diffusion coefficient (ADC) maps were compared between groups using voxel-based whole brain analyses. Both bipolar I and II groups had a FA decrease in the corpus callosum, cingulate and right prefrontal regions, and a ADC increase in the medial frontal, anterior cingulate, insular and temporal regions, compared to controls. The bipolar I group had a FA decrease in the right temporal white matter and a ADC increase in the frontal, temporal, parietal and thalamic regions, compared to the bipolar II group. The results suggest disrupted integrity of commissural fibers and white matter in the anterior paralimbic structures in bipolar disorder. Relative sparing of the dorsal system and long association fibers may differentiate bipolar II from I disorder. PMID:22008503

  11. White Matter Microstructure and Cognition in Adolescents with Congenital Heart Disease

    PubMed Central

    Rollins, Caitlin K.; Watson, Christopher G.; Asaro, Lisa A.; Wypij, David; Vajapeyam, Sridhar; Bellinger, David C.; DeMaso, David R.; Robertson, Richard L.; Newburger, Jane W.; Rivkin, Michael J.

    2014-01-01

    Objective To describe the relationship between altered white matter microstructure and neurodevelopment in children with d-transposition of the great arteries (d-TGA). Study design We report correlations between regional white matter microstructure as measured by fractional anisotropy (FA) and cognitive outcome in a homogeneous group of adolescents with d-TGA. Subjects with d-TGA (n=49) and controls (n=29) underwent diffusion tensor imaging and neurocognitive testing. In the group with d-TGA, we correlated neurocognitive scores with FA in 14 composite regions of interest in which subjects with d-TGA had lower FA than controls. Results Among the patients with d-TGA, mathematics achievement correlated with left parietal FA (r=0.39, p=0.006), inattention/hyperactivity symptoms with right precentral FA (r=?0.39, p=0.006) and left parietal FA (r=?0.30, p=0.04), executive function with right precentral FA (r=?0.30, p=0.04), and visual-spatial skills with right frontal FA(r=0.30, p=0.04). We also found an unanticipated correlation between memory and right posterior limb of the internal capsule FA (r=0.29, p=0.047). Conclusion Within the group with d-TGA, regions of reduced white matter microstructure are associated with cognitive performance in a pattern similar to healthy adolescents and adults. Diminished white matter microstructure may contribute to cognitive compromise in adolescents who underwent open-heart surgery in infancy. PMID:25217200

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2001-07-01

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

  14. White-matter microstructure and gray-matter volumes in adolescents with subthreshold bipolar symptoms.

    PubMed

    Paillère Martinot, M-L; Lemaitre, H; Artiges, E; Miranda, R; Goodman, R; Penttilä, J; Struve, M; Fadai, T; Kappel, V; Poustka, L; Conrod, P; Banaschewski, T; Barbot, A; Barker, G J; Büchel, C; Flor, H; Gallinat, J; Garavan, H; Heinz, A; Ittermann, B; Lawrence, C; Loth, E; Mann, K; Paus, T; Pausova, Z; Rietschel, M; Robbins, T W; Smolka, M N; Schumann, G; Martinot, J-L

    2014-04-01

    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 early WM microstructural alterations and whether those alterations would be associated with differences in gray-matter (GM) volumes. Forty-two adolescents with three core manic symptoms and no psychiatric diagnosis, and 126 adolescents matched by age and sex, with no psychiatric diagnosis or symptoms, were identified after screening the IMAGEN database of 2223 young adolescents recruited from the general population. After image quality control, voxel-wise statistics were performed on the diffusion parameters using tract-based spatial statistics in 25 SBP adolescents and 77 controls, and on GM and WM images using voxel-based morphometry in 30 SBP adolescents and 106 controls. As compared with healthy controls, adolescents with SBP displayed lower FA values in a number of WM tracts, particularly in the corpus callosum, cingulum, bilateral superior and inferior longitudinal fasciculi, uncinate fasciculi and corticospinal tracts. Radial diffusivity was mainly higher in posterior parts of bilateral superior and inferior longitudinal fasciculi, inferior fronto-occipital fasciculi and right cingulum. As compared with controls, SBP adolescents had lower GM volume in the left anterior cingulate region. This is the first study to investigate WM microstructure and GM morphometric variations in adolescents with SBP. The widespread FA alterations in association and projection tracts, associated with GM changes in regions involved in mood disorders, suggest altered structural connectivity in those adolescents. PMID:23628983

  15. White-matter microstructure and gray-matter volumes in adolescents with subthreshold bipolar symptoms

    PubMed Central

    Paillère Martinot, M-L; Lemaitre, H; Artiges, E; Miranda, R; Goodman, R; Penttilä, J; Struve, M; Fadai, T; Kappel, V; Poustka, L; Conrod, P; Banaschewski, T; Barbot, A; Barker, G J; Büchel, C; Flor, H; Gallinat, J; Garavan, H; Heinz, A; Ittermann, B; Lawrence, C; Loth, E; Mann, K; Paus, T; Pausova, Z; Rietschel, M; Robbins, T W; Smolka, M N; Schumann, G; Martinot, J-L; L, Reed; S, Williams; A, Lourdusamy; S, Costafreda; A, Cattrell; C, Nymberg; L, Topper; L, Smith; S, Havatzias; K, Stueber; C, Mallik; TK, Clarke; D, Stacey; Wong C, Peng; H, Werts; S, Williams; C, Andrew; S, Desrivieres; S, Zewdie; I, Häke; N, Ivanov; A, Klär; J, Reuter; C, Palafox; C, Hohmann; C, Schilling; K, Lüdemann; A, Romanowski; A, Ströhle; E, Wolff; M, Rapp; R, Brühl; A, Ihlenfeld; B, Walaszek; F, Schubert; C, Connolly; J, Jones; E, Lalor; E, McCabe; A, Ní Shiothcháin; R, Whelan; R, Spanagel; F, Leonardi-Essmann; W, Sommer; S, Vollstaedt-Klein; F, Nees; S, Steiner; M, Buehler; E, Stolzenburg; C, Schmal; F, Schirmbeck; P, Gowland; N, Heym; C, Newman; T, Huebner; S, Ripke; E, Mennigen; K, Muller; V, Ziesch; C, Büchel; U, Bromberg; L, Lueken; J, Yacubian; J, Finsterbusch; N, Bordas; S, de Bournonville; Z, Bricaud; Briand F, Gollier; J, Massicotte; JB, Poline; H, Vulser; Y, Schwartz; C, Lalanne; V, Frouin; B, Thyreau; J, Dalley; A, Mar; N, Subramaniam; D, Theobald; N, Richmond; M, de Rover; A, Molander; E, Jordan; E, Robinson; L, Hipolata; M, Moreno; M, Arroyo; D, Stephens; T, Ripley; H, Crombag; Y, Pena; M, Lathrop; D, Zelenika; S, Heath; D, Lanzerath; B, Heinrichs; T, Spranger; B, Fuchs; C, Speiser; F, Resch; J, Haffner; P, Parzer; R, Brunner; A, Klaassen; I, Klaassen; P, Constant; X, Mignon; T, Thomsen; S, Zysset; A, Vestboe; J, Ireland; J, Rogers

    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 early WM microstructural alterations and whether those alterations would be associated with differences in gray-matter (GM) volumes. Forty-two adolescents with three core manic symptoms and no psychiatric diagnosis, and 126 adolescents matched by age and sex, with no psychiatric diagnosis or symptoms, were identified after screening the IMAGEN database of 2223 young adolescents recruited from the general population. After image quality control, voxel-wise statistics were performed on the diffusion parameters using tract-based spatial statistics in 25 SBP adolescents and 77 controls, and on GM and WM images using voxel-based morphometry in 30 SBP adolescents and 106 controls. As compared with healthy controls, adolescents with SBP displayed lower FA values in a number of WM tracts, particularly in the corpus callosum, cingulum, bilateral superior and inferior longitudinal fasciculi, uncinate fasciculi and corticospinal tracts. Radial diffusivity was mainly higher in posterior parts of bilateral superior and inferior longitudinal fasciculi, inferior fronto-occipital fasciculi and right cingulum. As compared with controls, SBP adolescents had lower GM volume in the left anterior cingulate region. This is the first study to investigate WM microstructure and GM morphometric variations in adolescents with SBP. The widespread FA alterations in association and projection tracts, associated with GM changes in regions involved in mood disorders, suggest altered structural connectivity in those adolescents. PMID:23628983

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

    PubMed Central

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

    2015-01-01

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

  17. Comparing Prefrontal Gray and White Matter Contributions to Intelligence and Decision Making in Schizophrenia and Healthy Controls

    E-print Network

    Comparing Prefrontal Gray and White Matter Contributions to Intelligence and Decision Making (white matter) and OFC gray matter volume as well as lower neuropsychological scores. In addition. For patients, CB white matter but not OFC gray matter correlated with various aspects of intelligence

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

    E-print Network

    Gaser, Christian

    Research Report Gray and white matter reduction in hyposmic subjects -- A voxel-based morphometry of the gray and white matter in a group of subjects with an impaired but not complete loss of olfaction in a Matlab environment. The analysis revealed significant gray matter volume loss in the insular cortex

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

    E-print Network

    Jiang,Tianzi

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

  20. Alterations in white matter pathways in Angelman syndrome

    PubMed Central

    PETERS, SARIKA U; KAUFMANN, WALTER E; BACINO, CARLOS A; ANDERSON, ADAM W; ADAPA, PAVANI; CHU, ZILI; YALLAMPALLI, RAGINI; TRAIPE, ELFRIDES; HUNTER, JILL V; WILDE, ELISABETH A

    2010-01-01

    Aim Angelman syndrome is a neurogenetic disorder characterized by severe intellectual disability, absent speech, seizures, and outbursts of laughter. The aim of this study was to utilize diffusion tensor imaging (DTI) to examine alterations in white matter pathways in Angelman syndrome, with an emphasis on correlations with clinical severity. Methods DTI was used to examine the arcuate fasciculus (AF), uncinate fasciculus (UF), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), and the corpus callosum (CC). We enrolled 14 children aged 8 to 17 years (mean age 10y 8mo; SD 2y 7mo) with Angelman syndrome (seven male; seven female) and 13 typically developing children, aged 8 to 17 years, for comparison (five male; eight female; mean age 12y; SD 2y 9mo). Individuals with Angelman syndrome were assessed using standardized measures of development, language, and behaviour. Results The children with Angelman syndrome exhibited lower fractional anisotropy and increased radial diffusivity values than the comparison group for the AF, UF, ILF, and CC (p<0.006 corrected for multiple comparisons). They also had lower fractional anisotropy values for the IFOF and higher radial diffusivity values for the left IFOF (p<0.006). Additionally, children with Angelman syndrome had significantly higher apparent diffusion coefficient values in the AF, CC, ILF, and the left IFOF (p<0.006). Significant correlations were noted between DTI parameters and some of the clinical assessment outcomes (e.g. language, socialization, cognition) for three of the temporal pathways (AF, UF, ILF; p<0.05). Interpretation Changes in DTI parameters in individuals with Angelman syndrome suggest decreased/delayed myelination, decreased axonal density or diameter, or aberrant axonal organization. Our findings suggest a generalized white matter alteration throughout the brain in those with Angelman syndrome; however, only the alterations in temporal white matter pathways were associated with language and cognitive and social functioning. PMID:21121904

  1. White matter hyperintensities, hot flushes and estrogen - are they related?

    PubMed

    Pines, A

    2015-12-01

    White matter hyperintensities (WMH) are areas of high intensity observed in brain MRI scans. They are usually seen in normal aging but also in a number of neurological and psychiatric disorders. One of the underlying mechanisms is ischemia, expressed as small vessel disease. Since the volume of WMH may correlate with cognition, and an ongoing debate links postmenopausal hormone therapy with stroke and a decline in certain cognitive domains, several MRI studies have addressed this potential association. Two major randomized, placebo-controlled trials - WHIMS and KEEPS, the first including elderly women and the second recruiting recently menopausal women, did not demonstrate any safety concerns in this respect in hormone users. PMID:26329986

  2. Albuminuria, Cognitive Functioning and White Matter Hyperintensities in Homebound Elders

    PubMed Central

    Weiner, Daniel E.; Bartolomei, Keith; Scott, Tammy; Price, Lori Lyn; Griffith, John L.; Rosenberg, Irwin; Levey, Andrew S.; Folstein, Marshal F.; Sarnak, Mark J.

    2009-01-01

    Background Albuminuria, a kidney marker of microvascular disease, may herald microvascular disease elsewhere, including in the brain. Study Design Cross sectional. Setting and Participants Boston, MA (USA) elders receiving home health services to maintain independent living who consented to brain magnetic resonance imaging. Predictor Urine albumin to creatinine ratio (ACR). Outcome Performance on a cognitive battery assessing executive function and memory using principal components analysis and white matter hyperintensity volume on brain imaging, evaluated in logistic and linear regression models. Results Of 335 participants, mean age was 73.4 ± 8.1 years; 123 participants had microalbuminuria or macroalbuminuria. Each doubling of ACR was associated with worse executive function [?=-0.05 (p=0.005) in univariate and ?=-0.07 (p=0.004) in multivariable analyses controlling for age, sex, race, education, diabetes, cardiovascular disease, hypertension, medications, and estimated glomerular filtration rate] but not with worse memory or working memory. Individuals with microalbuminuria or macroalbuminuria were more likely to be in the lower versus the highest tertile of executive functioning [Odds ratio =1.18 (1.06 to 1.32) and 1.19 (1.05 to 1.35) per doubling of ACR in univariate and multivariable analyses, respectively]. Albuminuria was associated with qualitative white matter hyperintensity grade [Odds ratio =1.13 (1.02 to 1.25) and 1.15 (1.02 to 1.29) per doubling of ACR] in univariate and multivariable analyses, and with quantitative white matter hyperintensity volume [?=0.11 (p=0.007) and ?=0.10 (p=0.01)] in univariate and multivariable analyses of log-transformed data, respectively. Results were similar when excluding individuals with macroalbuminuria. Limitations Single measurement of ACR, indirect creatinine calibration and reliance on participant recall for elements of medical history Conclusions Albuminuria is associated with worse cognitive performance, particularly in executive functioning, as well as increased white matter hyperintensity volume. Albuminuria likely identifies greater brain microvascular disease burden. PMID:19070412

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

    PubMed Central

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

    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. Collaboration between fields is essential to understand the function of the white matter, but due to differences in methods and field-specific ‘language’, communication is often hindered. In this review, we try to address this hindrance by introducing the methods and providing a basic background to myelin biology and human imaging as a prelude to the other reviews within this special issue. PMID:25003711

  4. Oligodendroglial Alterations and the Role of Microglia in White Matter Injury: Relevance to Schizophrenia

    PubMed Central

    Chew, Li-Jin; Fusar-Poli, Paolo; Schmitz, Thomas

    2015-01-01

    Schizophrenia is a chronic and debilitating mental illness characterized by a broad range of abnormal behaviors, including delusions and hallucinations, impaired cognitive function, as well as mood disturbances and social withdrawal. Due to the heterogeneous nature of the disease, the causes of schizophrenia are very complex; its etiology is believed to involve multiple brain regions and the connections between them, and includes alterations in both gray and white matter regions. The onset of symptoms varies with age and severity, and there is some debate over a degenerative or developmental etiology. Longitudinal magnetic resonance imaging studies have detected progressive gray matter loss in the first years of disease, suggesting neurodegeneration; but there is also increasing recognition of a temporal association between clinical complications at birth and disease onset that supports a neurodevelopmental origin. Presently, neuronal abnormalities in schizophrenia are better understood than alterations in myelin-producing cells of the brain, the oligodendrocytes, which are the predominant constituents of white matter structures. Proper white matter development and its structural integrity critically impacts brain connectivity, which affects sensorimotor coordination and cognitive ability. Evidence of defective white matter growth and compromised white matter integrity has been found in individuals at high risk of psychosis, and decreased numbers of mature oligodendrocytes are detected in schizophrenia patients. Inflammatory markers, including proinflammatory cytokines and chemokines, are also associated with psychosis. A relationship between risk of psychosis, white matter defects and prenatal inflammation is being established. Animal models of perinatal brain injury are successful in producing white matter damage in the brain, typified by hypomyelination and/or dysmyelination, impaired motor coordination and prepulse inhibition of the acoustic startle reflex, recapitulating structural and functional characteristics observed in schizophrenia. In addition, elevated expression of inflammation-related genes in brain tissue and increased production of cytokines by blood cells from patients with schizophrenia indicate immunological dysfunction and abnormal inflammatory responses, which are also important underlying features in experimental models. Microglia, resident immune defenders of the central nervous system, play important roles in the development and protection of neural cells, but can contribute to injury under pathological conditions. This article discusses oligodendroglial changes in schizophrenia and focuses on microglial activity in the context of the disease, in neonatal brain injury and in various experimental models of white matter damage. These include disorders associated with premature birth, and animal models of perinatal bacterial and viral infection, oxygen deprivation (hypoxia) and excess (hyperoxia), and elevated systemic proinflammatory cytokine levels. We briefly review the effects of treatment with antipsychotic and anti-inflammatory agents in models of perinatal brain injury, and comment on the therapeutic potential of these strategies. By understanding the neurobiological basis of oligodendroglial abnormalities in schizophrenia, it is hoped that patients will benefit from the availability of targeted and more efficacious treatment options. PMID:23446060

  5. Differential relationships between apathy and depression with white matter microstructural changes and functional outcomes

    PubMed Central

    Lawrence, Andrew J.; Brookes, Rebecca L.; Barrick, Thomas R.; Morris, Robin G.; Husain, Masud; Markus, Hugh S.

    2015-01-01

    Small vessel disease is a stroke subtype characterized by pathology of the small perforating arteries, which supply the sub-cortical structures of the brain. Small vessel disease is associated with high rates of apathy and depression, thought to be caused by a disruption of white matter cortical-subcortical pathways important for emotion regulation. It provides an important biological model to investigate mechanisms underlying these key neuropsychiatric disorders. This study investigated whether apathy and depression can be distinguished in small vessel disease both in terms of their relative relationship with white matter microstructure, and secondly whether they can independently predict functional outcomes. Participants with small vessel disease (n = 118; mean age = 68.9 years; 65% male) defined as a clinical and magnetic resonance imaging confirmed lacunar stroke with radiological leukoaraiosis were recruited and completed cognitive testing, measures of apathy, depression, quality of life and diffusion tensor imaging. Healthy controls (n = 398; mean age = 64.3 years; 52% male) were also studied in order to interpret the degree of apathy and depression found within the small vessel disease group. Firstly, a multilevel structural equation modelling approach was used to identify: (i) the relationships between median fractional anisotropy and apathy, depression and cognitive impairment; and (ii) if apathy and depression make independent contributions to quality of life in patients with small vessel disease. Secondly, we applied a whole-brain voxel-based analysis to investigate which regions of white matter were associated with apathy and depression, controlling for age, gender and cognitive functioning. Structural equation modelling results indicated both apathy (r = ?0.23, P ? 0.001) and depression (r = ?0.41, P ? 0.001) were independent predictors of quality of life. A reduced median fractional anisotropy was significantly associated with apathy (r = ?0.38, P ? 0.001), but not depression (r = ?0.16, P = 0.09). On voxel-based analysis, apathy was associated with widespread reduction in white matter integrity, with the strongest effects in limbic association tracts such as the anterior cingulum, fornix and uncinate fasciculus. In contrast, when controlling for apathy, we found no significant relationship between our white matter parameters and symptoms of depression. In conclusion, white matter microstructural changes in small vessel disease are associated with apathy but not directly with depressive symptoms. These results suggest that apathy, but not depression, in small vessel disease is related to damage to cortical-subcortical networks associated with emotion regulation, reward and goal-directed behaviour. PMID:26490330

  6. Differential relationships between apathy and depression with white matter microstructural changes and functional outcomes.

    PubMed

    Hollocks, Matthew J; Lawrence, Andrew J; Brookes, Rebecca L; Barrick, Thomas R; Morris, Robin G; Husain, Masud; Markus, Hugh S

    2015-12-01

    Small vessel disease is a stroke subtype characterized by pathology of the small perforating arteries, which supply the sub-cortical structures of the brain. Small vessel disease is associated with high rates of apathy and depression, thought to be caused by a disruption of white matter cortical-subcortical pathways important for emotion regulation. It provides an important biological model to investigate mechanisms underlying these key neuropsychiatric disorders. This study investigated whether apathy and depression can be distinguished in small vessel disease both in terms of their relative relationship with white matter microstructure, and secondly whether they can independently predict functional outcomes. Participants with small vessel disease (n = 118; mean age = 68.9 years; 65% male) defined as a clinical and magnetic resonance imaging confirmed lacunar stroke with radiological leukoaraiosis were recruited and completed cognitive testing, measures of apathy, depression, quality of life and diffusion tensor imaging. Healthy controls (n = 398; mean age = 64.3 years; 52% male) were also studied in order to interpret the degree of apathy and depression found within the small vessel disease group. Firstly, a multilevel structural equation modelling approach was used to identify: (i) the relationships between median fractional anisotropy and apathy, depression and cognitive impairment; and (ii) if apathy and depression make independent contributions to quality of life in patients with small vessel disease. Secondly, we applied a whole-brain voxel-based analysis to investigate which regions of white matter were associated with apathy and depression, controlling for age, gender and cognitive functioning. Structural equation modelling results indicated both apathy (r = -0.23, P ? 0.001) and depression (r = -0.41, P ? 0.001) were independent predictors of quality of life. A reduced median fractional anisotropy was significantly associated with apathy (r = -0.38, P ? 0.001), but not depression (r = -0.16, P = 0.09). On voxel-based analysis, apathy was associated with widespread reduction in white matter integrity, with the strongest effects in limbic association tracts such as the anterior cingulum, fornix and uncinate fasciculus. In contrast, when controlling for apathy, we found no significant relationship between our white matter parameters and symptoms of depression. In conclusion, white matter microstructural changes in small vessel disease are associated with apathy but not directly with depressive symptoms. These results suggest that apathy, but not depression, in small vessel disease is related to damage to cortical-subcortical networks associated with emotion regulation, reward and goal-directed behaviour. PMID:26490330

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

    PubMed

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

    2015-03-01

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

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

    E-print Network

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

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

  9. Lipocalin 2 and Blood-Brain Barrier Disruption in White Matter after Experimental Subarachnoid Hemorrhage.

    PubMed

    Egashira, Yusuke; Hua, Ya; Keep, Richard F; Iwama, Toru; Xi, Guohua

    2016-01-01

    We reported previously that subarachnoid hemorrhage (SAH) causes acute white matter injury in mice. In this study, we investigated lipocalin 2 (LCN2) mediated blood-brain barrier (BBB) disruption in white matter, which may lead to subsequent injury. SAH was induced by endovascular perforation in wild-type (WT) and LCN2-knockout (LCN2(-/-)) mice. Sham mice underwent the same procedure without perforation. Mice underwent magnetic resonance imaging (MRI) 24 h after SAH to confirm the development of T2-hyperintensity in white matter. Western blotting and immunohistochemistry were performed to elucidate the mechanisms of LCN2-mediated white matter injury and BBB disruption. It was confirmed that LCN2 expression was significantly increased in white matter of WT mice after SAH by Western blotting (versus sham; p?white matter. In WT mice with SAH, albumin leakage along the white matter was prominently observed and was consistent with T2-hyperintensity on MRI. As with our previous report, LCN2(-/-) mice scarcely developed T2-hyperintensity on MRI or albumin leakage in white matter. Our results suggest that BBB leakage occurs in white matter after SAH and that LCN2 contributes to SAH-induced BBB disruption. PMID:26463936

  10. Limitations on the Developing Preterm Brain: Impact of Periventricular White Matter Lesions on Brain Connectivity and Cognition

    ERIC Educational Resources Information Center

    Pavlova, Marina A.; Krageloh-Mann, Ingeborg

    2013-01-01

    Brain lesions to the white matter in peritrigonal regions, periventricular leukomalacia, in children who were born prematurely represent an important model for studying limitations on brain development. The lesional pattern is of early origin and bilateral, that constrains the compensatory potential of the brain. We suggest that (i) topography and…

  11. Neuropathological Correlates of Temporal Pole White Matter Hyperintensities in CADASIL

    PubMed Central

    Yamamoto, Yumi; Ihara, Masafumi; Tham, Carina; Low, Roger WC; Slade, Janet Y; Moss, Tim; Oakley, Arthur E; Polvikoski, Tuomo; Kalaria, Raj N

    2009-01-01

    Background and Purpose White matter (WM) hyperintensities upon magnetic resonance imaging (MRI) or leukoaraiosis is characteristic of stroke syndromes. Increased MRI signals in the anterior temporal pole are suggested to be diagnostic for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), with 90% sensitivity and 100% specificity. The structural correlates of these specific WM hyperintensities seen on T2-weighted and FLAIR sequences in the temporal pole of CADASIL are unclear. We assessed pathological changes in post-mortem tissue from the temporal pole to reveal the cause of CADASIL specific WM hyperintensities. Materials & Methods A combination of tinctorial and immunostaining approaches and in vitro imaging methods were used to quantify the extent of perivascular space (PVS), arteriosclerosis determined as the sclerotic index (SI), WM myelination as the myelin index (MI) and damage within the WM as accumulated degraded myelin basic protein (dMBP) in samples of the anterior temporal pole from 9 CADASIL and 8 sporadic subcortical ischaemic vascular dementia (SIVD) cases, and 5 similar age (young) and 5 older controls. Luxol fast blue (LFB) stained serial sections from a CADASIL case were also used to reconstruct the temporal pole, which was then compared to the MR images. Results LFB sections used to reconstruct the temporal pole revealed an abundance of enlarged PVS in the WM that topographically appeared as indistinct opaque regions. The mean and total areas of the PVS per WM area (%PVS) were significantly greater in CADASIL compared to the controls. The MI was severely reduced in CADASIL in relation to the SIVD and control sample that was consistent with increased immunoreactivity of dMBP, indicating myelin degeneration. Cerebral microvessels associated with the PVS exhibited a 4.5 fold greater number of basophilic (hyalinised) vessels and a 57% increase in the SI values in CADASIL subjects compared to young controls. A significant correlation between the quantity of hyalinised vessels and SI values was also apparent (P<0.05). Conclusions Our findings suggest that MRI hyperintensities in the temporal pole of CADASIL patients are explained by enlarged PVS and degeneration of myelin accompanied by lack of drainage of the interstitial fluid rather than lacunar infarcts. Consistent with the lack of MR hypersignals in the temporal pole of older SIVD subjects, our observations imply greater progression of pathological changes in CADASIL patients. PMID:19359623

  12. Cerebral white-matter lesions in asymptomatic military divers.

    TOXLINE Toxicology Bibliographic Information

    Erdem I; Yildiz S; Uzun G; Sonmez G; Senol MG; Mutluoglu M; Mutlu H; Oner B

    2009-01-01

    INTRODUCTION: There is some concern that over a period of years, diving may produce cumulative neurological injury even in divers who have no history of decompression sickness. We evaluated asymptomatic divers and controls for cerebral white-matter lesions using magnetic resonance imaging (MRI).METHODS: The study enrolled 113 male military divers (34.4 +/- 5.6 yr) and 65 non-diving men (33.1 +/- 9.0 yr) in good health. Exclusion criteria included any condition that might be expected to produce neurological effects. Patent foramen ovale was not assessed. A questionnaire was used to elicit diving history. A 1.5-T MRI device was used to acquire T1, T2-weighted, and fluid attenuated inversion recovery (FLAIR) images of the brain. A lesion was counted if it appeared hyperintense on both T2-weighted and FLAIR images.RESULTS: MRI revealed brain lesions in 26 of 113 divers (23%) and in 7 of 65 (11%) controls, a difference that was statistically significant. There was no significant difference between the groups with respect to blood pressure, smoking history, or alcohol consumption, and no subject reported a history of head trauma or migraine. There was no relationship between MRI findings and age, diving history, or lipid profile in divers.DISCUSSION: The higher incidence of lesions in the cerebral white matter of divers confirms the possibility that cumulative, subclinical injury to the neurological system may affect the long-term health of military and recreational divers.

  13. Vanishing white matter disease in a spanish population.

    PubMed

    Turón-Viñas, Eulàlia; Pineda, Mercè; Cusí, Victòria; López-Laso, Eduardo; Del Pozo, Rebeca Losada; Gutiérrez-Solana, Luis González; Moreno, David Conejo; Sierra-Córcoles, Concha; Olabarrieta-Hoyos, Naiara; Madruga-Garrido, Marcos; Aguirre-Rodríguez, Javier; González-Álvarez, Verónica; O'Callaghan, Mar; Muchart, Jordi; Armstrong-Moron, Judith

    2014-01-01

    Vanishing white matter (VWM) leukoencephalopathy is one of the most prevalent hereditary white matter diseases. It has been associated with mutations in genes encoding eukaryotic translation initiation factor (eIF2B). We have compiled a list of all the patients diagnosed with VWM in Spain; we found 21 children. The first clinical manifestation in all of them was spasticity, with severe ataxia in six patients, hemiparesis in one child, and dystonic movements in another. They suffered from progressive cognitive deterioration and nine of them had epilepsy too. In four children, we observed optic atrophy and three also had progressive macrocephaly, which is not common in VWM disease. The first two cases were diagnosed before the 1980s. Therefore, they were diagnosed by necropsy studies. The last 16 patients were diagnosed according to genetics: we found mutations in the genes eIF2B5 (13 cases), eIF2B3 (2 cases), and eIF2B4 (1 case). In our report, the second mutation in frequency was c.318A>T; patients with this mutation all followed a slow chronic course, both in homozygous and heterozygous states. Previously, there were no other reports to confirm this fact. We also found some mutations not described in previous reports: c.1090C>T in eIF2B4, c.314A>G in eIF2B5, and c.877C>T in eIF2B5. PMID:25089094

  14. Mitochondrial dysfunction in central nervous system white matter disorders.

    PubMed

    Morató, Laia; Bertini, Enrico; Verrigni, Daniela; Ardissone, Anna; Ruiz, Montse; Ferrer, Isidre; Uziel, Graziella; Pujol, Aurora

    2014-11-01

    Defects of mitochondrial respiration and function had been proposed as a major culprit in the most common neurodegenerative diseases, including prototypic diseases of central nervous system (CNS) white matter such as multiple sclerosis. The importance of mitochondria for white matter is best exemplified in a group of defects of the mitochondria oxidative metabolism called mitochondria leukoencephalopathies or encephalomyopathies. These diseases are clinically and genetically heterogeneous, given the dual control of the respiratory chain by nuclear and mitochondrial DNA, which makes the precise diagnosis and classification challenging. Our understanding of disease pathogenesis is nowadays still limited. Here, we review current knowledge on pathogenesis and genetics, outlining diagnostic clues for the various forms of mitochondria disease. In particular, we underscore the value of magnetic resonance imaging (MRI) for the differential diagnosis of specific types of mitochondrial leukoencephalopathies, such as genetic defects on SDHFA1. The use of novel technologies for gene identification, such as whole-exome sequencing studies, is expected to shed light on novel molecular etiologies, broadening prenatal diagnosis, disease understanding, and therapeutic options. Current treatments are mostly palliative, but very promising novel gene and pharmacologic therapies are emerging, which may also benefit a growing list of secondary mitochondriopathies, such as the peroxisomal disease adrenoleukodystrophy. PMID:24865954

  15. Treatment Outcome-Related White Matter Differences in Veterans with Posttraumatic Stress Disorder.

    PubMed

    Kennis, Mitzy; van Rooij, Sanne J H; Tromp, Do P M; Fox, Andrew S; Rademaker, Arthur R; Kahn, René S; Kalin, Ned H; Geuze, Elbert

    2015-09-01

    Posttraumatic stress disorder (PTSD) is a debilitating disorder that has been associated with brain abnormalities, including white matter alterations. However, little is known about the effect of treatment on these brain alterations. To investigate the course of white matter alterations in PTSD, we used a longitudinal design investigating treatment effects on white matter integrity using diffusion tensor imaging (DTI). Diffusion tensor and magnetization transfer images were obtained pre- and posttreatment from veterans with (n=39) and without PTSD (n=22). After treatment, 16 PTSD patients were remitted, and 23 had persistent PTSD based on PTSD diagnosis. The dorsal and hippocampal cingulum bundle, stria terminalis, and fornix were investigated as regions of interest. Exploratory whole-brain analyses were also performed. Groups were compared with repeated-measures ANOVA for fractional anisotropy (FA), and magnetization transfer ratio. Persistently symptomatic PTSD patients had increasing FA of the dorsal cingulum over time, and at reassessment these FA values were higher than both combat controls and the remitted PTSD group. Group-by-time interactions for FA were found in the hippocampal cingulum, fornix, and stria terminalis, posterior corona radiata, and superior longitudinal fasciculus. Our results indicate that higher FA of the dorsal cingulum bundle may be an acquired feature of persistent PTSD that develops over time. Furthermore, treatment might have differential effects on the hippocampal cingulum, fornix, stria terminalis, posterior corona radiata, and superior longitudinal fasciculus in remitted vs persistent PTSD patients. This study contributes to a better understanding of the neural underpinnings of PTSD treatment outcome. PMID:25837284

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

    PubMed

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

    2015-08-01

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

  17. The axon-glia unit in white matter stroke: mechanisms of damage and recovery.

    PubMed

    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. PMID:25704204

  18. Systemic dendrimer-drug treatment of ischemia-induced neonatal white matter injury.

    PubMed

    Nance, Elizabeth; Porambo, Michael; Zhang, Fan; Mishra, Manoj K; Buelow, Markus; Getzenberg, Rachel; Johnston, Michael; Kannan, Rangaramanujam M; Fatemi, Ali; Kannan, Sujatha

    2015-09-28

    Extreme prematurity is a major risk factor for perinatal and neonatal brain injury, and can lead to white matter injury that is a precursor for a number of neurological diseases, including cerebral palsy (CP) and autism. Neuroinflammation, mediated by activated microglia and astrocytes, is implicated in the pathogenesis of neonatal brain injury. Therefore, targeted drug delivery to attenuate neuroinflammation may greatly improve therapeutic outcomes in models of perinatal white matter injury. In this work, we use a mouse model of ischemia-induced neonatal white matter injury to study the biodistribution of generation 4, hydroxyl-functionalized polyamidoamine dendrimers. Following systemic administration of the Cy5-labeled dendrimer (D-Cy5), we demonstrate dendrimer uptake in cells involved in ischemic injury, and in ongoing inflammation, leading to secondary injury. The sub-acute response to injury is driven by astrocytes. Within five days of injury, microglial proliferation and migration occurs, along with limited differentiation of oligodendrocytes and oligodendrocyte death. From one day to five days after injury, a shift in dendrimer co-localization occurred. Initially, dendrimer predominantly co-localized with astrocytes, with a subsequent shift towards microglia. Co-localization with oligodendrocytes reduced over the same time period, demonstrating a region-specific uptake based on the progression of the injury. We further show that systemic administration of a single dose of dendrimer-N-acetyl cysteine conjugate (D-NAC) at either sub-acute or delayed time points after injury results in sustained attenuation of the 'detrimental' pro-inflammatory response up to 9days after injury, while not impacting the 'favorable' anti-inflammatory response. The D-NAC therapy also led to improvement in myelination, suggesting reduced white matter injury. Demonstration of treatment efficacy at later time points in the postnatal period provides a greater understanding of how microglial activation and chronic inflammation can be targeted to treat neonatal brain injury. Importantly, it may also provide a longer therapeutic window. PMID:26184052

  19. Computerized evaluation method of white matter hyperintensities related to subcortical vascular dementia in brain MR images

    NASA Astrophysics Data System (ADS)

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

    2010-03-01

    We have developed a computerized evaluation method of white matter hyperintensity (WMH) regions for the diagnosis of vascular dementia (VaD) based on magnetic resonance (MR) images, and implemented the proposed method as a graphical interface program. The WMH regions were segmented using either a region growing technique or a level set method, one of which was selected by using a support vector machine. We applied the proposed method to MR images acquired from 10 patients with a diagnosis of VaD. The mean similarity index between WMH regions determined by a manual method and the proposed method was 78.2+/-11.0%. The proposed method could effectively assist neuroradiologists in evaluating WMH regions.

  20. Gray and White Matter Degenerations in Subjective Memory Impairment: Comparisons with Normal Controls and Mild Cognitive Impairment

    PubMed Central

    Hong, Yun Jeong; Yoon, Bora; Shim, Yong S.; Ahn, Kook Jin; Lee, Jae-Hong

    2015-01-01

    Subjective memory impairment (SMI) is now increasingly recognized as a risk factor of progression to dementia. This study investigated gray and white matter changes in the brains of SMI patients compared with normal controls and mild cognitive impairment (MCI) patients. We recruited 28 normal controls, 28 subjects with SMI, and 29 patients with MCI aged 60 or older. We analyzed gray and white matter changes using a voxel-based morphometry (VBM), hippocampal volumetry and regions of interest in diffusion tensor imaging (DTI). DTI parameters of corpus callosum and cingulum in SMI showed more white matter changes compared with those in normal controls, they were similar to those in MCI except in the hippocampus, which showed more degenerations in MCI. In VBM, SMI showed atrophy in the frontal, temporal, and parietal lobes compared with normal controls although it was not as extensive as that in MCI. Patients with SMI showed gray and white matter degenerations, the changes were distinct in white matter structures. SMI might be the first presenting symptom within the Alzheimer's disease continuum when combined with additional risk factors and neurodegenerative changes. PMID:26539011

  1. Aberrant white matter networks mediate cognitive impairment in patients with silent lacunar infarcts in basal ganglia territory.

    PubMed

    Tang, Jinfu; Zhong, Suyu; Chen, Yaojing; Chen, Kewei; Zhang, Junying; Gong, Gaolang; Fleisher, Adam S; He, Yong; Zhang, Zhanjun

    2015-09-01

    Silent lacunar infarcts, which are present in over 20% of healthy elderly individuals, are associated with subtle deficits in cognitive functions. However, it remains largely unclear how these silent brain infarcts lead to cognitive deficits and even dementia. Here, we used diffusion tensor imaging tractography and graph theory to examine the topological organization of white matter networks in 27 patients with silent lacunar infarcts in the basal ganglia territory and 30 healthy controls. A whole-brain white matter network was constructed for each subject, where the graph nodes represented brain regions and the edges represented interregional white matter tracts. Compared with the controls, the patients exhibited a significant reduction in local efficiency and global efficiency. In addition, a total of eighteen brain regions showed significantly reduced nodal efficiency in patients. Intriguingly, nodal efficiency-behavior associations were significantly different between the two groups. The present findings provide new aspects into our understanding of silent infarcts that even small lesions in subcortical brain regions may affect large-scale cortical white matter network, as such may be the link between subcortical silent infarcts and the associated cognitive impairments. Our findings highlight the need for network-level neuroimaging assessment and more medical care for individuals with silent subcortical infarcts. PMID:25873426

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

    PubMed

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

    2015-05-26

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

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

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

    E-print Network

    Wisconsin at Madison, University of

    -based morphometry (TBM) framework. In this paper, we show agreement between the TBM-based white matter connectivity based on tensor-based morphometry (TBM) [2]. The idea of correlating local morphological features that there is agreement between the TBM-based connectivity and the DTI-based white matter atlas. As an application, we

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

    E-print Network

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

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

    ERIC Educational Resources Information Center

    Back, Stephen A.

    2006-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  10. Classification of Multiple Sclerosis Patients from the Geometry and Texture of White Matter Lesions

    E-print Network

    Johansen, Adam

    Classification of Multiple Sclerosis Patients from the Geometry and Texture of White Matter Lesions, Coventry, UK Classification of Multiple Sclerosis Patients from the Geometry and Texture of White Matter, Coventry, UK Introduction Multiple Sclerosis (MS) is a chronic inflammatory- demyelinating disease

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

    ERIC Educational Resources Information Center

    Paus, Tomas

    2010-01-01

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

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

  13. White matter damage is related to ataxia severity in SCA3.

    PubMed

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

    2014-02-01

    Spinocerebellar ataxia type 3 (SCA3) is the most frequent inherited cerebellar ataxia in Europe, the US and Japan, leading to disability and death through motor complications. Although the affected protein ataxin-3 is found ubiquitously in the brain, grey matter atrophy is predominant in the cerebellum and the brainstem. White matter pathology is generally less severe and thought to occur in the brainstem, spinal cord, and cerebellar white matter. Here, we investigated both grey and white matter pathology in a group of 12 SCA3 patients and matched controls. We used voxel-based morphometry for analysis of tissue loss, and tract-based spatial statistics (TBSS) on diffusion magnetic resonance imaging to investigate microstructural pathology. We analysed correlations between microstructural properties of the brain and ataxia severity, as measured by the Scale for the Assessment and Rating of Ataxia (SARA) score. SCA3 patients exhibited significant loss of both grey and white matter in the cerebellar hemispheres, brainstem including pons and in lateral thalamus. On between-group analysis, TBSS detected widespread microstructural white matter pathology in the cerebellum, brainstem, and bilaterally in thalamus and the cerebral hemispheres. Furthermore, fractional anisotropy in a white matter network comprising frontal, thalamic, brainstem and left cerebellar white matter strongly and negatively correlated with SARA ataxia scores. Tractography identified the thalamic white matter thus implicated as belonging to ventrolateral thalamus. Disruption of white matter integrity in patients suffering from SCA3 is more widespread than previously thought. Moreover, our data provide evidence that microstructural white matter changes in SCA3 are strongly related to the clinical severity of ataxia symptoms. PMID:24272589

  14. Finite bounded expanding white hole universe without dark matter

    E-print Network

    John G. Hartnett

    2007-04-17

    The solution of Einstein's field equations in Cosmological General Relativity (CGR), where the Galaxy is at the center of a finite yet bounded spherically symmetrical isotropic gravitational field, is identical with the unbounded solution. This leads to the conclusion that the Universe may be viewed as a finite expanding white hole. The fact that CGR has been successful in describing the distance modulus verses redshift data of the high-redshift type Ia supernovae means that the data cannot distinguish between unbounded models and those with finite bounded radii of at least $c \\tau$. Also it is shown that the Universe is spatially flat at the current epoch and has been at all past epochs where it was matter dominated.

  15. White matter integrity and cognitive dysfunction: Radiological and neuropsychological correlations.

    PubMed

    Tomimoto, Hidekazu

    2015-12-01

    Cerebral white matter (WM) is comprised of nerve fibers interconnecting neurons in the cerebral cortex or the deep structures. With advancing age, WM frequently shows hyperintense lesions in T2-weighted or fluid-attenuated inversion recovery images in both the periventricular and deep WM. Patients with these WM lesions might manifest a variety of symptoms, such as parkinsonism, cognitive impairment, depression and apathy, when these WM lesions become sufficiently confluent and diffuse. However, there are inconsistencies with respect to their clinical significance, because patients with extensive WM lesions might remain asymptomatic. The present review focuses on the pathological mechanism underlying why the loss of integrity of nerve fibers in the WM induces neuropsychological symptoms. Geriatr Gerontol Int 2015; 15 (Suppl. 1): 3-9. PMID:26671151

  16. Systemic inflammation, intraventricular hemorrhage, and white matter injury

    PubMed Central

    LEVITON, Alan; ALLRED, Elizabeth N.; DAMMANN, Olaf; ENGELKE, Stephen; FICHOROVA, Raina N.; HIRTZ, Deborah; KUBAN, Karl C. K.; MENT, Laura R.; O'SHEA, T. Michael; PANETH, Nigel; SHAH, Bhavesh; SCHREIBER, Michael D.

    2014-01-01

    To see if the systemic inflammation profile of 123 infants born before the 28th week of gestation who had intraventricular hemorrhage (IVH) without white matter injury (WMI) differed from that of 68 peers who had both IVH and WMI, we compared both groups to 677 peers who had neither. Cranial ultrasound scans were read independently by multiple readers until concordance. The concentrations of 25 proteins were measured with multiplex arrays using an electrochemiluminescence system. Infants who had IVH and WMI were more likely than others to have elevated concentrations of CRP and IL-8 on days 1, 7, and 14, and elevated concentrations of SAA and TNF-alpha on 2 of these days. IVH should probably be viewed as two entities, IVH unaccompanied by WMI, and IVH accompanied by WMI. Each entity is associated with inflammation, but IVH accompanied by WMI has a stronger inflammatory signal than IVH unaccompanied by WMI. PMID:23112243

  17. Relationship Between White Matter Hyperintensities Penumbra and Cavity Formation.

    PubMed

    Zhang, Xiaoyu; Ding, Lingling; Yang, Lei; Qin, Wei; Li, Yue; Li, Shujuan; Hu, Wenli

    2016-01-01

    BACKGROUND Penumbra has been detected on the edge of white matter hyperintensities (WMH). The aim of our study was to investigate whether cavity formation is different between acute infarcts on the edge of WMH and those away from the edge. MATERIAL AND METHODS Ninety-six subjects with acute lacunar infarct ?25 mm in diameter were recruited. Subjects with infarct contacting or overlapping with WMH (on axial T2 or coronal FLAIR) were defined as the Edge Group (on the edge of the WMH). Those outside the edge of the WMH were the Non-edge Group. Vascular risk factors, clinical data, baseline infarct size, infarct sites, and severity of WMH (by Fazekas scale) were recorded. Cavity formation was identified by MR follow-up imaging. Risk factors for cavity formation were also investigated. RESULTS There were 37 (38.5%) subjects in the Edge Group and 59 (61.5%) in the Non-edge Group; 55 (57.3%) subjects had cavity formation in follow-up imaging. Subjects in the Edge Group had higher risk of developing cavities than those in the Non-edge Group (78.4% vs. 44.1%, p<0.05). In univariate analysis, subjects with cavity formation had larger infarct size and their infarcts were more often located in subcortical white matter. Vascular risk factors, clinical data, and WMH did not differ between subjects with cavity formation and those without. In logistic regression analysis, DWI infarct size and being in the Edge Group were independent risk factors for cavity formation. CONCLUSIONS Lacunar infarcts on the edge of WMH are more likely to develop cavities, suggesting that WMH penumbra affects cavity formation. PMID:26729408

  18. White Matter Integrity in Physically Fit Older Adults

    PubMed Central

    Tseng, B.Y.; Gundapuneedi, T.; Khan, M.A.; Diaz-Arrastia, R.; Levine, B.D.; Lu, H.; Huang, H.; Zhang, R.

    2013-01-01

    Background White matter (WM) integrity declines with normal aging. Physical activity may attenuate age-related WM integrity changes and improve cognitive function. This study examined brain WM integrity in Masters athletes who have engaged in life-long aerobic exercise training. We tested the hypothesis that life-long aerobic training is associated with improved brain WM integrity in older adults. Methods Ten Masters athletes (3 females, age=72.2±5.3yrs, endurance training>15yrs) and 10 sedentary older adults similar in age and educational level (2 females, age=74.5±4.3yrs) participated. MRI fluid-attenuated-inversion-recovery (FLAIR) images were acquired to assess white matter hyper intensities (WMH) volume. Diffusion tensor imaging (DTI) was performed to evaluate the WM microstructural integrity with a DTI-derived metric, fractional anisotropy (FA) and mean diffusivity (MD). Results After normalization to whole-brain volume, Masters athletes showed an 83% reduction in deep WMH volume relative to their sedentary counterparts (0.05 ± 0.05% vs. 0.29 ± 0.29%, p<0.05). In addition, we found an inverse relationship between aerobic fitness (VO2max) and deep WMH volume (r=?0.78, p<0.001). Using TBSS, Masters athletes showed higher FA values in the right superior corona radiata (SCR), both sides of superior longitudinal fasciculus (SLF), right inferior fronto-occipital fasciculus (IFO), and left inferior longitudinal fasciculus (ILF). In addition, Masters athletes also showed lower MD values in the left posterior thalamic radiation (PTR) and left cingulum hippocampus. Conclusions These findings suggest that life-long exercise is associated with reduced WMH and may preserve WM fiber microstructural integrity related to motor control and coordination in older adults. PMID:23769914

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

    NASA Astrophysics Data System (ADS)

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

    2013-02-01

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

  20. Hemodynamic and Metabolic Correlates of Perinatal White Matter Injury Severity

    PubMed Central

    Riddle, Art; Maire, Jennifer; Cai, Victor; Nguyen, Thuan; Gong, Xi; Hansen, Kelly; Grafe, Marjorie R.; Hohimer, A. Roger; Back, Stephen A.

    2013-01-01

    Background and Purpose Although the spectrum of perinatal white matter injury (WMI) in preterm infants is shifting from cystic encephalomalacia to milder forms of WMI, the factors that contribute to this changing spectrum are unclear. We hypothesized that the variability in WMI quantified by immunohistochemical markers of inflammation could be correlated with the severity of impaired blood oxygen, glucose and lactate. Methods We employed a preterm fetal sheep model of in utero moderate hypoxemia and global severe but not complete cerebral ischemia that reproduces the spectrum of human WMI. Since there is small but measurable residual brain blood flow during occlusion, we sought to determine if the metabolic state of the residual arterial blood was associated with severity of WMI. Near the conclusion of hypoxia-ischemia, we recorded cephalic arterial blood pressure, blood oxygen, glucose and lactate levels. To define the spectrum of WMI, an ordinal WMI rating scale was compared against an unbiased quantitative image analysis protocol that provided continuous histo-pathological outcome measures for astrogliosis and microgliosis derived from the entire white matter. Results A spectrum of WMI was observed that ranged from diffuse non-necrotic lesions to more severe injury that comprised discrete foci of microscopic or macroscopic necrosis. Residual arterial pressure, oxygen content and blood glucose displayed a significant inverse association with WMI and lactate concentrations were directly related. Elevated glucose levels were the most significantly associated with less severe WMI. Conclusions Our results suggest that under conditions of hypoxemia and severe cephalic hypotension, WMI severity measured using unbiased immunohistochemical measurements correlated with several physiologic parameters, including glucose, which may be a useful marker of fetal response to hypoxia or provide protection against energy failure and more severe WMI. PMID:24416093

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

    PubMed Central

    Mao, Hui

    2015-01-01

    Background Although chemotherapy and radiation treatment have contributed to increased survivorship, treatment-induced brain injury has been a concern when examining long-term intellectual outcomes of survivors. Specifically, disruption of brain white matter integrity and its relationship to intellectual outcomes in adult survivors of childhood brain tumors needs to be better understood. Methods Fifty-four participants underwent diffusion tensor imaging in addition to structural MRI and an intelligence test (IQ). Voxel-wise group comparisons of fractional anisotropy calculated from DTI data were performed using Tract Based Spatial Statistics (TBSS) on 27 survivors (14 treated with radiation with and without chemotherapy and 13 treated without radiation treatment on average over 13 years since diagnosis) and 27 healthy comparison participants. Whole brain white matter fractional anisotropy (FA) differences were explored between each group. The relationships between IQ and FA in the regions where statistically lower FA values were found in survivors were examined, as well as the role of cumulative neurological factors. Results The group of survivors treated with radiation with and without chemotherapy had lower IQ relative to the group of survivors without radiation treatment and the healthy comparison group. TBSS identified white matter regions with significantly different mean fractional anisotropy between the three different groups. A lower level of white matter integrity was found in the radiation with or without chemotherapy treated group compared to the group without radiation treatment and also the healthy control group. The group without radiation treatment had a lower mean FA relative to healthy controls. The white matter disruption of the radiation with or without chemotherapy treated survivors was positively correlated with IQ and cumulative neurological factors. Conclusions Lower long-term intellectual outcomes of childhood brain tumor survivors are associated with lower white matter integrity. Radiation and adjunct chemotherapy treatment may play a role in greater white matter disruption. The relationships between white matter integrity and IQ, as well as cumulative neurological risk factors exist in young adult survivors of childhood brain tumors. PMID:26147736

  2. White matter structural integrity differs between people with schizophrenia and healthy groups as a function of cognitive control.

    PubMed

    Schaeffer, David J; Rodrigue, Amanda L; Burton, Courtney R; Pierce, Jordan E; Unsworth, Nash; Clementz, Brett A; McDowell, Jennifer E

    2015-12-01

    A behavioral hallmark of schizophrenia is poor cognitive control. Recent evidence suggests that problems with cognitive control in schizophrenia are related to disconnectivity along major white matter fibers. Although deficits of cognitive control are common in schizophrenia, a proportion of otherwise healthy subjects show poor cognitive control performance. The present study sought to address this potential confound by comparing white matter integrity between a group with schizophrenia and otherwise healthy individuals with either high or low levels of cognitive control (based on working memory span performance). Diffusion tensor imaging was used to evaluate white matter integrity in 24 participants with schizophrenia, 24 healthy participants with high cognitive control (HCC), and 25 healthy participants with low cognitive control (LCC). To test for differences in fractional anisotropy (FA) across major white matter fiber tracts, a voxelwise region of interest analysis was conducted in standardized brain space. In a separate analysis, regions of interest were manually drawn in native brain space to isolate superior longitudinal fasciculus (SLF), a tract implicated in cognitive control performance. The voxelwise analysis demonstrated widespread lower FA in the schizophrenia group compared to the HCC group. With a high degree of concordance, the manual ROI analysis revealed lower FA in the schizophrenia group compared to the HCC group. Taken together, these results provide evidence to suggest that structural differences identified between healthy groups and schizophrenia may not be entirely specific to the disease process and can vary as a function of cognitive control capacity in the comparison group. PMID:26585221

  3. Age-related differences in white matter integrity and cognitive function are related to APOE status.

    PubMed

    Ryan, Lee; Walther, Katrin; Bendlin, Barbara B; Lue, Lih-Fen; Walker, Douglas G; Glisky, Elizabeth L

    2011-01-15

    While an extensive literature is now available on age-related differences in white matter integrity measured by diffusion MRI, relatively little is known about the relationships between diffusion and cognitive functions in older adults. Even less is known about whether these relationships are influenced by the apolipoprotein (APOE) ?4 allele, despite growing evidence that ?4 increases cognitive impairment in older adults. The purpose of the present study was to examine these relationships in a group of community-dwelling cognitively normal older adults. Data were obtained from a sample of 126 individuals (ages 52-92) that included 32 ?4 heterozygotes, 6 ?4 homozygotes, and 88 noncarriers. Two measures of diffusion, the apparent diffusion coefficient (ADC) and fractional anisotropy (FA), were obtained from six brain regions-frontal white matter, lateral parietal white matter, the centrum semiovale, the genu and splenium of the corpus callosum, and the temporal stem white matter-and were used to predict composite scores of cognitive function in two domains, executive function and memory function. Results indicated that ADC and FA differed with increasing age in all six brain regions, and these differences were significantly greater for ?4 carriers compared to noncarriers. Importantly, after controlling for age, diffusion measures predicted cognitive function in a region-specific way that was also influenced by ?4 status. Regardless of APOE status, frontal ADC and FA independently predicted executive function scores for all participants, while temporal lobe ADC additionally predicted executive function for ?4 carriers but not noncarriers. Memory scores were predicted by temporal lobe ADC but not frontal diffusion for all participants, and this relationship was significantly stronger in ?4 carriers compared to noncarriers. Taken together, age and temporal lobe ADC accounted for a striking 53% of the variance in memory scores within the ?4 carrier group. The results provide further evidence that APOE ?4 has a significant impact on the trajectory of age-related cognitive functioning in older adults. Possible mechanisms are discussed that could account for the associations between ?4, diffusion, and cognitive function, including the influence of ?4 on neural repair, oxidative stress, and the health of myelin-producing oligodendroglia. PMID:20804847

  4. White matter lesion extension to automatic brain tissue segmentation on MRI Renske de Boer a,b,

    E-print Network

    van Vliet, Lucas J.

    -, T2- or proton density-weighted MR images. Some use a fixed set of labeled samples, that were derived segmentation White matter lesions White matter hyperintensities A fully automated brain tissue segmentation

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

    PubMed

    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. PMID:24304583

  6. Genetics of white matter development: A DTI study of 705 twins and their siblings aged 12 to 29

    E-print Network

    Thompson, Paul

    Genetics of white matter development: A DTI study of 705 twins and their siblings aged 12 to 29 d Queensland Institute of Medical Research, Brisbane, Australia e Brain and Mind Research Institute Cognition Twins White matter Diffusion imaging Gene-environment interaction White matter microstructure

  7. White Matter Tracts Connected to the Medial Temporal Lobe Support the Development of Mnemonic Control.

    PubMed

    Wendelken, Carter; Lee, Joshua K; Pospisil, Jacqueline; Sastre, Marcos; Ross, Julia M; Bunge, Silvia A; Ghetti, Simona

    2015-09-01

    One of the most important factors driving the development of memory during childhood is mnemonic control, or the capacity to initiate and maintain the processes that guide encoding and retrieval operations. The ability to selectively attend to and encode relevant stimuli is a particularly useful form of mnemonic control, and is one that undergoes marked improvement over childhood. We hypothesized that structural integrity of white matter tracts, in particular those connecting medial temporal lobe memory regions to other cortical areas, and/or those connecting frontal and parietal control regions, should contribute to successful mnemonic control. To test this hypothesis, we examined the relationship between structural integrity of selected white matter tracts and an experimental measure of mnemonic control, involving enhancement of memory by attention at encoding, in 116 children aged 7-11 and 25 young adults. We observed a positive relationship between integrity of uncinate fasciculus and mnemonic enhancement across age groups. In adults, but not in children, we also observed an association between mnemonic enhancement and integrity of ventral cingulum bundle and ventral fornix/fimbria. Integrity of fronto-parietal tracts, including dorsal cingulum and superior longitudinal fasciculus, was unrelated to mnemonic enhancement. PMID:24675870

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

    PubMed Central

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

    2010-01-01

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

  9. Deferoxamine reduces intracerebral hemorrhage-induced white matter damage in aged rats

    PubMed Central

    Ni, Wei; Okauchi, Masanobu; Hatakeyama, Tetsuhiro; Gu, Yuxiang; Keep, Richard F.; Xi, Guohua; Hua, Ya

    2015-01-01

    Iron contributes to c-Jun N-terminal kinases (JNK) activation in young rats and white matter injury in piglets after intracerebral hemorrhage (ICH). In the present study, we examined the effect of deferoxamine on ICH-induced white matter injury and JNK activation and in aged rats. Male Fischer 344 rats (18 months old) had either an intracaudate injection of 100 µl of autologous blood or a needle insertion (sham). The rats were treated with deferoxamine or vehicle with different regimen (dosage, duration and time window). White matter injury and activation of JNK were examined. We found that a dose of DFX should at more than 10 mg/kg for a therapeutic duration more than 2 days with a therapeutic time window of 12 hours to reduce ICH-induced white matter loss at 2 months. ICH-induced white matter injury was associated with JNK activation. The protein levels of phosphorylated-JNK (P-JNK) were upregulated at day-1 after ICH and then gradually decreased. P-JNK immunoreactivity was mostly located in white matter bundles. ICH-induced JNK activation was reduced by DFX treatment. This study demonstrated that DFX can reduce ICH-induced JNK activation and white matter damage. PMID:25749188

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  13. Assessing White Matter Integrity as a Function of Abstinence Duration in Former Cocaine-Dependent Individuals

    PubMed Central

    Bell, Ryan P.; Foxe, John J.; Nierenberg, Jay; Hoptman, Matthew J.; Garavan, Hugh

    2010-01-01

    Current cocaine-dependent users show reductions in white matter (WM) integrity, especially in cortical regions associated with cognitive control that have been associated with inhibitory dysfunction. A key question is whether these white matter differences are present following abstinence from drug use. To address this, WM integrity was examined using diffusion tensor imaging (DTI) obtained on 43 cocaine abstinent patients (abstinence duration ranged between five days and 102 weeks) and 43 non-using controls. Additionally, a cross-sectional comparison separated the patients into three groups (short-term, mid-term and long-term) based upon duration of cocaine abstinence. The 43 cocaine abstinent patients showed lower fractional anisotropy (FA) in the left anterior callosal fibers, left genu of the corpus callosum, right superior longitudinal fasciculus, right callosal fibers and the superior corona radiata bilaterally when compared against non-using controls. Higher FA in the cocaine abstinent patients was observed in the splenium of the corpus callosum and right superior longitudinal fasciculus. Differences between the cocaine abstinent groups were observed bilaterally in the inferior longitudinal fasciculus, right anterior thalamic radiation, right ventral posterolateral nucleus of the thalamus, left superior corona radiata, superior longitudinal fasciculus bilaterally, right cingulum and the WM of the right precentral gyrus. The results identified WM differences between cocaine abstinent patients and controls as well as distinct differences between abstinent subgroups. The findings suggest that specific white matter differences persist throughout abstinence while other, spatially distinct, differences discriminate as a function of abstinence duration. These differences may, therefore, represent brain changes that mark recovery from addiction. PMID:21075564

  14. Increased white matter neuron density in a rat model of maternal immune activation - Implications for schizophrenia.

    PubMed

    Duchatel, Ryan J; Jobling, Phillip; Graham, Brett A; Harms, Lauren R; Michie, Patricia T; Hodgson, Deborah M; Tooney, Paul A

    2016-02-01

    Interstitial neurons are located among white matter tracts of the human and rodent brain. Post-mortem studies have identified increased interstitial white matter neuron (IWMN) density in the fibre tracts below the cortex in people with schizophrenia. The current study assesses IWMN pathology in a model of maternal immune activation (MIA); a risk factor for schizophrenia. Experimental MIA was produced by an injection of polyinosinic:polycytidylic acid (PolyI:C) into pregnant rats on gestational day (GD) 10 or GD19. A separate control group received saline injections. The density of neuronal nuclear antigen (NeuN(+)) and somatostatin (SST(+)) IWMNs was determined in the white matter of the corpus callosum in two rostrocaudally adjacent areas in the 12week old offspring of GD10 (n=10) or GD19 polyI:C dams (n=18) compared to controls (n=20). NeuN(+) IWMN density trended to be higher in offspring from dams exposed to polyI:C at GD19, but not GD10. A subpopulation of these NeuN(+) IWMNs was shown to express SST. PolyI:C treatment of dams induced a significant increase in the density of SST(+) IWMNs in the offspring when delivered at both gestational stages with more regionally widespread effects observed at GD19. A positive correlation was observed between NeuN(+) and SST(+) IWMN density in animals exposed to polyI:C at GD19, but not controls. This is the first study to show that MIA increases IWMN density in adult offspring in a similar manner to that seen in the brain in schizophrenia. This suggests the MIA model will be useful in future studies aimed at probing the relationship between IWMNs and schizophrenia. PMID:26385575

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

    PubMed Central

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

    2015-01-01

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

  16. Extensive White Matter Abnormalities in Patients with First-Episode Schizophrenia: A Diffusion Tensor Imaging (DTI) Study

    PubMed Central

    Lee, Sang-Hyuk; Kubicki, Marek; Asami, Takeshi; Seidman, Larry J.; Goldstein, Jill M.; Mesholam-Gately, Raquelle I.; McCarley, Robert W.; Shenton, Martha E.

    2013-01-01

    Background Previous voxelwise Diffusion Tensor Imaging (DTI) investigations of white matter in first-episode schizophrenia (FESZ) have been limited to the analysis of Fractional Anisotropy (FA) and mean diffusivity (MD), with their findings inconsistent in terms of the anatomical locations and extent of abnormalities. This study examines white matter abnormalities in FESZ, compared with healthy controls, using a tract-based spatial statistics (TBSS) approach applied to multiple measures of tract integrity, and correlates these findings with symptom severity. Methods Seventeen first-episode patients with schizophrenia and seventeen age- and gender-matched healthy controls (HC) participated in this imaging study where FA, MD, and axial and radial diffusivity were compared between the two groups using TBSS. Results First-episode patients with schizophrenia showed lower FA values in the genu and body of corpus callosum, the internal capsule, the external capsule, the fornix, the superior, inferior fronto-occipital fasciculus, the cingulum, and the uncinate fasciculus compared with HC. Increased MD and radial diffusivity were shown in virtually all white matter regions. There was no significant difference, however, observed for axial diffusivity between the two groups. Pearson correlation analysis showed that the FA values of the right inferior fronto-occipital fasciculus were positively correlated with positive symptoms, negative symptoms, and total correct items of the Wisconsin Card Sorting Test. FA values of right external capsule also showed significant positive correlation with category completed scores of the WCST. Conclusions These data suggest extensive, possibly myelin related white matter disruptions in FESZ. PMID:23290268

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

    PubMed

    Kono, Tatsuo; Moriyama, Nobuko; Tanaka, Ryuta; Iwasaki, Nobuaki; Arai, Jun-ichi

    2008-10-01

    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. PMID:18521588

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

    PubMed Central

    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 related periventricular loss of white matter tissue, as occurs in internal hydrocephalus. PMID:25938575

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

    PubMed

    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) < 0.05). We further examined the association of structural brain changes with clinical and neuropsychological data. White matter lesions rated visually were more prevalent and severe in myotonic dystrophy type 1 compared with controls, with frontal white matter most prominently affected in both disorders, and temporal lesions restricted to myotonic dystrophy type 1. Voxel-based morphometry analyses demonstrated extensive white matter involvement in all cerebral lobes, brainstem and corpus callosum in myotonic dystrophy types 1 and 2, while grey matter decrease (cortical areas, thalamus, putamen) was restricted to myotonic dystrophy type 1. Accordingly, we found more prominent white matter affection in myotonic dystrophy type 1 than myotonic dystrophy type 2 by diffusion tensor imaging. Association fibres throughout the whole brain, limbic system fibre tracts, the callosal body and projection fibres (e.g. internal/external capsules) were affected in myotonic dystrophy types 1 and 2. Central motor pathways were exclusively impaired in myotonic dystrophy type 1. We found mild executive and attentional deficits in our patients when neuropsychological tests were corrected for manual motor dysfunctioning. Regression analyses revealed associations of white matter affection with several clinical parameters in both disease entities, but not with neuropsychological performance. We showed that depressed mood and fatigue were more prominent in patients with myotonic dystrophy type 1 with less white matter affection (early disease stages), contrary to patients with myotonic dystrophy type 2. Thus, depression in myotonic dystrophies might be a reactive adjustment disorder rather than a direct consequence of structural brain damage. Associations of white matter affection with age/disease duration as well as patterns of cerebral water diffusion parameters pointed towards an ongoing process of myelin destruction and/or axonal loss in our cross-sectional study design. Our data suggest that both myotonic dystrophy types 1 and 2 are serious white matter diseases with prominent callosal body and limbic system affection. White matter changes dominated the extent of grey matter changes, which might argue against Wallerian degeneration as the major cause of white matter affection in myotonic dystrophies. PMID:22131273

  20. Anaerobic function of CNS white matter declines with age

    PubMed Central

    Hamner, Margaret A; Möller, Thomas; Ransom, Bruce R

    2011-01-01

    The mammalian central nervous system (CNS) is generally believed to be completely dependent on the presence of oxygen (O2) to maintain energy levels necessary for excitability. However, previous studies on CNS white matter (WM) have shown that a large subset of CNS-myelinated axons of mice aged 4 to 6 weeks remains excitable in the absence of O2. We investigated whether this surprising WM tolerance to anoxia varied with age. Acutely isolated mouse optic nerve (MON), a purely myelinated WM tract, was studied electrophysiologically. Excitability in the MONs from 1-month-, 4-month-, and 8-month-old mice was assessed quantitatively as the area under the supramaximal compound action potential (CAP). Anoxia-resistant WM function declined with age. After 60?minutes of anoxia, ?23% of the CAP remained in 1-month-old mice, 8% in 4-month-old mice, and ?0 in the 8-month-old group. Our results indicated that although some CNS axons function anaerobically in young adult animals, they lose this ability in later adulthood. This finding may help explain the clinical impression that favorable outcome after stroke and other brain injuries declines with age. PMID:21179073

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

    PubMed

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

    2015-07-01

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

  2. Are white matter abnormalities associated with “unexplained dizziness”?

    PubMed Central

    Ahmad, Hena; Cerchiai, Niccolò; Mancuso, Michelangelo; Casani, Augusto P.; Bronstein, Adolfo M.

    2015-01-01

    Introduction Although cerebral small vessel disease is a significant contributor to the development of imbalance and falls in the elderly, whether it causes dizziness is not known. Methods A retrospective case analysis was conducted for 122 dizzy patients referred to two neuro-otology tertiary centres in London and Pisa. Patients were divided into ‘explained’ causes of dizziness (e.g. benign positional vertigo, vestibular neuritis, orthostatic hypotension, cerebellar ataxias) and ‘unexplained’ dizziness. White matter hyperintensities (WMH) in MRI (T2 weighted and FLAIR sequences) were blindly rated according to the Fazekas scale. Results 122 patients; 58 (mean age = 72, SD = 7.95 years) in the ‘unexplained’ group and 64 (mean age = 72.01, SD = 8.28 years) in the ‘explained’ group were recruited. The overall frequency of lesions (Fazekas 1–3) significantly differed between groups (p = 0.011). The frequency of severe lesions (Fazekas 3) was significantly higher in the ‘unexplained’ group (22%) than in the ‘explained’ group (5%; p = 0.003). Conclusion Increased severity of WMH in cases of unexplained dizziness suggests that such abnormalities are likely contributory to the development of dizziness. WM lesions may induce dizziness either because patients perceive a degree of objective unsteadiness or by a disconnection syndrome involving vestibular or locomotor areas of the brain. PMID:26412160

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

    PubMed

    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. PMID:26441731

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  6. Brain asymmetry in the white matter making and globularity

    PubMed Central

    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. PMID:26441731

  7. Effects of White Matter Microstructure on Phase and Susceptibility Maps

    PubMed Central

    Wharton, Samuel; Bowtell, Richard

    2015-01-01

    Purpose To investigate the effects on quantitative susceptibility mapping (QSM) and susceptibility tensor imaging (STI) of the frequency variation produced by the microstructure of white matter (WM). Methods The frequency offsets in a WM tissue sample that are not explained by the effect of bulk isotropic or anisotropic magnetic susceptibility, but rather result from the local microstructure, were characterized for the first time. QSM and STI were then applied to simulated frequency maps that were calculated using a digitized whole-brain, WM model formed from anatomical and diffusion tensor imaging data acquired from a volunteer. In this model, the magnitudes of the frequency contributions due to anisotropy and microstructure were derived from the results of the tissue experiments. Results The simulations suggest that the frequency contribution of microstructure is much larger than that due to bulk effects of anisotropic magnetic susceptibility. In QSM, the microstructure contribution introduced artificial WM heterogeneity. For the STI processing, the microstructure contribution caused the susceptibility anisotropy to be significantly overestimated. Conclusion Microstructure-related phase offsets in WM yield artifacts in the calculated susceptibility maps. If susceptibility mapping is to become a robust MRI technique, further research should be carried out to reduce the confounding effects of microstructure-related frequency contributions. Magn Reson Med 73:1258–1269, 2015. © 2014 Wiley Periodicals, Inc. PMID:24619643

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

    PubMed Central

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

    2014-01-01

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

  9. Small white matter lesion detection in cerebral small vessel disease

    NASA Astrophysics Data System (ADS)

    Ghafoorian, Mohsen; Karssemeijer, Nico; van Uden, Inge; de Leeuw, Frank E.; Heskes, Tom; Marchiori, Elena; Platel, Bram

    2015-03-01

    Cerebral small vessel disease (SVD) is a common finding on magnetic resonance images of elderly people. White matter lesions (WML) are important markers for not only the small vessel disease, but also neuro-degenerative diseases including multiple sclerosis, Alzheimer's disease and vascular dementia. Volumetric measurements such as the "total lesion load", have been studied and related to these diseases. With respect to SVD we conjecture that small lesions are important, as they have been observed to grow over time and they form the majority of lesions in number. To study these small lesions they need to be annotated, which is a complex and time-consuming task. Existing (semi) automatic methods have been aimed at volumetric measurements and large lesions, and are not suitable for the detection of small lesions. In this research we established a supervised voxel classification CAD system, optimized and trained to exclusively detect small WMLs. To achieve this, several preprocessing steps were taken, which included a robust standardization of subject intensities to reduce inter-subject intensity variability as much as possible. A number of features that were found to be well identifying small lesions were calculated including multimodal intensities, tissue probabilities, several features for accurate location description, a number of second order derivative features as well as multi-scale annular filter for blobness detection. Only small lesions were used to learn the target concept via Adaboost using random forests as its basic classifiers. Finally the results were evaluated using Free-response receiver operating characteristic.

  10. Longitudinal White Matter Changes after Traumatic Axonal Injury

    PubMed Central

    Perez, Alison M.; Adler, Justin; Kulkarni, Nimay; Strain, Jeremy F.; Womack, Kyle B.; Diaz-Arrastia, Ramon

    2014-01-01

    Abstract Diffusion tensor imaging (DTI) has been useful in showing compromise after traumatic axonal injury (TAI) at the chronic stage; however, white matter (WM) compromise from acute stage of TAI to chronic stage is not yet well understood. This study aims to examine changes in WM integrity following TAI by obtaining DTI, on average, 1?d post injury and again approximately seven months post-injury. Sixteen patients with complicated mild to severe brain injuries consistent with TAI were recruited in the intensive care unit of a Level I trauma center. Thirteen of these patients were studied longitudinally over the course of the first seven months post-injury. The first scan occurred, on average, 1?d after injury and the second an average of seven months post-injury. Ten healthy individuals, similar to the cohort of patients, were recruited as controls. Whole brain WM and voxel-based analyses of DTI data were conducted. DTI metrics of interest included: fractional anisotropy (FA), mean diffusivity, axial diffusivity (AD), and radial diffusivity (RD). tract-based spatial statistics were used to examine DTI metrics spatially. Acutely, AD and RD increased and RD positively correlated with injury severity. Longitudinal analysis showed reduction in FA and AD (p<0.01), but no change in RD. Possible explanations for the microstructural changes observed over time are discussed. PMID:24738754

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

    NASA Astrophysics Data System (ADS)

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

    2010-03-01

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

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

    PubMed

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

    2015-07-01

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

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

    E-print Network

    Cambridge, University of

    !phenomena!such!as!the!appearance!of!"white(etching!areas"!or!"white(etching! cracks",!crack! confidence! in! the! mechanisms! of! failure,! it! is! necessary! to! be! able! to! reproduce! damage!particular!kind!of!microstructural!damage!in!the!form!of!regions!of!the! structure,! which! appear! white! in

  14. Novel homozygous DEAF1 variant suspected in causing white matter disease, intellectual disability, and microcephaly.

    PubMed

    Faqeih, Eissa A; Al-Owain, Mohammed; Colak, Dilek; Kenana, Rosan; Al-Yafee, Yusra; Al-Dosary, Mazhor; Al-Saman, Abdulaziz; Albalawi, Fadwa; Al-Sarar, Dalia; Domiaty, Dalia; Daghestani, Maha; Kaya, Namik

    2014-06-01

    DEAF1 encodes a transcriptional binding factor and is a regulator of serotonin receptor 1A. Its protein has a significant expression in the neurons of different brain regions and is involved in early embryonic development. In addition, its role in neural tube development is evident from the knockout mouse as many homozygotes have exencephaly. Heterozygous mutations of this gene have been linked to intellectual disability in addition to the gene's involvement in major depression, suicidal tendencies, and panic disorder. In this clinical report, we describe two children from a consanguineous family with intellectual disability, microcephaly, and hypotonia. The brain MRI of both patients showed bilateral and symmetrical white matter abnormalities, and one of the patients had a seizure disorder. Using whole exome sequencing combined with homozygosity mapping, a homozygous p.R226W (c.676C>T) mutation in DEAF1 was found in both patients. Furthermore, sequencing analysis confirmed complete segregation in tested family members and absence of the mutation in control cohort (n = 650). The mutation is located in a highly conserved structural domain that mediates DNA binding and therefore regulates transcriptional activity of its target molecules. This study indicates, for the first time to our knowledge, a hereditary role of DEAF1 in white matter abnormalities, microcephaly and syndromic intellectual disability. PMID:24668509

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  17. The gene for leukoencephalopathy with vanishing white matter is located on chromosome 3q27.

    PubMed

    Leegwater, P A; Könst, A A; Kuyt, B; Sandkuijl, L A; Naidu, S; Oudejans, C B; Schutgens, R B; Pronk, J C; van der Knaap, M S

    1999-09-01

    Leukoencephalopathy with vanishing white matter (VWM) is an autosomal recessive disorder with normal early development and, usually, childhood-onset neurological deterioration. At present, diagnosis of VWM is based on clinical examination and the results of repeat magnetic resonance imaging and magnetic resonance spectroscopy, which show that, with time, increasing amounts of the cerebral white matter vanish and are replaced by cerebrospinal fluid. We have performed a genome linkage screening of a panel of 19 families of different ethnic origins. Significant linkage to chromosome 3q27 was observed in a 7-cM interval between markers D3S3730 and D3S3592, with a maximum multipoint LOD score of 5.1 calculated from the entire data set. The results of genealogical studies have suggested that seven parents in four Dutch families with VWM may have inherited an allele for the disease from a common ancestor who lived at least eight generations ago. Analysis of these families provided further evidence for the localization of the gene for VWM to 3q27. The patients shared a haplotype spanning 5 cM between markers D3S1618 and D3S3592. In one family of a different ethnic background, the patient had, in the same region, homozygosity for 13 consecutive markers spanning at least 12 cM, suggesting consanguinity between the parents. A healthy sibling of this patient had the same homozygous haplotype, which suggests that the healthy sibling is presymptomatic for the disease. PMID:10441579

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

    PubMed Central

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

    2008-01-01

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

  19. Mapping of ApoE4 related white matter damage using diffusion MRI

    NASA Astrophysics Data System (ADS)

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

    2014-04-01

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

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

    PubMed Central

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

    2014-01-01

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

  1. Genetic associations of leukoaraiosis indicate pathophysiological mechanisms in white matter lesions etiology.

    PubMed

    Lin, Qing; Huang, Wen-Qing; Tzeng, Chi-Meng

    2015-01-01

    Leukoaraiosis (LA), also called white matter lesions (WMLs) and white matter hyperintensities (WMHs), is a frequent neuroimaging finding commonly seen on magnetic resonance imaging brain scans of elderly people with prevalence ranging from 50% to 100%. Although it remains asymptomatic, LA is not considered to be benign, and it is showed to be related to a host of poor clinical outcomes and increases the risk of disability, dementia, depression, stroke, and the overall morbidity and mortality. Pathologically, LA is characterized by loss of myelin and axons, patchy demyelination, and denudation of ependyma in regions of WMH. Age and hypertension are the most importantly established risk factors for LA. However, the precise pathogenic mechanisms remain unclear. Together with the previous findings, our recent genetic results strongly supported that LA is associated with immune response and neuroinflammation. Therefore, we confidently hypothesized that LA was not only a common neuroimaging phenomenon in the elderly but also an emerging neuroinflammatory disorder in the central nervous system. This article focusing on neuroimaging classification, genetics basis, and putative molecular mechanism introduced the basic knowledge and current status of LA and put forward some of our research ideas and results from our molecular genetics research, which may pave the way for deciphering the putative pathogenic mechanism, risk factor, epigenetic index, and its application in diagnostic agents or drug target for prevention and treatment. Thus, it could provide clinicians and researchers with a specific and modern overview of LA to enable the understanding of recent progress and future directions in this illness. PMID:25781674

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

    PubMed Central

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

    2015-01-01

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

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

    E-print Network

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

    2003-01-01

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

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

    PubMed

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

    2010-07-01

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

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

    E-print Network

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

    2015-03-17

    During adolescence, white matter microstructure undergoes an important stage of development. It is hypothesized that the alterations of brain connectivity that have a key role in autism spectrum conditions (ASCs) may interact with the development...

  6. Diffusion imaging of cerebral white matter in persons who stutter: evidence for network-level anomalies

    E-print Network

    Cai, Shanqing

    Deficits in brain white matter have been a main focus of recent neuroimaging studies on stuttering. However, no prior study has examined brain connectivity on the global level of the cerebral cortex in persons who stutter ...

  7. Depressive symptoms related to low fractional anisotropy of white matter underlying the right ventral anterior cingulate in older adults with atherosclerotic vascular disease

    PubMed Central

    Bijanki, Kelly R.; Matsui, Joy T.; Mayberg, Helen S.; Magnotta, Vincent A.; Arndt, Stephan; Johnson, Hans J.; Nopoulos, Peg; Paradiso, Sergio; McCormick, Laurie M.; Fiedorowicz, Jess G.; Epping, Eric A.; Moser, David J.

    2015-01-01

    We sought to characterize the relationship between integrity of the white matter underlying the ventral anterior cingulate (vAC) and depressive symptoms in older adults with atherosclerotic vascular disease (AVD), a condition associated with preferential degeneration of the white matter. The vAC was defined as including white matter underlying ventral Brodmann Area 24 and Brodmann Area 25, corresponding with the “subcallosal” and “subgenual” cingulate respectively. This region of interest was chosen based on the preponderance of evidence that the white matter in the region plays a critical role in the manifestation of depressive symptoms. Participants had current unequivocal diagnoses of AVD and were between 55 and 90 years-old. Fractional anisotropy (FA) was used as an index of white matter integrity and organization. Whole-brain mean diffusivity (MD) was used as an index of global white matter lesion burden. Depressive symptoms were measured using the Symptom Checklist-90-Revised (SCL-90-R) Depression Scale. Depressive symptoms were significantly related to low FA in the right vAC (r = -0.356, df = 30, p = 0.045) but not the left vAC (r = 0.024, df = 30, p = 0.896) after controlling for total brain MD (a statistical control for global white matter lesion burden). Further, depressive symptoms were significantly related to low FA in the right vAC (r = -0.361, df = 31, p = 0.039), but not the left vAC (r = 0.259, df = 31, p = 0.145) when controlled for the contralateral vAC FA. The correlation coefficients for this follow-up analysis were found to be significantly different between left and right vAC (Z = 2.310, p = 0.021). Poor white matter health in the vAC may be a biological mechanism for depressive symptoms in older adults with vascular disease. Further studies may corroborate that the right vAC plays a unique role in depressive symptom manifestation in cases where the white matter is preferentially affected, as is the case in AVD. This could lead to future targeting of the region for somatic antidepressant treatment, as well as the development of a precise approach for patients with white matter damage, which could produce significant improvement in quality of life, medical morbidity, and mortality. PMID:26236221

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

    PubMed Central

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

    2013-01-01

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

  9. Separation of ?-amyloid binding and white matter uptake of 18F-flutemetamol using spectral analysis

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-07-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    E-print Network

    Cambridge, University of

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

  13. Panencephalopathic type of Creutzfeldt-Jakob disease: primary involvement of the cerebral white matter

    PubMed Central

    Mizutani, Toshio; Okumura, Atsushi; Oda, Masaya; Shiraki, Hirotsugu

    1981-01-01

    Eight necropsy cases of a “panencephalopathic” type of Creutzfeldt-Jakob disease (CJD) in the Japanese are reported. The reasons why this type should be discussed separately from other types of CJD are that there is primary involvement of the cerebral white matter as well as the cerebral cortex, and that the white matter lesion of one Japanese human brain with CJD similar to the present group has been successfully transmitted to experimental animals. Images PMID:7012278

  14. Associations of White Matter Microstructure with Clinical and Demographic Characteristics in Heavy Drinkers

    PubMed Central

    Monnig, Mollie A.; Yeo, Ronald A.; Tonigan, J. Scott; McCrady, Barbara S.; Thoma, Robert J.; Sabbineni, Amithrupa; Hutchison, Kent E.

    2015-01-01

    Damage to the brain’s white matter is a signature injury of alcohol use disorders (AUDs), yet understanding of risks associated with clinical and demographic characteristics is incomplete. This study investigated alcohol problem severity, recent drinking behavior, and demographic factors in relation to white matter microstructure in heavy drinkers. Magnetic resonance imaging (MRI) scans, including diffusion tensor imaging (DTI), were collected from 324 participants (mean age = 30.9 ± 9.1 years; 30% female) who reported five or more heavy drinking episodes in the past 30 days. Drinking history and alcohol problem severity were assessed. A common white matter factor was created from fractional anisotropy (FA) values of five white matter tracts: body of corpus callosum, fornix, external capsule, superior longitudinal fasciculus, and cingulate gyrus. Previous research has implicated these tracts in heavy drinking. Structural equation modeling (SEM) analyses tested the hypothesis that, after controlling for duration of alcohol exposure, clinical and behavioral measures of alcohol use severity would be associated with lower white matter factor scores. Potential interactions with smoking status, gender, age, treatment-seeking status, and depression or anxiety symptoms also were tested. Controlling for number of years drinking, greater alcohol problem severity and recent drinking frequency were significantly associated with lower white matter factor scores. The effect of drinking frequency differed significantly for men and women, such that higher drinking frequency was linked to lower white matter factor scores in women but not in men. In conclusion, alcohol problem severity was a significant predictor of lower white matter FA in heavy drinkers, after controlling for duration of alcohol exposure. In addition, more frequent drinking contributed to lower FA in women but not men, suggesting gender-specific vulnerability to alcohol neurotoxicity. PMID:26529515

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

    PubMed Central

    de Jesus, Danilo R.; Stirpe, Tania; Felsky, Daniel; Schutter, Dennis J. L. G.; Daskalakis, Zafiris J.; Voineskos, Aristotle 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 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. PMID:23977291

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

    NASA Technical Reports Server (NTRS)

    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 increased WMH.

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

    PubMed

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

    2015-08-01

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

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

    ERIC Educational Resources Information Center

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

    2014-01-01

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

  19. Modality-spanning deficits in attention-deficit/hyperactivity disorder in functional networks, gray matter, and white matter.

    PubMed

    Kessler, Daniel; Angstadt, Michael; Welsh, Robert C; Sripada, Chandra

    2014-12-10

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

  20. Relationship Between White Matter Integrity, Attention, and Memory in Schizophrenia: A Diffusion Tensor Imaging Study

    PubMed Central

    Kubicki, Marek; Niznikiewicz, Margaret; Connor, Elizabeth; Ungar, Lida; Nestor, Paul; Bouix, Sylvain; Dreusicke, Mark; Kikinis, Ron; McCarley, Robert; Shenton, Martha

    2010-01-01

    Attention and memory deficits are among the most prominent cognitive disturbances observed in schizophrenia. It has been suggested that a disruption in anatomical connectivity between areas involved in attentional control might be responsible for these abnormalities. We used Diffusion Tensor Tractography and Color Stroop/Negative Priming(NP) paradigm to investigate integrity of Cingulum Bundle(CB), the main white matter tract interconnecting these regions, and its relationship with executive functions in patients with schizophrenia and matched controls. The Fractional Anisotropy(FA), was calculated along the CB pathways, and correlated with reaction times for each Stroop item, and both Stroop, and NP effects. Patients with schizophrenia demonstrated decreased CB integrity and diminished NP effect, compared with controls, but both groups showed Stroop effect. For patients only, reaction times for every item, as well as for Stroop effect, correlated with left CB FA. These findings suggest that CB integrity disruptions might compromise the executive processes in schizophrenia. PMID:20556231

  1. White Matter Damage Disorganizes Brain Functional Networks in Amnestic Mild Cognitive Impairment

    PubMed Central

    Garcés, Pilar; López, María Eugenia; Aurtenetxe, Sara; Cuesta, Pablo; Marcos, Alberto; Montejo, Pedro; Yus, Miguel; Hernández-Tamames, Juan Antonio; del Pozo, Francisco; Becker, James T.; Maestú, Fernando

    2014-01-01

    Abstract Although progressive functional brain network disruption has been one of the hallmarks of Alzheimer's Disease, little is known about the origin of this functional impairment that underlies cognitive symptoms. We investigated how the loss of white matter (WM) integrity disrupts the organization of the functional networks at different frequency bands. The analyses were performed in a sample of healthy elders and mild cognitive impairment (MCI) subjects. Spontaneous brain magnetic activity (measured with magnetoencephalography) was characterized with phase synchronization analysis, and graph theory was applied to the functional networks. We identified WM areas (using diffusion weighted magnetic resonance imaging) that showed a statistical dependence between the fractional anisotropy and the graph metrics. These regions are part of an episodic memory network and were also related to cognitive functions. Our data support the hypothesis that disruption of the anatomical networks influences the organization at the functional level resulting in the prodromal dementia syndrome of MCI. PMID:24617580

  2. White-Etching Matter in Bearing Steel. Part II: Distinguishing Cause and Effect in Bearing Steel Failure

    NASA Astrophysics Data System (ADS)

    Solano-Alvarez, W.; Bhadeshia, H. K. D. H.

    2014-10-01

    The premature failure of large bearings of the type used in wind turbines, possibly through a mechanism called "white-structure flaking", has triggered many studies of microstructural damage associated with "white-etching areas" created during rolling contact fatigue, although whether they are symptoms or causes of failure is less clear. Therefore, some special experiments have been conducted to prove that white-etching areas are the consequence, and not the cause, of damage. By artificially introducing a fine dispersion of microcracks in the steel through heat treatment and then subjecting the sample to rolling contact fatigue, manifestations of hard white-etching matter have been created to a much greater extent than samples similarly tested without initial cracks. A wide variety of characterization tools has been used to corroborate that the white areas thus created have the same properties as reported observations on real bearings. Evidence suggests that the formation mechanism of the white-etching regions involves the rubbing and beating of the free surfaces of cracks, debonded inclusions, and voids under repeated rolling contact. It follows that the focus in avoiding early failure should be in enhancing the toughness of the bearing steel in order to avoid the initial microscopic feature event.

  3. Persistent Homological Sparse Network Approach to Detecting White Matter Abnormality in Maltreated Children: MRI and DTI Multimodal Study

    PubMed Central

    Chung, Moo K.; Hanson, Jamie L.; Lee, Hyekyoung; Adluru, Nagesh; Alexander, Andrew L.; Davidson, Richard J.; Pollak, Seth D.

    2014-01-01

    We present a novel persistent homological sparse network analysis framework for characterizing white matter abnormalities in tensor-based morphometry (TBM) in magnetic resonance imaging (MRI). Traditionally TBM is used in quantifying tissue volume change in each voxel in a massive univariate fashion. However, this obvious approach cannot be used in testing, for instance, if the change in one voxel is related to other voxels. To address this limitation of univariate-TBM, we propose a new persistent homological approach to testing more complex relational hypotheses across brain regions. The proposed methods are applied to characterize abnormal white matter in maltreated children. The results are further validated using fractional anisotropy (FA) values in diffusion tensor imaging (DTI). PMID:24505679

  4. Frontal White Matter Anisotropy and Antidepressant Remission in Late-Life Depression

    PubMed Central

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

    2008-01-01

    Introduction Neuroanatomic features associated with antidepressant treatment outcomes in older depressed individuals are not well established. This study used diffusion tensor imaging to examine frontal white matter structure in depressed subjects undergoing a 12-week trial of sertraline. We hypothesized that remission would be associated with higher frontal anisotropy measures, and failure to remit with lower anisotropy. Methods 74 subjects with Major Depressive Disorder and age 60 years or older were enrolled in a twelve-week open-label trial of sertraline and completed clinical assessments and 1.5T magnetic resonance brain imaging. The apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in regions of interest placed in the white matter of the dorsolateral prefrontal cortex, anterior cingulate cortex, and corpus callosum. Differences in ADC and FA values between subjects who did and did not remit to treatment over the study period were assessed using generalized estimating equations, controlling for age, sex, medical comorbidity and baseline depression severity. Results Subjects who did not remit to sertraline exhibited higher FA values in the superior frontal gyri and anterior cingulate cortices bilaterally. There were no statistically significant associations between ADC measures and remission. Conclusions Failure to remit to sertraline is associated with higher frontal FA values. Functional imaging studies demonstrate that depression is characterized by functional disconnection between frontal and limbic regions. Those individuals where this disconnection is related to structural changes as detected by DTI may be more likely to respond to antidepressants. Trial Registration ClinicalTrials.gov NCT00339066 PMID:18813343

  5. Evaluation of White Matter Injury Patterns Underlying Neuropsychiatric Symptoms after Mild Traumatic Brain Injury.

    PubMed

    Alhilali, Lea M; Delic, Joseph A; Gumus, Serter; Fakhran, Saeed

    2015-12-01

    Purpose To determine if a central axonal injury underlies neuropsychiatric symptoms after mild traumatic brain injury (mTBI) by using tract-based spatial statistics analysis of diffusion-tensor images. Materials and Methods The institutional review board approved this study, with waiver of informed consent. Diffusion-tensor imaging and serial neurocognitive testing with the Immediate Post-Concussion Assessment and Cognitive Testing evaluation were performed in 45 patients with mTBI (38 with irritability, 32 with depression, and 18 with anxiety). Control subjects consisted of 29 patients with mTBI without neuropsychiatric symptoms. Fractional anisotropy and diffusivity maps were analyzed by using tract-based spatial statistics with a multivariate general linear model. Diffusion-tensor imaging findings were correlated with symptom severity, neurocognitive test scores, and time to recovery with the Pearson correlation coefficient. Results Compared with control subjects, patients with mTBI and depression had decreased fractional anisotropy in the superior longitudinal fasciculus (P = .006), white matter around the nucleus accumbens (P = .03), and anterior limb of the internal capsule (P = .02). Patients with anxiety had diminished fractional anisotropy in the vermis (P = .04). No regions of significantly decreased fractional anisotropy were seen in patients with irritability relative to control subjects. Injury in the region of the nucleus accumbens inversely correlated with recovery time in patients with depression (r = -0.480, P = .005). Conclusion Unique white matter injury patterns were seen for two major posttraumatic neuropsychiatric symptoms. Injury to the cerebellar vermis in patients with mTBI and anxiety may indicate underlying dysfunction in primitive fear conditioning circuits in the cerebellum. Involvement of the nucleus accumbens in depression after mTBI may suggest an underlying dysfunctional reward circuit that affects the prognosis in these patients. (©) RSNA, 2015. PMID:26079380

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

    PubMed Central

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

    2014-01-01

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

  7. Early Postnatal Myelin Content Estimate of White Matter via T1w/T2w Ratio

    PubMed Central

    Lee, Kevin; Cherel, Marie; Budin, Francois; Gilmore, John; Consing, Kirsten Zaldarriaga; Rasmussen, Jerod; Wadhwa, Pathik D.; Entringer, Sonja; Glasser, Matthew F.; Van Essen, David C.; Buss, Claudia; Styner, Martin

    2015-01-01

    Purpose To develop and evaluate a novel processing framework for the relative quantification of myelin content in cerebral white matter (WM) regions from brain MRI data via a computed ratio of T1 to T2 weighted intensity values. Data We employed high resolution (1mm3 isotropic) T1 and T2 weighted MRI from 46 (28 male, 18 female) neonate subjects (typically developing controls) scanned on a Siemens Tim Trio 3T at UC Irvine. Methods We developed a novel, yet relatively straightforward image processing framework for WM myelin content estimation based on earlier work by Glasser et al. We first co-register the structural MRI data to correct for motion. Then, background areas are masked out via a joint T1w and T2 foreground mask computed. Raw T1w/T2w-ratios images are computed next. For purpose of calibration across subjects, we first coarsely segment the fat-rich facial regions via an atlas co-registration. Linear intensity rescaling based on median T1w/T2w-ratio values in those facial regions yields calibrated T1w/T2w-ratio images. Mean values in lobar regions are evaluated using standard statistical analysis to investigate their interaction with age at scan. Results Several lobes have strongly positive significant interactions of age at scan with the computed T1w/T2w-ratio. Most regions do not show sex effects. A few regions show no measurable effects of change in myelin content change within the first few weeks of postnatal development, such as cingulate and CC areas, which we attribute to sample size and measurement variability. Conclusions We developed and evaluated a novel way to estimate white matter myelin content for use in studies of brain white matter development. PMID:26612964

  8. Early postnatal myelin content estimate of white matter via T1w/T2w ratio

    NASA Astrophysics Data System (ADS)

    Lee, Kevin; Cherel, Marie; Budin, Francois; Gilmore, John; Zaldarriaga Consing, Kirsten; Rasmussen, Jerod; Wadhwa, Pathik D.; Entringer, Sonja; Glasser, Matthew F.; Van Essen, David C.; Buss, Claudia; Styner, Martin

    2015-03-01

    To develop and evaluate a novel processing framework for the relative quantification of myelin content in cerebral white matter (WM) regions from brain MRI data via a computed ratio of T1 to T2 weighted intensity values. We employed high resolution (1mm3 isotropic) T1 and T2 weighted MRI from 46 (28 male, 18 female) neonate subjects (typically developing controls) scanned on a Siemens Tim Trio 3T at UC Irvine. We developed a novel, yet relatively straightforward image processing framework for WM myelin content estimation based on earlier work by Glasser, et al. We first co-register the structural MRI data to correct for motion. Then, background areas are masked out via a joint T1w and T2 foreground mask computed. Raw T1w/T2w-ratios images are computed next. For purpose of calibration across subjects, we first coarsely segment the fat-rich facial regions via an atlas co-registration. Linear intensity rescaling based on median T1w/T2w-ratio values in those facial regions yields calibrated T1w/T2wratio images. Mean values in lobar regions are evaluated using standard statistical analysis to investigate their interaction with age at scan. Several lobes have strongly positive significant interactions of age at scan with the computed T1w/T2w-ratio. Most regions do not show sex effects. A few regions show no measurable effects of change in myelin content change within the first few weeks of postnatal development, such as cingulate and CC areas, which we attribute to sample size and measurement variability. We developed and evaluated a novel way to estimate white matter myelin content for use in studies of brain white matter development.

  9. Effects of vascular risk factors and APOE ?4 on white matter integrity and cognitive decline

    PubMed Central

    Fratiglioni, Laura; Laukka, Erika J.; Lövdén, Martin; Kalpouzos, Grégoria; Keller, Lina; Graff, Caroline; Salami, Alireza; Bäckman, Lars

    2015-01-01

    Objective: To investigate the effects of vascular risk factors and APOE status on white matter microstructure, and subsequent cognitive decline among older people. Methods: This study included 241 participants (age 60 years and older) from the population-based Swedish National Study on Aging and Care in Kungsholmen in central Stockholm, Sweden, who were free of dementia and stroke at baseline (2001–2004). We collected data through interviews, clinical examinations, and laboratory tests. We measured fractional anisotropy (FA) and mean diffusivity (MD) on diffusion tensor imaging, and estimated volume of white matter hyperintensities using automatic segmentation. We assessed global cognitive function with the Mini-Mental State Examination at baseline and at 3- and/or 6-year follow-up. We analyzed the data using multivariate linear regression and linear mixed models. Results: Heavy alcohol consumption, hypertension, and diabetes were significantly associated with lower FA or higher MD (p < 0.05). When aggregating heavy alcohol consumption, hypertension, and diabetes together with current smoking, having an increasing number of these 4 factors concurrently was associated with decreasing FA and increasing MD (ptrend < 0.01), independent of white matter hyperintensities. Vascular risk factors and APOE ?4 allele interacted to negatively affect white matter microstructure; having multiple (?2) vascular factors was particularly detrimental to white matter integrity among APOE ?4 carriers. Lower tertile of FA and upper tertile of MD were significantly associated with faster Mini-Mental State Examination decline. Conclusions: Vascular risk factors are associated with reduced white matter integrity among older adults, which subsequently predicted faster cognitive decline. The detrimental effects of vascular risk factors on white matter microstructure were exacerbated among APOE ?4 carriers. PMID:25672924

  10. Cognitive State following Stroke: The Predominant Role of Preexisting White Matter Lesions

    PubMed Central

    Kliper, Efrat; Ben Assayag, Einor; Tarrasch, Ricardo; Artzi, Moran; Korczyn, Amos D.; Shenhar-Tsarfaty, Shani; Aizenstein, Orna; Hallevi, Hen; Mike, Anat; Shopin, Ludmila; Bornstein, Natan M.; Bashat, Dafna Ben

    2014-01-01

    Background and purpose 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. Methods 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. Results Structural equation modeling analysis of 142 patients confirmed the predominant role of white matter lesion volume (standardized path coefficient ??=??0.231) and normal appearing white matter integrity (??=??0.176) on the global cognitive score, while ischemic lesions' volume showed no such effect (??=?0.038). The model excluding the ischemic lesion presented better fit to the data (comparative fit index 0.9 versus 0.092). Conclusions 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. PMID:25153800

  11. Gray and White Matter Volumes and Cognitive Dysfunction in Drug-Naïve Newly Diagnosed Pediatric Epilepsy

    PubMed Central

    Lee, Jung Hwa; Kim, Song E.; Park, Chang-hyun; Yoo, Jeong Hyun; Lee, Hyang Woon

    2015-01-01

    Epilepsy patients often have cognitive dysfunction even at early stages of disease. We investigated the relationship between structural findings and neuropsychological status in drug-naïve newly diagnosed pediatric epilepsy patients. Thirty newly diagnosed pediatric epilepsy patients and 25 healthy control subjects aged 7~16 years were enrolled, who were assessed by the Korean version of the Wechsler Intelligence Scale for Children (K-WISC-III), the Stroop test, and the trail making test (TMT). Optimized voxel-based morphometry (VBM) was performed for both Gray Matter (GM) and White Matter (WM) volumes. Lower performance levels of verbal intelligence quotient, freedom from distractibility, and executive function were observed in epilepsy group. Interestingly, poor performance in these cognitive subdomains was correlated with regional VBM findings involving both GM and WM volumes, but with different patterns between groups. GM volumes revealed clear differences predominantly in the bilateral frontal regions. These findings indicate that certain cognitive functions may be affected in the early stage of epilepsy, not related to the long-standing epilepsy or medication, but more related to the neurocognitive developmental process in this age. Epilepsy can lead to neuroanatomical alterations in both GM and WM, which may affect cognitive functions, during early stages even before commencement of AED medication. PMID:26417604

  12. Community Influences on White Racial Attitudes: What Matters and Why?

    PubMed Central

    Taylor, Marylee C.; Mateyka, Peter J.

    2014-01-01

    Tracing the roots of racial attitudes in historical events and individual biographies has been a longstanding goal of race relations scholars. Recent years have seen a new development in racial attitude research: Local community context has entered the spotlight as a potential influence on racial views. The race composition of the locality has been the most common focus; evidence from earlier decades suggests that white Americans are more likely to hold anti-black attitudes if they live in areas where the African American population is relatively large. However, an influential 2000 article argued that the socioeconomic composition of the white community is a more powerful influence on white attitudes: In low-SES locales, “stress-inducing” deprivations and hardships in whites’ own lives purportedly lead them to disparage blacks. The study reported here re-assesses this “scapegoating” claim, using data from the 1998–2002 General Social Surveys linked to 2000 census information about communities. Across many dimensions of racial attitudes, there is pronounced influence of both local racial proportions and college completion rates among white residents. However, the economic dimension of SES exerts negligible influence on white racial attitudes, suggesting that local processes other than scapegoating must be at work. PMID:21910274

  13. Hemispheric Asymmetry in White Matter Connectivity of the Temporoparietal Junction with the Insula and Prefrontal Cortex

    PubMed Central

    Kucyi, Aaron; Moayedi, Massieh; Weissman-Fogel, Irit; Hodaie, Mojgan; Davis, Karen D.

    2012-01-01

    The temporoparietal junction (TPJ) is a key node in the brain's ventral attention network (VAN) that is involved in spatial awareness and detection of salient sensory stimuli, including pain. The anatomical basis of this network's right-lateralized organization is poorly understood. Here we used diffusion-weighted MRI and probabilistic tractography to compare the strength of white matter connections emanating from the right versus left TPJ to target regions in both hemispheres. Symmetry of structural connectivity was evaluated for connections between TPJ and target regions that are key cortical nodes in the right VAN (insula and inferior frontal gyrus) as well as target regions that are involved in salience and/or pain (putamen, cingulate cortex, thalamus). We found a rightward asymmetry in connectivity strength between the TPJ and insula in healthy human subjects who were scanned with two different sets of diffusion-weighted MRI acquisition parameters. This rightward asymmetry in TPJ-insula connectivity was stronger in females than in males. There was also a leftward asymmetry in connectivity strength between the TPJ and inferior frontal gyrus, consistent with previously described lateralization of language pathways. The rightward lateralization of the pathway between the TPJ and insula supports previous findings on the roles of these regions in stimulus-driven attention, sensory awareness, interoception and pain. The findings also have implications for our understanding of acute and chronic pains and stroke-induced spatial hemineglect. PMID:22536413

  14. Relating anatomical and social connectivity: white matter microstructure predicts emotional empathy.

    PubMed

    Parkinson, Carolyn; Wheatley, Thalia

    2014-03-01

    Understanding cues to the internal states of others involves a widely distributed network of brain regions. Although white matter (WM) connections are likely crucial for communication between these regions, the role of anatomical connectivity in empathic processing remains unexplored. The present study tested for a relationship between anatomical connectivity and empathy by assessing the WM microstructural correlates of affective empathy, which promotes interpersonal understanding through emotional reactions, and cognitive empathy, which does so via perspective taking. Associations between fractional anisotropy (FA) and the emotional (empathic concern, EC) and cognitive (perspective taking, PT) dimensions of empathy as assessed by the Interpersonal Reactivity Index were examined. EC was positively associated with FA in tracts providing communicative pathways within the limbic system, between perception and action-related regions, and between perception and affect-related regions, independently of individual differences in age, gender, and other dimensions of interpersonal reactivity. These findings provide a neuroanatomical basis for the rapid, privileged processing of emotional sensory information and the automatic elicitation of responses to the affective displays of others. PMID:23162046

  15. Reconsidering harbingers of dementia: progression of parietal lobe white matter hyperintensities predicts Alzheimer's disease incidence.

    PubMed

    Brickman, Adam M; Zahodne, Laura B; Guzman, Vanessa A; Narkhede, Atul; Meier, Irene B; Griffith, Erica Y; Provenzano, Frank A; Schupf, Nicole; Manly, Jennifer J; Stern, Yaakov; Luchsinger, José A; Mayeux, Richard

    2015-01-01

    Accumulating evidence implicates small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMH) on T2-weighted magnetic resonance imaging, in the pathogenesis and diagnosis of Alzheimer's disease (AD). Cross-sectional volumetric measures of WMH, particularly in the parietal lobes, are associated with increased risk of AD. In the present study, we sought to determine whether the longitudinal regional progression of WMH predicts incident AD above-and-beyond traditional radiological markers of neurodegeneration (i.e., hippocampal atrophy and cortical thickness). Three hundred three nondemented older adults (mean age = 79.24 ± 5.29) received high-resolution magnetic resonance imaging at baseline and then again 4.6 years (standard deviation = 1.01) later. Over the follow-up interval 26 participants progressed to AD. Using structural equation modeling, we calculated latent difference scores of parietal and nonparietal WMH, hippocampus volumes, and cortical thickness values in AD-related regions. Within the structural equation modeling framework, we determined whether baseline or change scores or both predicted AD conversion, while controlling for several time-invariant relevant variables. Smaller baseline hippocampus volume, change in hippocampus volume (i.e., atrophy), higher baseline parietal lobe WMH, and increasing parietal lobe WMH volume but not WMH in other regions or measures of cortical thickness, independently predicted progression to AD. The findings provide strong evidence that regionally accumulating WMH predict AD onset in addition to hallmark neurodegenerative changes typically associated with AD. PMID:25155654

  16. Diffuse and spatially variable white matter disruptions are associated with blast-related mild traumatic brain injury.

    PubMed

    Davenport, Nicholas D; Lim, Kelvin O; Armstrong, Michael T; Sponheim, Scott R

    2012-02-01

    Mild traumatic brain injury (mTBI) due to explosive blast is common among military service members and often associated with long term psychological and cognitive disruptions. Little is known about the neurological effects of blast-related mTBI and whether they differ from those of civilian, non-blast mTBI. Given that brain damage from blasts may be diffuse and heterogeneous, we tested the hypothesis that blast mTBI is associated with subtle white matter disruptions in the brain that are spatially inconsistent across individuals. We used diffusion tensor imaging to examine white matter integrity, as quantified by fractional anisotropy (FA), in a group of American military service members with (n=25) or without (n=33) blast-related mTBI who had been deployed as part of Operation Iraqi Freedom or Operation Enduring Freedom. History of civilian non-blast mTBI was equally common across groups, which enabled testing of both blast and non-blast mTBI effects on measures sensitive to (1) concentrated, spatially consistent (average FA within a region of interest [ROI]), (2) concentrated, spatially variable (number of ROIs with low average FA), and (3) diffuse (number of voxels with low FA) disruptions of white matter integrity. Blast mTBI was associated with a diffuse, global pattern of lower white matter integrity, and this pattern was not affected by previous civilian mTBI. Neither type of mTBI had an effect on the measures sensitive to more concentrated and spatially consistent white matter disruptions. Additionally, individuals with more than one blast mTBI tended to have a larger number of low FA voxels than individuals with a single blast injury. These results indicate that blast mTBI is associated with disrupted integrity of several white matter tracts, and that these disruptions are diluted by averaging across the large number of voxels within an ROI. The reported pattern of effects supports the conclusion that the neurological effects of blast mTBI are diffuse, widespread, and spatially variable. PMID:22040736

  17. Extreme Deep White Matter Hyperintensity Volumes Are Associated with African American Race

    PubMed Central

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

    2014-01-01

    Background African Americans (AAs) have a higher prevalence of extreme ischemic white matter hyperintesities (WMH) on magnetic resonance imaging (MRI) than do European Americans based on the Cardiovascular Health Study (CHS) score. Ischemic white matter disease, limited to the deep white matter, may be biologically distinct from disease in other regions and may reflect a previously observed trend toward increased risk of subcortical lacunar infarcts in AA. We hypothesized that extreme deep WMH volume (DWMV) or periventricular volume (PV) may also have higher prevalence in AAs. Thus, we studied extreme CHS scores and extreme DWMV and PV in a healthy population enriched for cardiovascular disease (CVD) risk factors. Methods We imaged the brains of 593 subjects who were first degree relatives of probands with early onset coronary disease prior to 60 years of age. WMHs were manually delineated on 3T cranial MRI by a trained radiology reader the location and volume of lesions were characterized using automated software. DWMV and PV were measured directly with automated software and the CHS score was determined by a Neuro-radiologist. Volumes were characterized as being in the upper 25% versus lower 75% of total lesion volume. Volumes in the upper quartile vs. the remaining were examined for AA versus European American (EA) race using multiple logistic regression (GEE adjusted for family relatedness) and adjusted for major vascular disease risk factors including age ? 55 years vs. younger than 55, sex, current smoking, obesity, hypertension, diabetes, and LDL>160. Results Participants were 58% women and 37% AA, with a mean age of 51.5±11.0 years (range, 29-74 years). AAs had significantly higher odds of having extreme DWMV (OR, 1.8; 95% CI, 1.2-2.9; p=0.0076) independent of age, sex, hypertension, and all other risk factors. AAs also had significantly higher odds of having extreme CHS scores ?3 (OR, 1.3; 95% CI, 1.1-3.6; p=0.025). Extreme PV was not significantly associated with AA race (OR, 1.3; 95% CI, 0.81-2.1; p=0.26). Conclusions AAs from families with early-onset CVD are more likely to have extreme DWMV (a subclinical form of cerebrovascular disease) and an extreme CHS score, but not extreme PV, independent of age and other CVD risk factors. These findings suggest that this AA population is at increased risk for DWMV and may be at increased risk for future subcortical stroke. Longitudinal studies are required to see if DWMV is predictive of symptomatic subcortical strokes in this population. PMID:24686322

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

    PubMed

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

    2015-06-01

    Understanding aging-related cognitive decline is of growing importance in aging societies, but relatively little is known about its neural substrates. Measures of white matter microstructure are known to correlate cross-sectionally with cognitive ability measures, but only a few small studies have tested for longitudinal relations among these variables. We tested whether there were coupled changes in brain white matter microstructure indexed by fractional anisotropy (FA) and three broad cognitive domains (fluid intelligence, processing speed, and memory) in a large cohort of human participants with longitudinal diffusion tensor MRI and detailed cognitive data taken at ages 73 years (n = 731) and 76 years (n = 488). Longitudinal changes in white matter microstructure were coupled with changes in fluid intelligence, but not with processing speed or memory. Individuals with higher baseline white matter FA showed less subsequent decline in processing speed. Our results provide evidence for a longitudinal link between changes in white matter microstructure and aging-related cognitive decline during the eighth decade of life. They are consistent with theoretical perspectives positing that a corticocortical "disconnection" partly explains cognitive aging. PMID:26041932

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

    PubMed Central

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

    2015-01-01

    Understanding aging-related cognitive decline is of growing importance in aging societies, but relatively little is known about its neural substrates. Measures of white matter microstructure are known to correlate cross-sectionally with cognitive ability measures, but only a few small studies have tested for longitudinal relations among these variables. We tested whether there were coupled changes in brain white matter microstructure indexed by fractional anisotropy (FA) and three broad cognitive domains (fluid intelligence, processing speed, and memory) in a large cohort of human participants with longitudinal diffusion tensor MRI and detailed cognitive data taken at ages 73 years (n = 731) and 76 years (n = 488). Longitudinal changes in white matter microstructure were coupled with changes in fluid intelligence, but not with processing speed or memory. Individuals with higher baseline white matter FA showed less subsequent decline in processing speed. Our results provide evidence for a longitudinal link between changes in white matter microstructure and aging-related cognitive decline during the eighth decade of life. They are consistent with theoretical perspectives positing that a corticocortical “disconnection” partly explains cognitive aging. PMID:26041932

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  1. Correlations between DTI and FLAIR images reveal the relationships of microscopic and macroscopic white matter degeneration in elderly subjects

    NASA Astrophysics Data System (ADS)

    Zhan, W.; Zhang, Y.; Lorenzen, P.; Mueller, S. G.; Schuff, N.; Weiner, M. W.

    2008-03-01

    Fluid attenuated inversion recovery (FLAIR) detects the T2 prolongation in whiter matter lesions (WML) measured on a macroscopic scale, whereas diffusion tensor imaging (DTI) more specifically detects the white matter (WM) integrity alterations as measured by water diffusion on a microscopic scale. Both techniques have been widely used to evaluate WM changes associated with aging, dementia and cerebral vascular disease, however, the relationship between white matter lesions (FLAIR) and changes of DTI remains largely unknown. We addressed this issue using a voxel based correlation analysis between DTI and FLAIR images acquired from 33 elderly subjects at 4T. The WML volume and intensity were correlated the fraction anisotropy (FA) or mean diffusivity (MD) across all the subjects on a voxelwise basis. Our results revealed that significant DTI-WML correlations occur at regions overlapping the major WML distributions with moderate intensity, and that no significant correlations were detected in periventricular regions where the FLAIR intensities are particularly high. We investigated WM degeneration as a continuum from normal WM to cerebrospinal fluid (CSF) using a two-compartment WM model. The simulation results indicated that the FLAIR intensity of WML reaches a maximum when the lesion severity is around 0.7, which is the same point where correlations between DTI and WML disappear. Based on these findings, WM degeneration in elderly subjects may be better characterized by using regional DTI-WML correlations in different stages of WM degeneration. DTI and FLAIR, taken together improve specificity for characterization of WM degeneration than each measure alone.

  2. White matter integrity is associated with cognitive processing in patients treated for a posterior fossa brain tumor.

    PubMed

    Palmer, Shawna L; Glass, John O; Li, Yimei; Ogg, Robert; Qaddoumi, Ibrahim; Armstrong, Gregory T; Wright, Karen; Wetmore, Cynthia; Broniscer, Alberto; Gajjar, Amar; Reddick, Wilburn E

    2012-09-01

    Children treated for posterior fossa tumors experience reduced cognitive processing speed and, after imaging, show damage to white matter (WM) tracts in the brain. This study explores relationships between white matter microstructure, assessed by fractional anisotropy (FA), and speed of cognitive processing using tract-based spatial statistics (TBSS). At 36 months after treatment with radiotherapy and chemotherapy, 40 patients completed an MRI examination and neuropsychological evaluation. Patients were matched with healthy control subjects based on age, sex, and race. Individual FA values were extracted from examinations for all voxels identified as having significant association between processing speed and FA using TBSS. The regions were labeled anatomically, and fiber tracts were grouped into larger fiber bundle categories based on their anatomical and functional associations. Analyses were performed between mean skeletal FA values in each of the fiber bundles and each of the cognitive processing scores controlling for age. Children 3 years after treatment for posterior fossa brain tumors demonstrate significantly lower processing speed associated with decreased FA, compared with their healthy peers. Commissural fibers in the corpus callosum were negatively affected by disease and therapy with detrimental consequence on patients' cognitive processing. Diffusion tensor imaging of the white matter tracts in the brain is relevant to determining potential mechanisms underlying clinically meaningful change in cognitive performance. Neuroprotective strategies are needed to preserve critical functions. PMID:22898373

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

    PubMed

    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. PMID:24534360

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-01-15

    Non-linear effects of age on white matter integrity are ubiquitous in the brain and indicate that these effects are more pronounced in certain brain regions at specific ages. Box-Cox analysis is a technique to increase the log-likelihood of linear relationships between variables by means of monotonic non-linear transformations. Here we employ Box-Cox transformations to flexibly and parsimoniously determine the degree of non-linearity of age-related effects on white matter integrity by means of model comparisons using a voxel-wise approach. Analysis of white matter integrity in a sample of adults between 20 and 89years of age (n=88) revealed that considerable portions of the white matter in the corpus callosum, cerebellum, pallidum, brainstem, superior occipito-frontal fascicle and optic radiation show non-linear effects of age. Global analyses revealed an increase in the average non-linearity from fractional anisotropy to radial diffusivity, axial diffusivity, and mean diffusivity. These results suggest that Box-Cox transformations are a useful and flexible tool to investigate more complex non-linear effects of age on white matter integrity and extend the functionality of the Box-Cox analysis in neuroimaging. PMID:26265158

  6. Bound Pool Fractions Complement Diffusion Measures to Describe White Matter Micro and Macrostructure

    PubMed Central

    Stikov, Nikola; Perry, Lee M.; Mezer, Aviv; Rykhlevskaia, Elena; Wandell, Brian A.; Pauly, John M.; Dougherty, Robert F.

    2010-01-01

    Diffusion imaging and bound pool fraction (BPF) mapping are two quantitative magnetic resonance imaging techniques that measure microstructural features of the white matter of the brain. Diffusion imaging provides a quantitative measure of the diffusivity of water in tissue. BPF mapping is a quantitative magnetization transfer (qMT) technique that estimates the proportion of exchanging protons bound to macromolecules, such as those found in myelin, and is thus a more direct measure of myelin content than diffusion. In this work, we combine BPF estimates of macromolecular content with measurements of diffusivity within human white matter tracts. Within the white matter, the correlation between BPFs and diffusivity measures such as fractional anisotropy and radial diffusivity was modest, suggesting that diffusion tensor imaging and bound pool fractions are complementary techniques. We found that several major tracts have high BPF, suggesting a higher density of myelin in these tracts. We interpret these results in the context of a quantitative tissue model. PMID:20828622

  7. An 8-month exercise intervention alters frontotemporal white matter integrity in overweight children.

    PubMed

    Schaeffer, David J; Krafft, Cynthia E; Schwarz, Nicolette F; Chi, Lingxi; Rodrigue, Amanda L; Pierce, Jordan E; Allison, Jerry D; Yanasak, Nathan E; Liu, Tianming; Davis, Catherine L; McDowell, Jennifer E

    2014-08-01

    In childhood, excess adiposity and low fitness are linked to poor academic performance, lower cognitive function, and differences in brain structure. Identifying ways to mitigate obesity-related alterations is of current clinical importance. This study examined the effects of an 8-month exercise intervention on the uncinate fasciculus, a white matter fiber tract connecting frontal and temporal lobes. Participants consisted of 18 unfit, overweight 8- to 11-year-old children (94% Black) who were randomly assigned to either an aerobic exercise (n?=?10) or a sedentary control group (n?=?8). Before and after the intervention, all subjects participated in a diffusion tensor MRI scan. Tractography was conducted to isolate the uncinate fasciculus. The exercise group showed improved white matter integrity as compared to the control group. These findings are consistent with an emerging literature suggesting beneficial effects of exercise on white matter integrity. PMID:24797659

  8. Ramsay Hunt syndrome: progressive mental deterioration in association with unusual cerebral white matter change.

    PubMed

    Kobayashi, K; Morikawa, K; Fukutani, Y; Miyazu, K; Nakamura, I; Yamaguchi, N; Watanabe, H

    1994-01-01

    An autopsied case of Ramsay Hunt syndrome with progressive dementia was reported. The clinical symptoms included progressive intellectual decline, myoclonus, generalized convulsive seizure, cerebellar ataxia and positive pyramidal signs. Neuropathological examination disclosed cerebral white matter demyelination marked in the frontal lobe and fibrillary gliosis predominantly in the subcortical U-fibers, grumose degeneration in the dentate nucleus and inferior olivary nucleus lesion. The skeletal muscle showed no ragged-red fiber. The present case can be included in Ramsay Hunt syndrome because of the absence of pathological hallmark of mitochondrial encephalomyopathy and of the presence of the degenerative lesions in the olivary and dentate nucleus without cerebellar Purkinje cell loss. The intellectual decline is a result of extensive frontal white matter change, and myoclonus and ataxia are closely associated with dentate grumose degeneration. The cerebral white matter change is an unusual finding and the present case might be a variant in Ramsay Hunt syndrome. PMID:8205732

  9. The Challenge of Understanding Cerebral White Matter Injury in the Premature Infant

    PubMed Central

    Elitt, Christopher M.; Rosenberg, Paul A.

    2014-01-01

    White matter injury in the premature infant leads to motor and more commonly behavioral and cognitive problems that are a tremendous burden to society. While there has been much progress in understanding unique vulnerabilities of developing oligodendrocytes over the past 30 years, there remain no proven therapies for the premature infant beyond supportive care. The lack of translational progress may be partially explained by the challenge of developing relevant animal models when the etiology remains unclear, as is the case in this disorder. There has been an emphasis on hypoxia-ischemia and infection/inflammation as upstream etiologies, but less consideration of other contributory factors. This review highlights the evolution of white matter pathology in the premature infant, discusses the prevailing proposed etiologies, critically analyzes a sampling of common animal models and provides detailed support for our hypothesis that nutritional and hormonal deprivation may be additional factors playing critical and overlooked roles in white matter pathology in the premature infant. PMID:24838063

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

    PubMed

    Kassmann, Celia M

    2014-03-01

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

  11. Diffusion tensor imaging white matter endophenotypes in patients with schizophrenia or psychotic bipolar disorder and their relatives.

    PubMed

    Skudlarski, Pawel; Schretlen, David J; Thaker, Gunvant K; Stevens, Michael C; Keshavan, Matcheri S; Sweeney, John A; Tamminga, Carol A; Clementz, Brett A; O'Neil, Kasey; Pearlson, Godfrey D

    2013-08-01

    OBJECTIVE Both schizophrenia and bipolar disorder are hypothesized to involve disordered brain connectivity. Prior studies show low white matter integrity, measured with diffusion tensor imaging, for both disorders. The authors studied disease specificity and endophenotypic status of these abnormalities by examining patients and their unaffected relatives. METHOD The 513 participants included probands with schizophrenia, probands with psychotic bipolar disorder, their first-degree relatives, and healthy comparison subjects. Fractional anisotropy measures of white matter integrity were collected at two sites as a part of the Bipolar-Schizophrenia Network on Intermediate Phenotypes project. Relatives with cluster A or B personality characteristics were further examined. RESULTS Both the probands with schizophrenia and those with psychotic bipolar disorder showed lower fractional anisotropy than the comparison subjects in multiple white matter regions; differences were more marked in schizophrenia. No significant differences existed between proband groups, but in some brain regions scores on a measure of the dimensional continuum between schizophrenia and bipolar disorder, the Schizo-Bipolar Scale, showed correlations with fractional anisotropy. Many regions affected in schizophrenia probands showed similar but smaller effects in relatives, with a continuous fractional anisotropy decrease from healthy subjects to relatives to cluster A/B relatives to probands. The pattern for psychotic bipolar disorder was similar but involved fewer brain regions. Effects in bipolar relatives were limited to younger subjects. Fractional anisotropy decreased with age in all groups; this decrease was exaggerated in schizophrenia but not psychotic bipolar disorder. CONCLUSIONS Fractional anisotropy was highly heritable, supporting its value as a potential endophenotype. PMID:23771210

  12. Behavioural, genetic and epigenetic determinants of white matter pathology in a new mouse model of chronic cerebral hypoperfusion 

    E-print Network

    Tsenkina, Yanina

    2013-07-06

    Recent clinical studies suggest that white matter pathology rather than grey matter abnormality is the major neurobiological substrate of age- related cognitive decline during “healthy” aging. According to this hypothesis, ...

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  14. White and Black Teachers' Job Satisfaction: Does Relational Demography Matter?

    ERIC Educational Resources Information Center

    Fairchild, Susan; Tobias, Robert; Corcoran, Sean; Djukic, Maja; Kovner, Christine; Noguera, Pedro

    2012-01-01

    Data on the impact of student, teacher, and principal racial and gender composition in urban schools on teacher work outcomes are limited. This study, a secondary data analysis of White and Black urban public school teachers using data taken from the restricted use 2003-04 Schools and Staffing Survey (SASS), examines the effects of relational…

  15. A Unified Parametric Model of White Matter Fiber Tracts

    E-print Network

    Chung, Moo K.

    previously used to classify tracts [4]. The Fourier coefficients are computed by the Fourier transform for explicitly param- eterizing white fiber tracts. The coordinates of tracts are parameterized using a Fourier be challenging to interpret and quantify. Whole brain tractography studies often generate many thousand tracts

  16. White matter imaging contributes to the multimodal diagnosis of frontotemporal lobar degeneration

    PubMed Central

    Brun, C.; Siddiqui, S.; Churgin, M.; Libon, D.; Yushkevich, P.; Zhang, H.; Boller, A.; Gee, J.; Grossman, M.

    2012-01-01

    Objective: To evaluate the distribution of white matter (WM) disease in frontotemporal lobar degeneration (FTLD) and Alzheimer disease (AD) and to evaluate the relative usefulness of WM and gray matter (GM) for distinguishing these conditions in vivo. Methods: Patients were classified as having FTLD (n = 50) or AD (n = 42) using autopsy-validated CSF values of total-tau:?-amyloid (t-tau:A?1–42) ratios. Patients underwent WM diffusion tensor imaging (DTI) and volumetric MRI of GM. We employed tract-specific analyses of WM fractional anisotropy (FA) and whole-brain GM density analyses. Individual patient classification was performed using receiver operator characteristic (ROC) curves with FA, GM, and a combination of the 2 modalities. Results: Regional FA and GM were significantly reduced in FTLD and AD relative to healthy seniors. Direct comparisons revealed significantly reduced FA in the corpus callosum in FTLD relative to AD. GM analyses revealed reductions in anterior temporal cortex for FTLD relative to AD, and in posterior cingulate and precuneus for AD relative to FTLD. ROC curves revealed that a multimodal combination of WM and GM provide optimal classification (area under the curve = 0.938), with 87% sensitivity and 83% specificity. Conclusions: FTLD and AD have significant WM and GM defects. A combination of DTI and volumetric MRI modalities provides a quantitative method for distinguishing FTLD and AD in vivo. PMID:22592372

  17. Localized Brain Volume and White Matter Integrity Alterations in Adolescent Anorexia Nervosa

    PubMed Central

    Frank, Guido K.W.; Shott, Megan E.; Hagman, Jennifer O.; Yang, Tony T.

    2014-01-01

    Objective The neurobiological underpinnings of anorexia nervosa (AN) are poorly understood. In this study we tested whether brain gray matter (GM) and white matter (WM) in adolescents with AN would show alterations comparable to adults. Method We used magnetic resonance imaging to study GM and WM volume, and diffusion tensor imaging to assess fractional anisotropy for WM integrity in 19 adolescents with AN and 22 controls. Results Individuals with AN showed greater left orbitofrontal, right insular, and bilateral temporal cortex GM, as well as temporal lobe WM volumes compared to controls. WM integrity in adolescents with AN was lower (lower fractional anisotropy) in fornix, posterior frontal, and parietal areas, but higher in anterior frontal, orbitofrontal, and temporal lobes. In individuals with AN, orbitofrontal GM volume correlated negatively with sweet taste pleasantness. An additional comparison of this study cohort with adult individuals with AN and healthy controls supported greater orbitofrontal cortex and insula volumes in AN across age groups. Conclusions This study indicates larger orbitofrontal and insular GM volumes, as well as lower fornix WM integrity in adolescents with AN, similar to adults. The pattern of larger anteroventral GM and WM volume as well as WM integrity, but lower WM integrity in posterior frontal and parietal regions may indicate that developmental factors such as GM pruning and WM growth could contribute to brain alterations in AN. The negative correlation between taste pleasantness and orbitofrontal cortex volume in individuals with AN could contribute to food avoidance in this disorder. PMID:24074473

  18. Towards improved animal models of neonatal white matter injury associated with cerebral palsy

    PubMed Central

    Silbereis, John C.; Huang, Eric J.; Back, Stephen A.; Rowitch, David H.

    2010-01-01

    Newborn neurological injuries are the leading cause of intellectual and motor disabilities that are associated with cerebral palsy. Cerebral white matter injury is a common feature in hypoxic-ischemic encephalopathy (HIE), which affects full-term infants, and in periventricular leukomalacia (PVL), which affects preterm infants. This article discusses recent efforts to model neonatal white matter injury using mammalian systems. We emphasize that a comprehensive understanding of oligodendrocyte development and physiology is crucial for obtaining new insights into the pathobiology of HIE and PVL as well as for the generation of more sophisticated and faithful animal models. PMID:21030421

  19. Language and reading skills in school-aged children and adolescents born preterm are associated with white matter properties on diffusion tensor imaging

    PubMed Central

    Feldman, Heidi M.; Lee, Eliana S.; Yeatman, Jason D.; Yeom, Kristen W.

    2013-01-01

    Children born preterm are at risk for deficits in language and reading. They are also at risk for injury to the white matter of the brain. The goal of this study was to determine whether performance in language and reading skills would be associated with white matter properties in children born preterm and full-term. Children born before 36 weeks gestation (n=23, mean±SD age 12.5±2.0 years, gestational age 28.7±2.5 weeks, birth weight 1184±431 g) and controls born after 37 weeks gestation (n=19, 13.1±2.1 years, 39.3±1.0 weeks, 3178±413 g) underwent a battery of language and reading tests. Diffusion Tensor Imaging (DTI) scans were processed using Tract-Based Spatial Statistics to generate a core white matter skeleton that was anatomically comparable across participants. Fractional anisotropy (FA) was the diffusion property used in analyses. In the full-term group, no regions of the whole FA-skeleton were associated with language and reading. In the preterm group, regions of the FA-skeleton were significantly associated with verbal IQ, linguistic processing speed, syntactic comprehension, and decoding. Combined, the regions formed a composite map of 22 clusters on 15 tracts in both hemispheres and in the ventral and dorsal streams. ROI analyses in the preterm group found that several of these regions also showed positive associations with receptive vocabulary, verbal memory, and reading comprehension. Some of the same regions showed weak negative correlations within the full-term group. Exploratory multiple regression in the preterm group found that specific white matter pathways were related to different aspects of language processing and reading, accounting for 27–44% of the variance. The findings suggest that higher performance in language and reading in a group of preterm but not full-term children is associated with higher fractional anisotropy of a bilateral and distributed white matter network. PMID:23088817

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2005-04-01

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

  2. Detection of organic matter in thin-sections of carbonate rocks using a white card

    NASA Astrophysics Data System (ADS)

    Folk, Robert L.

    1987-11-01

    Organic matter is revealed in exquisite detail when a white card is slipped beneath the thin-section and observation is made by oblique reflected light. The method is superior to fluorescence microscopy for highly matured organic matter. Examples are given from the Triassic Portoro limestone of Italy, revealing organic-rich crosses within dolomite crystals, selective bacterial diagenesis of pellet-rich limestones, and hydrocarbon migration along veins.

  3. White matter tract integrity metrics reflect the vulnerability of late-myelinating tracts in Alzheimer's disease?

    PubMed Central

    Benitez, Andreana; Fieremans, Els; Jensen, Jens H.; Falangola, Maria F.; Tabesh, Ali; Ferris, Steven H.; Helpern, Joseph A.

    2013-01-01

    Post-mortem and imaging studies have observed that white matter (WM) degenerates in a pattern inverse to myelin development, suggesting preferential regional vulnerabilities influencing cognitive decline in AD. This study applied novel WM tract integrity (WMTI) metrics derived from diffusional kurtosis imaging (DKI) to examine WM tissue properties in AD within this framework. Using data from amnestic mild cognitive impairment (aMCI, n = 12), AD (n = 14), and normal control (NC; n = 15) subjects, mixed models revealed interaction effects: specific WMTI metrics of axonal density and myelin integrity (i.e. axonal water fraction, radial extra-axonal diffusivity) in late-myelinating tracts (i.e. superior and inferior longitudinal fasciculi) changed in the course of disease, but were stable in the initial stages for early-myelinating tracts (i.e. posterior limb of the internal capsule, cerebral peduncles). WMTI metrics in late-myelinating tracts correlated with semantic verbal fluency, a cognitive function known to decline in AD. These findings corroborate the preferential vulnerability of late-myelinating tracts, and illustrate an application of WMTI metrics to characterizing the regional course of WM changes in AD. PMID:24319654

  4. ASSOCIATION OF GRM3 POLYMORPHISM WITH WHITE MATTER INTEGRITY IN SCHIZOPHRENIA

    PubMed Central

    Mounce, Joanna; Luo, Li; Caprihan, Arvind; Liu, Jingyu; Perrone-Bizzozero, Nora; Calhoun, Vince

    2014-01-01

    Background While the functional disconnectivity hypothesis of schizophrenia has received considerable attention, fewer studies have investigated the contribution of genotype to structural connectivity between brain regions in either schizophrenia patients or in healthy controls. In this study, we obtained diffusion tensor imaging (DTI) data and genome-wide single nucleotide polymorphism (SNP) data from 74 cases and 87 age- and gender-matched controls. Methods We used independent component analysis (ICA) to analyze fractional anisotropy (FA) values and correlated FA values with 121 SNPs in genes associated with myelination and/or schizophrenia risk. Results Using ICA, we identified 6 maximally independent components in which the majority of the voxels corresponded to known white matter (WM) tracts. Among these WM-enriched components, two had FA values that were significantly decreased in patients. In addition, we examined the relationship between FA values and genotype and found that a SNP located in the intronic region of the metabotropic glutamate receptor 3 gene, GRM3, shows a significant correlation with FA values in a component containing tracts from the cortico-cerebellar-thalamic-cortical circuit of patients but not controls. Conclusions Our findings strengthen the evidence for an association between GRM3 genotype and schizophrenia and suggest a role for glutamate neurotransmission in the establishment and maintenance of myelinated fibers. PMID:24680030

  5. Abnormal White Matter Blood-Oxygen-Level-Dependent Signals in Chronic Mild Traumatic Brain Injury.

    PubMed

    Astafiev, Serguei V; Shulman, Gordon L; Metcalf, Nicholas V; Rengachary, Jennifer; MacDonald, Christine L; Harrington, Deborah L; Maruta, Jun; Shimony, Joshua S; Ghajar, Jamshid; Diwakar, Mithun; Huang, Ming-Xiong; Lee, Roland R; Corbetta, Maurizio

    2015-08-15

    Concussion, or mild traumatic brain injury (mTBI), can cause persistent behavioral symptoms and cognitive impairment, but it is unclear if this condition is associated with detectable structural or functional brain changes. At two sites, chronic mTBI human subjects with persistent post-concussive symptoms (three months to five years after injury) and age- and education-matched healthy human control subjects underwent extensive neuropsychological and visual tracking eye movement tests. At one site, patients and controls also performed the visual tracking tasks while blood-oxygen-level-dependent (BOLD) signals were measured with functional magnetic resonance imaging. Although neither neuropsychological nor visual tracking measures distinguished patients from controls at the level of individual subjects, abnormal BOLD signals were reliably detected in patients. The most consistent changes were localized in white matter regions: anterior internal capsule and superior longitudinal fasciculus. In contrast, BOLD signals were normal in cortical regions, such as the frontal eye field and intraparietal sulcus, that mediate oculomotor and attention functions necessary for visual tracking. The abnormal BOLD signals accurately differentiated chronic mTBI patients from healthy controls at the single-subject level, although they did not correlate with symptoms or neuropsychological performance. We conclude that subjects with persistent post-concussive symptoms can be identified years after their TBI using fMRI and an eye movement task despite showing normal structural MRI and DTI. PMID:25758167

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

    PubMed

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

    2015-01-01

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

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  8. Abstract Though cerebral white matter injury is a fre-quently described phenomenon in aging and dementia, the

    E-print Network

    Laidlaw, David

    and dementia, the cause of white matter lesions has not been conclusively determined. Since the lesions reported in vascular and Alzheimer de- mentia, this model of cerebral hypoperfusion may serve established, white matter lesions have frequently been suggested to have a vascular origin. For example

  9. White Matter Development and Asymmetry Mapped using DTI in 12-21 Year Old Twins Neda Jahanshad1

    E-print Network

    Thompson, Paul

    White Matter Development and Asymmetry Mapped using DTI in 12-21 Year Old Twins Neda Jahanshad1 Queensland Institute of Medical Research, Brisbane, Australia 5 Brain and Mind Research Institute, University of research as we used diffusion tensor imaging (DTI) to examine white matter fiber architecture across three

  10. A method for the analysis of the geometrical relationship between white matter pathology and the vascular architecture of the brain

    E-print Network

    , for example, stroke, microcerebrovascular disease, and multiple sclerosis (MS). In our work, white matter; Morphometric analysis; White matter diseases; Multiple sclerosis; Multimodality data integration Introduction or multiple sclerosis (MS), is well established and of ever-increasing importance (Gutt- mann et al., 2000

  11. White matter integrity supports BOLD signal variability and cognitive performance in the aging human brain.

    PubMed

    Burzynska, Agnieszka Z; Wong, Chelsea N; Voss, Michelle W; Cooke, Gillian E; McAuley, Edward; Kramer, Arthur F

    2015-01-01

    Decline in cognitive performance in old age is linked to both suboptimal neural processing in grey matter (GM) and reduced integrity of white matter (WM), but the whole-brain structure-function-cognition associations remain poorly understood. Here we apply a novel measure of GM processing-moment-to-moment variability in the blood oxygenation level-dependent signal (SDBOLD)-to study the associations between GM function during resting state, performance on four main cognitive domains (i.e., fluid intelligence, perceptual speed, episodic memory, vocabulary), and WM microstructural integrity in 91 healthy older adults (aged 60-80 years). We modeled the relations between whole-GM SDBOLD with cognitive performance using multivariate partial least squares analysis. We found that greater SDBOLD was associated with better fluid abilities and memory. Most of regions showing behaviorally relevant SDBOLD (e.g., precuneus and insula) were localized to inter- or intra-network "hubs" that connect and integrate segregated functional domains in the brain. Our results suggest that optimal dynamic range of neural processing in hub regions may support cognitive operations that specifically rely on the most flexible neural processing and complex cross-talk between different brain networks. Finally, we demonstrated that older adults with greater WM integrity in all major WM tracts had also greater SDBOLD and better performance on tests of memory and fluid abilities. We conclude that SDBOLD is a promising functional neural correlate of individual differences in cognition in healthy older adults and is supported by overall WM integrity. PMID:25853882

  12. Accurate Masses for Navarro-Frenk-White Dark Matter Haloes

    E-print Network

    Evans, N W; Deason, A

    2011-01-01

    We consider the problem of estimating the virial mass of a dark halo from the positions and velocities of a tracer population. Although a number of general tools are available, more progress can be made if we are able to specify the functional form of the halo potential (although not its normalization). Here, we consider the particular case of the cosmologically motivated Navarro-Frenk-White (NFW) halo and develop two simple estimators. We demonstrate their effectiveness against numerical simulations and use them to provide new mass estimates of Carina, Fornax, Sculptor, and Sextans dSphs.

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

    ERIC Educational Resources Information Center

    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…

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

    PubMed

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

    2012-11-01

    Prior structural imaging studies of post-traumatic stress disorder (PTSD) have observed smaller volumes of the hippocampus and cingulate cortex, yet little is known about the integrity of white matter connections between these structures in PTSD samples. The few published studies using diffusion tensor imaging (DTI) to measure white matter integrity in PTSD have described individuals with focal trauma rather than chronically stressed individuals, which limits generalization of findings to this population; in addition, these studies have lacked traumatized comparison groups without PTSD. The present DTI study examined microstructural integrity of white matter tracts in a sample of highly traumatized African-American women with (n=25) and without (n=26) PTSD using a tract-based spatial statistical approach, with threshold-free cluster enhancement. Our findings indicated that, relative to comparably traumatized controls, decreased integrity (measured by fractional anisotropy) of the posterior cingulum was observed in participants with PTSD (p<0.05). These findings indicate that reduced microarchitectural integrity of the cingulum, a white matter fiber that connects the entorhinal and cingulate cortices, appears to be associated with PTSD symptomatology. The role of this pathway in problems that characterize PTSD, such as inadequate extinction of learned fear, as well as attention and explicit memory functions, are discussed. PMID:22871912

  15. A longitudinal diffusion tensor imaging study assessing white matter fiber tracts after sports related concussion

    E-print Network

    Osherson, Daniel

    -term effects, and the decision to return to play. In the present longitudinal study, we used diffusion tensorA longitudinal diffusion tensor imaging study assessing white matter fiber tracts after sports The extent of structural injury in sports related concussion is central to the course of recovery, long

  16. The white matter of the human cerebrum: Part I The occipital lobe by Heinrich Sachs

    PubMed Central

    Forkel, Stephanie J.; Mahmood, Sajedha; Vergani, Francesco; Catani, Marco

    2015-01-01

    This is the first complete translation of Heinrich Sachs' outstanding white matter atlas dedicated to the occipital lobe. This work is accompanied by a prologue by Prof Carl Wernicke who for many years was Sachs' mentor in Breslau and enthusiastically supported his work. PMID:25527430

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

    E-print Network

    Stanford University

    IEEE TRANSACTIONS ON VISUALIZATION AND COMPUTER GRAPHICS 1 Exploring Connectivity of the Brain Graphics Interaction Techniques, Computer Graphics Applications, Visualization, DTI, MR Trac- tography. I of white matter pathways. #12;IEEE TRANSACTIONS ON VISUALIZATION AND COMPUTER GRAPHICS 2 Based on magnetic

  18. Segmentation and characterisation of white matter tracts in late childhood and adolescence J. D. Clayden1

    E-print Network

    Edinburgh, University of

    960 Segmentation and characterisation of white matter tracts in late childhood and adolescence J. D and adolescence. However, there is some evidence for the existence of relationships between diffusion parameters childhood or adolescence (13 male, mean age 11.4 ± 3.0 yr, age range 7.1­18.6 yr). All subjects were healthy

  19. White Matter Hyperintensities and Their Associations with Suicidality in Psychiatrically Hospitalized Children and Adolescents.

    ERIC Educational Resources Information Center

    Ehrlich, Stefan; Noam, Gil G.; Lyoo, In Kyoon; Kwon, Bae J.; Clark, Megan A.; Renshaw, Perry F.

    2004-01-01

    Objective: Increasingly, researchers and clinicians are recognizing that there may be biological markers associated with increased risk of suicide. The objective of this study was to compare white matter hyperintensities in psychiatrically hospitalized children and youth with and without a history of suicide attempt while controlling for other…

  20. PGJ2 Provides Prolonged CNS Stroke Protection by Reducing White Matter Edema

    PubMed Central

    Nicholson, James D.; Puche, Adam C.; Guo, Yan; Weinreich, Daniel; Slater, Bernard J.; Bernstein, Steven L.

    2012-01-01

    Few clinically effective approaches reduce CNS-white matter injury. After early in-vivo white matter infarct, NF?B-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-?12,14-prostaglandin J2 (PGJ2), an analog of the metabolically active PGD2 metabolite. We evaluated PGJ2's effects and mechanisms using rodent anterior ischemic optic neuropathy (rAION); an in vivo white matter ischemia model. PGJ2 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 PGJ2 improves perfusion at 1 day post-infarct by reducing tissue edema. Our results suggest that PGJ2 acts by reducing NF?B signaling through preventing p65 nuclear localization and inhibiting inflammatory gene expression. Importantly, PGJ2 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. PGJ2 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. PMID:23284631

  1. White matter hemisphere asymmetries in healthy subjects and in schizophrenia: a diffusion tensor MRI study

    E-print Network

    of fiber tracts, includes generating a symmetrical group average template of the diffusion tensor to match tensor orientation and shape between images. A statistical evaluation of white matter asymmetry-higher-than-right anisotropic asymmetry in the anterior part of the corpus callosum, cingulum bundle, the optic radiation

  2. The Bone Morphogenetic Protein Antagonist Noggin Protects White Matter After Perinatal Hypoxia-ischemia

    PubMed Central

    Dizon, Maria L.V.; Maa, Tensing; Kessler, John A.

    2011-01-01

    Hypoxia-ischemia (HI) in the neonate leads to white matter injury and subsequently cerebral palsy. We find that expression of bone morphogenetic protein 4 (BMP4) increases in the neonatal mouse brain after unilateral common carotid artery ligation followed by hypoxia. Since signaling by the BMP family of factors is a potent inhibitor of oligodendroglial differentiation, we tested the hypothesis that antagonism of BMP signaling would prevent loss of oligodendroglia (OL) and white matter in a mouse model of perinatal HI. Perinatal HI was induced in transgenic mice in which the BMP antagonist noggin is overexpressed during oligodendrogenesis (pNSE-Noggin). Following perinatal HI, pNSE-Noggin mice had more oligodendroglial progenitor cells (OPCs) and more mature OL compared to wild type (WT) animals. The increase in OPC numbers did not result from proliferation but rather from increased differentiation from precursor cells. Immunofluorescence studies showed preservation of white matter in lesioned pNSE-Noggin mice compared to lesioned WT animals. Further, following perinatal HI, the pNSE-Noggin mice were protected from gait deficits. Together these findings indicate that the BMP-inhibitor noggin protects from HI-induced loss of oligodendroglial lineage cells and white matter as well as loss of motor function. PMID:21310236

  3. Sex differences in the IQ-white matter microstructure relationship: A DTI study

    PubMed Central

    Dunst, Beate; Benedek, Mathias; Koschutnig, Karl; Jauk, Emanuel; Neubauer, Aljoscha C.

    2014-01-01

    Sex differences in the relationship between general intelligence and brain structure are a topic of increasing research interest. Early studies focused mainly on gray and white matter differences using voxel-based morphometry, while more recent studies investigated neural fiber tracts using diffusion tensor imaging (DTI) to analyze the white matter microstructure. In this study we used tract-based spatial statistics (TBSS) on DTI to test how intelligence is associated with brain diffusion indices and to see whether this relationship differs between men and women. 63 Men and women divided into groups of lower and higher intelligence were selected. Whole-brain DTI scans were analyzed using TBSS calculating maps of fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). The results reveal that the white matter microstructure differs between individuals as a function of intelligence and sex. In men, higher intelligence was related to higher FA and lower RD in the corpus callosum. In women, in contrast, intelligence was not related to the white matter microstructure. The higher values of FA and lower values of RD suggest that intelligence is associated with higher myelination and/or a higher number of axons particularly in men. This microstructural difference in the corpus callosum may increase cognitive functioning by reducing inter-hemispheric transfer time and thus account for more efficient brain functioning in men. PMID:25238623

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

    PubMed Central

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

    2011-01-01

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

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  6. Sex differences in abnormal white matter development associated with conduct disorder in children.

    PubMed

    Decety, Jean; Yoder, Keith J; Lahey, Benjamin B

    2015-08-30

    Associations between white matter pathway abnormalities and antisocial personality disorder in adults are well replicated, and there is some evidence for an association of white matter abnormalities with conduct disorder (CD) in adolescents. In this study, white matter maturation using diffusion tensor imaging (DTI) was examined in 110 children aged 10.0 ± 0.8 years selected to vary widely in their numbers of CD symptoms. The results replicated age-related increases in fractional anisotropy (FA) found in previous studies. There was not a significant association between the number of CD symptoms and FA, but CD symptoms were found to be significantly associated with greater axial and radial diffusivity in a broad range of white matter tracts, particularly in girls. In complementary analyses, there were similar significant differences in axial and radial diffusivity between children who met diagnostic criteria for CD and healthy children with no symptoms of CD, particularly in girls. Brain structural abnormalities may contribute to the emergence of CD in childhood, perhaps playing a greater role in girls. PMID:26195297

  7. White matter microstructure on diffusion tensor imaging is associated with conventional magnetic resonance imaging findings and

    E-print Network

    Grill-Spector, Kalanit

    if sex, gestational age, birth- weight, white matter injury score from conventional magnetic resonance score, but not sex, gestational age, or birthweight. At site 1, fractional anisotropy was associated) were aged 9 to 16 years. They comprised 58 preterm children (site 1, n=25; and site 2, n=33) born

  8. Neonatal White Matter Abnormality Predicts Childhood Motor Impairment in Very Preterm Children

    ERIC Educational Resources Information Center

    Spittle, Alicia J.; Cheong, Jeanie; Doyle, Lex W.; Roberts, Gehan; Lee, Katherine J.; Lim, Jeremy; Hunt, Rod W.; Inder, Terrie E.; Anderson, Peter J.

    2011-01-01

    Aim: Children born very preterm are at risk for impaired motor performance ranging from cerebral palsy (CP) to milder abnormalities, such as developmental coordination disorder. White matter abnormalities (WMA) at term have been associated with CP in very preterm children; however, little is known about the impact of WMA on the range of motor…

  9. White Matter Abnormalities in Early-Onset Schizophrenia: A Voxel-Based Diffusion Tensor Imaging Study

    ERIC Educational Resources Information Center

    Kumra, Sanjiv; Ashtari, Manzar; Cervellione, Kelly L.; Henderson, Inika; Kester, Hana; Roofeh, David; Wu, Jinghui; Clarke, Tana; Thaden, Emily; Kane, John M.; Rhinewine, Joseph; Lencz, Todd; Diamond, Alan; Ardekani, Babak A.; Szeszko, Philip R.

    2005-01-01

    Objective: To investigate abnormalities in the structural integrity of brain white matter as suggested by diffusion tensor imaging in adolescents with early-onset schizophrenia (onset of psychosis by age 18). Method: Twenty-six patients with schizophrenia and 34 age- and gender-matched healthy volunteers received diffusion tensor imaging and…

  10. Inter-Parietal White Matter Development Predicts Numerical Performance in Young Children

    ERIC Educational Resources Information Center

    Cantlon, Jessica F.; Davis, Simon W.; Libertus, Melissa E.; Kahane, Jill; Brannon, Elizabeth M.; Pelphrey, Kevin A.

    2011-01-01

    In an effort to understand the role of interhemispheric transfer in numerical development, we investigated the relationship between children's developing knowledge of numbers and the integrity of their white matter connections between the cerebral hemispheres (the corpus callosum). We used diffusion tensor imaging (DTI) tractography analyses to…

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

    ERIC Educational Resources Information Center

    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…

  12. Early White-Matter Abnormalities of the Ventral Frontostriatal Pathway in Fragile X Syndrome

    ERIC Educational Resources Information Center

    Haas, Brian W.; Barnea-Goraly, Naama; Lightbody, Amy A.; Patnaik, Swetapadma S.; Hoeft, Fumiko; Hazlett, Heather; Piven, Joseph; Reiss, Allan L.

    2009-01-01

    Aim: Fragile X syndrome is associated with cognitive deficits in inhibitory control and with abnormal neuronal morphology and development. Method: In this study, we used a diffusion tensor imaging (DTI) tractography approach to reconstruct white-matter fibers in the ventral frontostriatal pathway in young males with fragile X syndrome (n = 17;…

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

    PubMed Central

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

    2015-01-01

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

  14. Voxel-Based MRI Intensitometry Reveals Extent of Cerebral White Matter Pathology in Amyotrophic Lateral

    E-print Network

    Gaser, Christian

    Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of upper and lower motor neurons Intensitometry Reveals Extent of Cerebral White Matter Pathology in Amyotrophic Lateral Sclerosis. PLoS ONE 9.prell@med.uni-jena.de . These authors contributed equally to this work. Introduction Amyotrophic lateral sclerosis (ALS) is a fatal

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  16. Proton MR spectroscopy features of normal appearing white matter in neurofibromatosis type 1.

    PubMed

    Alkan, Alpay; Sarac, Kaya; Kutlu, Ramazan; Yakinci, Cengiz; Sigirci, Ahmet; Aslan, Mehmet; Ozcan, Hamdi; Yologlu, Saim

    2003-11-01

    To determine whether differences exist between neurofibromatosis type 1 (NF1) patients with or without focal lesions and healthy normal volunteers in the metabolite ratios of normal appearing white matter, 27 patients with NF1 (with parenchymal lesion, MR positive, n: 17; without parenchymal lesions, MR negative, n: 10) and 20 healthy volunteers underwent MRI and short TE (31 ms) proton MR spectroscopy (MRS). In 17 patients with parenchymal lesions, 61 focal lesions were detected by MRI. MRS was performed from normal appearing frontal and posterior parietal white matter (FWM and PWM) in NF1 and from control groups. NAA/Cr, Cho/Cr and MI/Cr ratios were calculated. Significant increase in Cho/Cr and MI/Cr ratios were found in FWM and PWM in MR negative and positive groups when compared to control group. NAA/Cr ratio in MR positive group was significantly decreased in FWM compared to control group. There were no significant differences between FWM and PWM in all metabolite ratios of MR negative group. MI/Cr ratio in MR positive group was significantly elevated in PWM compared to FWM. Metabolite changes detected by MRS could indicate demyelination and gliosis in normal appearing white matter in all NF1 patients, and additionally neuroaxonal damage in the FWM of NF1 patients with focal lesions. For that reason, in the clinical evaluation and follow-up of these patients MRS features of normal appearing white matter should be considered in addition to focal lesions. PMID:14684211

  17. Prolonged focal application of polyethylene glycol induces conduction block in guinea pig spinal cord white matter

    E-print Network

    Shi, Riyi

    of Polyethylene Glycol (PEG) to injured mammalian spinal cords can offer significant yet limited res- toration injuries. In this study, isolated spinal cord white matter strips from adult guinea pigs were subjected spinal cord victims. Ó 2004 Elsevier Ltd. All rights reserved. Keywords: Axon; Membrane fusion; Neuronal

  18. White Matter Microstructure in Superior Longitudinal Fasciculus Associated with Spatial Working Memory Performance in Children

    ERIC Educational Resources Information Center

    Vestergaard, Martin; Madsen, Kathrine Skak; Baare, William F. C.; Skimminge, Arnold; Ejersbo, Lisser Rye; Ramsoy, Thomas Z.; Gerlach, Christian; Akeson, Per; Paulson, Olaf B.; Jernigan, Terry L.

    2011-01-01

    During childhood and adolescence, ongoing white matter maturation in the fronto-parietal cortices and connecting fiber tracts is measurable with diffusion-weighted imaging. Important questions remain, however, about the links between these changes and developing cognitive functions. Spatial working memory (SWM) performance improves significantly…

  19. Early Neglect Is Associated with Alterations in White Matter Integrity and Cognitive Functioning

    ERIC Educational Resources Information Center

    Hanson, Jamie L.; Adluru, Nagesh; Chung, Moo K.; Alexander, Andrew L.; Davidson, Richard J.; Pollak, Seth D.

    2013-01-01

    Cognitive deficits have been reported in children who experienced early neglect, especially children raised in institutionalized settings. Previous research suggests that early neglect may differentially affect the directional organization of white matter in the prefrontal cortex (PFC). This may be one mechanism to explain cognitive deficits…

  20. Grid-Mapped Freeze-Fracture Analysis of Gap Junctions in Gray and White Matter

    E-print Network

    Rash, John E.

    Grid-Mapped Freeze-Fracture Analysis of Gap Junctions in Gray and White Matter of Adult Rat Central-to-glia coupling hypotheses, we used ``grid-mapped freeze fracture,'' conventional thin-section electron microscopy coupling and glial coupling involved separate and distinct pathways. Finally, putative water channels (i

  1. Does White Matter Matter? Spatio-temporal Dynamics of Task Switching in Aging

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

    Zhao, Tengda; Duan, Fei; Liao, Xuhong; Dai, Zhengjia; Cao, Miao; He, Yong; Shu, Ni

    2015-01-01

    The multiband EPI sequence has been developed for the human connectome project to accelerate MRI data acquisition. However, no study has yet investigated the test-retest (TRT) reliability of the graph metrics of white matter (WM) structural brain networks constructed from this new sequence. Here, we employed a multiband diffusion MRI (dMRI) dataset with repeated scanning sessions and constructed both low- and high-resolution WM networks by volume- and surface-based parcellation methods. The reproducibility of network metrics and its dependence on type of construction procedures was assessed by the intra-class correlation coefficient (ICC). We observed conserved topological architecture of WM structural networks constructed from the multiband dMRI data as previous findings from conventional dMRI. For the global network properties, the first order metrics were more reliable than second order metrics. Between two parcellation methods, networks with volume-based parcellation showed better reliability than surface-based parcellation, especially for the global metrics. Between different resolutions, the high-resolution network exhibited higher TRT performance than the low-resolution in terms of the global metrics with a large effect size, whereas the low-resolution performs better in terms of local (region and connection) properties with a relatively low effect size. Moreover, we identified that the association and primary cortices showed higher reproducibility than the paralimbic/limbic regions. The important hub regions and rich-club connections are more reliable than the non-hub regions and connections. Finally, we found WM networks from the multiband dMRI showed higher reproducibility compared with those from the conventional dMRI. Together, our results demonstrated the fair to good reliability of the WM structural brain networks from the multiband EPI sequence, suggesting its potential utility for exploring individual differences and for clinical applications. PMID:25741265

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

    PubMed

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

    2016-01-01

    We have previously shown that intracerebral hemorrhage-induced brain injury is less in rats bred for high aerobic capacity (high capacity runners; HCR) compared with those bred for low aerobic capacity (low capacity runners; LCRs). Thrombin, an essential component in the coagulation cascade, is produced after cerebral hemorrhage. Intraventricular injection of thrombin causes significant hydrocephalus and white matter damage. In the present study, we examined the effect of exercise capacity on thrombin-induced hydrocephalus and white matter damage. Mid-aged (13-month-old) female LCRs (n?=?13) and HCRs (n?=?12) rats were used in this study. Rats received an intraventricular injection of thrombin (3 U, 50 ?l). All rats underwent magnetic resonance imaging (MRI) at 24 h and were then euthanized for brain histology and Western blot. The mortalities were 20 % in LCRs and 33 % in HCRs after thrombin injection (p?>?0.05). No rats died after saline injection. Intraventricular thrombin injection resulted in hydrocephalus and periventricular white matter damage as determined on MRI. In LCR rats, thrombin induced significant ventricle enlargement (23.0?±?2.3 vs12.8?±?1.9 mm(3) in LCR saline group; p?white matter lesion (9.3?±?7.6 vs 0.6?±?0.5 mm(3) in LCR saline group, p?white matter lesions (2.6?±?1.2 mm(3) vs 9.3?±?7.6 mm(3) in LCRs, p?white matter. These changes were significantly reduced in HCR rats. Intraventricular injection of thrombin caused more white matter damage and hydrocephalus in rats with low aerobic capacity. A differential effect of thrombin may contribute to differences in the effects of cerebral hemorrhage with aerobic capacity. PMID:26463978

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

    NASA Astrophysics Data System (ADS)

    Caffini, Matteo; Bergsland, Niels; 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.

  5. Associations between White Matter Hyperintensities and ? Amyloid on Integrity of Projection, Association, and Limbic Fiber Tracts Measured with Diffusion Tensor MRI

    PubMed Central

    Chao, Linda L.; DeCarli, Charles; Kriger, Stephen; Truran, Diana; Zhang, Yu; Laxamana, Joel; Villeneuve, Sylvia; Jagust, William J.; Sanossian, Nerses; Mack, Wendy J.; Chui, Helena C.; Weiner, Michael W.

    2013-01-01

    The goal of this study was to assess the relationship between A? deposition and white matter pathology (i.e., white matter hyperintensities, WMH) on microstructural integrity of the white matter. Fifty-seven participants (mean age: 78±7 years) from an ongoing multi-site research program who spanned the spectrum of normal to mild cognitive impairment (Clinical dementia rating 0–0.5) and low to high risk factors for arteriosclerosis and WMH pathology (defined as WMH volume >0.5% total intracranial volume) were assessed with positron emission tomography (PET) with Pittsburg compound B (PiB) and magnetic resonance and diffusion tensor imaging (DTI). Multivariate analysis of covariance were used to investigate the relationship between A? deposition and WMH pathology on fractional anisotropy (FA) from 9 tracts of interest (i.e., corona radiata, internal capsule, cingulum, parahippocampal white matter, corpus callosum, superior longitudinal, superior and inferior front-occipital fasciculi, and fornix). WMH pathology was associated with reduced FA in projection (i.e., internal capsule and corona radiate) and association (i.e., superior longitudinal, superior and inferior fronto-occipital fasciculi) fiber tracts. A? deposition (i.e., PiB positivity) was associated with reduced FA in the fornix and splenium of the corpus callosum. There were interactions between PiB and WMH pathology in the internal capsule and parahippocampal white matter, where A? deposition reduced FA more among subjects with WMH pathology than those without. However, accounting for apoE ?4 genotype rendered these interactions insignificant. Although this finding suggests that apoE4 may increase amyloid deposition, both in the parenchyma (resulting in PiB positivity) and in blood vessels (resulting in amyloid angiopathy and WMH pathology), and that these two factors together may be associated with compromised white matter microstructural integrity in multiple brain regions, additional studies with a longitudinal design will be necessary to resolve this issue. PMID:23762308

  6. Fermionic matter under the effects of high magnetic fields and its consequences in white dwarfs

    NASA Astrophysics Data System (ADS)

    Otoniel, E.; Malheiro, M.; Coelho, J. G.

    2015-07-01

    We investigate a recently proposed effect of strong magnetic fields in Fermionicmatter that is important to the structure of magnetic white dwarfs. This work is highly relevant in view of the recent observations of magnetized white dwarfs (B ? 108-9 G), and possible candidates for white dwarfs pulsars as an alternative descriptions for SGRs and AXPs. Here, we consider the matter inside white dwarfs composed by ions surrounded by an electron degenerate Fermi gas subject to a strong magnetic field. We investigate the effect of the Landau levels due to the huge magnetic field on the equation of state (EoS). We see that the behaviour of the equation of state as a function of the mass and energy density is much stiffer when only one Landau level is occupied. We also investigate the regime of lower magnetic fields where many Landau levels are occupied.

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

    PubMed Central

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

    2014-01-01

    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 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 disorders. PMID:25016097

  8. Improved longitudinal [(18)F]-AV45 amyloid PET by white matter reference and VOI-based partial volume effect correction.

    PubMed

    Brendel, Matthias; Högenauer, Marcus; Delker, Andreas; Sauerbeck, Julia; Bartenstein, Peter; Seibyl, John; Rominger, Axel

    2015-03-01

    Amyloid positron-emission-tomography (PET) offers an important research and diagnostic tool for investigating Alzheimer's disease (AD). The majority of amyloid PET studies have used the cerebellum as a reference region, and clinical studies have not accounted for atrophy-based partial volume effects (PVE). Longitudinal studies using cerebellum as reference tissue have revealed only small mean increases and high inter-subject variability in amyloid binding. We aimed to test the effects of different reference regions and PVE-correction (PVEC) on the discriminatory power and longitudinal performance of amyloid PET. We analyzed [(18)F]-AV45 PET and T1-weighted MRI data of 962 subjects at baseline and two-year follow-up data of 258 subjects. Cortical composite volume-of-interest (VOI) values (COMP) for tracer uptake were generated using either full brain atlas VOIs, gray matter segmented VOIs or gray matter segmented VOIs after VOI-based PVEC. Standard-uptake-value ratios (SUVR) were calculated by scaling the COMP values to uptake in cerebellum (SUVRCBL), brainstem (SUVRBST) or white matter (SUVRWM). Mean SUV, SUVR, and changes after PVEC were compared at baseline between diagnostic groups of healthy controls (HC; N=316), mild cognitive impairment (MCI; N=483) and AD (N=163). Receiver operating characteristics (ROC) were calculated for the discriminations between HC, MCI and AD, and expressed as area under the curve (AUC). Finally, the longitudinal [(18)F]-AV45-PET data were used to analyze the impact of quantitation procedures on apparent changes in amyloid load over time. Reference region SUV was most constant between diagnosis groups for the white matter. PVEC led to decreases of COMP-SUV in HC (-18%) and MCI (-10%), but increases in AD (+7%). Highest AUCs were found when using PVEC with white matter scaling for the contrast between HC/AD (0.907) or with brainstem scaling for the contrast between HC/MCI (0.658). Longitudinal increases were greatest in all diagnosis groups with application of PVEC, and inter-subject variability was lowest for the white matter reference. Thus, discriminatory power of [(18)F]-AV45-PET was improved by use of a VOI-based PVEC and white matter or brainstem rather than cerebellum reference region. Detection of longitudinal amyloid increases was optimized with PVEC and white matter reference tissue. PMID:25482269

  9. Contributions of bilateral white matter to chronic aphasia symptoms as assessed by diffusion tensor MRI

    PubMed Central

    Geva, Sharon; Correia, Marta M.; Warburton, Elizabeth A.

    2015-01-01

    Language reorganisation following stroke has been studied widely. However, while studies of brain activation and grey matter examined both hemispheres, studies of white matter changes have mostly focused on the left hemisphere. Here we examined the relationship between bilateral hemispheric white matter and aphasia symptoms. 15 chronic stroke patients with aphasia and 18 healthy adults were studied using Diffusion Weighted Imaging data. By applying histogram analysis, Tract-Based Spatial Statistics, tractography and lesion-tract overlap methods, it was found that damage to the left hemisphere in general, and to the arcuate fasciculus in particular, correlated with impairments on word repetition, object naming, sentence comprehension and homophone and rhyme judgement. However, no such relationship was found in the right hemisphere. It is suggested that while some language function in aphasia can be explained by damage to the left arcuate fasciculus, it cannot be explained by looking at the contra-lesional tract. PMID:26401977

  10. Variability of localization and intensity of damage of the white matter of the brain and cerebellum in genetically conditioned diseases.

    PubMed

    Ka?uza, J; Marsza?, E; Jamroz, E; Pietruszewski, J

    1999-01-01

    The investigations were based on 3 cases with Leigh, 5 cases with Krabbe's, 4 cases of Alpers, 2 cases with Sandhoff, 1 case with Alexander's disease and 1 case with metachromatic leukodystrophy. In 1 case included into the study we have diagnosed nonketotic hyperglycinemia II. All the diseases under examination are recognized as genetically conditioned or are supposed to be of genetic origin. Damage of the white matter in a more delineated form in certain regions was found in Leigh disease. The changes demonstrated a variable degree of intensity from demyelination to necrosis. More extensive lesions of white matter in gyri and semivoal centrum were found in diseases with simultaneously damaged gray matter e.g. in Alpers and Sandhoff disease. The most extensive changes of diffuse demyelination were found in Krabbe's and Alexander's disease. In these diseases demyelination was accompanied with specific morphological structures e.g. globoidal cells (Krabbe's disease) and Rosenthal fibers (Alexander's disease). The peculiar type of demyelination was characteristic for nonketotic hyperglycinemia of type II. It was expressed by demyelination with vacuolization. PMID:10705640

  11. Structural covariance of superficial white matter in mild Alzheimer's disease compared to normal aging

    PubMed Central

    Carmeli, Cristian; Fornari, Eleonora; Jalili, Mahdi; Meuli, Reto; Knyazeva, Maria G

    2014-01-01

    Introduction Interindividual variations in regional structural properties covary across the brain, thus forming networks that change as a result of aging and accompanying neurological conditions. The alterations of superficial white matter (SWM) in Alzheimer's disease (AD) are of special interest, since they follow the AD-specific pattern characterized by the strongest neurodegeneration of the medial temporal lobe and association cortices. Methods Here, we present an SWM network analysis in comparison with SWM topography based on the myelin content quantified with magnetization transfer ratio (MTR) for 39 areas in each hemisphere in 15 AD patients and 15 controls. The networks are represented by graphs, in which nodes correspond to the areas, and edges denote statistical associations between them. Results In both groups, the networks were characterized by asymmetrically distributed edges (predominantly in the left hemisphere). The AD-related differences were also leftward. The edges lost due to AD tended to connect nodes in the temporal lobe to other lobes or nodes within or between the latter lobes. The newly gained edges were mostly confined to the temporal and paralimbic regions, which manifest demyelination of SWM already in mild AD. Conclusion This pattern suggests that the AD pathological process coordinates SWM demyelination in the temporal and paralimbic regions, but not elsewhere. A comparison of the MTR maps with MTR-based networks shows that although, in general, the changes in network architecture in AD recapitulate the topography of (de)myelination, some aspects of structural covariance (including the interhemispheric asymmetry of networks) have no immediate reflection in the myelination pattern. PMID:25328848

  12. White Matter and Cognitive Changes in Veterans Diagnosed with Alcoholism and PTSD

    PubMed Central

    Maksimovskiy, Arkadiy L; McGlinchey, Regina E; Fortier, Catherine B; Salat, David H; Milberg, William P; Oscar-Berman, Marlene

    2014-01-01

    Alcoholism frequently occurs in returning U.S. Veterans, and is often comorbid with Post Traumatic Stress Disorder (PTSD). The goal of this study was to investigate the relationship between white matter changes and neuropsychological alterations in Operation Enduring Freedom, and/or Operation Iraqi Freedom (OEF/OIF) alcoholic Veterans with two primary aims: (1) to examine the relationship of alcoholism to brain structure and function while controlling for the potential effects of comorbid PTSD, and (2) to examine whether the effects of alcoholism are moderated by the quantity of lifetime alcohol consumption. Our sample consisted of 71 deployed OEF/OIF Veterans stratified into four groups: alcoholics without PTSD, alcoholics with PTSD, participants with PTSD without comorbid alcoholism, and control participants without alcoholism or PTSD. Participants were given an extensive neuropsychological and psychiatric assessment battery, as well as Magnetic Resonance Diffusion Tensor Imaging (DT-MRI) scans. Results showed that disruption of executive functioning, and abnormal fractional anisotropy (FA; a measure of axonal integrity) within the frontal subcortical and dorsolateral frontal-parietal regions, occurred independently of the effects of PTSD. Furthermore, these cognitive and neuronal alterations were unique to the most severe subgroup of alcoholics who consumed the greatest amount of alcohol over the course of their lifetime, as compared to the rest of the sample. Axonal integrity within this subgroup, in regions underlying the frontal subcortical area, was shown to be decreased independently of cognitive changes. Integrity of axons underlying the dorsolateral frontal-parietal region, however, was increased. We hypothesized that this is a compensatory mechanism for executive dysfunction. PMID:24855633

  13. Quantitative approaches for assessment of white matter hyperintensities in elderly populations

    PubMed Central

    Brickman, Adam M.; Sneed, Joel R.; Provenzano, Frank A.; Garcon, Ernst; Johnert, Lauren; Muraskin, Jordan; Yeung, Lok-Kin; Zimmerman, Molly E.; Roose, Steven P.

    2011-01-01

    White matter hyperintensities (WMH) are areas of increased signal on T2-weighted magnetic resonance imaging (MRI), including fluid attenuated inverse recovery sequences. Total and regional WMH burden (i.e., volume or severity) has been associated with myriad cognitive, neurological, and psychiatric conditions among older adults. In the current report, we illustrate two approaches to quantify periventricular, deep, and total WMH and examine their reliability and criterion validity among 28 elderly patients enrolled in a depression treatment trial. The first approach, an operator-driven quantitative approach, involves visual inspection of individual MRI scans and manual labeling using a three-step series of procedures. The second approach, a fully automated quantitative approach, uses a processing stream that involves image segmentation, voxel intensity thresholding, and seed growing to label WMH and calculate their volume automatically. There was good agreement in WMH quantification between the two approaches (Cronbach’s alpha values from 0.835 to 0.968). Further, severity of WMH was significantly associated with worse depression and increased age, and these associations did not differ significantly between the two quantification approaches. We provide evidence for good reliability and criterion validity for two approaches for WMH volume determination. The operator-driven approach may be better suited for smaller studies with highly trained raters, whereas the fully automated quantitative approach may be more appropriate for larger, high-throughput studies. PMID:21680159

  14. Indirect association of DAT1 genotype with executive function through white matter volume in orbitofrontal cortex.

    PubMed

    Chung, Tammy; Ferrell, Robert; Clark, Duncan B

    2015-04-30

    The dopamine transporter (DAT1) gene has been associated with impulsivity and executive functioning. Further, DAT1 has been associated with brain structural characteristics and resting state connectivity. This study tested an indirect effect model in which DAT1 genotype (9-repeat (9R) carriers vs 10-repeat (10R) homozygotes) is linked to phenotypes representing impulsivity and executive function (planning behavior) through effects on white matter (WM) volumes in prefrontal cortex (PFC), particularly orbitofrontal cortex (OFC). Adolescents (ages 14-18, n=38) were recruited from substance use treatment (n=22) and the community (n=16) to increase phenotype variation. Results indicated that DAT1 10/10 genotype was associated with lower WM volume in the PFC, specifically the left OFC. Further, lower WM volume in the left OFC predicted more difficulties in self-reported planning behavior, but not impulsivity. Indirect effect analysis indicated that lower WM volume in the left OFC mediated the association between DAT1 10/10 genotype and difficulties in planning behavior. Results suggest a brain structural mechanism, involving lower WM volume in the left OFC, as a link in the association between DAT1 genotype and a specific aspect of executive function. Genetic effects on regional WM volume that are linked to behavioral outcomes could ultimately inform the development of tailored interventions that address an individual?s unique risk factors. PMID:25704259

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

    PubMed

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

    2015-12-01

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

  16. Physical Activity and Cardiorespiratory Fitness Are Beneficial for White Matter in Low-Fit Older Adults

    PubMed Central

    Burzynska, Agnieszka Zofia; Chaddock-Heyman, Laura; Voss, Michelle W.; Wong, Chelsea N.; Gothe, Neha P.; Olson, Erin A.; Knecht, Anya; Lewis, Andrew; Monti, Jim M.; Cooke, Gillian E.; Wojcicki, Thomas R.; Fanning, Jason; Chung, Hyondo David; Awick, Elisabeth; McAuley, Edward; Kramer, Arthur F.

    2014-01-01

    Physical activity (PA) and cardiorespiratory fitness (CRF) are associated with better cognitive function in late life, but the neural correlates for these relationships are unclear. To study these correlates, we examined the association of both PA and CRF with measures of white matter (WM) integrity in 88 healthy low-fit adults (age 60–78). Using accelerometry, we objectively measured sedentary behavior, light PA, and moderate to vigorous PA (MV-PA) over a week. We showed that greater MV-PA was related to lower volume of WM lesions. The association between PA and WM microstructural integrity (measured with diffusion tensor imaging) was region-specific: light PA was related to temporal WM, while sedentary behavior was associated with lower integrity in the parahippocampal WM. Our findings highlight that engaging in PA of various intensity in parallel with avoiding sedentariness are important in maintaining WM health in older age, supporting public health recommendations that emphasize the importance of active lifestyle. PMID:25229455

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

    PubMed Central

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

    2015-01-01

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

  18. Cerebellar White Matter Abnormalities following Primary Blast Injury in US Military Personnel

    PubMed Central

    Mac Donald, Christine; Johnson, Ann; Cooper, Dana; Malone, Thomas; Sorrell, James; Shimony, Joshua; Parsons, Matthew; Snyder, Abraham; Raichle, Marcus; Fang, Raymond; Flaherty, Stephen; Russell, Michael; Brody, David L.

    2013-01-01

    Little is known about the effects of blast exposure on the human brain in the absence of head impact. Clinical reports, experimental animal studies, and computational modeling of blast exposure have suggested effects on the cerebellum and brainstem. In US military personnel with isolated, primary blast-related ‘mild’ traumatic brain injury and no other known insult, we found diffusion tensor MRI abnormalities consistent with cerebellar white matter injury in 3 of 4 subjects. No abnormalities in other brain regions were detected. These findings add to the evidence supporting the hypothesis that primary blast exposure contributes to brain injury in the absence of head impact and that the cerebellum may be particularly vulnerable. However, the clinical effects of these abnormalities cannot be determined with certainty; none of the subjects had ataxia or other detected evidence of cerebellar dysfunction. The details of the blast events themselves cannot be disclosed at this time, thus additional animal and computational modeling will be required to dissect the mechanisms underlying primary blast-related traumatic brain injury. Furthermore, the effects of possible subconcussive impacts and other military-related exposures cannot be determined from the data presented. Thus many aspects of topic will require further investigation. PMID:23409052

  19. Knowledge-based Automated Reconstruction of Human Brain White Matter Tracts Using a Path-Finding Approach with Dynamic Programming

    PubMed Central

    Li, Muwei; Ratnanather, J Tilak; Miller, Michael I.; Mori, Susumu

    2013-01-01

    It has been shown that the anatomy of major white matter tracts can be delineated using diffusion tensor imaging (DTI) data. Tract reconstruction, however, often suffers from a large number of false-negative results when a simple line propagation algorithm is used. This limits the application of this technique to only the core of prominent white matter tracts. By employing probabilistic path-generation algorithms, connectivity between a larger number of anatomical regions can be studied, but an increase in the number of false-positive results is inevitable. One of the causes of the inaccuracy is the complex axonal anatomy within a voxel; however, high-angular resolution (HAR) methods have been proposed to ameliorate this limitation. However, HAR data are relatively rare due to the long scan times required and the low signal-to-noise ratio. In this study, we tested a probabilistic path-finding method in which two anatomical regions with known connectivity were pre-defined and a path that maximized agreement with the DTI data was searched. To increase the accuracy of the trajectories, knowledge-based anatomical constraints were applied. The reconstruction protocols were tested using DTI data from 19 normal subjects to examine test-retest reproducibility and cross-subject variability. Fifty-two tracts were found to be reliably reconstructed using this approach, which can be viewed on our website. PMID:24135166

  20. Individual differences in regional prefrontal gray matter morphometry and fractional anisotropy are associated with different constructs of executive function.

    PubMed

    Smolker, H R; Depue, B E; Reineberg, A E; Orr, J M; Banich, M T

    2015-05-01

    Although the relationship between structural differences within the prefrontal cortex (PFC) and executive function (EF) has been widely explored in cognitively impaired populations, little is known about this relationship in healthy young adults. Using optimized voxel-based morphometry (VBM), surface-based morphometry (SBM), and fractional anisotropy (FA) we determined the association between regional PFC grey matter (GM) morphometry and white matter tract diffusivity with performance on tasks that tap different aspects of EF as drawn from Miyake et al.'s three-factor model of EF. Reductions in both GM volume (VBM) and cortical folding (SBM) in the ventromedial PFC (vmPFC), ventrolateral PFC (vlPFC), and dorsolateral PFC (dlPFC) predicted better common EF, shifting-specific, and updating-specific performance, respectively. Despite capturing different components of GM morphometry, voxel- and surface-based findings were highly related, exhibiting regionally overlapping relationships with EF. Increased white matter FA in fiber tracts that connect the vmPFC and vlPFC with posterior regions of the brain also predicted better common EF and shifting-specific performance, respectively. These results suggest that the neural mechanisms supporting distinct aspects of EF may differentially rely on distinct regions of the PFC, and at least in healthy young adults, are influenced by regional morphometry of the PFC and the FA of major white matter tracts that connect the PFC with posterior cortical and subcortical regions. PMID:24562372

  1. Diffusion kurtosis imaging probes cortical alterations and white matter pathology following cuprizone induced demyelination and spontaneous remyelination.

    PubMed

    Guglielmetti, C; Veraart, J; Roelant, E; Mai, Z; Daans, J; Van Audekerke, J; Naeyaert, M; Vanhoutte, G; Delgado Y Palacios, R; Praet, J; Fieremans, E; Ponsaerts, P; Sijbers, J; Van der Linden, A; Verhoye, M

    2016-01-15

    Although MRI is the gold standard for the diagnosis and monitoring of multiple sclerosis (MS), current conventional MRI techniques often fail to detect cortical alterations and provide little information about gliosis, axonal damage and myelin status of lesioned areas. Diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) provide sensitive and complementary measures of the neural tissue microstructure. Additionally, specific white matter tract integrity (WMTI) metrics modelling the diffusion in white matter were recently derived. In the current study we used the well-characterized cuprizone mouse model of central nervous system demyelination to assess the temporal evolution of diffusion tensor (DT), diffusion kurtosis tensor (DK) and WMTI-derived metrics following acute inflammatory demyelination and spontaneous remyelination. While DT-derived metrics were unable to detect cuprizone induced cortical alterations, the mean kurtosis (MK) and radial kurtosis (RK) were found decreased under cuprizone administration, as compared to age-matched controls, in both the motor and somatosensory cortices. The MK remained decreased in the motor cortices at the end of the recovery period, reflecting long lasting impairment of myelination. In white matter, DT, DK and WMTI-derived metrics enabled the detection of cuprizone induced changes differentially according to the stage and the severity of the lesion. More specifically, the MK, the RK and the axonal water fraction (AWF) were the most sensitive for the detection of cuprizone induced changes in the genu of the corpus callosum, a region less affected by cuprizone administration. Additionally, microgliosis was associated with an increase of MK and RK during the acute inflammatory demyelination phase. In regions undergoing severe demyelination, namely the body and splenium of the corpus callosum, DT-derived metrics, notably the mean diffusion (MD) and radial diffusion (RD), were among the best discriminators between cuprizone and control groups, hence highlighting their ability to detect both acute and long lasting changes. Interestingly, WMTI-derived metrics showed the aptitude to distinguish between the different stages of the disease. Both the intra-axonal diffusivity (Da) and the AWF were found to be decreased in the cuprizone treated group, Da specifically decreased during the acute inflammatory demyelinating phase whereas the AWF decrease was associated to the spontaneous remyelination and the recovery period. Altogether our results demonstrate that DKI is sensitive to alterations of cortical areas and provides, along with WMTI metrics, information that is complementary to DT-derived metrics for the characterization of demyelination in both white and grey matter and subsequent inflammatory processes associated with a demyelinating event. PMID:26525654

  2. Liquid metal feeding through dendritic region in Ni-Hard white iron

    SciTech Connect

    Oryshchyn, Danylo B.; Dogan, Omer N.

    2005-01-01

    Liquid permeability in the dendritic regions is one of the factors that determine porosity formation and macro segregation in castings. Permeability in the dendritic structure of Ni-Hard white iron was measured as a function of temperature. Effect of microstructural coarsening on the permeability was also investigated. Permeability increased with coarsening dendritic structure in Ni-Hard white iron.

  3. White matter changes in dementia: role of impaired drainage of interstitial fluid.

    PubMed

    Weller, Roy O; Hawkes, Cheryl A; Kalaria, Raj N; Werring, David J; Carare, Roxana O

    2015-01-01

    White matter abnormalities on magnetic resonance imaging (MRI) are associated with dementia and include white matter hyperintensities (WMH; also termed leukoaraiosis) and visible perivascular spaces (PVS). We review the potential role of impaired drainage of interstitial fluid in the pathogenesis of WMH and PVS. Whereas the volume of extracellular space in the grey matter is tightly controlled, fluid accumulates and expands the extracellular spaces of the white matter in acute hydrocephalus, vasogenic edema and WMH. Although there are no conventional lymphatic vessels in the brain, there is very effective lymphatic drainage for fluid and solutes along restricted pathways in the basement membranes of cerebral capillaries and arteries in young individuals. Lymphatic drainage of the brain is impaired with age and in association with apolipoprotein E ?4, risk factors for Alzheimer's disease and cerebral amyloid angiopathy (CAA). Deposition of proteins in the lymphatic drainage pathways in the walls of cerebral arteries with age is recognized as protein elimination failure angiopathy (PEFA), as in CAA and cerebral autosomal dominant arteriopathy and leukoencephalopathy (CADASIL). Facilitating perivascular lymphatic drainage from the aging brain may play a significant role in the prevention of CAA, WMH and Alzheimer's disease and may enhance the efficacy of immunotherapy for Alzheimer's disease. PMID:25521178

  4. Parameter comparison of white matter diffusion tensor imaging (DTI) in rhesus macaques (Macaca mulatta).

    PubMed

    Mo, Yin; Chao, Fang; Song, Ming; Liu, Ci-Rong; Liu, Hui-Lang; Qian, Xi-Ying; Zhao, Xu-Dong

    2014-05-01

    In this study, we analyzed diffusion tensor imaging (DTI) results of brain white matter in rhesus macaques (Macaca mulatta) with four different parameter settings and found that the sequence A (b=1 000 s/mm(2), spatial resolution=1.25 mm×1.25 mm× 1.25 mm, numbers of direction=33, NSA=3) and B (b=800 s/mm(2), spatial resolution=1.25 mm×1.25 mm×1.25 mm, numbers of direction=33, NSA=3) could accurately track coarse fibers. The fractional anisotropy (FA) derived from sequence C (b=1 000s/mm(2), spatial resolution=0.55 mm×0.55 mm×2.5 mm, direction number=33, NSA=3) was too fuzzy to be used in tracking white matter fibers. By comparison, the high resolution and the FA with high contrast of gray matter and white matter derived from sequence D (b=800 s/mm(2), spatial resolution=1.0 mm×1.0 mm ×1.0 mm, numbers of direction=33, NSA=3) qualified in its application in tracking both thick and thin fibers, making it an optimal DTI setting for rhesus macaques. PMID:24866488

  5. Probabilistic atlases of default mode, executive control and salience network white matter tracts: an fMRI-guided diffusion tensor imaging and tractography study

    PubMed Central

    Figley, Teresa D.; Bhullar, Navdeep; Courtney, Susan M.; Figley, Chase R.

    2015-01-01

    Diffusion tensor imaging (DTI) is a powerful MRI technique that can be used to estimate both the microstructural integrity and the trajectories of white matter pathways throughout the central nervous system. This fiber tracking (aka, “tractography”) approach is often carried out using anatomically-defined seed points to identify white matter tracts that pass through one or more structures, but can also be performed using functionally-defined regions of interest (ROIs) that have been determined using functional MRI (fMRI) or other methods. In this study, we performed fMRI-guided DTI tractography between all of the previously defined nodes within each of six common resting-state brain networks, including the: dorsal Default Mode Network (dDMN), ventral Default Mode Network (vDMN), left Executive Control Network (lECN), right Executive Control Network (rECN), anterior Salience Network (aSN), and posterior Salience Network (pSN). By normalizing the data from 32 healthy control subjects to a standard template—using high-dimensional, non-linear warping methods—we were able to create probabilistic white matter atlases for each tract in stereotaxic coordinates. By investigating all 198 ROI-to-ROI combinations within the aforementioned resting-state networks (for a total of 6336 independent DTI tractography analyses), the resulting probabilistic atlases represent a comprehensive cohort of functionally-defined white matter regions that can be used in future brain imaging studies to: (1) ascribe DTI or other white matter changes to particular functional brain networks, and (2) compliment resting state fMRI or other functional connectivity analyses. PMID:26578930

  6. White-matter pathways for speech and language processing.

    PubMed

    Friederici, Angela D

    2015-01-01

    The language-relevant brain regions, Brodmann's area in the inferior frontal cortex and Wernicke's area in the superior temporal cortex, are connected via long-range fiber bundles, which are located dorsally and ventrally to the sylvian fissure. These dorsal and ventral pathways consist of a number of partly parallel-running fiber tracts, which can be differentiated by their termination regions and by the particular language functions of these termination regions. Dorsally, there are two major fiber tracts connecting the posterior temporal cortex with the frontal cortex: one terminating in the premotor cortex that subserves sensory-to-motor mapping and one terminating in posterior Broca's area, the pars opercularis, that supports the processing of complex syntactic structures. Ventrally, two language-related fiber tracts are discussed: one connects the inferior frontal cortex, i.e., the pars triangularis and orbitalis, with Wernicke's area and supports semantic processes and another one connects the most ventral portions of the inferior frontal cortex, including the frontal operculum, with the anterior temporal cortex. This latter ventral tract is suggested to subserve elementary combinatorial processes in language. Together these fiber tracts guarantee the transmission of information between different brain regions within the neural language network. PMID:25726269

  7. DTI Study of Cerebral Normal-Appearing White Matter in Hereditary Neuropathy With Liability to Pressure Palsies (HNPP).

    PubMed

    Wang, Wei-Wei; Song, Chun-Li; Huang, Liang; Song, Qing-Wei; Liang, Zhan-Hua; Wei, Qiang; Hu, Jia-Ni; Miao, Yan-Wei; Wu, Bing; Xie, Lizhi

    2015-10-01

    The majority of previous studies on hereditary neuropathy with liability to pressure palsies (HNPP) were focused on peripheral nerves, whereas cerebral alterations in HNPP have been less attended to. In this work, Diffusion tensor imaging (DTI) was used to detect the changes in WM, especially in the normal-appearing white matter (NAWM) in HNPP patients for its sensitivity in probing the microstructure of WM, the sensitive metric was searched for probing cerebral alterations and the regional distribution of cerebral abnormalities was identified. Twelve HNPP patients and 12 age- and gender-matched healthy controls underwent the conventional MRI, DTI scan, and electrophysiological examination. The conventional MRI images were first analyzed to identify abnormal intense regions and the NAWM regions. NAWM refers to the white matter regions that do not include the lesions on conventional MRI. The apparent diffusion coefficient and fractional anisotropy (FA) values of the NAWM were then measured and compared between patient and control groups. The sensitivity and specificity of 3 methods and the cerebral regional distribution of MR signal abnormalities were further analyzed. Hyperintense foci were observed on T2 weighted image and fluid attenuated inversion recovery images in 6 patients. Compared to the controls, FA values of the patients were significantly lower in bilateral frontal, orbitofrontal, and temporal NAWMs; whereas the electrophysiological examination results of patients and controls exhibited no statistically significant difference. The sensitivity of FA value was higher than that of electrophysiological examination and conventional MRI. The majority of abnormal signals on conventional MRI images and abnormal FA values were located in the frontal and temporal lobes. The results of our study show cerebral WM changes in HNPP patients. FA value in DTI has been shown to be sensitive to the cerebral microstructural changes in HNPP. The frontal lobe is the predilection site that is most involved in HNPP. PMID:26512614

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

    PubMed

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

    2015-10-01

    Lifespan is a dynamic process with remarkable changes in brain structure and function. Previous neuroimaging studies have indicated age-related microstructural changes in specific white matter tracts during development and aging. However, the age-related alterations in the topological architecture of the white matter structural connectome across the human lifespan remain largely unknown. Here, a cohort of 113 healthy individuals (ages 9-85) with both diffusion and structural MRI acquisitions were examined. For each participant, the high-resolution white matter structural networks were constructed by deterministic fiber tractography among 1024 parcellation units and were quantified with graph theoretical analyses. The global network properties, including network strength, cost, topological efficiency, and robustness, followed an inverted U-shaped trajectory with a peak age around the third decade. The brain areas with the most significantly nonlinear changes were located in the prefrontal and temporal cortices. Different brain regions exhibited heterogeneous trajectories: the posterior cingulate and lateral temporal cortices displayed prolonged maturation/degeneration compared with the prefrontal cortices. Rich-club organization was evident across the lifespan, whereas hub integration decreased linearly with age, especially accompanied by the loss of frontal hubs and their connections. Additionally, age-related changes in structural connections were predominantly located within and between the prefrontal and temporal modules. Finally, based on the graph metrics of structural connectome, accurate predictions of individual age were obtained (r?=?0.77). Together, the data indicated a dynamic topological organization of the brain structural connectome across human lifespan, which may provide possible structural substrates underlying functional and cognitive changes with age. PMID:26173024

  9. White Matter Fractional Anisotropy Correlates With Speed of Processing and Motor Speed in Young Childhood Cancer Survivors

    SciTech Connect

    Aukema, Eline J.; Oudhuis, Nienke; Vos, Frans M.; Reneman, Liesbeth; Last, Bob F.; Grootenhuis, Martha A.

    2009-07-01

    Purpose: To determine whether childhood medulloblastoma and acute lymphoblastic leukemia (ALL) survivors have decreased white matter fractional anisotropy (WMFA) and whether WMFA is related to the speed of processing and motor speed. Methods and Materials: For this study, 17 patients (6 medulloblastoma, 5 ALL treated with high-dose methotrexate (MTX) (4 x 5 g/m{sup 2}) and 6 with low-dose MTX (3 x 2 g/m{sup 2})) and 17 age-matched controls participated. On a 3.0-T magnetic resonance imaging (MRI) scanner, diffusion tensor imaging (DTI) was performed, and WMFA values were calculated, including specific regions of interest (ROIs), and correlated with the speed of processing and motor speed. Results: Mean WMFA in the patient group, mean age 14 years (range 8.9 - 16.9), was decreased compared with the control group (p = 0.01), as well as WMFA in the right inferior fronto-occipital fasciliculus (IFO) (p = 0.03) and in the genu of the corpus callosum (gCC) (p = 0.01). Based on neurocognitive results, significant positive correlations were present between processing speed and WMFA in the splenium (sCC) (r = 0.53, p = 0.03) and the body of the corpus callosum (bCC) (r = 0.52, p = 0.03), whereas the right IFO WMFA was related to motor speed (r = 0.49, p < 0.05). Conclusions: White matter tracts, using a 3.0-T MRI scanner, show impairment in childhood cancer survivors, medulloblastoma survivors, and also those treated with high doses of MTX. In particular, white matter tracts in the sCC, bCC and right IFO are positively correlated with speed of processing and motor speed.

  10. 75 FR 20812 - Proposed Information Collection; Comment Request; Northwest Region Pacific Whiting Shoreside...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-21

    ... From the Federal Register Online via the Government Printing Office DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration Proposed Information Collection; Comment Request; Northwest Region Pacific Whiting Shoreside Fishery Monitoring and Catch Accounting Program AGENCY: National...

  11. 75 FR 20812 - Proposed Information Collection; Comment Request; Northwest Region Pacific Whiting Shoreside...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-21

    ... Region Pacific Whiting Shoreside Fishery Monitoring and Catch Accounting Program AGENCY: National Oceanic... part of its fishery management responsibilities, NOAA's National Marine Fisheries Service collects..., Management Analyst, Office of the Chief Information Officer. BILLING CODE 3510-22-P...

  12. Abnormal Organization of White Matter Network in Patients with No Dementia after Ischemic Stroke

    PubMed Central

    Shi, Lin; Wang, Defeng; Chu, Winnie C. W.; Liu, Shangping; Xiong, Yunyun; Wang, Yilong; Wang, Yongjun; Wong, Lawrence K. S.; Mok, Vincent C. T.

    2013-01-01

    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 help in understanding the mechanism of cognitive impairment and functional compensation occurred in patients with chronic stroke. PMID:24349063

  13. Decomposition of brain diffusion imaging data uncovers latent schizophrenias with distinct patterns of white matter anisotropy.

    PubMed

    Arnedo, Javier; Mamah, Daniel; Baranger, David A; Harms, Michael P; Barch, Deanna M; Svrakic, Dragan M; de Erausquin, Gabriel A; Cloninger, C Robert; Zwir, Igor

    2015-10-15

    Fractional anisotropy (FA) analysis of diffusion tensor-images (DTI) has yielded inconsistent abnormalities in schizophrenia (SZ). Inconsistencies may arise from averaging heterogeneous groups of patients. Here we investigate whether SZ is a heterogeneous group of disorders distinguished by distinct patterns of FA reductions. We developed a Generalized Factorization Method (GFM) to identify biclusters (i.e., subsets of subjects associated with a subset of particular characteristics, such as low FA in specific regions). GFM appropriately assembles a collection of unsupervised techniques with Non-negative Matrix Factorization to generate biclusters, rather than averaging across all subjects and all their characteristics. DTI tract-based spatial statistics images, which output is the locally maximal FA projected onto the group white matter skeleton, were analyzed in 47 SZ and 36 healthy subjects, identifying 8 biclusters. The mean FA of the voxels of each bicluster was significantly different from those of other SZ subjects or 36 healthy controls. The eight biclusters were organized into four more general patterns of low FA in specific regions: 1) genu of corpus callosum (GCC), 2) fornix (FX)+external capsule (EC), 3) splenium of CC (SCC)+retrolenticular limb (RLIC)+posterior limb (PLIC) of the internal capsule, and 4) anterior limb of the internal capsule. These patterns were significantly associated with particular clinical features: Pattern 1 (GCC) with bizarre behavior, pattern 2 (FX+EC) with prominent delusions, and pattern 3 (SCC+RLIC+PLIC) with negative symptoms including disorganized speech. The uncovered patterns suggest that SZ is a heterogeneous group of disorders that can be distinguished by different patterns of FA reductions associated with distinct clinical features. PMID:26151103

  14. Whiteness.

    PubMed

    Altman, Neil

    2006-01-01

    This paper seeks to make meaning of the experience of being white in the United States at this point in history. The self-awareness of white people is limited by a blind spot around the meaning and impact of being white in a multiracial society. Using psychoanalytic and literary methodology, the author seeks to cast light with which to explore this blind spot. Everyday experiences are used to illustrate the widely pervasive impact of race in the lives of white people, and a clinical vignette illustrates how race might show up in a white-on-white psychotherapy. Enactments within this paper are noted when they are evident to the author PMID:16482960

  15. Secure attachment status is associated with white matter integrity in healthy young adults.

    PubMed

    Serra, Mauro; De Pisapia, Nicola; Rigo, Paola; Papinutto, Nico; Jager, Justin; Bornstein, Marc H; Venuti, Paola

    2015-12-16

    The present study investigates associations between security of attachment in the mother-child relationship and patterns of brain connectivity in young adults. We hypothesized that secure attachment would relate to more efficient connectivity in white matter association fibers due to increased myelination. Attachment security was measured in 53 young adults using the Kerns Security Scale; anatomical information was acquired using diffusion tensor imaging. Higher fractional anisotropy, an index of directionality of diffusion, related to security of attachment in four left-hemisphere white matter association fibers (uncinate fasciculus, cingulum, superior longitudinal fasciculus, and inferior fronto-occipital fasciculus). As expected, this result was mainly ascribable to increased myelination, which has been independently associated with attachment security. Security of attachment may have an identifiable biological basis. Our research demonstrates the feasibility of coupling neuroimaging tools with clinical investigation. PMID:26559724

  16. White matter abnormalities in an adult patient with l-2-hydroxyglutaric aciduria.

    PubMed

    Yamamoto, Toshiyuki; Yoshioka, Seiichiro; Tsurusaki, Yoshinori; Shino, Shimada; Shimojima, Keiko; Shigematsu, Yosuke; Takeuchi, Yoshihiro; Matsumoto, Naomichi

    2016-01-01

    l-2-Hydroxyglutaric aciduria (l-2-HGA) is a rare inborn error of metabolism. Mainly, patients with this disorder exhibit neurological symptoms and characteristic neuroradiological findings, such as subcortical white matter abnormalities, which are believed to be caused by the toxicity of the accumulation of l-2-hydroxyglutaric acid. A genotype-first approach of the whole exome sequence was used to identify compound heterozygous mutations, c.584A>G (p.Y195C) and c.772T>C (p.C258R), in L2HGDH, the gene responsible for this disorder, in an adult patient with intellectual disability and intractable epilepsy. A retrospective assay confirmed the increased concentrations of 2-hydroxyglutaric acid in the urine. These results suggested that neuroradiological findings of subcortical white matter abnormalities are characteristic of l-2-HGA and that clinical exome sequencing has sufficient power to compensate for insufficient clinical evaluations. PMID:25982940

  17. Pharmacological Effects of Erythropoietin and its Derivative Carbamyl erythropoietin in Cerebral White Matter Injury

    NASA Astrophysics Data System (ADS)

    Liu, Wei

    Periventricular leukomalacia (PVL) is the predominant form of brain injury in the premature infant and the most common cause of cerebral palsy, yet no therapy currently exists for this serious human disorder. As PVL often occurs in preterm infants suffering from cerebral hypoxia/ischemia with or without prior exposure to maternal-fetal infection/inflammation, we used hypoxia/ischemia with or without lipopolysaccharide (LPS) injection, to produce clinically relevant PVL-like lesions in the white matter in postnatal day six (P6) mice. We studied the white matter pathology under different conditions, such as different durations of hypoxia and different doses of LPS, to evaluate the effects of those etiological factors on neonatal white matter injury. Distinct related pathological events were investigated at different time points during the progression of PVL. We used immunohistochemistry, histological analysis, and electron microscopy (EM) to study demylination that occurs in the white matter area, which is consistent with the pathology of human PVL. Previous studies have shown that erythropoietin (EPO) and its derivative carbamylated EPO (CEPO) are neuroprotective in various experimental models of brain injury. However, none of these studies investigated their efficacy against white matter injury using appropriate animal models of PVL. We produced unilateral or bilateral white matter injury in P6 mice using unilateral carotid ligation (UCL) followed by hypoxia (6% oxygen, 35 min) or by UCL/hypoxia plus LPS injection, respectively. We administered a single intraperitoneal (i.p.) dose of EPO or CEPO (5000 IU/kg) immediately after the insult, and found both drugs to provide significant protection against white matter injury in PVL mice compared to vehicle-treated groups. In addition, EPO and CEPO treatments attenuated neurobehavioral dysfunctions in an acute manner after PVL injury. EPO and CEPO have relatively few adverse effects, and thus may be a therapeutic agent with translational potential for PVL, which is the primary injury underlying cerebral palsy. After confirming the neuroprotective effects of EPO and CEPO on PVL mice, we continued to study the mechanisms relating to their functions. As we learned from our lab's previous study, microglia play an important role in the pathogenesis of PVL, linking multiple effectors downstream of hypoxia-ischemia and inflammation. We found that EPO and CEPO inhibit microglial activation and reduced the severity of injury. Furthermore, we found that EPO and CEPO decreased the activity of poly (ADP-ribose) polymerase-1 (PARP-1) in activated microglia. PARP-1 activity increases in response to many insults, such as infection, ischemia and toxicity. Therefore, we hypothesized that EPO and CEPO decrease microglial activation by inhibiting PARP-1 activity, and thus leading to protection against inflammation and cell death. Besides pharmacological studies of EPO and CEPO on PVL, we also investigated other endogenous factors that may affect neonatal white matter injury. Heat shock proteins (HSPs) are important chaperones that facilitate appropriate protein folding and modification. HSP60, a chaperonin located in the mitochondria, is one of these important molecules that promote appropriate protein folding. HSP60 expression levels increased significantly in the brains of PVL mice compared with control animals. In microglial cell culture, we found that after LPS treatment, HSP60 expression levels increased both inside microglial cells and in the extracellular medium. In addition, we noted enhanced HSP60 immunoreactivity in the brains of PVL mice, which localized inside activated microglial cells and extracellularly. The rise in HSP60 activity after hypoxia-ischemia and LPS administration implies that it potentially functions as one of the triggers of microglial activation and central nervous system inflammation.

  18. Depression in small-vessel disease relates to white matter ultrastructural damage, not disability

    PubMed Central

    Herbert, Vanessa; Lawrence, Andrew J.; Morris, Robin G.; Markus, Hugh S.

    2014-01-01

    Objective: To determine whether cerebral small-vessel disease (SVD) is a specific risk factor for depression, whether any association is mediated via white matter damage, and to study the role of depressive symptoms and disability on quality of life (QoL) in this patient group. Methods: Using path analyses in cross-sectional data, we modeled the relationships among depression, disability, and QoL in patients with SVD presenting with radiologically confirmed lacunar stroke (n = 100), and replicated results in a second SVD cohort (n = 100). We then compared the same model in a non-SVD stroke cohort (n = 50) and healthy older adults (n = 203). In a further study, to determine the role of white matter damage in mediating the association with depression, a subgroup of patients with SVD (n = 101) underwent diffusion tensor imaging (DTI). Results: Reduced QoL was associated with depression in patients with SVD, but this association was not mediated by disability or cognition; very similar results were found in the replication SVD cohort. In contrast, the non-SVD stroke group and the healthy older adult group showed a direct relationship between disability and depression. The DTI study showed that fractional anisotropy, a marker of white matter damage, was related to depressive symptoms in patients with SVD. Conclusion: These results suggest that in stroke patients without SVD, disability is an important causal factor for depression, whereas in SVD stroke, other factors specific to this stroke subtype have a causal role. White matter damage detected on DTI is one factor that mediates the association between SVD and depression. PMID:25230999

  19. Inflammation and white matter degeneration persist for years after a single traumatic brain injury

    PubMed Central

    Johnson, Victoria E.; Stewart, Janice E.; Begbie, Finn D.; Trojanowski, John Q.; Smith, Douglas H.

    2013-01-01

    A single traumatic brain injury is associated with an increased risk of dementia and, in a proportion of patients surviving a year or more from injury, the development of hallmark Alzheimer’s disease-like pathologies. However, the pathological processes linking traumatic brain injury and neurodegenerative disease remain poorly understood. Growing evidence supports a role for neuroinflammation in the development of Alzheimer’s disease. In contrast, little is known about the neuroinflammatory response to brain injury and, in particular, its temporal dynamics and any potential role in neurodegeneration. Cases of traumatic brain injury with survivals ranging from 10 h to 47 years post injury (n = 52) and age-matched, uninjured control subjects (n = 44) were selected from the Glasgow Traumatic Brain Injury archive. From these, sections of the corpus callosum and adjacent parasaggital cortex were examined for microglial density and morphology, and for indices of white matter pathology and integrity. With survival of ?3 months from injury, cases with traumatic brain injury frequently displayed extensive, densely packed, reactive microglia (CR3/43- and/or CD68-immunoreactive), a pathology not seen in control subjects or acutely injured cases. Of particular note, these reactive microglia were present in 28% of cases with survival of >1 year and up to 18 years post-trauma. In cases displaying this inflammatory pathology, evidence of ongoing white matter degradation could also be observed. Moreover, there was a 25% reduction in the corpus callosum thickness with survival >1 year post-injury. These data present striking evidence of persistent inflammation and ongoing white matter degeneration for many years after just a single traumatic brain injury in humans. Future studies to determine whether inflammation occurs in response to or, conversely, promotes white matter degeneration will be important. These findings may provide parallels for studying neurodegenerative disease, with traumatic brain injury patients serving as a model for longitudinal investigations, in particular with a view to identifying potential therapeutic interventions. PMID:23365092

  20. Modeling of Anatomical Information in Clustering of White Matter Fiber Trajectories Using Dirichlet Distribution.

    PubMed

    Maddah, Mahnaz; Zöllei, Lilla; Grimson, W Eric L; Wells, William M

    2008-07-15

    In this work, we describe a white matter trajectory clustering algorithm that allows for incorporating and appropriately weighting anatomical information. The influence of the anatomical prior reflects confidence in its accuracy and relevance. It can either be defined by the user or it can be inferred automatically. After a detailed description of our novel clustering framework, we demonstrate its properties through a set of preliminary experiments. PMID:21625356

  1. Sleep duration is associated with white matter hyperintensity volume in older adults: the Northern Manhattan Study.

    PubMed

    Ramos, Alberto R; Dong, Chuanhui; Rundek, Tatjana; Elkind, Mitchell S V; Boden-Albala, Bernadette; Sacco, Ralph L; Wright, Clinton B

    2014-10-01

    Self-reports of long or short sleep durations have indicated an association with cardiovascular morbidity and mortality, but there are limited data evaluating their association with white matter hyperintensity volume (WMHV), a marker of cerebral small vessel disease. We conducted a cross-sectional analysis of self-reported sleep duration to test for a correlation with white matter hyperintensities, measured by quantitative magnetic resonance imaging (MRI), in the Northern Manhattan Study. We used multivariable linear regression models to assess associations between both short (<6 h) and long (?9 h) sleep durations and log-transformed WMHV, adjusting for demographic, behavioural and vascular risk factors. A total of 1244 participants, mean age 70 ± 9 years, 61% women and 68% Hispanics were analysed with magnetic resonance brain imaging and self-reported sleep duration. Short sleep was reported by 23% (n = 293) and long sleep by 10% (n = 121) of the sample. Long sleep (? = 0.178; P = 0.035), but not short sleep (? = -0.053; P = 0.357), was associated with greater log-WMHV in fully adjusted models. We observed an interaction between sleep duration, diabetes mellitus and log-WMHV (P = 0.07). In fully adjusted models, stratified analysis showed that long sleep duration was associated with greater WMHV only in those with diabetes (? = 0.78; P = 0.0314), but not in those without diabetes (? = 0.022; P = 0.2), whereas short sleep was not associated with white matter hyperintensities in those with or without diabetes. In conclusion, long sleep duration was associated with a greater burden of white matter lesions in this stroke-free urban sample. The association was seen mainly among those with diabetes mellitus. PMID:25040435

  2. Enhancement of the white matter following prophylactic therapy of the central nervous system for leukemia

    SciTech Connect

    Shalen, P.R.; Ostrow; P.T.; Glass, P.J.

    1981-08-01

    A case of fatal necrotizing leukoencephalopathy following prophylactic therapy of the central nervous system for acute lymphoblastic leukemia is reported. The clinical, CT, and neuropathological findings are described. The CT scan demonstrated symmetrical white-matter enhancement. Histological analysis was consistent with the effects of irradiation and methotrexate. The differential diagnosis of the clinical and CT findings is discussed. Brain biopsy is the diagnostic procedure of choice.

  3. Longitudinal Brain White Matter Alterations in Minimal Hepatic Encephalopathy before and after Liver Transplantation

    PubMed Central

    Lin, Wei-Che; Chou, Kun-Hsien; Chen, Chao-Long; Chen, Hsiu-Ling; Lu, Cheng-Hsien; Li, Shau-Hsuan; Huang, Chu-Chung; Lin, Ching-Po; Cheng, Yu-Fan

    2014-01-01

    Cerebral edema is the common pathogenic mechanism for cognitive impairment in minimal hepatic encephalopathy. Whether complete reversibility of brain edema, cognitive deficits, and their associated imaging can be achieved after liver transplantation remains an open question. To characterize white matter integrity before and after liver transplantation in patients with minimal hepatic encephalopathy, multiple diffusivity indices acquired via diffusion tensor imaging was applied. Twenty-eight patients and thirty age- and sex-matched healthy volunteers were included. Multiple diffusivity indices were obtained from diffusion tensor images, including mean diffusivity, fractional anisotropy, axial diffusivity and radial diffusivity. The assessment was repeated 6–12 month after transplantation. Differences in white matter integrity between groups, as well as longitudinal changes, were evaluated using tract-based spatial statistical analysis. Correlation analyses were performed to identify first scan before transplantation and interval changes among the neuropsychiatric tests, clinical laboratory tests, and diffusion tensor imaging indices. After transplantation, decreased water diffusivity without fractional anisotropy change indicating reversible cerebral edema was found in the left anterior cingulate, claustrum, postcentral gyrus, and right corpus callosum. However, a progressive decrease in fractional anisotropy and an increase in radial diffusivity suggesting demyelination were noted in temporal lobe. Improved pre-transplantation albumin levels and interval changes were associated with better recoveries of diffusion tensor imaging indices. Improvements in interval diffusion tensor imaging indices in the right postcentral gyrus were correlated with visuospatial function score correction. In conclusion, longitudinal voxel-wise analysis of multiple diffusion tensor imaging indices demonstrated different white matter changes in minimal hepatic encephalopathy patients. Transplantation improved extracellular cerebral edema and the results of associated cognition tests. However, white matter demyelination may advance in temporal lobe. PMID:25166619

  4. Reading Performance Correlates with White-Matter Properties in Preterm and Term Children

    ERIC Educational Resources Information Center

    Andrews, James S.; Ben-Shachar, Michal; Yeatman, Jason D.; Flom, Lynda L.; Luna, Beatriz; Feldman, Heidi M.

    2010-01-01

    Aim: We used diffusion tensor imaging to investigate the association between white-matter integrity and reading ability in a cohort of 28 children. Nineteen preterm children (14 males, five females; mean age 11y 11mo [SD 1y 10mo], mean gestational age 30.5wks (SD 3.2), mean birthweight was 1455g [SD 625]); and nine term children (five males, four…

  5. White matter integrity in alcohol-naive youth with a family history of alcohol use disorders

    PubMed Central

    Squeglia, L. M.; Jacobus, J.; Brumback, T.; Meloy, M. J.; Tapert, S. F.

    2014-01-01

    Background Understanding pre-existing neural vulnerabilities found in youth who are family history positive (FHP) for alcohol use disorders could help inform preventative interventions created to delay initiation age and escalation of heavy drinking. The goal of this study was to compare indices of white matter integrity using diffusion tensor imaging (DTI) between FHP and family history negative (FHN) youth using a sample of 94 alcohol-naive adolescents and to examine if differences were associated with global and domain-specific cognitive functioning. Method Participants were 48 FHP and 46 FHN demographically matched, healthy, substance-naive 12- to 14-year-olds (54% female) recruited from local middle schools. Participants completed a neuropsychological test battery and magnetic resonance imaging session, including DTI. Results FHP youth had higher fractional anisotropy and axial diffusivity, and lower radial and mean diffusivity, than FHN youth in 19 clusters spanning projection, association and interhemispheric white matter tracts. Findings were replicated after controlling for age, gender, socio-economic status, grade and pubertal development. Groups did not differ significantly on global or domain-specific neuropsychological test scores. Conclusions FHP teens showed higher white matter integrity, but similar cognitive functioning, to FHN youth. More mature neural features could be related to more precocious behaviors, such as substance use initiation, in FHP youth. Future research exploring white matter maturation before and after substance use initiation will help elucidate the neuro-developmental trajectories in youth at risk for substance use disorders, to inform preventive efforts and better understand the sequelae of adolescent alcohol and drug use. PMID:25066702

  6. Sleep Duration is Associated with White Matter Hyperintensity Volume in Older Adults: The Northern Manhattan Study

    PubMed Central

    Ramos, Alberto R.; Dong, Chuanhui; Rundek, Tatjana; Elkind, Mitchell S.V.; Boden-Albala, Bernadette; Sacco, Ralph L.; Wright, Clinton B.

    2014-01-01

    Summary Self-reports of long or short sleep durations have indicated an association with cardiovascular morbidity and mortality, but there are limited data evaluating their association with white matter hyperintensity volume (WMHV), a marker of cerebral small vessel disease. We conducted a cross-sectional analysis of self-reported sleep duration to test for a correlation with white matter hyperintensities, measured by quantitative MRI in the Northern Manhattan Study. We used multivariable linear regression models to assess associations between both short (< 6 hours) and long (? 9 hours) sleep durations and log-transformed WMHV, adjusting for demographic, behavioral and vascular risk factors. A total of 1244 participants, mean age 70 ± 9 years, 61% women and 68% Hispanics were analyzed with magnetic resonance brain imaging and self-reported sleep duration. Short sleep was reported by 23% (n = 293), and long sleep by 10% (n=121) of the sample. Long sleep (? = 0.178; p = 0.035), but not short sleep (? = ?0.053; p = 0.357), was associated with greater log-WMHV in fully adjusted models. We observed an interaction between sleep duration, diabetes mellitus, and log-WMHV (p = 0.07). In fully adjusted models, stratified analysis showed that long sleep duration was associated with greater WMHV only in those with diabetes (? = 0.78; p = 0.0314), but not in non-diabetics (? = 0.022; p = 0.2), whereas short sleep was not associated with white matter hyperintensities in those with diabetes or non-diabetics. In conclusion, long sleep duration was associated with a greater burden of white matter lesions in this stroke-free urban sample. The association was mainly seen among those with diabetes mellitus. PMID:25040435

  7. Reduced subventricular zone proliferation and white matter damage in juvenile ferrets with kaolin-induced hydrocephalus.

    PubMed

    Di Curzio, Domenico L; Buist, Richard J; Del Bigio, Marc R

    2013-10-01

    Hydrocephalus is a neurological condition characterized by altered cerebrospinal fluid (CSF) flow with enlargement of ventricular cavities in the brain. A reliable model of hydrocephalus in gyrencephalic mammals is necessary to test preclinical hypotheses. Our objective was to characterize the behavioral, structural, and histological changes in juvenile ferrets following induction of hydrocephalus. Fourteen-day old ferrets were given an injection of kaolin (aluminum silicate) into the cisterna magna. Two days later and repeated weekly until 56 days of age, magnetic resonance (MR) imaging was used to assess ventricle size. Behavior was examined thrice weekly. Compared to age-matched saline-injected controls, severely hydrocephalic ferrets weighed significantly less, their postures were impaired, and they were hyperactive prior to extreme debilitation. They developed significant ventriculomegaly and displayed white matter destruction. Reactive astroglia and microglia detected by glial fibrillary acidic protein (GFAP) and Iba-1 immunostaining were apparent in white matter, cortex, and hippocampus. There was a hydrocephalus-related increase in activated caspase 3 labeling of apoptotic cells (7.0 vs. 15.5%) and a reduction in Ki67 labeling of proliferating cells (23.3 vs. 5.9%) in the subventricular zone (SVZ). Reduced Olig2 immunolabeling suggests a depletion of glial precursors. GFAP content was elevated. Myelin basic protein (MBP) quantitation and myelin biochemical enzyme activity showed early maturational increases. Where white matter was not destroyed, the remaining axons developed myelin similar to the controls. In conclusion, the hydrocephalus-induced periventricular disturbances may involve developmental impairments in cell proliferation and glial precursor cell populations. The ferret should prove useful for testing hypotheses about white matter damage and protection in the immature hydrocephalic brain. PMID:23769908

  8. 40 CFR 52.227 - Control strategy and regulations: Particulate matter, Metropolitan Los Angeles Intrastate Region.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...regulations: Particulate matter, Metropolitan Los Angeles Intrastate Region. 52.227...regulations: Particulate matter, Metropolitan Los Angeles Intrastate Region. (a...for particulate matter in the Metropolitan Los Angeles Intrastate Region....

  9. 40 CFR 52.227 - Control strategy and regulations: Particulate matter, Metropolitan Los Angeles Intrastate Region.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...regulations: Particulate matter, Metropolitan Los Angeles Intrastate Region. 52.227...regulations: Particulate matter, Metropolitan Los Angeles Intrastate Region. (a...for particulate matter in the Metropolitan Los Angeles Intrastate Region....

  10. 40 CFR 52.228 - Regulations: Particulate matter, Southeast Desert Intrastate Region.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...Regulations: Particulate matter, Southeast Desert Intrastate Region. 52.228 Section...Regulations: Particulate matter, Southeast Desert Intrastate Region. (a) The following...for particulate matter in the Southeast Desert Intrastate Region. (1) Imperial...

  11. 40 CFR 52.228 - Regulations: Particulate matter, Southeast Desert Intrastate Region.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...Regulations: Particulate matter, Southeast Desert Intrastate Region. 52.228 Section...Regulations: Particulate matter, Southeast Desert Intrastate Region. (a) The following...for particulate matter in the Southeast Desert Intrastate Region. (1) Imperial...

  12. 40 CFR 52.228 - Regulations: Particulate matter, Southeast Desert Intrastate Region.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...Regulations: Particulate matter, Southeast Desert Intrastate Region. 52.228 Section...Regulations: Particulate matter, Southeast Desert Intrastate Region. (a) The following...for particulate matter in the Southeast Desert Intrastate Region. (1) Imperial...

  13. 40 CFR 52.228 - Regulations: Particulate matter, Southeast Desert Intrastate Region.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...Regulations: Particulate matter, Southeast Desert Intrastate Region. 52.228 Section...Regulations: Particulate matter, Southeast Desert Intrastate Region. (a) The following...for particulate matter in the Southeast Desert Intrastate Region. (1) Imperial...

  14. 40 CFR 52.228 - Regulations: Particulate matter, Southeast Desert Intrastate Region.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...Regulations: Particulate matter, Southeast Desert Intrastate Region. 52.228 Section...Regulations: Particulate matter, Southeast Desert Intrastate Region. (a) The following...for particulate matter in the Southeast Desert Intrastate Region. (1) Imperial...

  15. White matter microstructure in schizophrenia: effects of disorder, duration and medication

    PubMed Central

    Kanaan, Richard; Barker, Gareth; Brammer, Michael; Giampietro, Vincent; Shergill, Sukhwinder; Woolley, James; Picchioni, Marco; Toulopoulou, Timothea; McGuire, Philip

    2009-01-01

    Background Diffusion tensor magnetic resonance imaging studies in schizophrenia to date have been largely inconsistent. This may reflect variation in methodology, and the use of small samples with differing illness duration and medication exposure. Aims To determine the extent and location of white matter microstructural changes in schizophrenia, using optimised diffusion tensor imaging in a large patient sample, and to consider the effects of illness duration and medication exposure. Method Scans from 76 patients with schizophrenia and 76 matched controls were used to compare fractional anisotropy, a measure of white matter microstructural integrity, between the groups. Results We found widespread clusters of reduced fractional anisotropy in patients, affecting most major white matter tracts. These reductions did not correlate with illness duration, and there was no difference between age-matched chronically and briefly medicated patients. Conclusions The finding of widespread fractional anisotropy reductions in our larger sample of patients with schizophrenia may explain some of the inconsistent findings of previous, smaller studies. PMID:19252154

  16. Glioma follow white matter tracts: a multiscale DTI-based model.

    PubMed

    Engwer, Christian; Hillen, Thomas; Knappitsch, Markus; Surulescu, Christina

    2015-09-01

    Gliomas are a class of rarely curable tumors arising from abnormal glia cells in the human brain. The understanding of glioma spreading patterns is essential for both radiological therapy as well as surgical treatment. Diffusion tensor imaging (DTI) allows to infer the white matter fibre structure of the brain in a noninvasive way. Painter and Hillen (J Theor Biol 323:25-39, 2013) used a kinetic partial differential equation to include DTI data into a class of anisotropic diffusion models for glioma spread. Here we extend this model to explicitly include adhesion mechanisms between glioma cells and the extracellular matrix components which are associated to white matter tracts. The mathematical modelling follows the multiscale approach proposed by Kelkel and Surulescu (Math Models Methods Appl Sci 23(3), 2012). We use scaling arguments to deduce a macroscopic advection-diffusion model for this process. The tumor diffusion tensor and the tumor drift velocity depend on both, the directions of the white matter tracts as well as the binding dynamics of the adhesion molecules. The advanced computational platform DUNE enables us to accurately solve our macroscopic model. It turns out that the inclusion of cell binding dynamics on the microlevel is an important factor to explain finger-like spread of glioma. PMID:25212910

  17. Virtual in vivo interactive dissection of white matter fasciculi in the human brain.

    PubMed

    Catani, Marco; Howard, Robert J; Pajevic, Sinisa; Jones, Derek K

    2002-09-01

    This work reports the use of diffusion tensor magnetic resonance tractography to visualize the three-dimensional (3D) structure of the major white matter fasciculi within living human brain. Specifically, we applied this technique to visualize in vivo (i) the superior longitudinal (arcuate) fasciculus, (ii) the inferior longitudinal fasciculus, (iii) the superior fronto-occipital (subcallosal) fasciculus, (iv) the inferior frontooccipital fasciculus, (v) the uncinate fasciculus, (vi) the cingulum, (vii) the anterior commissure, (viii) the corpus callosum, (ix) the internal capsule, and (x) the fornix. These fasciculi were first isolated and were then interactively displayed as a 3D-rendered object. The virtual tract maps obtained in vivo using this approach were faithful to the classical descriptions of white matter anatomy that have previously been documented in postmortem studies. Since we have been able to interactively delineate and visualize white matter fasciculi over their entire length in vivo, in a manner that has only previously been possible by histological means, "virtual in vivo interactive dissection" (VIVID) adds a new dimension to anatomical descriptions of the living human brain. PMID:12482069

  18. Differential diagnosis of white matter diseases in the tropics: An overview

    PubMed Central

    Pandit, Lekha

    2009-01-01

    In hospitals in the tropics, the availability of magnetic resonance imaging (MRI) facilities in urban areas and especially in teaching institutions have resulted in white matter diseases being frequently reported in a variety of clinical settings. Unlike the west where multiple sclerosis (MS) is the commonest white matter disease encountered, in the tropics, there are myriad causes for the same. Infectious and post infectious disorders probably account for the vast majority of these diseases. Human immunodeficiency virus (HIV) infection tops the list of infective conditions. Central nervous system (CNS) tuberculosis occasionally presents with patchy parenchymal lesions unaccompanied by meningeal involvement. Human T cell leukemia virus (HTLV) infection and cystic inflammatory lesions such as neurocysticercosis are important causes to be considered in the differential diagnosis. Diagnosing post infectious demyelinating disorders is equally challenging since more than a third of cases seen in the tropics do not present with history of past infection or vaccinations. Metabolic and deficiency disorders such as Wernicke's encephalopathy, osmotic demyelinating syndrome associated with extra pontine lesions and Vitamin B12 deficiency states can occassionaly cause confusion in diagnosis. This review considers a few important disorders which manifest with white matter changes on MRI and create diagnostic difficulties in a population in the tropics. PMID:20151003

  19. Increased HLA-E expression in white matter lesions in multiple sclerosis.

    PubMed

    Durrenberger, Pascal F; Webb, Louise V; Sim, Malcolm J W; Nicholas, Richard S; Altmann, Daniel M; Boyton, Rosemary J

    2012-12-01

    The molecular mechanisms underpinning central nervous system damage in multiple sclerosis (MS) are complex and it is widely accepted that there is an autoimmune component. Both adaptive and innate immune effector mechanisms are believed to contribute to tissue disease aetiology. HLA-E is a non-classical MHC class Ib molecule that acts as the ligand for the NKG2A inhibitory receptor present on natural killer (NK) and CD8+ cells. Peptide binding and stabilization of HLA-E is often considered to signal infection or cell stress. Here we examine the up-regulation of HLA-E in MS brain tissue. Expression is significantly increased in white matter lesions in the brain of MS patients compared with white matter of neurologically healthy controls. Furthermore, using quantitative immunohistochemistry and confocal microscopy, we show increased HLA-E protein expression in endothelial cells of active MS lesions. Non-inflammatory chronic lesions express significantly less HLA-E protein, comparable to levels found in white matter from controls. Increased HLA-E protein levels were associated with higher scores of inflammation. These results suggest the potential for an effect in central nervous system pathogenesis from HLA-E modulation in stressed tissue. Co-localization with infiltrating CD8+ cells implicates a possible role for HLA-E-restricted regulatory CD8+ cells, as has been proposed in other autoimmune diseases. PMID:23039207

  20. White matter abnormalities and impaired attention abilities in children born very preterm.

    PubMed

    Murray, Andrea L; Thompson, Deanne K; Pascoe, Leona; Leemans, Alexander; Inder, Terrie E; Doyle, Lex W; Anderson, Jacqueline F I; Anderson, Peter J

    2016-01-01

    While attention impairments are commonly observed in very preterm (<32weeks' gestational age) children, neuroanatomical correlates of these difficulties are unclear. We aimed to determine whether the microstructural organization of key white matter tracts thought to be involved in attention (cingulum bundle, superior longitudinal fasciculi, reticular activating system, and corpus callosum) were altered in very preterm children compared with term-born controls. We also aimed to determine whether alterations in microstructural organization of these tracts were associated with attention functioning in very preterm children. One hundred and forty-nine very preterm children and 36 term-born controls underwent neuroimaging and assessment of their attention abilities at 7years. Constrained spherical deconvolution and probabilistic tractography was used to identify the key white matter tracts. Altered microstructural organization and reduced tract volume within reticular activating system and corpus callosum were found in the very preterm group compared with the control group. Diffusion and volume changes in the cingulum bundle, superior longitudinal fasciculi, reticular activating system, and corpus callosum were related to variations in attention functioning in the very preterm children. These findings emphasize that white matter tract integrity is associated with later attentional abilities in very preterm children. PMID:26318524

  1. Age-associated white matter lesions: the MRC Cognitive Function and Ageing Study.

    PubMed

    Wharton, Stephen B; Simpson, Julie E; Brayne, Carol; Ince, Paul G

    2015-01-01

    Cerebral white matter lesions (WML) are common in the aging brain and are associated with dementia and depression. They are associated with vascular risk factors and small vessel disease, suggesting an ischemic origin, but recent pathology studies suggest a more complex pathogenesis. Studies using samples from the population-representative Medical Research Council Cognitive Function and Ageing Study neuropathology cohort used post-mortem magnetic resonance imaging to identify WML for further study. Expression of hypoxia-related molecules and other injury and protective cellular pathways in candidate immunohistochemical and gene expression microarray studies support a role for hypoxia/ischemia. However, these approaches also suggest that immune activation, blood-brain barrier dysfunction, altered cell metabolic pathways and glial cell injury contribute to pathogenesis. These abnormalities are not confined to WML, but are also found in apparently normal white matter in brains with lesions, suggesting a field effect of white matter abnormality within which lesions arise. WML are an active pathology with a complex pathogenesis that may potentially offer a number of primary and secondary intervention targets. PMID:25521175

  2. Altered white matter connectivity in never-medicated patients with schizophrenia.

    PubMed

    Mandl, René C W; Rais, Monica; van Baal, Gertrudis Caroline M; van Haren, Neeltje E M; Cahn, Wiepke; Kahn, René S; Hulshoff Pol, Hilleke E

    2013-09-01

    Numerous diffusion tensor imaging (DTI) studies have implicated white matter brain tissue abnormalities in schizophrenia. However, the vast majority of these studies included patient populations that use antipsychotic medication. Previous research showed that medication intake can affect brain morphology and the question therefore arises to what extent the reported white matter aberrations can be attributed to the disease rather than to the use of medication. In this study we included 16 medication-naïve patients with schizophrenia and compared them to 23 healthy controls to exclude antipsychotic medication use as a confounding factor. For each subject DTI scans and magnetization transfer imaging (MTI) scans were acquired. A new tract-based analysis was used that combines fractional anisoptropy (FA), mean diffusivity (MD) and magnetization transfer ratio (MTR) to examine group differences in 12 major white matter fiber bundles. Significant group differences in combined FA, MD, MTR values were found for the right uncinate fasciculus and the left arcuate fasciculus. Additional analysis revealed that the largest part of both tracts showed an increase in MTR in combination with an increase in MD for patients with schizophrenia. We interpret these group-related differences as disease-related axonal or glial aberrations that cannot be attributed to antipsychotic medication use. PMID:22461372

  3. Lessons from a Mouse Model Characterizing Features of Vascular Cognitive Impairment with White Matter Changes

    PubMed Central

    Ihara, Masafumi; Tomimoto, Hidekazu

    2011-01-01

    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. PMID:22132331

  4. Linking White and Grey Matter in Schizophrenia: Oligodendrocyte and Neuron Pathology in the Prefrontal Cortex

    PubMed Central

    Höistad, Malin; Segal, Devorah; Takahashi, Nagahide; Sakurai, Takeshi; Buxbaum, Joseph D.; Hof, Patrick R.

    2009-01-01

    Neuronal circuitry relies to a large extent on the presence of functional myelin produced in the brain by oligodendrocytes. Schizophrenia has been proposed to arise partly from altered brain connectivity. Brain imaging and neuropathologic studies have revealed changes in white matter and reduction in myelin content in patients with schizophrenia. In particular, alterations in the directionality and alignment of axons have been documented in schizophrenia. Moreover, the expression levels of several myelin-related genes are decreased in postmortem brains obtained from patients with schizophrenia. These findings have led to the formulation of the oligodendrocyte/myelin dysfunction hypothesis of schizophrenia. In this review, we present a brief overview of the neuropathologic findings obtained on white matter and oligodendrocyte status observed in schizophrenia patients, and relate these changes to the processes of brain maturation and myelination. We also review recent data on oligodendrocyte/myelin genes, and present some recent mouse models of myelin deficiencies. The use of transgenic and mutant animal models offers a unique opportunity to analyze oligodendrocyte and neuronal changes that may have a clinical impact. Lastly, we present some recent morphological findings supporting possible causal involvement of white and grey matter abnormalities, in the aim of determining the morphologic characteristics of the circuits whose alteration leads to the cortical dysfunction that possibly underlies the pathogenesis of schizophrenia. PMID:19636386

  5. Robust and efficient linear registration of white-matter fascicles in the space of streamlines.

    PubMed

    Garyfallidis, Eleftherios; Ocegueda, Omar; Wassermann, Demian; Descoteaux, Maxime

    2015-08-15

    The neuroscientific community today is very much interested in analyzing specific white matter bundles like the arcuate fasciculus, the corticospinal tract, or the recently discovered Aslant tract to study sex differences, lateralization and many other connectivity applications. For this reason, experts spend time manually segmenting these fascicles and bundles using streamlines obtained from diffusion MRI tractography. However, to date, there are very few computational tools available to register these fascicles directly so that they can be analyzed and their differences quantified across populations. In this paper, we introduce a novel, robust and efficient framework to align bundles of streamlines directly in the space of streamlines. We call this framework Streamline-based Linear Registration. We first show that this method can be used successfully to align individual bundles as well as whole brain streamlines. Additionally, if used as a piecewise linear registration across many bundles, we show that our novel method systematically provides higher overlap (Jaccard indices) than state-of-the-art nonlinear image-based registration in the white matter. We also show how our novel method can be used to create bundle-specific atlases in a straightforward manner and we give an example of a probabilistic atlas construction of the optic radiation. In summary, Streamline-based Linear Registration provides a solid registration framework for creating new methods to study the white matter and perform group-level tractometry analysis. PMID:25987367

  6. DTI Tractography and White Matter Fiber Tract Characteristics in Euthymic Bipolar I Patients and Healthy Control Subjects

    PubMed Central

    Irimia, Andrei; Leow, Alex D.; Bartzokis, George; Moody, Teena D.; Jennings, Robin G.; Alger, Jeffry R.; Van Horn, John Darrell; Altshuler, Lori L.

    2012-01-01

    With the introduction of diffusion tensor imaging (DTI), structural differences in white matter (WM) architecture between psychiatric populations and healthy controls can be systematically observed and measured. In particular, DTI-tractography can be used to assess WM characteristics over the entire extent of WM tracts and aggregated fiber bundles. Using 64-direction DTI scanning in 27 participants with bipolar disorder (BD) and 26 age-and-gender-matched healthy control subjects, we compared relative length, density, and fractional anisotrophy (FA) of WM tracts involved in emotion regulation or theorized to be important neural components in BD neuropathology. We interactively isolated 22 known white matter tracts using region-of-interest placement (TrackVis software program) and then computed relative tract length, density, and integrity. BD subjects demonstrated significantly shorter WM tracts in the genu, body and splenium of the corpus callosum compared to healthy controls. Additionally, bipolar subjects exhibited reduced fiber density in the genu and body of the corpus callosum, and in the inferior longitudinal fasciculus bilaterally. In the left uncinate fasciculus, however, BD subjects exhibited significantly greater fiber density than healthy controls. There were no significant differences between groups in WM tract FA for those tracts that began and ended in the brain. The significance of differences in tract length and fiber density in BD is discussed. PMID:23070746

  7. 48 echo T2 myelin imaging of white matter in first-episode schizophrenia: Evidence for aberrant myelination

    PubMed Central

    Lang, Donna J.M.; Yip, Eugene; MacKay, Alexander L.; Thornton, Allen E.; Vila-Rodriguez, Fidel; MacEwan, G. William; Kopala, Lili C.; Smith, Geoffrey N.; Laule, Cornelia; MacRae, Cassie B.; Honer, William G.

    2014-01-01

    Myelin water imaging provides a novel strategy to assess myelin integrity and corresponding clinical relationships in psychosis, of particular relevance in frontal white matter regions. In the current study, T2 myelin water imaging was used to assess the myelin water fraction (MWF) signal from frontal areas in a sample of 58 individuals experiencing first-episode psychosis (FEP) and 44 healthy volunteers. No differences in frontal MWF were observed between FEP subjects and healthy volunteers; however, differences in normal patterns of associations between frontal MWF and age, education and IQ were seen. Significant positive relationships between frontal MWF and age, North American Adult Reading Test (NAART) IQ, and years of completed education were observed in healthy volunteers. In contrast, only the relationship between frontal MWF and NAART IQ was significant after Bonferroni correction in the FEP group. Additionally, significant positive relationships between age and MWF in the anterior and posterior internal capsules, the genu, and the splenium were observed in healthy volunteers. In FEP subjects, only the relationship between age and MWF in the splenium was statistically significant. Frontal MWF was not associated with local white matter volume. Altered patterns of association between age, years of education, and MWF in FEP suggest that subtle disturbances in myelination may be present early in the course of psychosis. PMID:25379454

  8. Differentiating therapy-induced leukoencephalopathy from unmyelinated white matter in children treated for acute lymphoblastic leukemia (ALL)

    NASA Astrophysics Data System (ADS)

    Reddick, Wilburn E.; Glass, John O.; Pui, Ching-Hon

    2003-05-01

    Reliably detecting subtle therapy-induced leukoencephalopathy in children treated for cancer is a challenging task due to its nearly identical MR properties and location with unmyelinated white matter. T1, T2, PD, and FLAIR images were collected for 44 children aged 1.7-18.7 (median 5.9) years near the start of therapy for ALL. The ICBM atlas and corresponding apriori maps were spatially normalized to each patient and resliced using SPM99 software. A combined imaging set consisting of MR images and WM, GM and CSF apriori maps were then analyzed with a Kohonen Self-Organizing Map. Vectors from hyperintense regions were compared to normal appearing genu vectors from the same patient. Analysis of the distributions of the differences, calculated on T2 and FLAIR images, revealed two distinct groups. The first large group, assumed normal unmyelinated white matter, consisted of 37 patients with changes in FLAIR ranging from 80 to 147 (mean 117-/+17) and T2 ranging from 92 to 217 (mean 144-/+28). The second group, assumed leukoencephalopathy, consisted of seven patients with changes in FLAIR ranging from 154 to 196 (mean 171-/+19) and T2 ranging from 190 to 287 (mean 216-/+33). A threshold was established for both FLAIR (change > 150) and T2 (change > 180).

  9. Vulnerability of white matter structure and function to chronic cerebral hypoperfusion and the effects of pharmacological modulation 

    E-print Network

    McQueen, Jamie

    2014-06-28

    The structural integrity of the white matter is required for neuronal communication within the brain which is essential for normal cognitive function. Post-mortem and clinical imaging studies of elderly individuals have ...

  10. Absence of white matter changes on magnetic resonance imaging in children treated with CNS prophylaxis therapy for leukemia

    SciTech Connect

    Kramer, J.H.; Norman, D.; Brant-Zawadzki, M.; Ablin, A.; Moore, I.M.

    1988-03-01

    Previous studies have shown that magnetic resonance imaging (MRI) is sensitive to white matter changes in children receiving cranial radiation of 3000 cGy or greater. The current study used MRI to investigate the integrity of white matter in children receiving 1800 to 2400 cGy of cranial radiation. Ten survivors of acute lymphoblastic leukemia (ALL) who received intrathecal methotrexate (MTX) and either 1800 or 2400 cGy of cranial radiation were studied with MRI and neuropsychologic testing. Magnetic resonance (MR) scans were normal in nine of ten patients. One patient had prominent and asymmetrical lateral ventricles and mildly enlarged cortical sulci. White matter tracts were normal in appearance. However, seven of nine children had below average intellectual functioning. Results indicate that children receiving less than 2500 cGy of cranial radiation fail to show white matter changes on MRI, despite evidence of cognitive impairment.

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

    PubMed Central

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

    2014-01-01

    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. PMID:25186429

  12. Maximum Principal Strain and Strain Rate Associated with Concussion Diagnosis Correlates with Changes in Corpus Callosum White Matter Indices

    PubMed Central

    MCALLISTER, THOMAS W.; FORD, JAMES C.; JI, SONGBAI; BECKWITH, JONATHAN G.; FLASHMAN, LAURA A.; PAULSEN, KEITH; GREENWALD, RICHARD M.

    2014-01-01

    On-field monitoring of head impacts, combined with finite element (FE) biomechanical simulation, allow for predictions of regional strain associated with a diagnosed concussion. However, attempts to correlate these predictions with in vivo measures of brain injury have not been published. This article reports an approach to and preliminary results from the correlation of subject-specific FE model-predicted regions of high strain associated with diagnosed concussion and diffusion tensor imaging to assess changes in white matter integrity in the corpus callosum (CC). Ten football and ice hockey players who wore instrumented helmets to record head impacts sustained during play completed high field magnetic resonance imaging preseason and within 10 days of a diagnosed concussion. The Dartmouth Subject-Specific FE Head model was used to generate regional predictions of strain and strain rate following each impact associated with concussion. Maps of change in fractional anisotropy (FA) and median diffusivity (MD) were generated for the CC of each athlete to correlate strain with change in FA and MD. Mean and maximum strain rate correlated with change in FA (Spearman ? = 0.77, p = 0.01; 0.70, p = 0.031), and there was a similar trend for mean and maximum strain (0.56, p = 0.10; 0.6, p = 0.07), as well as for maximum strain with change in MD (?0.63, p = 0.07). Change in MD correlated with injury-to-imaging interval (? = ?0.80, p = 0.006) but change in FA did not (? = 0.18, p = 0.62). These results provide preliminary confirmation that model-predicted strain and strain rate in the CC correlate with changes in indices of white matter integrity. PMID:21994062

  13. White Matter Hyperintensity in Ischemic Stroke Patients: It May Regress Over Time

    PubMed Central

    Kim, Hyeong-Ryul; Kim, Woojun; Yang, Dong Won

    2015-01-01

    Background and Purpose White matter hyperintensities (WMH) are frequently observed on MRI in ischemic stroke patients as well as in normal elderly individuals. Besides the progression of WMH, the regression of WMH has been rarely reported. Thus, we aimed to investigate how WMH change over time in patients with ischemic stroke, particularly focusing on regression. Methods We enrolled ischemic stroke patients who underwent brain MRI more than twice with at least a 6 month time-interval. Based on T2-weighted or FLAIR MRI, WMH were visually assessed, followed by semiautomatic volume measurement. Progression or regression of WMH change was defined when 0.25 cc increase or decrease was observed and it was also combined with visible change. A statistical analysis was performed on the pattern of WMH change over time and factors associated with change. Results A total of 100 patients were enrolled. Their age (mean±SD) was 67.5±11.8 years and 63 were male. The imaging time-interval (mean) was 28.0 months. WMH progressed in 27, regressed in 9 and progressed in distinctive regions and regressed in others in 5 patients. A multiple logistic regression model showed that age (odds ratio[OR] 2.51, 90% confidence interval[CI] 1.056-5.958), male gender (OR 2.957, 95% CI 1.051-9.037), large vessel disease (OR 1.955, 95% CI 1.171-3.366), and renal dysfunction (OR 2.900, 90% CI 1.045-8.046) were associated with progression. Regarding regression, no significant factor was found in the multivariate analysis. Conclusions In 21.5% of ischemic stroke patients, regression of WMH was observed. WMH progression was observed in a third of ischemic stroke patients. PMID:25692108

  14. Principal eigenvector field segmentation for reproducible diffusion tensor tractography of white matter structures.

    PubMed

    Rathore, Ram K S; Gupta, Rakesh K; Agarwal, Shruti; Trivedi, Richa; Tripathi, Rajendra P; Awasthi, Rishi

    2011-10-01

    The study was aimed to test the feasibility of utilizing an algorithmically determinable stable fiber mass (SFM) map obtained by an unsupervised principal eigenvector field segmentation (PEVFS) for automatic delineation of 18 white matter (WM) tracts: (1) corpus callosum (CC), (2) tapetum (TP), (3) inferior longitudinal fasciculus (ILF), (4) uncinate fasciculus (UNC), (5) inferior fronto-occipital fasciculus (IFO), (6) optic pathways (OP), (7) superior longitudinal fasciculus (SLF), (8) arcuate fasciculus (AF), (9) fornix (FX), (10) cingulum (CG), (11) anterior thalamic radiation (ATR), (12) superior thalamic radiation (STR), (13) posterior thalamic radiation (PTR), (14) corticospinal/corticopontine tract (CST/CPT), (15) medial lemniscus (ML), (16) superior cerebellar peduncle (SCP), (17) middle cerebellar peduncle (MCP) and (18) inferior cerebellar peduncle (ICP). Diffusion tensor imaging (DTI)-derived fractional anisotropy (FA) and the principal eigenvector field have been used to create the SFM consisting of a collection of linear voxel structures which are grouped together by color-coding them into seven natural classes to provide PEVFS signature segments which greatly facilitate the selection of regions of interest (ROIs) for fiber tractography using just a single mouse click, as compared with a manual drawing of ROIs in the classical approach. All the 18 fiber bundles have been successfully reconstructed, in all the subjects, using the single ROIs provided by the SFM approach, with their reproducibility characterized by the fact that the ROI selection is user independent. The essentially automatic PEVFS method is robust, efficient and compares favorably with the classical ROI methods for diffusion tensor tractography (DTT). PMID:21664783

  15. Genome-wide association studies of cerebral white matter lesion burden: the CHARGE Consortium

    PubMed Central

    Fornage, Myriam; Debette, Stephanie; Bis, Joshua C.; Schmidt, Helena; Ikram, M. Arfan; Dufouil, Carole; Sigurdsson, Sigurdur; Lumley, Thomas; DeStefano, Anita L.; Fazekas, Franz; Vrooman, Henri A.; Shibata, Dean K.; Maillard, Pauline; Zijdenbos, Alex; Smith, Albert V.; Gudnason, Haukur; de Boer, Renske; Cushman, Mary; Mazoyer, Bernard; Heiss, Gerardo; Vernooij, Meike W.; Enzinger, Christian; Glazer, Nicole L.; Beiser, Alexa; Knopman, David S.; Cavalieri, Margherita; Niessen, Wiro J.; Harris, Tamara B.; Petrovic, Katja; Lopez, Oscar L.; Au, Rhoda; Lambert, Jean-Charles; Hofman, Albert; Gottesman, Rebecca F.; Garcia, Melissa; Heckbert, Susan R.; Atwood, Larry D.; Catellier, Diane J.; Uitterlinden, Andre G.; Yang, Qiong; Smith, Nicholas L.; Aspelund, Thor; Romero, Jose R.; Rice, Kenneth; Taylor, Kent D.; Nalls, Michael A.; Rotter, Jerome I.; Sharret, Richey; van Duijn, Cornelia M.; Amouyel, Philippe; Wolf, Philip A.; Gudnason, Vilmundur; van der Lugt, Aad; Boerwinkle, Eric; Psaty, Bruce M.; Seshadri, Sudha; Tzourio, Christophe; Breteler, Monique M.B.; Mosley, Thomas H.; Schmidt, Reinhold; Longstreth, W.T.; DeCarli, Charles; Launer, Lenore J.

    2011-01-01

    Objective White matter hyperintensities (WMH) detectable by magnetic resonance imaging (MRI)are part of the spectrum of vascular injury associated with aging of the brain and are thought to reflect ischemic damage to the small deep cerebral vessels. WMH are associated with an increased risk of cognitive and motor dysfunction, dementia, depression, and stroke. Despite a significant heritability, few genetic loci influencing WMH burden have been identified. Methods We performed a meta-analysis of genome-wide association studies (GWAS) for WMH burden in 9,361 stroke-free individuals of European descent from 7 community-based cohorts. Significant findings were tested for replication in 3,024 individuals from 2 additional cohorts. Results We identified 6 novel risk-associated single nucleotide polymorphisms (SNPs)in one locus on chromosome 17q25 encompassing 6 known genes including WBP2, TRIM65, TRIM47, MRPL38, FBF1, and ACOX1. The most significant association was for rs3744028 (Pdiscovery= 4.0×10?9; Preplication =1.3×10?7; Pcombined =4.0×10?15). Other SNPs in this region also reaching genome-wide significance are rs9894383 (P=5.3×10?9), rs11869977 (P=5.7×10?9), rs936393 (P=6.8×10?9), rs3744017 (P=7.3×10?9), and rs1055129 (P=4.1×10?8). Variant alleles at these loci conferred a small increase in WMH burden (4–8% of the overall mean WMH burden in the sample). Interpretation This large GWAS of WMH burden in community-based cohorts of individuals of European descent identifies a novel locus on chromosome 17. Further characterization of this locus may provide novel insights into the pathogenesis of cerebral WMH. PMID:21681796

  16. White matter lesion segmentation using machine learning and weakly labeled MR images

    NASA Astrophysics Data System (ADS)

    Xie, Yuchen; Tao, Xiaodong

    2011-03-01

    We propose a fast, learning-based algorithm for segmenting white matter (WM) lesions for magnetic resonance (MR) brain images. The inputs to the algorithm are T1, T2, and FLAIR images. Unlike most of the previously reported learning-based algorithms, which treat expert labeled lesion map as ground truth in the training step, the proposed algorithm only requires the user to provide a few regions of interest (ROI's) containing lesions. An unsupervised clustering algorithm is applied to segment these ROI's into areas. Based on the assumption that lesion voxels have higher intensity on FLAIR image, areas corresponding to lesions are identified and their probability distributions in T1, T2, and FLAIR images are computed. The lesion segmentation in 3D is done by using the probability distributions to generate a confidence map of lesion and applying a graph based segmentation algorithm to label lesion voxels. The initial lesion label is used to further refine the probability distribution estimation for the final lesion segmentation. The advantages of the proposed algorithm are: 1. By using the weak labels, we reduced the dependency of the segmentation performance on the expert discrimination of lesion voxels in the training samples; 2. The training can be done using labels generated by users with only general knowledge of brain anatomy and image characteristics of WM lesion, instead of these carefully labeled by experienced radiologists; 3. The algorithm is fast enough to make interactive segmentation possible. We test the algorithm on nine ACCORD-MIND MRI datasets. Experimental results show that our algorithm agrees well with expert labels and outperforms a support vector machine based WM lesion segmentation algorithm.

  17. The relationship between carotid artery plaque stability and white matter ischemic injury

    PubMed Central

    Berman, Sara E.; Wang, Xiao; Mitchell, Carol C.; Kundu, Bornali; Jackson, Daren C.; Wilbrand, Stephanie M.; Varghese, Tomy; Hermann, Bruce P.; Rowley, Howard A.; Johnson, Sterling C.; Dempsey, Robert J.

    2015-01-01

    Higher local carotid artery strain has previously been shown to be a characteristic of unstable carotid plaques. These plaques may be characterized by microvascular changes that predispose to intraplaque hemorrhage, increasing the likelihood of embolization. Little is known however, about how these strain indices correspond with imaging markers of brain health and metrics of brain structure. White matter hyperintensities (WMHs), which are bright regions seen on T2-weighted brain MRI imaging, are postulated to result from cumulative ischemic vascular injury. Consequently, we hypothesized that plaques that are more prone to microvascular changes and embolization, represented by higher strain indices on ultrasound, would be associated with an increased amount of WMH lesion volume. This relationship would suggest not only emboli as a cause for the brain degenerative changes, but more importantly, a common microvascular etiology for large and small vessel contributions to this process. Subjects scheduled to undergo a carotid endarterectomy were recruited from a neurosurgery clinic. Prior to surgery, participating subjects underwent both ultrasound strain imaging and brain MRI scans as part of a larger clinical study on vascular health and cognition. A linear regression found that maximum absolute strain and peak to peak strain in the surgical side carotid artery were predictive of WMH burden. Furthermore, the occurrence of microembolic signals monitored using transcranial Doppler (TCD) ultrasound examinations also correlated with increasing lesion burden. It is becoming increasingly recognized that cognitive decline is often multifactorial in nature. One contributing extra-brain factor may be changes in the microvasculature that produce unstable carotid artery plaques. In this study, we have shown that higher strain indices in carotid artery plaques are significantly associated with an increased WMH burden, a marker of vascular mediated brain damage. PMID:26448914

  18. Electroconvulsive therapy mediates neuroplasticity of white matter microstructure in major depression.

    PubMed

    Lyden, H; Espinoza, R T; Pirnia, T; Clark, K; Joshi, S H; Leaver, A M; Woods, R P; Narr, K L

    2014-01-01

    Whether plasticity of white matter (WM) microstructure relates to therapeutic response in major depressive disorder (MDD) remains uncertain. We examined diffusion tensor imaging (DTI) correlates of WM structural connectivity in patients receiving electroconvulsive therapy (ECT), a rapidly acting treatment for severe MDD. Tract-Based Spatial Statistics (TBSS) applied to DTI data (61 directions, 2.5 mm(3) voxel size) targeted voxel-level changes in fractional anisotropy (FA), and radial (RD), axial (AD) and mean diffusivity (MD) in major WM pathways in MDD patients (n=20, mean age: 41.15 years, 10.32 s.d.) scanned before ECT, after their second ECT and at transition to maintenance therapy. Comparisons made at baseline with demographically similar controls (n=28, mean age: 39.42 years, 12.20 s.d.) established effects of diagnosis. Controls were imaged twice to estimate scanning-related variance. Patients showed significant increases of FA in dorsal fronto-limbic circuits encompassing the anterior cingulum, forceps minor and left superior longitudinal fasciculus between baseline and transition to maintenance therapy (P<0.05, corrected). Decreases in RD and MD were observed in overlapping regions and the anterior thalamic radiation (P<0.05, corrected). Changes in DTI metrics associated with therapeutic response in tracts showing significant ECT effects differed between patients and controls. All measures remained stable across time in controls. Altered WM microstructure in pathways connecting frontal and limbic areas occur in MDD, are modulated by ECT and relate to therapeutic response. Increased FA together with decreased MD and RD, which trend towards normative values with treatment, suggest increased fiber integrity in dorsal fronto-limbic pathways involved in mood regulation. PMID:24713861

  19. Gray matter blood flow and volume are reduced in association with white matter hyperintensity lesion burden: a cross-sectional MRI study

    PubMed Central

    Crane, David E.; Black, Sandra E.; Ganda, Anoop; Mikulis, David J.; Nestor, Sean M.; Donahue, Manus J.; MacIntosh, Bradley J.

    2015-01-01

    Cerebral White Matter Hyperintensities (WMH) are associated with vascular risk factors and age-related cognitive decline. WMH have primarily been associated with global white matter and gray matter (GM) changes and less is known about regional effects in GM. The purpose of this study was to test for an association between WMH and two GM imaging measures: cerebral blood flow (CBF) and voxel-based morphometry (VBM). Twenty-six elderly adults with mild to severe WMH participated in this cross-sectional 3 Tesla magnetic resonance imaging (MRI) study. MRI measures of GM CBF and VBM were derived from arterial spin labeling (ASL) and T1-weighted images, respectively. Fluid-attenuated inversion recovery (FLAIR) images were used to quantify the WMH lesion burden (mL). GM CBF and VBM data were used as dependent variables. WMH lesion burden, age and sex were used in a regression model. Visual rating of WMH with the Fazekas method was used to compare the WMH lesion volume regression approach. WMH volume was normally distributed for this group (mean volume of 22.7 mL, range: 2.2–70.6 mL). CBF analysis revealed negative associations between WMH volume and CBF in the left anterior putamen, subcallosal, accumbens, anterior caudate, orbital frontal, anterior insula, and frontal pole (corrected p < 0.05). VBM analysis revealed negative associations between WMH and GM volume in lingual gyrus, intracalcarine, and bilateral hippocampus (corrected p < 0.05). The visual rating scale corroborated the regression findings (corrected p < 0.05). WMH lesion volume was associated with intra-group GM CBF and structural differences in this cohort of WMH adults with mild to severe lesion burden. PMID:26217223

  20. Enriched White-Matter Connectivity Networks for Accurate Identification of MCI Patients

    PubMed Central

    Wee, Chong-Yaw; Yap, Pew-Thian; Denny, Kevin; Browndyke, Jeffrey N.; Potter, Guy G.; Welsh-Bohmer, Kathleen A.; Wang, Lihong; Shen, Dinggang

    2010-01-01

    Mild cognitive impairment (MCI), often a prodromal phase of Alzheimer’s disease (AD), is frequently considered to be good target for early diagnosis and therapeutic interventions of AD. Recent emergence of reliable network characterization techniques has made it possible to understand neurological disorders at a whole-brain connectivity level. Accordingly, we propose an effective network-based multivariate classification algorithm, using a collection of measures derived from white-matter (WM) connectivity networks, to accurately identify MCI patients from normal controls. An enriched description of WM connections, utilizing six physiological parameters, i.e., fiber count, fractional anisotropy (FA), mean diffusivity (MD), and principal diffusivities (?1, ?2, ?3), results in six connectivity networks for each subject to account for the connection topology and the biophysical properties of the connections. Upon parcellating the brain into 90 regions-of-interest (ROIs), these properties can be quantified for each pair of regions with common traversing fibers. For building an MCI classifier, clustering coefficient of each ROI in relation to the remaining ROIs is extracted as feature for classification. These features are then ranked according to their Pearson correlation with respect to the clinical labels, and are further sieved to select the most discriminant subset of features using a SVM-based feature selection algorithm. Finally, support vector machines (SVMs) are trained using the selected subset of features. Classification accuracy was evaluated via leave-one-out cross-validation to ensure generalization of performance. The classification accuracy given by our enriched description of WM connections is 88.9%, which is an increase of at least 14.8% from that using simple WM connectivity description with any single physiological parameter. A cross-validation estimation of the generalization performance shows an area of 0.929 under the receiver operating characteristic (ROC) curve, indicating excellent diagnostic power. It was also found, based on the selected features, that portions of the prefrontal cortex, orbitofrontal cortex, parietal lobe and insula regions provided the most discriminant features for classification, in line with results reported in previous studies. Our MCI classification framework, especially the enriched description of WM connections, allows accurate early detection of brain abnormalities, which is of paramount importance for treatment management of potential AD patients. PMID:20970508

  1. Aortic pulse wave velocity predicts focal white matter hyperintensities in a biracial cohort of older adults.

    PubMed

    Rosano, Caterina; Watson, Nora; Chang, Yuefang; Newman, Anne B; Aizenstein, Howard J; Du, Yan; Venkatraman, Vijay; Harris, Tamara B; Barinas-Mitchell, Emma; Sutton-Tyrrell, Kim

    2013-01-01

    Although the cross-sectional relationship of arterial stiffness with cerebral small vessel disease is consistently shown in middle-aged and young-old adults, it is less clear whether these associations remain significant over time in very old adults. We hypothesize that arterial stiffness is longitudinally associated with white matter characteristics, and associations are stronger within watershed areas. Neuroimaging was obtained in 2006-2008 from 303 elderly (mean age 82.9 years, 59% women, 41% black) with pulse wave velocity (PWV) measures in 1997-1998. Multivariable regression models estimated the coefficients for PWV (cm/sec) in relationship to presence, severity, and spatial distribution of white matter hyperintensities (WMH), gray matter volume, and fractional anisotropy from diffusion tensor, adjusting for demographic, cardiovascular risk factors, and diseases from 1997-1998 to 2006-2008. Higher PWV in 1997-1998 was associated with greater WMH volume in 2006-2008 within the left superior longitudinal fasciculus (age and total brain WMH adjusted, P=0.023), but not with WMH in other tracts or with fractional anisotropy or gray matter volume from total brain (P>0.2). Associations were stronger in blacks than in whites, remaining significant in fully adjusted models. Elderly with WMH in tracts related to processing speed and memory are more likely to have had higher PWV values 10 years prior, before neuroimaging data being available. Future studies should address whether arterial stiffness can serve as an early biomarker of covert brain structural abnormalities and whether early arterial stiffness control can promote successful brain aging, especially in black elderly. PMID:23172923

  2. mGluR5 protect astrocytes from ischemic damage in postnatal CNS white matter

    PubMed Central

    Vanzulli, Ilaria; Butt, Arthur M.

    2015-01-01

    Astrocytes perform essential neuron-supporting functions in the central nervous system (CNS) and their disruption has devastating effects on neuronal integrity in multiple neuropathologies. Although astrocytes are considered resistant to most pathological insults, ischemia can result in astrocyte injury and astrocytes in postnatal white matter are particularly vulnerable. Metabotropic glutamate receptors (mGluR) are neuroprotective in ischemia and are widely expressed by astrocytes throughout CNS grey matter, but their potential cytoprotective role in astrocytes had not been determined. Here, we identify functional expression of group I mGluR in white matter astrocytes and demonstrate their activation protects astrocytes from ischemic damage in the postnatal mouse optic nerve. Optic nerve astrocytes are shown to express mGluR5 using immunolabelling of sections and explant cultures from transgenic reporter mice in which GFAP drives expression of EGFP. In addition, using Fluo-4 calcium imaging in isolated intact optic nerves, we show that the group I/II mGluR agonist ACPD and the specific group I mGluR agonist DHPG evoke glial Ca2+ signals that were significantly inhibited by the group I mGluR antagonist AIDA. A key finding is that activation of group I mGluR protects astrocytes against oxygen-glucose deprivation (OGD) in situ, in isolated intact optic nerves from GFAP-EGFP mice. This study identifies a role for group I mGluR in protecting astrocytes against ischemia in postnatal white matter and suggests this may be a strategy for limiting damage in neuropathologies involving excitotoxity. PMID:26189008

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

    E-print Network

    Early gray-matter and white-matter concentration in infancy predict later language skills: A whole Keywords: Voxel-based morphometry Infancy Cerebellum Hippocampus Posterior limb of the internal capsule children indicate that brain and behavioral responses early in infancy pre- dict later performance

  4. Protective effects of activated protein C on neurovascular unit in a rat model of intrauterine infection-induced neonatal white matter injury.

    PubMed

    Jin, Sheng-Juan; Liu, Yan; Deng, Shi-Hua; Lin, Tu-Lian; Rashid, Abid; Liao, Li-Hong; Ning, Qin; Luo, Xiao-Ping

    2015-12-01

    Activated protein C (APC), a natural anticoagulant, has been reported to exert direct vasculoprotective, neural protective, anti-inflammatory, and proneurogenic activities in the central nervous system. This study was aimed to explore the neuroprotective effects and potential mechanisms of APC on the neurovascular unit of neonatal rats with intrauterine infection-induced white matter injury. Intraperitoneal injection of 300 ?g/kg lipopolysaccharide (LPS) was administered consecutively to pregnant Sprague-Dawley rats at embryonic days 19 and 20 to establish the rat model of intrauterine infection- induced white matter injury. Control rats were injected with an equivalent amount of sterile saline on the same time. APC at the dosage of 0.2 mg/kg was intraperitoneally injected to neonatal rats immediately after birth. Brain tissues were collected at postnatal day 7 and stained with hematoxylin and eosin (H&E). Immunohistochemistry was used to evaluate myelin basic protein (MBP) expression in the periventricular white matter region. Blood-brain barrier (BBB) permeability and brain water content were measured using Evens Blue dye and wet/dry weight method. Double immunofluorescence staining and real-time quantitative PCR were performed to detect microglial activation and the expression of protease activated receptor 1 (PAR1). Typical pathological changes of white matter injury were observed in rat brains exposed to LPS, and MBP expression in the periventricular region was significantly decreased. BBB was disrupted and the brain water content was increased. Microglia were largely activated and the mRNA and protein levels of PAR1 were elevated. APC administration ameliorated the pathological lesions of the white matter and increased MBP expression. BBB permeability and brain water content were reduced. Microglia activation was inhibited and the PAR1 mRNA and protein expression levels were both down-regulated. Our results suggested that APC exerted neuroprotective effects on multiple components of the neurovascular unit in neonatal rats with intrauterine infection- induced white matter injury, and the underlying mechanisms might involve decreased expression of PAR1. PMID:26670444

  5. Intracellular distribution of psychotropic drugs in the grey and white matter of the brain: the role of lysosomal trapping

    PubMed Central

    Daniel, W?adys?awa A; Wójcikowski, Jacek; Pa?ucha, Agnieszka

    2001-01-01

    Since the brain is not a homogenous organ (i.e. the phospholipid pattern and density of lysosomes may vary in its different regions), in the present study we examined the uptake of psychotropic drugs by vertically cut slices of whole brain, grey (cerebral cortex) and white (corpus callosum, internal capsule) matter of the brain and by neuronal and astroglial cell cultures.Moreover, we assessed the contribution of lysosomal trapping to total drug uptake (total uptake=lysosomal trapping+phospholipid binding) by tissue slices or cells conducting experiments in the presence and absence of ‘lysosomal inhibitors', i.e., the lysosomotropic compound ammonium chloride (20?mM) or the Na+/H+-ionophore monensin (10??M), which elevated the internal pH of lysosomes. The initial concentration of psychotropic drug in the incubation medium was 5??M.Both total uptake and lysosomal trapping of the antidepressants investigated (imipramine, amitriptyline, fluoxetine, sertraline) and neuroleptics (promazine, perazine, thioridazine) were higher in the grey matter and neurones than in the white matter and astrocytes, respectively. Lysosomal trapping of the psychotropics occurred mainly in neurones where thioridazine sertraline and perazine showed the highest degree of lysosomotropism.Distribution interactions between antidepressants and neuroleptics took place in neurones via mutual inhibition of lysosomal trapping of drugs.A differential number of neuronal and glial cells in the brain may mask the lysosomal trapping and the distribution interactions of less potent lysosomotropic drugs in vertically cut brain slices.A reduction (via a distribution interaction) in the concentration of psychotropics in lysosomes (depot), which leads to an increase in their level in membranes and tissue fluids, may intensify the pharmacological action of the combined drugs. PMID:11606321

  6. Alterations in the Cerebral White Matter of Genetic High Risk Offspring of Patients with Schizophrenia Spectrum Disorder

    PubMed Central

    Francis, Alan N; Bhojraj, Tejas S; Prasad, Konasale M.; Montrose, Debra; Eack, Shaun M; Rajarethinam, Rajaprabhakaran; van Elst, Ludger T; Keshavan, Matcheri S

    2012-01-01

    Alterations in White Matter (WM) may be seen in young relatives at risk and may underlie vulnerability to Schizophrenia. We were interested in exploring which of the WM regions were altered in adolescent offspring at familial risk for Schizophrenia. We examined structural alterations in the offspring of subjects with Schizophrenia or Schizoaffective disorder (HR; n=65; 36 males) and healthy controls (HC; n=80: 37 males) matched for age and education. MRI images were collected using a GE 1.5T scanner at the University of Pittsburgh Medical Center. Image processing was done using FreeSurfer (MGH) by an experienced rater blind to clinical data. We used multivariate analysis of covariance, with intracranial volume (p> 0.05) and age as covariates. High Risk offspring had significant reductions in total WM, hemispheric WM and WM within left parietal and left cingulate cortices. Male offspring had more pronounced right hemisphere WM reductions than females. PMID:22910323

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

    ERIC Educational Resources Information Center

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

    2015-01-01

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

  8. Visualization of the Interaction of Multiple Sclerosis Lesions with Adjacent White Matter Fibers Using Streamtubes and Streamsurfaces

    E-print Network

    Laidlaw, David

    Visualization of the Interaction of Multiple Sclerosis Lesions with Adjacent White Matter Fibers of Multiple Sclerosis. N Engl J Med, 338:278­285, 1998. [4] Ferguson et al. Axonal damage in acute. Brain, 120 matter lesion volume and distribution in multiple sclerosis. Brain, 123(9):1845­9, September 2000. [6

  9. Heritability of fractional anisotropy in human white matter: a comparison of Human Connectome Project and ENIGMA-DTI data.

    PubMed

    Kochunov, Peter; Jahanshad, Neda; Marcus, Daniel; Winkler, Anderson; Sprooten, Emma; Nichols, Thomas E; Wright, Susan N; Hong, L Elliot; Patel, Binish; Behrens, Timothy; Jbabdi, Saad; Andersson, Jesper; Lenglet, Christophe; Yacoub, Essa; Moeller, Steen; Auerbach, Eddie; Ugurbil, Kamil; Sotiropoulos, Stamatios N; Brouwer, Rachel M; Landman, Bennett; Lemaitre, Hervé; den Braber, Anouk; Zwiers, Marcel P; Ritchie, Stuart; van Hulzen, Kimm; Almasy, Laura; Curran, Joanne; deZubicaray, Greig I; Duggirala, Ravi; Fox, Peter; Martin, Nicholas G; McMahon, Katie L; Mitchell, Braxton; Olvera, Rene L; Peterson, Charles; Starr, John; Sussmann, Jessika; Wardlaw, Joanna; Wright, Margie; Boomsma, Dorret I; Kahn, Rene; de Geus, Eco J C; Williamson, Douglas E; Hariri, Ahmad; van 't Ent, Dennis; Bastin, Mark E; McIntosh, Andrew; Deary, Ian J; Hulshoff Pol, Hilleke E; Blangero, John; Thompson, Paul M; Glahn, David C; Van Essen, David C

    2015-05-01

    The degree to which genetic factors influence brain connectivity is beginning to be understood. Large-scale efforts are underway to map the profile of genetic effects in various brain regions. The NIH-funded Human Connectome Project (HCP) is providing data valuable for analyzing the degree of genetic influence underlying brain connectivity revealed by state-of-the-art neuroimaging methods. We calculated the heritability of the fractional anisotropy (FA) measure derived from diffusion tensor imaging (DTI) reconstruction in 481 HCP subjects (194/287 M/F) consisting of 57/60 pairs of mono- and dizygotic twins, and 246 siblings. FA measurements were derived using (Enhancing NeuroImaging Genetics through Meta-Analysis) ENIGMA DTI protocols and heritability estimates were calculated using the SOLAR-Eclipse imaging genetic analysis package. We compared heritability estimates derived from HCP data to those publicly available through the ENIGMA-DTI consortium, which were pooled together from five-family based studies across the US, Europe, and Australia. FA measurements from the HCP cohort for eleven major white matter tracts were highly heritable (h(2)=0.53-0.90, p<10(-5)), and were significantly correlated with the joint-analytical estimates from the ENIGMA cohort on the tract and voxel-wise levels. The similarity in regional heritability suggests that the additive genetic contribution to white matter microstructure is consistent across populations and imaging acquisition parameters. It also suggests that the overarching genetic influence provides an opportunity to define a common genetic search space for future gene-discovery studies. Uniquely, the measurements of additive genetic contribution performed in this study can be repeated using online genetic analysis tools provided by the HCP ConnectomeDB web application. PMID:25747917

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

    NASA Astrophysics Data System (ADS)

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

    2012-02-01

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

  11. The relationship between working memory and cerebral white matter volume in survivors of childhood brain tumors treated with conformal radiation therapy.

    PubMed

    Jacola, Lisa M; Ashford, Jason M; Reddick, Wilburn E; Glass, John O; Ogg, Robert J; Merchant, Thomas E; Conklin, Heather M

    2014-08-01

    Survivors of childhood brain tumors (BTs) treated with CNS-directed therapy show changes in cerebral white matter that are related to neurocognitive late effects. We examined the association between white matter volume and working memory ability in survivors treated with conformal radiation therapy (CRT). Fifty survivors (25 males, age at assessment = 13.14 ± 2.88, age at CRT = 7.41 ± 3.41 years) completed Digit Span from the Wechsler Intelligence Scales for Children, 4th Edition and experimental Self-Ordered Search (SOS) tasks as measures of working memory. Caregiver ratings were obtained using the Behavior Rating Inventory of Executive Function. MRI exams were acquired on a 1.5 T scanner. Volumes of normal appearing white matter (NAWM) were quantified using a well-validated automated segmentation and classification program. Correlational analyses demonstrated that NAWM volumes were significantly larger in males and participants with tumors located in the infratentorial space. Correlations between NAWM volume and Digit Span Backward were distributed across anterior and posterior regions, with evidence for greater right hemisphere involvement (r = .32-.34, p ? .05). Correlations between NAWM volume with Digit Span Backward (r = .44-.52; p ? .05) and NAWM volume with SOS-Object Total (r = .45-.52, p ? .05) were of greater magnitude in females. No relationship was found between NAWM volume and caregiver report. Working memory performance in survivors of pediatric BTs treated with CRT are related to regionally specific NAWM volume. Developmental differences in cerebral myelination may explain findings of greater risk for neurocognitive late effects in female survivors. Future studies are needed to better isolate vulnerable white matter pathways, thus facilitating the development of neuroprotective interventions. PMID:24847967

  12. Microstructural White Matter Properties Mediate the Association between APOE and Perceptual Speed in Very Old Persons without Dementia

    PubMed Central

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

    2015-01-01

    Background Reduced white matter integrity, as indicated by lower fractional anisotropy (FA) and higher mean diffusivity (MD), has been related to poorer perceptual speed (PS) performance. As the ?4 allele has been associated with lower white matter integrity in old age, this represents a potential mechanism through which APOE may affect PS. Objective To examine whether the association between APOE and PS is mediated by white matter microstructure in very old persons without dementia. Method Participants were selected from the population-based SNAC-K study. After excluding persons with dementia, preclinical dementia, and other neurological disorders, 652 persons (age range 78–90) were included in the study, of which 89 had data on diffusion tensor imaging (DTI). We used structural equation modeling to form seven latent white matter factors (FA and MD) and one latent PS factor. Separate analyses were performed for FA and MD and mediational analyses were carried out for tracts where significant associations were observed to both APOE and PS. Results APOE was associated with white matter microstructure in 2 out of 14 tracts; ?4 carriers had significantly lower FA in forceps major and higher MD in the cortico-spinal tract. Allowing the white matter microstructure indicators in these tracts to mediate the association between APOE and PS resulted in a markedly attenuated association between these variables. Bootstrapping statistics in the subsample with DTI data (n = 89) indicated that FA in forceps major significantly mediated the association between APOE and PS (indirect effect: -0.070, 95% bias corrected CIs -0.197 to -0.004). Conclusion Lower white matter integrity may represent one of several mechanisms through which APOE affects PS performance in elderly persons free of dementia and preclinical dementia. PMID:26252210

  13. miRNAs are required for the terminal differentiation of white matter astrocytes in the developing CNS.

    PubMed

    Li, X; Chen, Y; Chi, Q; Hu, X; Xu, X; Zhang, Z; Qiu, M; Zheng, K

    2016-01-15

    While the regulation of the neurogenesis and oligodendrogenesis by microRNAs has been intensively studied, little is known about the role of microRNAs (miRNAs) in the development of astrocytes. Here, we report that microRNAs play an essential role in the differentiation and maturation of white matter astrocytes in mouse spinal cord tissues. In glial fibrillary acidic protein (GFAP)/Dicer conditional mutants, the initial generation of astrocyte progenitor cells was normal in the spinal cord. However, there was a much reduced number of GFAP+ astrocytes with shorter processes in the white matter of mutant tissues. In contrast, the expression of gray matter protoplasmic astrocyte marker was not affected. Together, our studies indicated that miRNAs are required for the differentiation and morphological maturation of white matter fibrous astrocytes in the developing spinal cord. PMID:26556063

  14. White Matter Microstructure in Transsexuals and Controls Investigated by Diffusion Tensor Imaging

    PubMed Central

    Kranz, Georg S.; Hahn, Andreas; Kaufmann, Ulrike; Küblböck, Martin; Hummer, Allan; Ganger, Sebastian; Seiger, Rene; Winkler, Dietmar; Swaab, Dick F.; Windischberger, Christian; Kasper, Siegfried; Lanzenberger, Rupert

    2015-01-01

    Biological causes underpinning the well known gender dimorphisms in human behavior, cognition, and emotion have received increased attention in recent years. The advent of diffusion-weighted magnetic resonance imaging has permitted the investigation of the white matter microstructure in unprecedented detail. Here, we aimed to study the potential influences of biological sex, gender identity, sex hormones, and sexual orientation on white matter microstructure by investigating transsexuals and healthy controls using diffusion tensor imaging (DTI). Twenty-three female-to-male (FtM) and 21 male-to-female (MtF) transsexuals, as well as 23 female (FC) and 22 male (MC) controls underwent DTI at 3 tesla. Fractional anisotropy, axial, radial, and mean diffusivity were calculated using tract-based spatial statistics (TBSS) and fiber tractography. Results showed widespread significant differences in mean diffusivity between groups in almost all white matter tracts. FCs had highest mean diffusivities, followed by FtM transsexuals with lower values, MtF transsexuals with further reduced values, and MCs with lowest values. Investigating axial and radial diffusivities showed that a transition in axial diffusivity accounted for mean diffusivity results. No significant differences in fractional anisotropy maps were found between groups. Plasma testosterone levels were strongly correlated with mean, axial, and radial diffusivities. However, controlling for individual estradiol, testosterone, or progesterone plasma levels or for subjects’ sexual orientation did not change group differences. Our data harmonize with the hypothesis that fiber tract development is influenced by the hormonal environment during late prenatal and early postnatal brain development. PMID:25392513

  15. Hyperoxia Causes Maturation-Dependent Cell Death in the Developing White Matter

    PubMed Central

    Gerstner, Bettina; DeSilva, Tara M.; Genz, Kerstin; Armstrong, Amy; Brehmer, Felix; Neve, Rachael L.; Felderhoff-Mueser, Ursula; Volpe, Joseph J.; Rosenberg, Paul A.

    2009-01-01

    Periventricular leukomalacia is the predominant injury in the preterm infant leading to cerebral palsy. Oxygen exposure may be an additional cause of brain injury in these infants. In this study, we investigated pathways of maturation-dependent oligodendrocyte (OL) death induced by hyperoxia in vitro and in vivo. Developing and mature OLs were subjected to 80% oxygen (0–24 h). Lactate dehydrogenase (LDH) assay was used to assess cell viability. Furthermore, 3-, 6-, and 10-d-old rat pups were subjected to 80% oxygen (24 h), and their brains were processed for myelin basic protein staining. Significant cell death was detected after 6–24 h incubation in 80% oxygen in pre-OLs (O4+,O1?), but not in mature OLs (MBP+). Cell death was executed by a caspase-dependent apoptotic pathway and could be blocked by the pan-caspase inhibitor zVAD-fmk. Overexpression of BCL2 (Homo sapiens B-cell chronic lymphocytic leukemia/lymphoma 2) significantly reduced apoptosis. Accumulation of superoxide and generation of reactive oxygen species (ROS) were detected after 2 h of oxygen exposure. Lipoxygenase inhibitors 2,3,5-trimethyl-6-(12-hydroxy-5–10-dodecadiynyl-1,4-benzoquinone and N-benzyl-N-hydroxy-5-phenylpentamide fully protected the cells from oxidative injury. Overexpression of superoxide dismutase (SOD1) dramatically increased injury to pre-OLs but not to mature OLs. We extended these studies by testing the effects of hyperoxia on neonatal white matter. Postnatal day 3 (P3) and P6 rats, but not P10 pups, showed bilateral reduction in MBP (myelin basic protein) expression with 24 h exposure to 80% oxygen. Hyperoxia causes oxidative stress and triggers maturation-dependent apoptosis in pre-OLs, which involves the generation of ROS and caspase activation, and leads to white matter injury in the neonatal rat brain. These observations may be relevant to white matter injury observed in premature infants. PMID:18234901

  16. Neurovascular coupling, cerebral white matter integrity, and response to cocoa in older people

    PubMed Central

    Hurwitz, Shelley; Salat, David H.; Greve, Douglas N.; Fisher, Naomi D.L.

    2013-01-01

    Objective: To investigate the relationship between neurovascular coupling and cognitive function in elderly individuals with vascular risk factors and to determine whether neurovascular coupling could be modified by cocoa consumption. Methods: Sixty older people (aged 72.9 ± 5.4 years) were studied in a parallel-arm, double-blind clinical trial of neurovascular coupling and cognition in response to 24 hours and 30 days of cocoa consumption. Cognitive measures included Mini-Mental State Examination and Trail Making Test A and B. Neurovascular coupling was measured from the beat-to-beat blood flow velocity responses in the middle cerebral arteries to the N-Back Task. In a subset of MRI-eligible participants, cerebral white matter structural integrity was also measured. Results: Neurovascular coupling was associated with Trails B scores (p = 0.002) and performance on the 2-Back Task. Higher neurovascular coupling was also associated with significantly higher fractional anisotropy in cerebral white matter hyperintensities (p = 0.02). Finally, 30 days of cocoa consumption was associated with increased neurovascular coupling (5.6% ± 7.2% vs ?2.4% ± 4.8%; p = 0.001) and improved Trails B times (116 ± 78 seconds vs 167 ± 110 seconds; p = 0.007) in those with impaired neurovascular coupling at baseline. Conclusion: There is a strong correlation between neurovascular coupling and cognitive function, and both can be improved by regular cocoa consumption in individuals with baseline impairments. Better neurovascular coupling is also associated with greater white matter structural integrity. PMID:23925758

  17. Longitudinal Processing Speed Impairments in Males with Autism and the Effects of White Matter Microstructure

    PubMed Central

    Travers, Brittany G.; Bigler, Erin D.; Tromp, Do P. M.; Adluru, Nagesh; Froehlich, Alyson L.; Ennis, Chad; Lange, Nicholas; Nielsen, Jared A.; Prigge, Molly B. D.; Alexander, Andrew L.; Lainhart, Janet E.

    2014-01-01

    The present study used an accelerated longitudinal design to examine group differences and age-related changes in processing speed in 81 individuals with Autism Spectrum Disorder (ASD) compared to 56 age-matched individuals with typical development (ages 6–39 years). Processing speed was assessed using the Wechsler Intelligence Scale for Children-3rd edition (WISC-III) and the Wechsler Adult Intelligence Scale-3rd edition (WAIS-III). Follow-up analyses examined processing speed subtest performance and relations between processing speed and white matter microstructure (as measured with diffusion tensor imaging [DTI] in a subset of these participants). After controlling for full scale IQ, the present results show that processing speed index standard scores were on average 12 points lower in the group with ASD compared to the group with typical development. There were, however, no significant group differences in standard score age-related changes within this age range. For subtest raw scores, the group with ASD demonstrated robustly slower processing speeds in the adult versions of the IQ test (i.e., WAIS-III) but not in the child versions (WISC-III), even though age-related changes were similar in both the ASD and typically developing groups. This pattern of results may reflect difficulties that become increasingly evident in ASD on more complex measures of processing speed. Finally, DTI measures of whole-brain white matter microstructure suggested that fractional anisotropy (but not mean diffusivity, radial diffusivity, or axial diffusivity) made significant but small-sized contributions to processing speed standard scores across our entire sample. Taken together, the present findings suggest that robust decreases in processing speed may be present in ASD, more pronounced in adulthood, and partially attributable to white matter microstructural integrity. PMID:24269298

  18. Characterizing the white matter hyperintensity penumbra with cerebral blood flow measures

    PubMed Central

    Promjunyakul, N.; Lahna, D.; Kaye, J.A.; Dodge, H.H.; Erten-Lyons, D.; Rooney, W.D.; Silbert, L.C.

    2015-01-01

    Objective White matter hyperintensities (WMHs) are common with age, grow over time, and are associated with cognitive and motor impairments. Mechanisms underlying WMH growth are unclear. We aimed to determine the presence and extent of decreased normal appearing white matter (NAWM) cerebral blood flow (CBF) surrounding WMHs to identify ‘WM at risk’, or the WMH CBF penumbra. We aimed to further validate cross-sectional finding by determining whether the baseline WMH penumbra CBF predicts the development of new WMHs at follow-up. Methods Sixty-one cognitively intact elderly subjects received 3 T MPRAGE, FLAIR, and pulsed arterial spin labeling (PASL). Twenty-four subjects returned for follow-up MRI. The inter-scan interval was 18 months. A NAWM layer mask, comprised of fifteen layers, 1 mm thick each surrounding WMHs, was generated for periventricular (PVWMH) and deep (DWMH) WMHs. Mean CBF for each layer was computed. New WMH and persistent NAWM voxels for each penumbra layer were defined from follow-up MRI. Results CBF in the area surrounding WMHs was significantly lower than the total brain NAWM, extending approximately 12 mm from both the established PVWMH and DWMH. Voxels with new WMH at follow-up had significantly lower baseline CBF than voxels that maintained NAWM, suggesting that baseline CBF can predict the development of new WMHs over time. Conclusions A CBF penumbra exists surrounding WMHs, which is associated with future WMH expansion. ASL MRI can be used to monitor interventions to increase white matter blood flow for the prevention of further WM damage and its cognitive and motor consequences. PMID:26106546

  19. White matter microstructure in transsexuals and controls investigated by diffusion tensor im