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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. Regional white matter microstructure in very preterm infants: Predictors and 7 year outcomes

    PubMed Central

    Thompson, Deanne K.; Lee, Katherine J; Egan, Gary F.; Warfield, Simon K.; Doyle, Lex W.; Anderson, Peter J.; Inder, Terrie E.

    2014-01-01

    The aims of this study were to investigate regional white matter microstructural differences between very preterm (<30 weeks’ gestational age and/or <1250g) and full term (≥37 weeks’ gestational age) infants at term corrected age with diffusion tensor imaging, and to explore perinatal predictors of diffusion measures, and the relationship between regional diffusion measures and neurodevelopmental outcomes at age 7 years in very preterm children. Mean (p=0.003), axial (p=0.008), and radial diffusivity (p=0.003) in total white matter were increased in very preterm compared with full term infants, with similar fractional anisotropy in the two groups. There was little evidence that group-wise differences were specific to any of the 8 regions studied for each hemisphere. Perinatal white matter abnormality and intraventricular hemorrhage (grade III or IV) were associated with increased diffusivity in the white matter of very preterm infants. Higher white matter diffusivity measures of the inferior occipital and cerebellar region at term equivalent age were associated with increased risk of impairments in motor and executive function at 7 years in very preterm children, but there was little evidence for associations with IQ or memory impairment. In conclusion, myelination is likely disrupted or delayed in very preterm infants, especially those with perinatal brain abnormality. Altered diffusivity at term-equivalent age helps explain impaired functioning at 7 years. This study defines the nature of microstructural alterations in very preterm infant white matter, assists in understanding the associated risk factors, and is the first study to reveal an important link between inferior occipital and cerebellar white matter disorganization in infancy, and executive and motor functioning 7 years later. PMID:24405815

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

    PubMed Central

    Kennedy, Kristen M.; Raz, Naftali

    2009-01-01

    Even successful aging is associated with regional brain shrinkage and deterioration of the cerebral white matter. Aging also brings about an increase in vascular risk, and vascular impairment may be a potential mechanism behind the observed patterns of aging. The goals of this study were to characterize the normal age-differences in white matter integrity in several brain regions across the adult lifespan, and to assess the modifying effect of vascular risk on the observed pattern of regional white matter integrity. We estimated fractional anisotropy and diffusivity of white matter in nine cerebral regions of interest in 77 healthy adults (1984 years old). There was a widespread reduction of white matter anisotropy with age, and prefrontal and occipital regions evidenced the greatest age-related differences. Diffusivity increased with age, and the magnitude of age differences increased beginning with the middle of the fifth decade. Vascular risk factors modified age differences in white matter integrity. Clinically diagnosed and treated arterial hypertension was associated with reduced white matter anisotropy and increased diffusivity beyond the effects of age. In the normotensive participants, elevation of arterial pulse pressure (a surrogate of arterial stiffness) was linked to deterioration of the white matter integrity in the frontal regions. Although the causal role of vascular risk in brain aging is unclear, the observed pattern of effects suggests that vascular risk may drive the expansion of age-related white matter damage from anterior to posterior regions. PMID:19712671

  7. Regional white matter change in pre-symptomatic Huntington's disease: a diffusion tensor imaging study.

    PubMed

    Reading, Sarah A J; Yassa, Michael A; Bakker, Arnold; Dziorny, Adam C; Gourley, Lisa M; Yallapragada, Venu; Rosenblatt, Adam; Margolis, Russell L; Aylward, Elizabeth H; Brandt, Jason; Mori, Susumu; van Zijl, Peter; Bassett, Susan S; Ross, Christopher A

    2005-10-30

    The pathology of Huntington's disease (HD) is characterized by diffuse brain atrophy, with the most substantial neuronal loss occurring in the caudate and putamen. Recent evidence suggests that there may be more widespread neuronal degeneration with significant involvement of extrastriate structures, including white matter. In this study of pre-symptomatic carriers of the HD genetic mutation, we have used diffusion tensor imaging to examine the integrity and organization of white matter in a group of individuals who previously demonstrated abnormalities in response to a functional magnetic resonance imaging paradigm. Our results indicate that, before the onset of manifest HD, there are regional decreases in fractional anisotropy, indicating early white matter disorganization. PMID:16199141

  8. White matter lesions in Fabry disease occur in 'prior' selectively hypometabolic and hyperperfused brain regions.

    PubMed

    Moore, David F; Altarescu, Gheona; Barker, W Craig; Patronas, Nicholas J; Herscovitch, Peter; Schiffmann, Raphael

    2003-12-30

    Fabry disease is an X-linked disorder associated with early onset stroke. We previously found a significantly elevated cerebral blood flow (CBF) in patients with Fabry disease. We set to determine whether elevated resting CBF in Fabry disease is primarily a cerebrovascular abnormality or is secondary to enhanced neuronal metabolism. The relationship of cerebral metabolism and blood flow to Fabry leukoencephalopathy was also investigated. We measured the global and regional cerebral metabolic rate of glucose using 18-fluoro-deoxyglucose (FDG) and PET in 16 patients with Fabry disease (7 patients with leukoaraiotic lesions and 9 without) and in 7 control subjects. MRI fluid attenuated inversion recovery (FLAIR) studies were also performed in the patient and control groups. All control subjects had normal MRI FLAIR studies with no high-signal deep white matter lesions (WML). Patients were partitioned into FLAIR lesion and non-FLAIR lesion groups. We found no evidence of cerebral glucose hypermetabolism in Fabry disease. On the contrary, significantly decreased regional cerebral glucose metabolism (rCMRGlu) was found particularly in the deep white matter in the Fabry non-lesion group and exacerbated in the lesion group. Lesion-susceptible regions were relatively hyperperfused in non-lesion patients compared to the control group. We conclude that the elevated rCBF and decreased white matter rCMRGlu indicates a dissociation between metabolism and blood flow suggesting chronic deep white matter metabolic insufficiency. PMID:14698356

  9. 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…

  10. 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

  11. Extensive piano practicing has regionally specific effects on white matter development.

    PubMed

    Bengtsson, Sara L; Nagy, Zoltn; Skare, Stefan; Forsman, Lea; Forssberg, Hans; Ulln, Fredrik

    2005-09-01

    Using diffusion tensor imaging, we investigated effects of piano practicing in childhood, adolescence and adulthood on white matter, and found positive correlations between practicing and fiber tract organization in different regions for each age period. For childhood, practicing correlations were extensive and included the pyramidal tract, which was more structured in pianists than in non-musicians. Long-term training within critical developmental periods may thus induce regionally specific plasticity in myelinating tracts. PMID:16116456

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

    PubMed

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

    2015-07-01

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

  13. 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

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

    PubMed

    Sarma, Manoj K; Nagarajan, Rajakumar; Keller, Margaret A; Kumar, Rajesh; Nielsen-Saines, Karin; Michalik, David E; Deville, Jaime; Church, Joseph A; Thomas, M Albert

    2014-01-01

    Despite the success of antiretroviral therapy (ART), perinatally infected HIV remains a major health problem worldwide. Although advance neuroimaging studies have investigated structural brain changes in HIV-infected adults, regional gray matter (GM) and white matter (WM) volume changes have not been reported in perinatally HIV-infected adolescents and young adults. In this cross-sectional study, we investigated regional GM and WM changes in 16 HIV-infected youths receiving ART (age 17.02.9years) compared with age-matched 14 healthy controls (age 16.32.3years) using magnetic resonance imaging (MRI)-based high-resolution T1-weighted images with voxel based morphometry (VBM) analyses. White matter atrophy appeared in perinatally HIV-infected youths in brain areas including the bilateral posterior corpus callosum (CC), bilateral external capsule, bilateral ventral temporal WM, mid cerebral peduncles, and basal pons over controls. Gray matter volume increase was observed in HIV-infected youths for several regions including the left superior frontal gyrus, inferior occipital gyrus, gyrus rectus, right mid cingulum, parahippocampal gyrus, bilateral inferior temporal gyrus, and middle temporal gyrus compared with controls. Global WM and GM volumes did not differ significantly between groups. These results indicate WM injury in perinatally HIV-infected youths, but the interpretation of the GM results, which appeared as increased regional volumes, is not clear. Further longitudinal studies are needed to clarify if our results represent active ongoing brain infection or toxicity from HIV treatment resulting in neuronal cell swelling and regional increased GM volume. Our findings suggest that assessment of regional GM and WM volume changes, based on VBM procedures, may be an additional measure to assess brain integrity in HIV-infected youths and to evaluate success of current ART therapy for efficacy in the brain. PMID:24380059

  15. 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

  16. 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

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

    PubMed Central

    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 age-sensitive cognitive tasks in a sample of healthy adults (N = 52, age 19–81 years). White matter integrity was assessed by fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in multiple regions of interest (genu and splenium of corpus callosum, internal capsule limbs, prefrontal, temporal, superior/posterior parietal, occipital white matter) and related to processing speed, working memory, inhibition, task switching, and episodic memory. We found that age and regional white matter integrity differentially influenced cognitive performance. Age-related degradation in anterior brain areas was associated with decreased processing speed and poorer working memory, whereas reduced inhibition and greater task switching costs were linked to decline in posterior areas. Poorer episodic memory was associated with age-related differences in central white matter regions. The observed multiple dissociations among specific age-sensitive cognitive skills and their putative neuroanatomical substrates support the view that age-related cognitive declines are unlikely to stem from a single cause. PMID:19166865

  18. 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, Jos 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

  19. Regional gray and white matter volume associated with Stroop interference: evidence from voxel-based morphometry.

    PubMed

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

    2012-02-01

    During Stroop tasks, subjects experience cognitive interference when they resolve interferences such as identifying the ink color of a printed word while ignoring the word's identity. Stroop paradigms are commonly used as an index of attention deficits and a tool for investigating the functions of the frontal lobes and other associated structures. Despite these uses and the vast amount of attention given to Stroop paradigms, the regional gray matter volume/regional white matter volume (rGMV/rWMV) correlates of Stroop interference have not yet been identified at the whole brain level in normal adults. We examined this issue using voxel-based morphometry in right-handed healthy young adults. We found significant negative relationships between the Stroop interference rate and rGMV in the anterior cingulate cortex (ACC), right inferior frontal gyrus, and cerebellum. Furthermore, we found relationships between the Stroop interference rate and rWMV in bilateral anatomical clusters that extended around extensive WM regions in the dorsal part of the frontal lobe. These findings are the first to reveal rGMV/rWMV that underlie the performance of the Stroop task, a widely used psychological paradigm at the whole brain level. Of note, our findings support the notion that ACC contributes to Stroop performance and show the involvement of regions that have been implicated in response inhibition and attention. PMID:21988892

  20. 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

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

    PubMed

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

    2013-03-01

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

  2. 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

  3. 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 ...

  4. Relation of Regional Grey and White Matter Volumes to Current BMI and Future Increases in BMI: A Prospective MRI Study

    PubMed Central

    Yokum, S.; Ng, J.; Stice, E.

    2014-01-01

    Objective This study tested whether global and regional brain volumes correlated with body mass index (BMI) and increases in BMI over 1-year follow-up. Methods Eighty-three young females (M age = 18.4, SD = 2.8; BMI range = 17.3–38.9) were scanned using magnetic resonance imaging (MRI). Voxel-based morphometry was used to assess global brain volume and regional grey matter (GM) and white matter (WM) volumes in regions implicated in taste, reward, and inhibitory control. Results Obese participants had less total GM volume than lean and overweight participants. Obese participants had lower total WM volume than overweight participants. BMI correlated with higher WM volumes in the middle temporal gyrus, fusiform gyrus, parahippocampal gyrus, Rolandic operculum, and dorsal striatum. Trend-level reduced GM volumes in the superior frontal gyrus and middle frontal gyrus were related to increases in BMI over 1-year follow-up. Conclusion Findings suggest that BMI is related to global and regional differences in brain matter volume in female adolescents. Most importantly, findings suggest that low GM volume in regions implicated in inhibitory control are related to future weight gain. Results taken in conjunction with prior findings suggest that abnormalities in regional GM volumes, but not WM volumes increase the risk for future weight gain and abnormalities in regional WM volumes but not GM volumes are secondary to weight gain. PMID:21894161

  5. Prefrontal Ischemia in the Rat Leads to Secondary Damage and Inflammation in Remote Gray and White Matter Regions

    PubMed Central

    Weishaupt, Nina; Zhang, Angela; Deziel, Robert A.; Tasker, R. Andrew; Whitehead, Shawn N.

    2016-01-01

    Secondary damage processes, such as inflammation and oxidative stress, can exacerbate an ischemic lesion and spread to adjacent brain regions. Yet, few studies investigate how regions remote from the infarct could also suffer from degeneration and inflammation in the aftermath of a stroke. To find out to what extent far-remote brain regions are affected after stroke, we used a bilateral endothelin-1-induced prefrontal infarct rat model. Brain regions posterior to the prefrontal cortical infarct were analyzed for ongoing neurodegeneration using FluoroJadeB (FJB) and for neuroinflammation using Iba1 and OX-6 immunohistochemistry 28 days post-stroke. The FJB-positive dorsomedial nucleus of the thalamus (DMN) and retrosplenial area (RSA) of the cortex displayed substantial neuroinflammation. Significant neuronal loss was only observed within the cortex. Significant microglia recruitment and activation in the FJB-positive internal capsule indicates remote white matter pathology. These findings demonstrate that even regions far remote from an infarct are affected predictably based on anatomical connectivity, and that white matter inflammation is an integral part of remote pathology. The delayed nature of this pathology makes it a valid target for preventative treatment, potentially with an extended time window of opportunity for therapeutic intervention using anti-inflammatory agents. PMID:26973455

  6. White matter microstructure alterations in bipolar disorder

    PubMed Central

    Bellani, Marcella; Perlini, Cinzia; Ferro, Adele; Cerruti, Stefania; Rambaldelli, Gianluca; Isola, Miriam; Cerini, Roberto; Dusi, Nicola; Andreone, Nicola; Balestrieri, Matteo; Mucelli, Roberto Pozzi; Tansella, Michele; Brambilla, Paolo

    2012-01-01

    Summary Genetic, neuropathological and magnetic resonance imaging findings support the presence of diffuse white matter cytoarchitectural disruption in bipolar disorder. In this study, diffusion-weighted imaging (DWI) was applied to study cortical white matter microstructure organisation in 24 patients with DSM-IV bipolar disorder and 35 matched normal controls. DWI images were obtained using a 1.5 Tesla scanner and apparent diffusion coefficient (ADC) values were determined over regions of interest placed, bilaterally, in the frontal, temporal, parietal, and occipital white matter. Significantly increased ADC values were found in bipolar patients with respect to normal controls in the right temporal lobe, left parietal lobe and bilateral occipital lobes. ADC values did not associate significantly with age or with clinical variables (p>0.05). Diffuse cortical white matter alterations on DWI in bipolar disorder denote widespread disruption of white matter integrity and may be due to altered myelination and/or axonal integrity. PMID:22687164

  7. MTI of white matter hyperintensities.

    PubMed

    Fazekas, Franz; Ropele, Stefan; Enzinger, Christian; Gorani, Faton; Seewann, Alexandra; Petrovic, Katja; Schmidt, Reinhold

    2005-12-01

    The severity of tissue changes associated with incidental white matter hyperintensities (WMH) in the elderly cannot be sufficiently determined by conventional MRI. We, therefore, performed a regional analysis of the magnetization transfer ratio (MTR) maps obtained on a 1.5 T scanner from 198 neurologically asymptomatic participants of the Austrian Stroke Prevention Study (mean age 70, age range 52-87 years) in regard to WMH and predefined areas of normal appearing brain tissue. Fluid attenuated inversion recovery MRI was used to grade lesion severity and for lesion volume measurements. The MTR of WMH was always significantly lower than that of normal appearing white matter (NAWM) with an overall relative reduction of approximately 10% and decreased significantly with increasing scores of WMH severity (P = 0.02) and WMH volume (r = -0.24, P = 0.0016). NAWM MTR was not different between subjects with very few and extensive WMH and the WMH volume was associated with NAWM MTR of the frontal lobes only. Concerning a possible impact on cerebral functioning the MTR of the frontal NAWM was significantly associated with fine motor dexterity (P = 0.04) but not with cognitive performance. A significant decline of the MTR with aging was seen in both NAWM and cortex but not in WMH. We conclude that MTR measurements can serve to quantify WMH associated tissue damage. It is predominantly focal, relatively mild, increases with lesion size and may have remote effects on the frontal white matter. PMID:15958507

  8. 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-m-square measurement grid, and two or more regions of interest within each tissue were also imaged using a 25m-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 1660cm(-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

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

    PubMed

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

    1989-08-01

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

  10. 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.

  11. Cerebral White Matter

    PubMed Central

    Schmahmann, Jeremy D.; Smith, Eric E.; Eichler, Florian S.; Filley, Christopher M.

    2013-01-01

    Lesions of the cerebral white matter (WM) result in focal neurobehavioral syndromes, neuropsychiatric phenomena, and dementia. The cerebral WM contains fiber pathways that convey axons linking cerebral cortical areas with each other and with subcortical structures, facilitating the distributed neural circuits that subserve sensorimotor function, intellect, and emotion. Recent neuroanatomical investigations reveal that these neural circuits are topographically linked by five groupings of fiber tracts emanating from every neocortical area: (1) cortico-cortical association fibers; (2) corticostriatal fibers; (3) commissural fibers; and cortico-subcortical pathways to (4) thalamus and (5) pontocerebellar system, brain stem, and/or spinal cord. Lesions of association fibers prevent communication between cortical areas engaged in different domains of behavior. Lesions of subcortical structures or projection/striatal fibers disrupt the contribution of subcortical nodes to behavior. Disconnection syndromes thus result from lesions of the cerebral cortex, subcortical structures, and WM tracts that link the nodes that make up the distributed circuits. The nature and the severity of the clinical manifestations of WM lesions are determined, in large part, by the location of the pathology: discrete neurological and neuropsychiatric symptoms result from focal WM lesions, whereas cognitive impairment across multiple domainsWM dementiaoccurs in the setting of diffuse WM disease. We present a detailed review of the conditions affecting WM that produce these neurobehavioral syndromes, and consider the pathophysiology, clinical effects, and broad significance of the effects of aging and vascular compromise on cerebral WM, in an attempt to help further the understanding, diagnosis, and treatment of these disorders. PMID:18990132

  12. The superficial white matter in Alzheimer's disease.

    PubMed

    Phillips, Owen R; Joshi, Shantanu H; Piras, Fabrizio; Orfei, Maria Donata; Iorio, Mariangela; Narr, Katherine L; Shattuck, David W; Caltagirone, Carlo; Spalletta, Gianfranco; Di Paola, Margherita

    2016-04-01

    White matter abnormalities have been shown in the large deep fibers of Alzheimer's disease patients. However, the late myelinating superficial white matter comprised of intracortical myelin and short-range association fibers has not received much attention. To investigate this area, we extracted a surface corresponding to the superficial white matter beneath the cortex and then applied a cortical pattern-matching approach which allowed us to register and subsequently sample diffusivity along thousands of points at the interface between the gray matter and white matter in 44 patients with Alzheimer's disease (Age: 71.02 ± 5.84, 16M/28F) and 47 healthy controls (Age 69.23 ± 4.45, 19M/28F). In patients we found an overall increase in the axial and radial diffusivity across most of the superficial white matter (P < 0.001) with increases in diffusivity of more than 20% in the bilateral parahippocampal regions and the temporal and frontal lobes. Furthermore, diffusivity correlated with the cognitive deficits measured by the Mini-Mental State Examination scores (P < 0.001). The superficial white matter has a unique microstructure and is critical for the integration of multimodal information during brain maturation and aging. Here we show that there are major abnormalities in patients and the deterioration of these fibers relates to clinical symptoms in Alzheimer's disease. Hum Brain Mapp 37:1321-1334, 2016. © 2016 Wiley Periodicals, Inc. PMID:26801955

  13. Longitudinal absolute metabolite quantification of white and gray matter regions in healthy controls using proton MR spectroscopic imaging.

    PubMed

    Wiebenga, Oliver T; Klauser, Antoine M; Nagtegaal, Gijsbert J A; Schoonheim, Menno M; Barkhof, Frederik; Geurts, Jeroen J G; Pouwels, Petra J W

    2014-03-01

    The purpose of this study was to evaluate quality parameters, metabolite concentrations and concentration ratios, and to investigate the reproducibility of quantitative proton magnetic resonance spectroscopic imaging ((1)H-MRSI) of selected white and gray matter regions of healthy adults. 2D-quantitative short-TE (1)H-MRSI spectra were obtained at 1.5T from the healthy human brain. Subjects (n?=?12) were scanned twice with an interval of six months. Absolute metabolite concentrations were obtained based on coil loading, taking into account differences in sensitivity of the phased-array head coil. Spectral quality parameters, absolute metabolite concentrations, concentration ratios, and their reproducibility were determined and compared between time-points using a repeated measures general linear model. The quality of the spectra of selected brain areas was good, as determined by a mean spectral linewidth between 4.8 and 7.3 Hz (depending on the region). No significant differences between the two time-points were observed for spectral quality, concentrations, or concentration ratios. The mean intrasubject coefficient of variation (CoV) varied between 4.0 and 8.5% for total N-acetylaspartate, 7.2 and 10.8% for total creatine, 5.9 and 9.8% for myo-inositol, and 8.0 and 13.3% for choline, and remained below 20% for glutamate. CoV was generally lower when concentration ratios were considered. The study shows that longitudinal quantitative short-TE (1)H-MRSI generates reproducible absolute metabolite concentrations in healthy human white and gray matter. This may serve as a background for longitudinal clinical studies in adult patients. PMID:24399803

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.…

  20. APOE-ε4 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, ε4 carriers had higher WMH volume particularly in parietal and occipital lobes. In ESPRIT, ε4 carriers had elevated WMH particularly in parietal and temporal lobes. In the combined analysis, ε4 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 ε4 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. 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 isa 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

  2. 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

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

    PubMed Central

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

    2012-01-01

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

  4. White matter involvement in sporadic Creutzfeldt-Jakob disease

    PubMed Central

    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.

    2014-01-01

    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

  5. Mobile NBM - android medical mobile application designed to help in learning how to identify the different regions of interest in the brain’s white matter

    PubMed Central

    2014-01-01

    Background One of the most critical tasks when conducting neurological studies is identifying the different regions of interest in the brain’s white matter. Currently few programs or applications are available that serve as an interactive guide in this process. This is why a mobile application has been designed and developed in order to teach users how to identify the referred regions of the brain. It also enables users to share the results obtained and take an examination on the knowledge thus learnt. In order to provide direct user-user or user-developer contact, the project includes a website and a Twitter account. Results An application has been designed with a basic, minimalist look, which anyone can access easily in order to learn to identify a specific region in the brain’s white matter. A survey has also been conducted on people who have used it, which has shown that the application is attractive both in the student (final mean satisfaction of 4.2/5) and in the professional (final mean satisfaction of 4.3/5) environment. The response obtained in the online part of the project reflects the high practical value and quality of the application, as shown by the fact that the website has seen a large number of visitors (over 1000 visitors) and the Twitter account has a high number of followers (over 280 followers). Conclusions Mobile NBM is the first mobile application to be used as a guide in the process of identifying a region of interest in the brain’s white matter. Although initially not many areas are available in the application, new ones can be added as required by users in their respective studies. Apart from the application itself, the online resources provided (website and Twitter account) significantly enhance users’ experience. PMID:25037858

  6. Cerebral white matter deficiencies in pedophilic men.

    PubMed

    Cantor, James M; Kabani, Noor; Christensen, Bruce K; Zipursky, Robert B; Barbaree, Howard E; Dickey, Robert; Klassen, Philip E; Mikulis, David J; Kuban, Michael E; Blak, Thomas; Richards, Blake A; Hanratty, M Katherine; Blanchard, Ray

    2008-02-01

    The present investigation sought to identify which brain regions distinguish pedophilic from nonpedophilic men, using unbiased, automated analyses of the whole brain. T1-weighted magnetic resonance images (MRIs) were acquired from men who demonstrated illegal or clinically significant sexual behaviors or interests (n = 65) and from men who had histories of nonsexual offenses but no sexual offenses (n = 62). Sexual interest in children was assessed by participants' admissions of pedophilic interest, histories of committing sexual offenses against children, and psychophysiological responses in the laboratory to erotic stimuli depicting children or adults. Automated parcellation of the MRIs revealed significant negative associations between pedophilia and white matter volumes of the temporal and parietal lobes bilaterally. Voxel-based morphometry corroborated the associations and indicated that the regions of lower white matter volumes followed, and were limited to, two major fiber bundles: the superior fronto-occipital fasciculus and the right arcuate fasciculus. No significant differences were found in grey matter or in cerebrospinal fluid (CSF). Because the superior fronto-occipital and arcuate fasciculi connect the cortical regions that respond to sexual cues, these results suggest (1) that those cortical regions operate as a network for recognizing sexually relevant stimuli and (2) that pedophilia results from a partial disconnection within that network. PMID:18039544

  7. 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

  8. Developmental regulation of AMPA receptor subunit expression in forebrain and relationship to regional susceptibility to hypoxic/ischemic injury: Part II. Human cerebral white matter and cortex

    PubMed Central

    Talos, Delia M.; Follett, Pamela L.; Folkerth, Rebecca D.; Fishman, Rachel E.; Trachtenberg, Felicia L.; Volpe, Joseph J.; Jensen, Frances E.

    2010-01-01

    This report is the second of a two-part evaluation of developmental differences in α–amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor subunit expression in cell populations within white matter and cortex. In Part I, we report that in rat, developmental expression of Ca2+ permeable (GluR2-lacking) AMPARs correlated at the regional and cellular level with increased susceptibility to hypoxia/ischemia (H/I), suggesting an age-specific role of these receptors in the pathogenesis of brain injury. Part II examines the regional and cellular progression of AMPAR subunits in human white matter and cortex from midgestation through early childhood. Similar to the rodent, there is a direct correlation between selective vulnerability to H/I and expression of GluR2-lacking AMPARs in human brain. In midgestational cases aged 20-24 postconceptional weeks (PCW) and in premature infants (25-37 PCW), we found that radial glia, premyelinating oligodendrocytes and subplate neurons transiently expressed GluR2-lacking AMPARs. Notably, prematurity represents a developmental window of selective vulnerability for white matter injury, such as periventricular leukomalacia (PVL). During term (38-42 PCW) and post-term neonatal (43-46 PCW) periods, age windows characterized by increased susceptibility to cortical injury and seizures, GluR2 expression was low in the neocortex, specifically on cortical pyramidal and non-pyramidal neurons. This study indicates that Ca2+ permeable AMPAR blockade may represent an age-specific therapeutic strategy for potential use in humans. Furthermore, these data help validate specific rodent maturational stages as appropriate models for evaluation of H/I pathophysiology. PMID:16680761

  9. 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…

  10. 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

  11. White matter abnormalities in Methcathinone abusers with an extrapyramidal syndrome

    PubMed Central

    Stepens, Ainārs; Stagg, Charlotte Jane; Platkājis, Ardis; Boudrias, Marie-Hélène; Johansen-Berg, Heidi; Donaghy, Michael

    2013-01-01

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

  12. 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.

  13. Genetics Home Reference: Leukoencephalopathy with vanishing white matter

    MedlinePLUS

    ... Genetic disorder catalog Conditions > Leukoencephalopathy with vanishing white matter On this page: Description Genetic changes Inheritance Diagnosis ... May 2013 What is leukoencephalopathy with vanishing white matter? Leukoencephalopathy with vanishing white matter is a progressive ...

  14. 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

  15. White Matter Atlas Generation using HARDI based Automated Parcellation

    PubMed Central

    Bloy, Luke; Ingalhalikar, Madhura; Eavani, Harini; Schultz, Robert T.; Roberts, Timothy P.L.; Verma, Ragini

    2011-01-01

    Most diffusion imaging studies have used subject registration to an atlas space for enhanced quantification of anatomy. However, standard diffusion tensor atlases lack information in regions of fiber crossing and are based on adult anatomy. The degree of error associated with applying these atlases to studies of children for example has not yet been estimated but may lead to suboptimal results. This paper describes a novel technique for generating population-specific high angular resolution diffusion imaging (HARDI)-based atlases consisting of labeled regions of homogenous white matter. Our approach uses a fiber orientation distribution (FOD) diffusion model and a data driven clustering algorithm. White matter regional labeling is achieved by our automated data driven clustering algorithm that has the potential to delineate white matter regions based on fiber complexity and orientation. The advantage of such an atlas is that it is study specific and more comprehensive in describing regions of white matter homogeneity as compared to standard anatomical atlases. We have applied this state of the art technique to a dataset consisting of adolescent and preadolescent children, creating one of the first examples of a HARDI-based atlas, thereby establishing the feasibility of the atlas creation framework. The white matter regions generated by our automated clustering algorithm have lower FOD variance than when compared to the regions created from a standard anatomical atlas. PMID:21893205

  16. 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.

  17. Interactive effects of apolipoprotein e4 and diabetes risk on later myelinating white matter regions in neurologically healthy older aged adults

    PubMed Central

    Foley, Jessica M.; Salat, David H.; Stricker, Nikki H.; Zink, Tyler A.; Grande, Laura J.; McGlinchey, Regina E.; Milberg, William P.; Leritz, Elizabeth C.

    2014-01-01

    Possession of the apolipoprotein e4 (APOE4) allele and diabetes risk are independently related to reduced white matter (WM) integrity that may contribute to the development of Alzheimer's disease (AD). The purpose of this study is to examine the interactive effects of APOE4 and diabetes risk on later myelinating WM regions among healthy elderly at risk for AD. A sample of 107 healthy elderly (80 APOE4−/27 APOE4+) underwent structural MRI/ DTI data were prepared using TBSS and a-priori ROIs were extracted from T1-based WM parcellations. ROIs included later myelinating frontal/temporal/parietal WM regions and control regions, measured by fractional anisotropy (FA). There were no APOE group differences on DTI for any ROI. Within the APOE4 group, we found negative relationships between HAIC/fasting glucose and APOE4 on FA for all later myelinating WM regions, but not for early/middle myelinating control regions. Results also showed APOE4/diabetes risk interactions for WM underlying supramarginal, superior temporal, precuneus, superior parietal, and superior frontal regions. Results suggest interactive effects of APOE4 and diabetes risk on later myelinating WM regions, which supports preclinical detection of AD among this particularly susceptible subgroup. PMID:24381137

  18. Longitudinal white matter changes in frontotemporal dementia subtypes.

    PubMed

    Lam, Bonnie Y K; Halliday, Glenda M; Irish, Muireann; Hodges, John R; Piguet, Olivier

    2014-07-01

    Frontotemporal dementia is a degenerative brain condition characterized by focal atrophy affecting the frontal and temporal lobes predominantly. Changes in white matter with disease progression and their relationship to grey matter atrophy remain unknown in FTD. This study aimed to establish longitudinal white matter changes and compare these changes to regional grey matter atrophy in the main FTD subtypes. Diffusion and T?-weighted images were collected from behavioral-variant FTD (bvFTD: 12), progressive non-fluent aphasia (PNFA: 10), semantic dementia (SD: 11), and 15 controls at baseline and 12 months apart. Changes in white matter integrity were established by fractional anisotropy, mean, axial and radial diffusivity measurements using tract-based spatial statistics. Patterns of cortical grey matter atrophy were measured using voxel-based morphometry. At baseline, bvFTD showed severe cross-sectional changes in orbitofrontal and anterior temporal tracts, which progressed to involve posterior temporal and occipital white matter over the 12-month. In PNFA, cross-sectional changes occurred bilaterally in frontotemporal white matter (left > right), with longitudinal changes more prominent on the right. Initial white matter changes in SD were circumscribed to the left temporal lobe, with longitudinal changes extending to bilateral frontotemporal tracts. In contrast, progression of grey matter change over time was less pronounced in all FTD subtypes. Mean diffusivity was most sensitive in detecting baseline changes while fractional anisotropy and radial diffusivity revealed greatest changes over time, possibly reflecting different underlying pathological processes with disease progression. Our results indicate that investigations of white matter changes reveal important differences across FTD syndromes with disease progression. PMID:25050433

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

    PubMed

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

    2014-09-01

    The normal myelination of neuronal axons is essential to neurodevelopment, allowing fast inter-neuronal communication. The most dynamic period of myelination occurs in the first few years of life, in concert with a dramatic increase in cognitive abilities. How these processes relate, however, is still unclear. Here we aimed to use a data-driven technique to parcellate developing white matter into regions with consistent white matter growth trajectories and investigate how these regions related to cognitive development. In a large sample of 183 children aged 3 months to 4 years, we calculated whole brain myelin volume fraction (VFM ) maps using quantitative multicomponent relaxometry. We used spatial independent component analysis (ICA) to blindly segment these quantitative VFM images into anatomically meaningful parcels with distinct developmental trajectories. We further investigated the relationship of these trajectories with standardized cognitive scores in the same children. The resulting components represented a mix of unilateral and bilateral white matter regions (e.g., cortico-spinal tract, genu and splenium of the corpus callosum, white matter underlying the inferior frontal gyrus) as well as structured noise (misregistration, image artifact). The trajectories of these regions were associated with individual differences in cognitive abilities. Specifically, components in white matter underlying frontal and temporal cortices showed significant relationships to expressive and receptive language abilities. Many of these relationships had a significant interaction with age, with VFM becoming more strongly associated with language skills with age. These data provide evidence for a changing coupling between developing myelin and cognitive development. PMID:24578096

  20. White matter and deep gray matter hemodynamic changes in multiple sclerosis patients with clinically isolated syndrome.

    PubMed

    Papadaki, Efrosini Z; Mastorodemos, Vasileios C; Amanakis, Emmanouil Z; Tsekouras, Konstantinos C; Papadakis, Antonis E; Tsavalas, Nikolaos D; Simos, Panagiotis G; Karantanas, Apostolos H; Plaitakis, Andreas; Maris, Thomas G

    2012-12-01

    The dynamic susceptibility contrast magnetic resonance imaging perfusion technique was used to investigate possible hemodynamic changes in normal appearing white matter and deep gray matter (DGM) of 30 patients with clinically isolated syndrome (CIS) and 30 patients with relapsing-remitting multiple sclerosis. Thirty normal volunteers were studied as controls. Cerebral blood volume, cerebral blood flow (CBF), and mean transit time values were estimated. Normalization was achieved for each subject with respect to average values of CBF and mean transit time of the hippocampi's dentate gyrus. Measurements concerned three regions of normal white matter of normal volunteers, normal appearing white matter of CIS and patients with relapsing-remitting multiple sclerosis, and DGM regions, bilaterally. All measured normal appearing white matter and DGM regions of the patients with CIS had significantly higher cerebral blood volume and mean transit time values, while averaged DGM regions had significantly lower CBF values, compared to those of normal volunteers (P < 0.001). Regarding patients with relapsing-remitting multiple sclerosis, all measured normal appearing white matter and DGM regions showed lower CBF values than those of normal volunteers and lower cerebral blood volume and CBF values compared to patients with CIS (P < 0.001). These data provide strong evidence that hemodynamic changes--affecting both white and DGM--may occur even at the earliest stage of multiple sclerosis, with CIS patients being significantly different than relapsing-remitting multiple sclerosis patients. PMID:22367604

  1. 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

  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. White Matter Microstructure in Idiopathic Craniocervical Dystonia

    PubMed Central

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

    2015-01-01

    Background Dystonias are hyperkinetic movement disorders characterized by involuntary muscle contractions resulting in abnormal torsional movements and postures. Recent neuroimaging studies in idiopathic craniocervical dystonia (CCD) have uncovered the involvement of multiple areas, including cortical ones. Our goal was to evaluate white matter (WM) microstructure in subjects with CCD using diffusion tensor imaging (DTI) analysis. Methods We compared 40 patients with 40 healthy controls. Patients were then divided into subgroups: cervical dystonia, blepharospasm, blepharospasm + oromandibular dystonia, blepharospasm + oromandibular dystonia + cervical dystonia, using tract-based spatial statistics. We performed a region of interest-based analysis and tractography as confirmatory tests. Results There was no significant difference in the mean fractional anisotropy (FA) and mean diffusivity (MD) between the groups in any analysis. Discussion The lack of DTI changes in CCD suggests that the WM tracts are not primarily affected. PMID:26056610

  4. 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 etal., 2007; Song etal., 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 etal. (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 whostutter. 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 etal., 2006). PMID:23140891

  5. The Reduction of Regional Cerebral Blood Flow in Normal-Appearing White Matter Is Associated with the Severity of White Matter Lesions in Elderly: A Xeon-CT Study

    PubMed Central

    Han, Jinghao; Hong, Zhen

    2014-01-01

    White matter lesions (WMLs) in normal elderly are related to chronic ischemia, and progression of WML occurs mostly in moderate to severe disease. However, the mechanism is uncertain. Thus, we enrolled fifty-six normal elderly patients without large artery disease. The severity of WML on MRI was graded as grade 0, I, II and III using the modified Fazekas scale. Cerebral blood flow (CBF) was measured by Xenon-CT. We found that CBF (mL/100 g/min) within periventricular lesions and in the right and left centrum semiovales were 20.33, 21.27 and 21.03, respectively, in group I; 16.33, 15.55 and 15.91, respectively, in group II; and 14.05, 14.46 and 14.23, respectively, in group III. CBF of normal-appearing white matter (NAWM) around periventricular areas and in the right and left centrum semiovales were 20.79, 22.26 and 22.15, respectively, in group 0; 21.12, 22.17 and 22.25, respectively, in group I; 18.02, 19.45 and 19.62, respectively, in group II; and 16.38, 18.18 and 16.74, respectively, in group III. Significant reductions in CBF were observed not only within lesions but also in NAWM surrounding the lesions. In addition, CBF was reduced significantly within lesions compared to NAWM of the same grade. Furthermore, CBF was reduced significantly in NAWM in grades II and III when compared to grades 0 and I. Our finding indicates that ischemia may play a role in the pathogenesis of WML. Additionally, our finding provides an alternative explanation for finding that the progression of WML occurred more commonly in patients with moderate to severe WML. PMID:25401786

  6. Brain white matter volume abnormalities in Lesch-Nyhan disease and its variants

    PubMed Central

    Varvaris, Mark; Vannorsdall, Tracy D.; Gordon, Barry; Harris, James C.; Jinnah, H.A.

    2015-01-01

    Objective: We sought to examine brain white matter abnormalities based on MRI in adults with Lesch-Nyhan disease (LND) or an attenuated variant (LNV) of this rare, X-linked neurodevelopmental disorder of purine metabolism. Methods: In this observational study, we compared 21 adults with LND, 17 with LNV, and 33 age-, sex-, and race-matched healthy controls using voxel-based morphometry and analysis of covariance to identify white matter volume abnormalities in both patient groups. Results: Patients with classic LND showed larger reductions of white (26%) than gray (17%) matter volume relative to healthy controls. Those with LNV showed comparable reductions of white (14%) and gray (15%) matter volume. Both patient groups demonstrated reduced volume in medial inferior white matter regions. Compared with LNV, the LND group showed larger reductions in inferior frontal white matter adjoining limbic and temporal regions and the motor cortex. These regions likely include such long association fibers as the superior longitudinal and uncinate fasciculi. Conclusions: Despite earlier reports that LND primarily involves the basal ganglia, this study reveals substantial white matter volume abnormalities. Moreover, white matter deficits are more severe than gray matter deficits in classic LND, and also characterize persons with LNV. The brain images acquired for these analyses cannot precisely localize white matter abnormalities or determine whether they involve changes in tract orientation or anisotropy. However, clusters of reduced white matter volume identified here affect regions that are consistent with the neurobehavioral phenotype. PMID:25503620

  7. Alterations in diffusion properties of white matter in Williams syndrome

    PubMed Central

    Arlinghaus, Lori R.; Thornton-Wells, Tricia A.; Dykens, Elisabeth M.; Anderson, Adam W.

    2011-01-01

    Diffusion tensor imaging (DTI) was used to investigate the involvement of brain white matter in Williams syndrome (WS), a genetic neurodevelopmental disorder. Whole-brain DTIs were obtained from 16 young adults with WS and 16 normal controls. A voxel-based analysis was performed to compare fractional anisotropy (FA) values between the two groups. A tract-based analysis was also performed to compare FA values between the two groups along two major white matter tracts that pass through the external capsule: the uncinate and inferior fronto-occipital fasciculi. Several regions of both increased and decreased FA were found within major white matter tracts that connect functional regions that have previously been implicated in the cognitive and neurological symptoms of the syndrome. The tract-based analysis provided additional insight into the involvement of specific white matter tracts implicated in the voxel-based analysis within the external capsule. The results from this study support previously reported changes in white matter diffusion properties in WS and demonstrate the potential usefulness for tract-based analysis in future studies of the disorder. PMID:21907520

  8. Microinfarct disruption of white matter structure

    PubMed Central

    Auriel, Eitan; Edlow, Brian L.; Reijmer, Yael D.; Fotiadis, Panagiotis; Ramirez-Martinez, Sergi; Ni, Jun; Reed, Anne K.; Vashkevich, Anastasia; Schwab, Kristin; Rosand, Jonathan; Viswanathan, Anand; Wu, Ona; Gurol, M. Edip

    2014-01-01

    Objective: To evaluate the local effect of small asymptomatic infarctions detected by diffusion-weighted imaging (DWI) on white matter microstructure using longitudinal structural and diffusion tensor imaging (DTI). Methods: Nine acute to subacute DWI lesions were identified in 6 subjects with probable cerebral amyloid angiopathy who had undergone high-resolution MRI both before and after DWI lesion detection. Regions of interest (ROIs) corresponding to the site of the DWI lesion (lesion ROI) and corresponding site in the nonlesioned contralateral hemisphere (control ROI) were coregistered to the pre- and postlesional scans. DTI tractography was additionally performed to reconstruct the white matter tracts containing the ROIs. DTI parameters (fractional anisotropy [FA], mean diffusivity [MD]) were quantified within each ROI, the 6-mm lesion-containing tract segments, and the entire lesion-containing tract bundle. Lesion/control FA and MD ratios were compared across time points. Results: The postlesional scans (performed a mean 7.1 4.7 months after DWI lesion detection) demonstrated a decrease in median FA lesion/control ROI ratio (1.08 to 0.93, p = 0.038) and increase in median MD lesion/control ROI ratio (0.97 to 1.17, p = 0.015) relative to the prelesional scans. There were no visible changes on postlesional high-resolution T1-weighted and fluid-attenuated inversion recovery images in 4 of 9 lesion ROIs and small (25 mm) T1 hypointensities in the remaining 5. No postlesional changes in FA or MD ratios were detected in the 6-mm lesion-containing tract segments or full tract bundles. Conclusions: Asymptomatic DWI lesions produce chronic local microstructural injury. The cumulative effects of these widely distributed lesions may directly contribute to small-vesselrelated vascular cognitive impairment. PMID:24920857

  9. MR volume segmentation of gray matter and white matter using manual thresholding: Dependence on image brightness

    SciTech Connect

    Harris, G.J.; Barta, P.E.; Peng, L.W.; Lee, S.; Brettschneider, P.D.; Shah, A.; Henderer, J.D.; Schlaepfer, T.E.; Pearlson, G.D. Tufts Univ. School of Medicine, Boston, MA )

    1994-02-01

    To describe a quantitative MR imaging segmentation method for determination of the volume of cerebrospinal fluid, gray matter, and white matter in living human brain, and to determine the method's reliability. We developed a computer method that allows rapid, user-friendly determination of cerebrospinal fluid, gray matter, and white matter volumes in a reliable manner, both globally and regionally. This method was applied to a large control population (N = 57). Initially, image brightness had a strong correlation with the gray-white ratio (r = .78). Bright images tended to overestimate, dim images to underestimate gray matter volumes. This artifact was corrected for by offsetting each image to an approximately equal brightness. After brightness correction, gray-white ratio was correlated with age (r = -.35). The age-dependent gray-white ratio was similar to that for the same age range in a prior neuropathology report. Interrater reliability was high (.93 intraclass correlation coefficient). The method described here for gray matter, white matter, and cerebrospinal fluid volume calculation is reliable and valid. A correction method for an artifact related to image brightness was developed. 12 refs., 3 figs.

  10. White Matter atrophy in Alzheimer Disease variants

    PubMed Central

    Migliaccio, Raffaella; Agosta, Federica; Possin, Katherine L.; Rabinovici, Gil D.; Miller, Bruce L.; Gorno-Tempini, Maria Luisa

    2013-01-01

    Background In comparison to late-onset Alzheimer’s disease (LO-AD, onset > 65), early age-of-onset Alzheimer’s disease (EO-AD, onset<65 years) more often presents with language, visuospatial and/or executive impairment, often occurring earlier than a progressive memory deficit. The logopenic variant of primary progressive aphasia (lv-PPA) and the posterior cortical atrophy (PCA) have recently been described as possible atypical variants of EO-AD. Lv-PPA is characterized by isolated language deficit, while PCA is characterized by predominant visuospatial deficits. Severe hemispheric grey matter (GM) atrophy associated with EO-AD, lv-PPA and PCA has been described, but regional patterns of white matter (WM) damage are still poorly understood. Methods Using structural MRI and voxel-based morphometry, we investigated WM damage in 16 EO-AD, 13 PCA, 10 lv-PPA, and 14 LO-AD patients at presentation, and 72 age-matched controls. Results In EO-AD, PCA and lv-PPA patients, WM atrophy was centered on lateral temporal and parietal regions, including cingulum and posterior corpus callosum. Compared to controls, lv-PPA patients showed a more severe left parietal damage, and PCA showed a more severe occipital atrophy. Moreover, EO-AD had greater cingulum atrophy compared with LO-AD. LO-AD showed WM damage in medial temporal regions and less extensive hemispheric involvement. Conclusions Patterns of WM damage in EO-AD, lv-PPA and PCA are consistent with the clinical syndromes and GM atrophy patterns. WM injury in AD atypical variants may contribute to symptoms and disease pathogenesis. PMID:23021625

  11. Abnormalities in White Matter Microstructure Associated with Chronic Ketamine Use

    PubMed Central

    Edward Roberts, R; Curran, H Valerie; Friston, Karl J; Morgan, Celia J A

    2014-01-01

    Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that has been found to induce schizophrenia-type symptoms in humans and is a potent and fast-acting antidepressant. It is also a relatively widespread drug of abuse, particularly in China and the UK. Acute administration has been well characterized, but the effect of extended periods of ketamine use—on brain structure in humans—remains poorly understood. We measured indices of white matter microstructural integrity and connectivity in the brain of 16 ketamine users and 16 poly-drug-using controls, and we used probabilistic tractography to quantify changes in corticosubcortical connectivity associated with ketamine use. We found a reduction in the axial diffusivity profile of white matter in a right hemisphere network of white matter regions in ketamine users compared with controls. Within the ketamine-user group, we found a significant positive association between the connectivity profile between the caudate nucleus and the lateral prefrontal cortex and dissociative experiences. These findings suggest that chronic ketamine use may be associated with widespread disruption of white matter integrity, and white matter pathways between subcortical and prefrontal cortical areas may in part predict individual differences in dissociative experiences due to ketamine use. PMID:23929545

  12. Gestational iron deficiency differentially alters the structure and function of white and gray matter brain regions of developing rats.

    PubMed

    Greminger, Allison R; Lee, Dawn L; Shrager, Peter; Mayer-Prschel, Margot

    2014-07-01

    Gestational iron deficiency (ID) has been associated with a wide variety of central nervous system (CNS) impairments in developing offspring. However, a focus on singular regions has impeded an understanding of the CNS-wide effects of this micronutrient deficiency. Because the developing brain requires iron during specific phases of growth in a region-specific manner, we hypothesized that maternal iron deprivation would lead to region-specific impairments in the CNS of offspring. Female rats were fed an iron control (Fe+) or iron-deficient (Fe-) diet containing 240 or 6 ?g/g iron during gestation and lactation. The corpus callosum (CC), hippocampus, and cortex of the offspring were analyzed at postnatal day 21 (P21) and/or P40 using structural and functional measures. In the CC at P40, ID was associated with reduced peak amplitudes of compound action potentials specific to myelinated axons, in which diameters were reduced by ?20% compared with Fe+ controls. In the hippocampus, ID was associated with a 25% reduction in basal dendritic length of pyramidal neurons at P21, whereas branching complexity was unaffected. We also identified a shift toward increased proximal branching of apical dendrites in ID without an effect on overall length compared with Fe+ controls. ID also affected cortical neurons, but unlike the hippocampus, both apical and basal dendrites displayed a uniform decrease in branching complexity, with no significant effect on overall length. These deficits culminated in significantly poorer performance of P40 Fe- offspring in the novel object recognition task. Collectively, these results demonstrate that non-anemic gestational ID has a significant and region-specific impact on neuronal development and may provide a framework for understanding and recognizing the presentation of clinical symptoms of ID. PMID:24744313

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

    PubMed

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

    2014-10-01

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

  14. White matter hyperintensities are positively associated with cortical thickness in Alzheimer's disease.

    PubMed

    Jacobs, Heidi I L; Clerx, Lies; Gronenschild, Ed H B M; Aalten, Pauline; Verhey, Frans R J

    2014-01-01

    White matter hyperintensities are associated with an increased risk of Alzheimer's disease (AD). White matter hyperintensities are believed to disconnect brain areas. We examined the topographical association between white matter hyperintensities and cortical thickness in controls, mild cognitive impairment (MCI), and AD patients. We examined associations between white matter hyperintensities and cortical thickness among 18 older cognitively healthy participants, 18 amnestic MCI, and 17 mild AD patients. These associations were cluster-size corrected for multiple comparisons. In controls, a positive association between white matter hyperintensities and cortical thickness was found in lateral temporal gyri. In MCI patients, white matter hyperintensities were positively related to cortical thickness in frontal, temporal, and parietal areas. Positive associations between white matter hyperintensities and cortical thickness in AD patients were confined to parietal areas. The results of the interaction group by white matter hyperintensities on cortical thickness were consistent with the findings of positive associations in the parietal lobe for MCI and AD patients separately. In the frontal areas, controls and AD patients showed inverse associations between white matter hyperintensities and cortical thickness, while MCI patients still showed a positive association. These results suggest that a paradoxical relationship between white matter hyperintensities and cortical thickness could be a consequence of neuroinflammatory processes induced by AD-pathology and white matter hyperintensities. Alternatively, it might reflect a region-specific and disease-stage dependent compensatory hypertrophy in response to a compromised network. PMID:24169238

  15. 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 (1833 years) and 10 middle-aged (4264 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 250350ms and in left inferior prefrontal cortex from 350450ms (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 250350ms, 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

  16. White Matter Hyperintensities and Changes in White Matter Integrity in Patients with Alzheimers Disease

    PubMed Central

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

    2012-01-01

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

  17. Mild Cognitive Impairment is Associated With White Matter Integrity Changes in Late-Myelinating Regions Within the Corpus Callosum.

    PubMed

    Stricker, Nikki H; Salat, David H; Kuhn, Taylor P; Foley, Jessica M; Price, Jenessa S; Westlye, Lars T; Esterman, Michael S; McGlinchey, Regina E; Milberg, William P; Leritz, Elizabeth C

    2016-02-01

    Degenerative brain changes in Alzheimer's disease may occur in reverse order of normal brain development based on the retrogenesis model. This study tested whether evidence of reverse myelination was observed in mild cognitive impairment (MCI) using a data-driven analytic approach based on life span developmental data. Whole-brain high-resolution diffusion tensor imaging scans were obtained for 31 patients with MCI and 79 demographically matched healthy older adults. Comparisons across corpus callosum (CC) regions of interest (ROIs) showed decreased fractional anisotropy (FA) in the body but not in the genu or splenium; early-, middle-, and late-myelinating ROIs restricted to the CC revealed decreased FA in late- but not early- or middle-myelinating ROIs. Voxelwise group differences revealed areas of lower FA in MCI, but whole-brain differences were equally distributed across early-, middle-, and late-myelinating regions. Overall, results within the CC support the retrogenesis model, although caution is needed when generalizing these results beyond the CC. PMID:25904759

  18. 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

  19. Specific white matter tissue microstructure changes associated with obesity

    PubMed Central

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

    2016-01-01

    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

  20. Regional White Matter Atrophy–Based Classification of Multiple Sclerosis in Cross-Sectional and Longitudinal Data

    PubMed Central

    Sampat, M.P.; Berger, A.M.; Healy, B.C.; Hildenbrand, P.; Vass, J.; Meier, D.S.; Chitnis, T.; Weiner, H.L.; Bakshi, R.; Guttmann, C.R.G.

    2009-01-01

    Background and Purpose The different clinical subtypes of multiple sclerosis (MS) may reflect underlying differences in affected neuroanatomic regions. Our aim was to analyze the effectiveness of jointly using the inferior subolivary medulla oblongata volume (MOV) and the cross-sectional area of the corpus callosum in distinguishing patients with relapsing-remitting multiple sclerosis (RRMS), secondary-progressive multiple sclerosis (SPMS), and primary-progressive multiple sclerosis (PPMS). Materials and Methods We analyzed a cross-sectional dataset of 64 patients (30 RRMS, 14 SPMS, 20 PPMS) and a separate longitudinal dataset of 25 patients (114 MR imaging examinations). Twelve patients in the longitudinal dataset had converted from RRMS to SPMS. For all images, the MOV and corpus callosum were delineated manually and the corpus callosum was parcellated into 5 segments. Patients from the cross-sectional dataset were classified as RRMS, SPMS, or PPMS by using a decision tree algorithm with the following input features: brain parenchymal fraction, age, disease duration, MOV, total corpus callosum area and areas of 5 segments of the corpus callosum. To test the robustness of the classification technique, we applied the results derived from the cross-sectional analysis to the longitudinal dataset. Results MOV and central corpus callosum segment area were the 2 features retained by the decision tree. Patients with MOV >0.94 cm3 were classified as having RRMS. Patients with progressive MS were further subclassified as having SPMS if the central corpus callosum segment area was <55.12 mm2, and as having PPMS otherwise. In the cross-sectional dataset, 51/64 (80%) patients were correctly classified. For the longitudinal dataset, 88/114 (77%) patient time points were correctly classified as RRMS or SPMS. Conclusions Classification techniques revealed differences in affected neuroanatomic regions in subtypes of multiple sclerosis. The combination of central corpus callosum segment area and MOV provides good discrimination among patients with RRMS, SPMS, and PPMS. PMID:19696139

  1. 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

  2. A proton spectroscopy study of white matter in children with autism.

    PubMed

    Hardan, Antonio Y; Fung, Lawrence K; Frazier, Thomas; Berquist, Sean W; Minshew, Nancy J; Keshavan, Matcheri S; Stanley, Jeffrey A

    2016-04-01

    White matter abnormalities have been described in autism spectrum disorder (ASD) with mounting evidence implicating these alterations in the pathophysiology of the aberrant connectivity reported in this disorder. The goal of this investigation is to further examine white matter structure in ASD using proton magnetic resonance spectroscopy ((1)H MRS). Multi-voxel, short echo-time in vivo(1)H MRS data were collected from 17 male children with ASD and 17 healthy age- and gender-matched controls. Key (1)H MRS metabolite ratios relative to phosphocreatine plus creatine were obtained from four different right and left white matter regions. Significantly lower N-acetylaspartate/creatine ratios were found in the anterior white matter regions of the ASD group when compared to controls. These findings reflect impairment in neuroaxonal white matter tissue and shed light on the neurobiologic underpinnings of white matter abnormalities in ASD by implicating an alteration in myelin and/or axonal development in this disorder. PMID:26593330

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

    PubMed Central

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

    2014-01-01

    The normal myelination of neuronal axons is essential to neurodevelopment, allowing fast inter-neuronal communication. The most dynamic period of myelination occurs in the first few years of life, in concert with a dramatic increase in cognitive abilities. How these processes relate, however, is still unclear. Here we aimed to use a data-driven technique to parcellate developing white matter into regions with consistent white matter growth trajectories and investigate how these regions related to cognitive development. In a large sample of 183 children aged 3 months to 4 years, we calculated whole brain myelin volume fraction (VFM) maps using quantitative multicomponent relaxometry. We used spatial independent component analysis (ICA) to blindly segment these quantitative VFM images into anatomically meaningful parcels with distinct developmental trajectories. We further investigated the relationship of these trajectories with standardized cognitive scores in the same children. The resulting components represented a mix of unilateral and bilateral white matter regions (e.g., cortico-spinal tract, genu and splenium of the corpus callosum, white matter underlying the inferior frontal gyrus) as well as structured noise (misregistration, image artifact). The trajectories of these regions were associated with individual differences in cognitive abilities. Specifically, components in white matter underlying frontal and temporal cortices showed significant relationships to expressive and receptive language abilities. Many of these relationships had a significant interaction with age, with VFM becoming more strongly associated with language skills with age. These data provide evidence for a changing coupling between developing myelin and cognitive development. Hum Brain Mapp 35:44754487, 2014. PMID:24578096

  4. Structural neuroimaging in Alzheimer's disease: do white matter hyperintensities matter?

    PubMed Central

    Brickman, Adam M.; Muraskin, Jordan; Zimmerman, Molly E.

    2009-01-01

    The targeted brain dysfunction that accompanies aging can have a devastating effect on cognitive and intellectual abilities. A significant proportion of older adults experience precipitous cognitive decline that negatively impacts functional activities. Such individuals meet clinical diagnostic criteria for dementia, which is commonly attributed to Alzheimer's disease (AD). Structural neuroimaging, including magnetic resonance imaging (MRI), has contributed significantly to our understanding of the morphological and pathology-related changes that may underlie normal and disease-associated cognitive change in aging. White matter hyperintensities (WMH), which are distributed patches of increased hyperintense signal on T2-weighted MRI, are among the most common structural neuroimaging findings in older adults. In recent years, WMH have emerged as robust radiological correlates of cognitive decline. Studies suggest that WMH distributed in anterior brain regions are related to decline in executive abilities that is typical of normal aging, whereas WMH distributed in more posterior brain regions are common in AD. Although epidemiological, observational, and pathological studies suggest that WMH may be ischemic in origin and caused by consistent or variable hypoperfusion, there is emerging evidence that they may also reflect vascular deposition of (?-amyloid, particularly when they are distributed in posterior areas and are present in patients with AD. Findings from the literature highlight the potential contribution of small-vessel cerebrovascular disease to the pathogenesis of AD, and suggest a mechanistic interaction, but future longitudinal studies using multiple imaging modalities are required to fully understand the complex role of WMH in AD. PMID:19585953

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

    PubMed

    Navas-Snchez, Francisco J; Alemn-Gmez, Yasser; Snchez-Gonzalez, Javier; Guzmn-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

  6. 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 2570% 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

  7. Inflammatory Pathways Link Socioeconomic Inequalities to White Matter Architecture

    PubMed Central

    Gianaros, Peter J.; Marsland, Anna L.; Sheu, Lei K.; Erickson, Kirk I.; Verstynen, Timothy D.

    2013-01-01

    Socioeconomic disadvantage confers risk for aspects of ill health that may be mediated by systemic inflammatory influences on the integrity of distributed brain networks. Following this hypothesis, we tested whether socioeconomic disadvantage related to the structural integrity of white matter tracts connecting brain regions of distributed networks, and whether such a relationship would be mediated by anthropometric, behavioral, and molecular risk factors associated with systemic inflammation. Otherwise healthy adults (N= 155, aged 3050 years, 78 men) completed protocols assessing multilevel indicators of socioeconomic position (SEP), anthropometric and behavioral measures of adiposity and cigarette smoking, circulating levels of C-reactive protein (CRP), and white matter integrity by diffusion tensor imaging. Mediation modeling was used to test associations between SEP indicators and measures of white matter tract integrity, as well as indirect mediating paths. Measures of tract integrity followed a socioeconomic gradient: individuals completing more schooling, earning higher incomes, and residing in advantaged neighborhoods exhibited increases in white matter fractional anisotropy and decreases in radial diffusivity, relative to disadvantaged individuals. Moreover, analysis of indirect paths showed that adiposity, cigarette smoking, and CRP partially mediated these effects. Socioeconomic inequalities may relate to diverse health disparities via inflammatory pathways impacting the structural integrity of brain networks. PMID:22772650

  8. White Matter Microstructural Integrity in Youth With Type 1 Diabetes

    PubMed Central

    Antenor-Dorsey, Jo Ann V.; Meyer, Erin; Rutlin, Jerrel; Perantie, Dana C.; White, Neil H.; Arbelaez, Ana Maria; Shimony, Joshua S.; Hershey, Tamara

    2013-01-01

    Decreased white and gray matter volumes have been reported in youth with type 1 diabetes mellitus (T1DM), but the effects of hyperglycemia on white matter integrity have not been quantitatively assessed during brain development. We performed diffusion tensor imaging, using two complimentary approachesregion-of-interest and voxelwise tract-based spatial statisticsto quantify white matter integrity in a large retrospective study of T1DM youth and control participants. Exposure to chronic hyperglycemia, severe hyperglycemic episodes, and severe hypoglycemia, as defined in the Diabetes Control and Complications Trial (DCCT), were estimated through medical records review, HbA1c levels, and interview of parents and youth. We found lower fractional anisotropy in the superior parietal lobule and reduced mean diffusivity in the thalamus in the T1DM group. A history of three or more severe hyperglycemic episodes was associated with reduced anisotropy and increased diffusivity in the superior parietal lobule and increased diffusivity in the hippocampus. These results add microstructural integrity of white matter to the range of structural brain alterations seen in T1DM youth and suggest vulnerability of the superior parietal lobule, hippocampus, and thalamus to glycemic extremes during brain development. Longitudinal analyses will be necessary to determine how these alterations change with age or additional glycemic exposure. PMID:23139349

  9. Improved segmentation of white matter tracts with adaptive Riemannian metrics.

    PubMed

    Hao, Xiang; Zygmunt, Kristen; Whitaker, Ross T; Fletcher, P Thomas

    2014-01-01

    We present a novel geodesic approach to segmentation of white matter tracts from diffusion tensor imaging (DTI). Compared to deterministic and stochastic tractography, geodesic approaches treat the geometry of the brain white matter as a manifold, often using the inverse tensor field as a Riemannian metric. The white matter pathways are then inferred from the resulting geodesics, which have the desirable property that they tend to follow the main eigenvectors of the tensors, yet still have the flexibility to deviate from these directions when it results in lower costs. While this makes such methods more robust to noise, the choice of Riemannian metric in these methods is ad hoc. A serious drawback of current geodesic methods is that geodesics tend to deviate from the major eigenvectors in high-curvature areas in order to achieve the shortest path. In this paper we propose a method for learning an adaptive Riemannian metric from the DTI data, where the resulting geodesics more closely follow the principal eigenvector of the diffusion tensors even in high-curvature regions. We also develop a way to automatically segment the white matter tracts based on the computed geodesics. We show the robustness of our method on simulated data with different noise levels. We also compare our method with tractography methods and geodesic approaches using other Riemannian metrics and demonstrate that the proposed method results in improved geodesics and segmentations using both synthetic and real DTI data. PMID:24211814

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

    PubMed Central

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

    2014-01-01

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

  11. 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…

  12. 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

  13. Associations Between White Matter Microstructure and Infants’ Working Memory

    PubMed Central

    Short, Sarah J.; Elison, Jed T.; Goldman, Barbara Davis; Styner, Martin; Gu, Hongbin; Connelly, Mark; Maltbie, Eric; Woolson, Sandra; Lin, Weili; Gerig, Guido; Reznick, J. Steven; Gilmore, John H.

    2013-01-01

    Working memory emerges in infancy and plays a privileged role in subsequent adaptive cognitive development. The neural networks important for the development of working memory during infancy remain unknown. We used diffusion tensor imaging (DTI) and deterministic fiber tracking to characterize the microstructure of white matter fiber bundles hypothesized to support working memory in 12-month-old infants (n=73). Here we show robust associations between infants’ visuospatial working memory performance and microstructural characteristics of widespread white matter. Significant associations were found for white matter tracts that connect brain regions known to support working memory in older children and adults (genu, anterior and superior thalamic radiations, anterior cingulum, arcuate fasciculus, and the temporal-parietal segment). Better working memory scores were associated with higher FA and lower RD values in these selected white matter tracts. These tract-specific brain-behavior relationships accounted for a significant amount of individual variation above and beyond infants’ gestational age and developmental level, as measured with the Mullen Scales of Early Learning. Working memory was not associated with global measures of brain volume, as expected, and few associations were found between working memory and control white matter tracts. To our knowledge, this study is among the first demonstrations of brain-behavior associations in infants using quantitative tractography. The ability to characterize subtle individual differences in infant brain development associated with complex cognitive functions holds promise for improving our understanding of normative development, biomarkers of risk, experience-dependent learning and neuro-cognitive periods of developmental plasticity. PMID:22989623

  14. Age exacerbates HIV-associated white matter abnormalities.

    PubMed

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

    2016-04-01

    Both HIV disease and advanced age have been associated with alterations to cerebral white matter, as measured with white matter hyperintensities (WMH) on fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI), and more recently with diffusion tensor imaging (DTI). This study investigates the combined effects of age and HIV serostatus on WMH and DTI measures, as well as the relationships between these white matter measures, in 88 HIV seropositive (HIV+) and 49 seronegative (HIV-) individuals aged 23-79 years. A whole-brain volumetric measure of WMH was quantified from FLAIR images using a semi-automated process, while fractional anisotropy (FA) was calculated for 15 regions of a whole-brain white matter skeleton generated using tract-based spatial statistics (TBSS). An age by HIV interaction was found indicating a significant association between WMH and older age in HIV+ participants only. Similarly, significant age by HIV interactions were found indicating stronger associations between older age and decreased FA in the posterior limbs of the internal capsules, cerebral peduncles, and anterior corona radiata in HIV+ vs. HIV- participants. The interactive effects of HIV and age were stronger with respect to whole-brain WMH than for any of the FA measures. Among HIV+ participants, greater WMH and lower anterior corona radiata FA were associated with active hepatitis C virus infection, a history of AIDS, and higher current CD4 cell count. Results indicate that age exacerbates HIV-associated abnormalities of whole-brain WMH and fronto-subcortical white matter integrity. PMID:26446690

  15. 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

  16. 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

  17. 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 (2432weeks 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

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

    PubMed

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

    2015-02-01

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

  19. White matter astrocytes in health and disease

    PubMed Central

    Lundgaard, Iben; Osório, Maria Joana; Kress, Benjamin; Sanggaard, Simon; Nedergaard, Maiken

    2014-01-01

    Myelination by oligodendrocytes is a highly specialized process that relies on intimate interactions between the axon and oligodendrocyte. Astrocytes also have an important part in facilitating myelination in the CNS, however, comparatively less is known about how they affect myelination. This review therefore summarizes the literature and explores lingering questions surrounding differences between white matter and grey matter astrocytes, how astrocytes support myelination, how their dysfunction in pathological states contributes to myelin pathologies and how astrocytes may facilitate remyelination. We propose that astrocytes in the white matter are specialized to facilitate myelination and myelin maintenance by clearance of extracellular ions and neurotransmitters and by secretion of pro-myelinating factors. Aditionally, astrocytes-oligodendrocyte coupling via gapjunctions is crucial for both myelin formation and maintenance, due to K+ buffering and possibly metabolic support for oligodendrocytes via the panglia syncytium. Dysfunctional astrocytes aberrantly affect oligodendrocytes, exemplified by a number of leukodystrophies in which astrocytic pathology is known as the direct cause of myelin pathology. Conversely, in primary demyelinating diseases, such as multiple sclerosis, astrocytes may facilitate remyelination. We suggest that specific manipulation of astrocytes could help prevent myelin pathologies and successfully restore myelin sheaths after demyelination. PMID:24231735

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

    PubMed

    Kper, Michael; Rabe, K; Esser, S; Gizewski, E R; Husstedt, I W; Maschke, M; Obermann, M

    2011-06-01

    In this cross-sectional study we used magnetic resonance imaging (MRI)-based voxel based morphometry (VBM) in a sample of HIV positive patients to detect structural gray and white matter changes. Forty-eight HIV positive subjects with (n = 28) or without (n = 20) cognitive deficits (mean age 48.5 9.6 years) and 48 age- and sex-matched HIV negative controls underwent MRI for VBM analyses. Clinical testing in HIV patients included the HIV dementia scale (HDS), Unified Parkinson's Disease Rating Scale (UPDRS) and the grooved pegboard test. Comparing controls with HIV positive patients with cognitive dysfunction (n = 28) VBM showed gray matter decrease in the anterior cingulate and temporal cortices along with white matter reduction in the midbrain region. These changes were more prominent with increasing cognitive decline, when assigning HIV patients to three cognitive groups (not impaired, mildly impaired, overtly impaired) based on performance in the HIV dementia scale. Regression analysis including all HIV positive patients with available data revealed that prefrontal gray matter atrophy in HIV was associated with longer disease duration (n = 48), while motor dysfunction (n = 48) was associated with basal ganglia gray matter atrophy. Lower CD4 cell count (n = 47) correlated with decrease of occipital gray matter. Our results provide evidence for atrophy of nigro-striatal and fronto-striatal circuits in HIV. This pattern of atrophy is consistent with motor dysfunction and dysexecutive syndrome found in HIV patients with HIV-associated neurocognitive disorder. PMID:21207051

  1. Age-Related White Matter Changes

    PubMed Central

    Xiong, Yun Yun; Mok, Vincent

    2011-01-01

    Age-related white matter changes (WMC) are considered manifestation of arteriolosclerotic small vessel disease and are related to age and vascular risk factors. Most recent studies have shown that WMC are associated with a host of poor outcomes, including cognitive impairment, dementia, urinary incontinence, gait disturbances, depression, and increased risk of stroke and death. Although the clinical relevance of WMC has been extensively studied, to date, only very few clinical trials have evaluated potential symptomatic or preventive treatments for WMC. In this paper, we reviewed the current understanding in the pathophysiology, epidemiology, clinical importance, chemical biomarkers, and treatments of age-related WMC. PMID:21876810

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

    PubMed Central

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

    2015-01-01

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

  3. Microstructural White Matter Changes in Primary Torsion Dystonia

    PubMed Central

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

    2015-01-01

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

  4. Computational Representation of White Matter Fiber Orientations

    PubMed Central

    Ferreira da Silva, Adelino R.

    2013-01-01

    We present a new methodology based on directional data clustering to represent white matter fiber orientations in magnetic resonance analyses for high angular resolution diffusion imaging. A probabilistic methodology is proposed for estimating intravoxel principal fiber directions, based on clustering directional data arising from orientation distribution function (ODF) profiles. ODF reconstructions are used to estimate intravoxel fiber directions using mixtures of von Mises-Fisher distributions. The method focuses on clustering data on the unit sphere, where complexity arises from representing ODF profiles as directional data. The proposed method is validated on synthetic simulations, as well as on a real data experiment. Based on experiments, we show that by clustering profile data using mixtures of von Mises-Fisher distributions it is possible to estimate multiple fiber configurations in a more robust manner than currently used approaches, without recourse to regularization or sharpening procedures. The method holds promise to support robust tractographic methodologies and to build realistic models of white matter tracts in the human brain. PMID:24023538

  5. 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

  6. White matter neuroanatomical differences in young children who stutter

    PubMed Central

    Zhu, David C.; Choo, Ai Leen; Angstadt, Mike

    2015-01-01

    The ability to express thoughts through fluent speech production is a most human faculty, one that is often taken for granted. Stuttering, which disrupts the smooth flow of speech, affects 5% of preschool-age children and 1% of the general population, and can lead to significant communication difficulties and negative psychosocial consequences throughout one’s lifetime. Despite the fact that symptom onset typically occurs during early childhood, few studies have yet examined the possible neural bases of developmental stuttering during childhood. Here we present a diffusion tensor imaging study that examined white matter measures reflecting neuroanatomical connectivity (fractional anisotropy) in 77 children [40 controls (20 females), 37 who stutter (16 females)] between 3 and 10 years of age. We asked whether previously reported anomalous white matter measures in adults and older children who stutter that were found primarily in major left hemisphere tracts (e.g. superior longitudinal fasciculus) are also present in younger children who stutter. All children exhibited normal speech, language, and cognitive development as assessed through a battery of assessments. The two groups were matched in chronological age and socioeconomic status. Voxel-wise whole brain comparisons using tract-based spatial statistics and region of interest analyses of fractional anisotropy were conducted to examine white matter changes associated with stuttering status, age, sex, and stuttering severity. Children who stutter exhibited significantly reduced fractional anisotropy relative to controls in white matter tracts that interconnect auditory and motor structures, corpus callosum, and in tracts interconnecting cortical and subcortical areas. In contrast to control subjects, fractional anisotropy changes with age were either stagnant or showed dissociated development among major perisylvian brain areas in children who stutter. These results provide first glimpses into the neuroanatomical bases of early childhood stuttering, and possible white matter developmental changes that may lead to recovery versus persistent stuttering. The white matter changes point to possible structural connectivity deficits in children who stutter, in interrelated neural circuits that enable skilled movement control through efficient sensorimotor integration and timing of movements. PMID:25619509

  7. Gray and white matter correlates of navigational ability in humans.

    PubMed

    Wegman, Joost; Fonteijn, Hubert M; van Ekert, Janneke; Tyborowska, Anna; Jansen, Clemens; Janzen, Gabriele

    2014-06-01

    Humans differ widely in their navigational abilities. Studies have shown that self-reports on navigational abilities are good predictors of performance on navigation tasks in real and virtual environments. The caudate nucleus and medial temporal lobe regions have been suggested to subserve different navigational strategies. The ability to use different strategies might underlie navigational ability differences. This study examines the anatomical correlates of self-reported navigational ability in both gray and white matter. Local gray matter volume was compared between a group (N = 134) of good and bad navigators using voxel-based morphometry (VBM), as well as regional volumes. To compare between good and bad navigators, we also measured white matter anatomy using diffusion tensor imaging (DTI) and looked at fractional anisotropy (FA) values. We observed a trend toward higher local GM volume in right anterior parahippocampal/rhinal cortex for good versus bad navigators. Good male navigators showed significantly higher local GM volume in right hippocampus than bad male navigators. Conversely, bad navigators showed increased FA values in the internal capsule, the white matter bundle closest to the caudate nucleus and a trend toward higher local GM volume in the caudate nucleus. Furthermore, caudate nucleus regional volume correlated negatively with navigational ability. These convergent findings across imaging modalities are in line with findings showing that the caudate nucleus and the medial temporal lobes are involved in different wayfinding strategies. Our study is the first to show a link between self-reported large-scale navigational abilities and different measures of brain anatomy. PMID:24038667

  8. 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

  9. 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

  10. White Matter Changes in Tinnitus: Is It All Age and Hearing Loss?

    PubMed

    Yoo, Hye Bin; De Ridder, Dirk; Vanneste, Sven

    2016-02-01

    Tinnitus is a condition characterized by the perception of auditory phantom sounds. It is known as the result of complex interactions between auditory and nonauditory regions. However, previous structural imaging studies on tinnitus patients showed evidence of significant white matter changes caused by hearing loss that are positively correlated with aging. Current study focused on which aspects of tinnitus pathologies affect the white matter integrity the most. We used the diffusion tensor imaging technique to acquire images that have higher contrast in brain white matter to analyze how white matter is influenced by tinnitus-related factors using voxel-based methods, region of interest analysis, and deterministic tractography. As a result, white matter integrity in chronic tinnitus patients was both directly affected by age and also mediated by the hearing loss. The most important changes in white matter regions were found bilaterally in the anterior corona radiata, anterior corpus callosum, and bilateral sagittal strata. In the tractography analysis, the white matter integrity values in tracts of right parahippocampus were correlated with the subjective tinnitus loudness. PMID:26477359

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

    PubMed

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

    2016-04-15

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

  12. Altering cortical connectivity: Remediation-induced changes in the white matter of poor readers

    PubMed Central

    Keller, Timothy A.; Just, Marcel Adam

    2009-01-01

    SUMMARY Neuroimaging studies using diffusion tensor imaging (DTI) have revealed regions of cerebral white matter with decreased microstructural organization (lower fractional anisotropy or FA) among poor readers. We examined whether 100 hours of intensive remedial instruction affected the white matter of 810-year-old poor readers. Prior to instruction, poor readers had significantly lower FA than good readers in a region of the left anterior centrum semiovale. The instruction resulted in a change in white matter (significantly increased FA), and in the very same region. The FA increase was correlated with a decrease in radial diffusivity (but not with a change in axial diffusivity), suggesting that myelination had increased. Furthermore, the FA increase was correlated with improvement in phonological decoding ability, clarifying the cognitive locus of the effect. The results demonstrate for the first time the capability of a behavioral intervention to bring about a positive change in cortico-cortical white matter tracts. PMID:20005820

  13. White matter in learning, cognition and psychiatric disorders

    PubMed Central

    Fields, R. Douglas

    2008-01-01

    White matter is the brain region underlying the gray matter cortex, composed of neuronal fibers coated with electrical insulation called myelin. Previously of interest in demyelinating diseases such as multiple sclerosis, myelin is attracting new interest as an unexpected contributor to a wide range of psychiatric disorders, including depression and schizophrenia. This is stimulating research into myelin involvement in normal cognitive function, learning and IQ. Myelination continues for decades in the human brain; it is modifiable by experience, and it affects information processing by regulating the velocity and synchrony of impulse conduction between distant cortical regions. Cell-culture studies have identified molecular mechanisms regulating myelination by electrical activity, and myelin also limits the critical period for learning through inhibitory proteins that suppress axon sprouting and synaptogenesis. PMID:18538868

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

    PubMed Central

    Maniega, Susana Muoz; Valds Hernndez, 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 invivo 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?9m2s?1 (area under curve, 0.982; 95% CI, 0.9750.989). 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

  15. 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…

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

    ERIC Educational Resources Information Center

    Schmithorst, Vincent J.; Yuan, Weihong

    2010-01-01

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

  17. 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

  18. 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

  19. Asperger syndrome: a simple matter of white matter?

    PubMed

    Ellis; Gunter

    1999-05-01

    Asperger syndrome, one of the Pervasive Developmental Disorders, is formally diagnosed on the basis of a cluster of cognitive, social and motor signs. It is also associated with poor visuo-spatial skills, good verbal performance, gauche social behaviour and clumsiness. Many of the difficulties evident in those with Asperger syndrome are closely associated with right-hemisphere dysfunction. In this respect they also resemble signs used to diagnose what has been labelled Nonverbal Learning Disorder. Here, these are treated as being the same or closely-related disorders with a possible common underlying aetiology; that is, a neurodevelopmental abnormality affecting white matter. This review examines the ability of this approach to account for a wide range of characteristics of the Asperger syndrome, and contrasts this with a theory-of-mind approach, which, although able to account for the primary features of Asperger syndrome, is less successful at explaining some of its secondary features. PMID:10322476

  20. 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

  1. 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.

  2. 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

  3. Competing physiological pathways link individual differences in weight and abdominal adiposity to white matter microstructure

    PubMed Central

    Verstynen, Timothy D.; Weinstein, Andrea; Erickson, Kirk I.; Sheu, Lei K.; Marsland, Anna L.; Gianaros, Peter J.

    2013-01-01

    Being overweight or obese is associated with reduced white matter integrity throughout the brain. It is not yet clear which physiological systems mediate the association between inter-individual variation in adiposity and white matter. We tested whether composite indicators of cardiovascular, lipid, glucose, and inflammatory factors would mediate the adiposity-related variation in white matter microstructure, measured with diffusion tensor imaging on a group of neurologically healthy adults (N=155). A composite factor representing adiposity (comprised of body mass index and waist circumference) was negatively associated fractional anisotropy, and increased radial diffusivity, throughout the brain, a pattern linked to myelin structure changes in non-human animal models. A similar global negative association was found for factors representing inflammation and, to a lesser extent, glucose regulation. In contrast, factors for blood pressure and dyslipidemia had positive associations with white matter in isolated brain regions. Taken together, these competing influences on the diffusion signal were significant mediators linking adiposity to white matter and explained up to fifty-percent of the adiposity-white matter variance. These results provide the first evidence for contrasting physiological pathways, a globally distributed immunity-linked negative component and a more localized vascular-linked positive component, that associate adiposity to individual differences in the microstructure of white matter tracts in otherwise healthy adults. PMID:23639257

  4. 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

  5. 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

  6. White Matter Hyperintensities and Hypobaric Exposure

    PubMed Central

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

    2014-01-01

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

  7. 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

  8. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  11. 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

  12. Superficial White Matter: Effects of Age, Sex, and Hemisphere

    PubMed Central

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

    2013-01-01

    Abstract Structural and diffusion imaging studies demonstrate effects of age, sex, and asymmetry in many brain structures. However, few studies have addressed how individual differences might influence the structural integrity of the superficial white matter (SWM), comprised of short-range association (U-fibers), and intracortical axons. This study thus applied a sophisticated computational analysis approach to structural and diffusion imaging data obtained from healthy individuals selected from the International Consortium for Brain Mapping (ICBM) database across a wide adult age range (n=65, age: 1874 years, all Caucasian). Fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) were sampled and compared at thousands of spatially matched SWM locations and within regions-of-interest to examine global and local variations in SWM integrity across age, sex, and hemisphere. Results showed age-related reductions in FA that were more pronounced in the frontal SWM than in the posterior and ventral brain regions, whereas increases in RD and AD were observed across large areas of the SWM. FA was significantly greater in left temporoparietal regions in men and in the posterior callosum in women. Prominent leftward FA and rightward AD and RD asymmetries were observed in the temporal, parietal, and frontal regions. Results extend previous findings restricted to the deep white matter pathways to demonstrate regional changes in the SWM microstructure relating to processes of demyelination and/or to the number, coherence, or integrity of axons with increasing age. SWM fiber organization/coherence appears greater in the left hemisphere regions spanning language and other networks, while more localized sex effects could possibly reflect sex-specific advantages in information strategies. PMID:23461767

  13. 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

  14. Pathophysiology of glia in perinatal white matter injury.

    PubMed

    Back, Stephen A; Rosenberg, Paul A

    2014-11-01

    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 (pre-OLs). The developmental predilection for WMI to occur during prematurity appears to be related to both the timing of appearance and regional distribution of susceptible pre-OLs 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 respond to WMI with a rapid robust proliferative response that results in a several fold regeneration of pre-OLs that fail to terminally differentiate along their normal developmental time course. Pre-OL maturation arrest appears to be related in part to inhibitory factors that derive from reactive astrocytes in chronic lesions. Recent high field magnetic resonance imaging (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

  15. 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

  16. 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

  17. Evaluating the accuracy of diffusion MRI models in white matter.

    PubMed

    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

  18. White Matter Neurons in Young Adult and Aged Rhesus Monkey

    PubMed Central

    Mortazavi, Farzad; Wang, Xiyue; Rosene, Douglas L.; Rockland, Kathleen S.

    2016-01-01

    In humans and non-human primates (NHP), white matter neurons (WMNs) persist beyond early development. Their functional importance is largely unknown, but they have both corticothalamic and corticocortical connectivity and at least one subpopulation has been implicated in vascular regulation and sleep. Several other studies have reported that the density of WMNs in humans is altered in neuropathological or psychiatric conditions. The present investigation evaluates and compares the density of superficial and deep WMNs in frontal (FR), temporal (TE), and parietal (Par) association regions of four young adult and four aged male rhesus monkeys. A major aim was to determine whether there was age-related neuronal loss, as might be expected given the substantial age-related changes known to occur in the surrounding white matter environment. Neurons were visualized by immunocytochemistry for Neu-N in coronal tissue sections (30 μm thickness), and neuronal density was assessed by systematic random sampling. Per 0.16 mm2 sampling box, this yielded about 40 neurons in the superficial WM and 10 in the deep WM. Consistent with multiple studies of cell density in the cortical gray matter of normal brains, neither the superficial nor deep WM populations showed statistically significant age-related neuronal loss, although we observed a moderate decrease with age for the deep WMNs in the frontal region. Morphometric analyses, in contrast, showed significant age effects in soma size and circularity. In specific, superficial WMNs were larger in FR and Par WM regions of the young monkeys; but in the TE, these were larger in the older monkeys. An age effect was also observed for soma circularity: superficial WMNs were more circular in FR and Par of the older monkeys. This second, morphometric result raises the question of whether other age-related morphological, connectivity, or molecular changes occur in the WMNs. These could have multiple impacts, given the wide range of putative WMN functions and their involvement in both corticothalamic and corticocortical circuitry. PMID:26941613

  19. Etiology-based classification of brain white matter hyperintensity on magnetic resonance imaging

    PubMed Central

    Leite, Mariana; Rittner, Letícia; Appenzeller, Simone; Ruocco, Heloísa Helena; Lotufo, Roberto

    2015-01-01

    Abstract. Brain white matter lesions found upon magnetic resonance imaging are often observed in psychiatric or neurological patients. Individuals with these lesions present a more significant cognitive impairment when compared with individuals without them. We propose a computerized method to distinguish tissue containing white matter lesions of different etiologies (e.g., demyelinating or ischemic) using texture-based classifiers. Texture attributes were extracted from manually selected regions of interest and used to train and test supervised classifiers. Experiments were conducted to evaluate texture attribute discrimination and classifiers’ performances. The most discriminating texture attributes were obtained from the gray-level histogram and from the co-occurrence matrix. The best classifier was the support vector machine, which achieved an accuracy of 87.9% in distinguishing lesions with different etiologies and an accuracy of 99.29% in distinguishing normal white matter from white matter lesions. PMID:26158080

  20. 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

  1. 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

  2. Incidental multifocal white matter lesions in pediatric magnetic resonance imaging.

    PubMed

    Fisch, Naama; Konen, Osnat; Halevy, Ayelet; Cohen, Roni; Shuper, Avinoam

    2012-07-01

    This study sought to describe the occurrence and potential significance of white matter abnormalities of unknown cause on pediatric cranial magnetic resonance scans, and to review the literature. We included 16 children in whom white matter abnormalities were incidentally revealed on magnetic resonance scans performed during a 7-year period at a tertiary pediatric medical center. Background data were retrospectively collected from medical files. White matter lesions were classified by size, location, and extent. Indications for imaging included convulsive disorder (n = 5), headache (n = 5), endocrine disorder (n = 4), and others. Patients' abnormalities did not correlate with the locations and patterns of white matter lesions. No changes in lesions were evident over time. Given the absence of evident benefits from repeated imaging studies, we suggest they are not warranted in every patient, and should be tailored according to clinical course. Further investigations of incidental intracranial findings are required in this age group. PMID:22704009

  3. Genetics Home Reference: Leukoencephalopathy with vanishing white matter

    MedlinePLUS

    ... central nervous system's white matter, which consists of nerve fibers covered by myelin. Myelin is the fatty substance that insulates and protects nerves. In most cases, people with leukoencephalopathy with vanishing ...

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

    PubMed Central

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

    2012-01-01

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

  5. Pathological Correlates of White Matter Hyperintensities on MRI

    PubMed Central

    Shim, Yong S.; Yang, Dong-Won; Roe, Catherine M.; Coats, Mary A.; Benzinger, Tammie L.; Xiong, Chengjie; Galvin, James E.; Cairns, Nigel J.; Morris, John C.

    2014-01-01

    Background/Aims We investigated the histopathological correlates of White matter hyperintensities (WMHs) in participants with Alzheimer's disease (AD), cerebrovascular disease, and aged controls. Methods We reviewed 57 participants who had both neuroimaging and neuropathology. In addition to AD pathology, cortical microinfarcts, lacunes, and cerebral hemorrhages were assessed. Small vessel disease included arteriolosclerosis and cerebral amyloid angiopathy. Postmortem brain tissue corresponding to regions of WMHs were investigated in 14 participants; variables included: demyelination of the deep and periventricular WM, atrophy of the ventricular ependyma, and thickness of blood vessels. Partial Spearman rank test and linear regression analysis, adjusted for age at the clinical evaluation and the duration to death, were performed. Results The severity of arteriosclerosis was correlated with the MRI-estimated volume of periventricular hyperintensity (PVH). Deep white matter hyperintensity (DWMH) volume was correlated with the presence of cortical microinfarcts and cerebral hemorrhages. The severity of the breakdown of the ventricular lining was correlated with PVHs and DWMHs correlated with the severity of deep WM demyelination. The diameter of small blood vessels was not associated with WMHs. Conclusion WMHs are consistent with small vessel disease and increased tissue water content. We found no association between WMHs and thickness of small blood vessels. PMID:25401390

  6. Cortical demyelination and diffuse white matter injury in multiple sclerosis.

    PubMed

    Kutzelnigg, Alexandra; Lucchinetti, Claudia F; Stadelmann, Christine; Brck, Wolfgang; Rauschka, Helmut; Bergmann, Markus; Schmidbauer, Manfred; Parisi, Joseph E; Lassmann, Hans

    2005-11-01

    Focal demyelinated plaques in white matter, which are the hallmark of multiple sclerosis pathology, only partially explain the patient's clinical deficits. We thus analysed global brain pathology in multiple sclerosis, focusing on the normal-appearing white matter (NAWM) and the cortex. Autopsy tissue from 52 multiple sclerosis patients (acute, relapsing-remitting, primary and secondary progressive multiple sclerosis) and from 30 controls was analysed using quantitative morphological techniques. New and active focal inflammatory demyelinating lesions in the white matter were mainly present in patients with acute and relapsing multiple sclerosis, while diffuse injury of the NAWM and cortical demyelination were characteristic hallmarks of primary and secondary progressive multiple sclerosis. Cortical demyelination and injury of the NAWM, reflected by diffuse axonal injury with profound microglia activation, occurred on the background of a global inflammatory response in the whole brain and meninges. There was only a marginal correlation between focal lesion load in the white matter and diffuse white matter injury, or cortical pathology, respectively. Our data suggest that multiple sclerosis starts as a focal inflammatory disease of the CNS, which gives rise to circumscribed demyelinated plaques in the white matter. With chronicity, diffuse inflammation accumulates throughout the whole brain, and is associated with slowly progressive axonal injury in the NAWM and cortical demyelination. PMID:16230320

  7. White matter changes in elderly people: MR-pathologic correlations.

    PubMed

    Matsusue, Eiji; Sugihara, Shuji; Fujii, Shinya; Ohama, Eisaku; Kinoshita, Toshibumi; Ogawa, Toshihide

    2006-07-01

    Magnetic resonance (MR) imaging features of white matter lesions, often seen in the elderly, are correlated with histologic findings. Dilatation of perivascular spaces is seen, especially in the frontal and/or parietal subcortical white matter; the spaces are less than 3 mm in diameter and have sharp margins with no perifocal abnormality. Old lacunar infarcts are larger than 3 mm in diameter and are irregularly shaped and accompanied by perifocal myelin pallor and gliosis. Periventricular hyperintensity, including cap and rim, histologically shows myelin pallor, dilatation of perivascular spaces, discontinuity of the ependymal lining, and subependymal gliosis. Deep and subcortical white matter hyperintensity reflects myelin pallor and dilatation of perivascular spaces. Diffuse white matter lesion, seen in Binswanger's disease, shows myelin pallor and tissue rarefaction associated with loss of myelin and axons. U-fibers are usually well preserved. Severe arteriosclerosis and arteriolosclerosis are usually seen in the white matter. Knowledge of the pathologic features of incidental changes in white matter helps in understanding MR imaging findings. PMID:17008766

  8. 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

  9. Synergistic Effects of Age on Patterns of White and Gray Matter Volume across Childhood and Adolescence1,2,3

    PubMed Central

    Krongold, Mark; Cooper, Cassandra; Lebel, Catherine

    2015-01-01

    Abstract The human brain develops with a nonlinear contraction of gray matter across late childhood and adolescence with a concomitant increase in white matter volume. Across the adult population, properties of cortical gray matter covary within networks that may represent organizational units for development and degeneration. Although gray matter covariance may be strongest within structurally connected networks, the relationship to volume changes in white matter remains poorly characterized. In the present study we examined age-related trends in white and gray matter volume using T1-weighted MR images from 360 human participants from the NIH MRI study of Normal Brain Development. Images were processed through a voxel-based morphometry pipeline. Linear effects of age on white and gray matter volume were modeled within four age bins, spanning 4-18 years, each including 90 participants (45 male). White and gray matter age-slope maps were separately entered into k-means clustering to identify regions with similar age-related variability across the four age bins. Four white matter clusters were identified, each with a dominant direction of underlying fibers: anteriorposterior, leftright, and two clusters with superiorinferior 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

  10. 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

  11. 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...

  12. 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

  13. 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

  14. White matter plasticity in the cerebellum of elite basketball athletes.

    PubMed

    Park, In Sung; Lee, Ye Na; Kwon, Soonwook; Lee, Nam Joon; Rhyu, Im Joo

    2015-12-01

    Recent neuroimaging studies indicate that learning a novel motor skill induces plastic changes in the brain structures of both gray matter (GM) and white matter (WM) that are associated with a specific practice. We previously reported an increased volume of vermian lobules VI-VII (declive, folium, and tuber) in elite basketball athletes who require coordination for dribbling and shooting a ball, which awakened the central role of the cerebellum in motor coordination. However, the precise factor contributing to the increased volume was not determined. In the present study, we compared the volumes of the GM and WM in the sub-regions of the cerebellar vermis based on manual voxel analysis with the ImageJ program. We found significantly larger WM volumes of vermian lobules VI-VII (declive, folium, and tuber) in elite basketball athletes in response to long-term intensive motor learning. We suggest that the larger WM volumes of this region in elite basketball athletes represent a motor learning-induced plastic change, and that the WM of this region likely plays a critical role in coordination. This finding will contribute to gaining a deeper understanding of motor learning-evoked WM plasticity. PMID:26770877

  15. White matter plasticity in the cerebellum of elite basketball athletes

    PubMed Central

    Park, In Sung; Lee, Ye Na; Kwon, Soonwook; Lee, Nam Joon

    2015-01-01

    Recent neuroimaging studies indicate that learning a novel motor skill induces plastic changes in the brain structures of both gray matter (GM) and white matter (WM) that are associated with a specific practice. We previously reported an increased volume of vermian lobules VI-VII (declive, folium, and tuber) in elite basketball athletes who require coordination for dribbling and shooting a ball, which awakened the central role of the cerebellum in motor coordination. However, the precise factor contributing to the increased volume was not determined. In the present study, we compared the volumes of the GM and WM in the sub-regions of the cerebellar vermis based on manual voxel analysis with the ImageJ program. We found significantly larger WM volumes of vermian lobules VI-VII (declive, folium, and tuber) in elite basketball athletes in response to long-term intensive motor learning. We suggest that the larger WM volumes of this region in elite basketball athletes represent a motor learning-induced plastic change, and that the WM of this region likely plays a critical role in coordination. This finding will contribute to gaining a deeper understanding of motor learning-evoked WM plasticity. PMID:26770877

  16. 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

  17. 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 19982000 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

  18. 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

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

    PubMed

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

    2016-04-01

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

  20. 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

  1. Atypical Frontal-Striatal-Thalamic Circuit White Matter Development in Pediatric Obsessive Compulsive Disorder

    PubMed Central

    Fitzgerald, Kate D.; Liu, Yanni; Reamer, Elyse N.; Taylor, Stephan F.; Welsh, Robert C.

    2015-01-01

    Objective Atypical development of frontal-striatal-thalamic circuitry (FSTC) has been hypothesized to underlie the early course of obsessive-compulsive disorder (OCD); however, the development of FSTC white matter tracts remains to be studied in young patients. Method To address this gap, we scanned 36 patients with pediatric OCD compared to 27 healthy controls, aged 8 to 19 years, with diffusion tensor imaging (DTI) to measure fractional anisotropy (FA), an index of white matter coherence. Tract-based spatial statistics (TBSS) were used to test differential effects of age on FA, across the whole brain, in those with OCD compared to healthy youth, followed by analyses in a priori regions of interest (anterior corpus callosum, anterior cingulum bundle and anterior limb of the internal capsule [ALIC]) to further characterize developmental differences between groups. Results Patients with OCD showed more pronounced age-related increases in FA than controls in regions of interest, as well as several other white matter tracts. In patients, greater FA in anterior cingulum bundle correlated with more severe symptoms after controlling for age. Conclusions Our findings support theories of atypical FSTC maturation in pediatric OCD by providing the first evidence for altered trajectories of white matter development in anterior corpus callosum, anterior cingulum bundle, and ALIC in young patients. Steeper age-related increases of FA in these and other select white matter tracts in OCD, compared to healthy controls, may derive from an early delay in white matter development and/or prolonged white matter growth, but confirmation of these possibilities awaits longitudinal work. PMID:25440312

  2. 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 antibodypositive 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

  3. Radiation effects on cerebral white matter: MR evaluation

    SciTech Connect

    Tsuruda, J.S.; Kortman, K.E.; Bradley, W.G.; Wheeler, D.C.; Van Dalsem, W.; Bradley, T.P.

    1987-07-01

    The purpose of this study was to evaluate the white-matter changes associated with cranial radiation by MR imaging. The MR scans of 95 patients receiving conventional external beam radiation for a wide variety of central nervous system tumors were reviewed. Moderately T2-weighted spin-echo images with a 2000-msec repetition time and 56-msec-echo time were analyzed for white-matter abnormalities without knowledge of the patient's history. These were correlated with radiation dose, port, and time interval since completion of therapy, and then compared with an age-matched control group of 180 patients with nonirradiated, space-occupying, intracranial lesions. Radiation-related lesions were characterized as symmetric, high-signal foci in the periventricular white matter. Relative sparing of the posterior fossa, basal ganglia, and internal capsules was noted. In patients older than 20 years, these changes paralleled those seen in ischemia but were more prevalent (p less than .005). In 25 patients with sequential MR scans, these findings remained stable. In those patients with limited treatment fields, for example, pituitary adenomas, no statistical differences were seen between radiation-treated and nontreated groups. Cerebral white-matter changes that mimic deep white-matter infarction are frequently seen in response to therapeutic radiation. There is a variable incidence of radiation effects, becoming more marked in older patients. MR interpretation must consider the neuropathologic consequences of therapeutic radiation, which include demyelination, microvascular occlusion, and blood-brain barrier breakdown.

  4. Relations between white matter maturation and reaction time in childhood.

    PubMed

    Scantlebury, Nadia; Cunningham, Todd; Dockstader, Colleen; Laughlin, Suzanne; Gaetz, William; Rockel, Conrad; Dickson, Jolynn; Mabbott, Donald

    2014-01-01

    White matter matures with age and is important for the efficient transmission of neuronal signals. Consequently, white matter growth may underlie the development of cognitive processes important for learning, including the speed of information processing. To dissect the relationship between white matter structure and information processing speed, we administered a reaction time task (finger abduction in response to visual cue) to 27 typically developing, right-handed children aged 4 to 13. Magnetoencephalography and Diffusion Tensor Imaging were used to delineate white matter connections implicated in visual-motor information processing. Fractional anisotropy (FA) and radial diffusivity (RD) of the optic radiation in the left hemisphere, and FA and mean diffusivity (MD) of the optic radiation in the right hemisphere changed significantly with age. MD and RD decreased with age in the right inferior fronto-occipital fasciculus, and bilaterally in the cortico-spinal tracts. No age-related changes were evident in the inferior longitudinal fasciculus. FA of the cortico-spinal tract in the left hemisphere and MD of the inferior fronto-occipital fasciculus of the right hemisphere contributed uniquely beyond the effect of age in accounting for reaction time performance of the right hand. Our findings support the role of white matter maturation in the development of information processing speed. PMID:24168858

  5. Decreased white matter integrity in mesial temporal lobe epilepsy: a machine learning approach.

    PubMed

    An, Jie; Fang, Peng; Wang, Wensheng; Liu, Zhenyin; Hu, Dewen; Qiu, Shijun

    2014-07-01

    Statistical analysis on diffusion tensor imaging has been used extensively in mesial temporal lobe epilepsy (mTLE) and most studies report decrease in fractional anisotropy (FA) in multiple white matter regions. However, these findings vary across studies and between regions. Therefore, in this study, we used tract-based spatial statistics along with machine learning approaches to investigate the whole-brain white matter changes between 17 left mTLE patients and 15 right mTLE patients and 34 matched healthy controls. The results showed that the three groups could be distinguished from each other with promising accuracy. Compared with controls, the FA value of the most discriminating voxels was decreased in the ipsilateral limbic system, corpus callosum, and temporal white matter in both patient groups. Compared with right mTLE, left mTLE had decreased FA in the left temporal white matter, whereas right mTLE had decreased FA in the right frontal and temporal white matter, and right posterior corona radiata. These findings not only provide useful information for lateralization of the seizure focus but can also be used as a potential biomarker for the diagnosis and treatment of the mTLE. This may be helpful in assessment of patients with mTLE when no lesion is detected on visual evaluation. PMID:24918460

  6. Strategic white matter tracts for processing speed deficits in age-related small vessel disease

    PubMed Central

    Duering, Marco; Gesierich, Benno; Seiler, Stephan; Pirpamer, Lukas; Gonik, Mariya; Hofer, Edith; Jouvent, Eric; Duchesnay, Edouard; Chabriat, Hugues; Ropele, Stefan; Schmidt, Reinhold

    2014-01-01

    Objective: Cerebral small vessel disease is the most common cause of vascular cognitive impairment and typically manifests with slowed processing speed. We investigated the impact of lesion location on processing speed in age-related small vessel disease. Methods: A total of 584 community-dwelling elderly underwent brain MRI followed by segmentation of white matter hyperintensities. Processing speed was determined by the timed measure of the Trail Making Test part B. The impact of the location of white matter hyperintensities was assessed by voxel-based lesion-symptom mapping and graph-based statistical models on regional lesion volumes in major white matter tracts. Results: Voxel-based lesion-symptom mapping identified multiple voxel clusters where the presence of white matter hyperintensities was associated with slower performance on the Trail Making Test part B. Clusters were located bilaterally in the forceps minor and anterior thalamic radiation. Region of interestbased Bayesian network analyses on lesion volumes within major white matter tracts depicted the same tracts as direct predictors for an impaired Trail Making Test part B performance. Conclusions: Our findings highlight damage to frontal interhemispheric and thalamic projection fiber tracts harboring frontal-subcortical neuronal circuits as a predictor for processing speed performance in age-related small vessel disease. PMID:24793184

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

    PubMed Central

    Giezendanner, Stéphanie; Fisler, Melanie Sarah; Soravia, Leila Maria; Andreotti, Jennifer; Walther, Sebastian; Wiest, Roland; Dierks, Thomas; Federspiel, Andrea

    2016-01-01

    Background White matter (WM) fibers connect different brain regions and are critical for proper brain function. However, little is known about the cerebral blood flow in WM and its relation to WM microstructure. Recent improvements in measuring cerebral blood flow (CBF) by means of arterial spin labeling (ASL) suggest that the signal in white matter may be detected. Its implications for physiology needs to be extensively explored. For this purpose, CBF and its relation to anisotropic diffusion was analyzed across subjects on a voxel-wise basis with tract-based spatial statistics (TBSS) and also across white matter tracts within subjects. Methods Diffusion tensor imaging and ASL were acquired in 43 healthy subjects (mean age = 26.3 years). Results CBF in WM was observed to correlate positively with fractional anisotropy across subjects in parts of the splenium of corpus callosum, the right posterior thalamic radiation (including the optic radiation), the forceps major, the right inferior fronto-occipital fasciculus, the right inferior longitudinal fasciculus and the right superior longitudinal fasciculus. Furthermore, radial diffusivity correlated negatively with CBF across subjects in similar regions. Moreover, CBF and FA correlated positively across white matter tracts within subjects. Conclusion The currently observed findings on a macroscopic level might reflect the metabolic demand of white matter on a microscopic level involving myelination processes or axonal function. However, the exact underlying physiological mechanism of this relationship needs further evaluation. PMID:26942763

  8. Spatial Characteristics of White Matter Abnormalities in Schizophrenia

    PubMed Central

    White, Tonya

    2013-01-01

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

  9. 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

  10. 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

  11. Pathologic correlates of incidental MRI white matter signal hyperintensities.

    PubMed

    Fazekas, F; Kleinert, R; Offenbacher, H; Schmidt, R; Kleinert, G; Payer, F; Radner, H; Lechner, H

    1993-09-01

    We related the histopathologic changes associated with incidental white matter signal hyperintensities on MRIs from 11 elderly patients (age range, 52 to 82 years) to a descriptive classification for such abnormalities. Punctate, early confluent, and confluent white matter hyperintensities corresponded to increasing severity of ischemic tissue damage, ranging from mild perivascular alterations to large areas with variable loss of fibers, multiple small cavitations, and marked arteriolosclerosis. Microcystic infarcts and patchy rarefaction of myelin were also characteristic for irregular periventricular high signal intensity. Hyperintense periventricular caps and a smooth halo, however, were of nonischemic origin and constituted areas of demyelination associated with subependymal gliosis and discontinuity of the ependymal lining. Based on these findings, our classification appears to reflect both the different etiologies and severities of incidental MRI signal abnormalities, if it is modified to treat irregular periventricular and confluent deep white matter hyperintensities together. PMID:8414012

  12. White Matter Abnormalities in Pediatric Obsessive-Compulsive Disorder

    PubMed Central

    Gruner, Patricia; Vo, An; Ikuta, Toshikazu; Mahon, Katie; Peters, Bart D; Malhotra, Anil K; Ulu?, Aziz M; Szeszko, Philip R

    2012-01-01

    Obsessive-compulsive disorder (OCD) is a prevalent and often severely disabling illness with onset generally in childhood or adolescence. Although white matter deficits have been implicated in the neurobiology of OCD, few studies have been conducted in pediatric patients when the brain is still developing and have examined their functional correlates. In this study, 23 pediatric OCD patients and 23 healthy volunteers, between the ages of 9 and 17 years, matched for sex, age, handedness, and IQ, received a diffusion tensor imaging exam on a 3T GE system and a brief neuropsychological battery tapping executive functions. Patient symptom severity was assessed using the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). Patients with OCD exhibited significantly greater fractional anisotropy compared to matched controls in the left dorsal cingulum bundle, splenium of the corpus callosum, right corticospinal tract, and left inferior fronto-occipital fasciculus. There were no regions of significantly lower fractional anisotropy in patients compared to controls. Higher fractional anisotropy in the splenium was significantly correlated with greater obsession severity on the CY-BOCS in the subgroup of psychotropic drug-nave patients. Among patients, there was a significant association between greater fractional anisotropy in the dorsal cingulum bundle and better performance on measures of response inhibition and cognitive control. The overall findings suggest a pattern of greater directional coherence of white matter tracts in OCD very early in the course of illness, which may serve a compensatory mechanism, at least for response inhibition functions typically subserved by the cingulum bundle. PMID:22871914

  13. 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 μl 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 μl 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 < 0.05). Systemic treatment with ZnPP attenuated the loss of MBP-labeled bundles (p < 0.01) and area (p < 0.01). In conclusion, marked 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

  14. White matter microstructure in untreated first episode bipolar disorder with psychosis: comparison with schizophrenia

    PubMed Central

    Lu, Lisa H; Zhou, Xiaohong Joe; Keedy, Sarah K; Reilly, James L; Sweeney, John A

    2012-01-01

    Objectives White matter abnormalities have been reported in bipolar disorder. The present study aimed to investigate white matter integrity in untreated first episode patients with psychotic bipolar disorder using diffusion tensor imaging, and to compare observations with those from untreated first episode schizophrenia patients. Methods Fractional anisotropy and mean diffusivity were measured in first episode psychotic patients with bipolar disorder (n = 13) or schizophrenia (n = 21) and healthy individuals (n = 18). Group differences were evaluated using voxel based morphometry. Axial and radial diffusivity were examined in regions with altered fractional anisotropy in post-hoc analyses. Results Patients with bipolar disorder showed lower fractional anisotropy than healthy controls in several white matter tracts. Compared with schizophrenia patients, bipolar disorder patients showed lower fractional anisotropy in the cingulum, internal capsule, posterior corpus callosum, tapetum, and occipital white matter including posterior thalamic radiation and inferior longitudinal fasciculus/inferior fronto-occipital fasciculus. Lower fractional anisotropy in bipolar disorder was characterized by increased radial diffusion rather than axial diffusion along the orientation of fiber tracts. Across several white matter tracts, both patient groups showed greater mean diffusivity than healthy individuals. Conclusions Selectively increased radial diffusivity in bipolar disorder patients suggests structural disorganization in fiber tract coherence of neurodevelopmental origin or alterations in myelin sheaths along fiber tracts. In contrast, increased isotropic diffusion along white matter tracts in schizophrenia patients with alterations in both radial and axial diffusivity suggests increased water content outside of axonal space. Thus, the present results suggest that different pathophysiological mechanisms may underlie white matter microstructural abnormalities in bipolar disorder and schizophrenia. PMID:22085473

  15. COMT genotype affects brain white matter pathways in attention-deficit/hyperactivity disorder.

    PubMed

    Hong, Soon-Beom; Zalesky, Andrew; Park, Subin; Yang, Young-Hui; Park, Min-Hyeon; Kim, BoAh; Song, In-Chan; Sohn, Chul-Ho; Shin, Min-Sup; Kim, Bung-Nyun; Cho, Soo-Churl; Kim, Jae-Won

    2015-01-01

    Increased dopamine availability may be associated with impaired structural maturation of brain white matter connectivity. This study aimed to derive a comprehensive, whole-brain characterization of large-scale axonal connectivity differences in attention-deficit/hyperactivity disorder (ADHD) associated with catechol-O-methyltransferase gene (COMT) Val158Met polymorphism. Using diffusion tensor imaging, whole-brain tractography, and an imaging connectomics approach, we characterized altered white matter connectivity in youth with ADHD who were COMT Val-homozygous (N?=?29) compared with those who were Met-carriers (N?=?29). Additionally, we examined whether dopamine transporter gene (DAT1) and dopamine D4 receptor gene (DRD4) polymorphisms were associated with white matter differences. Level of attention was assessed using the continuous performance test before and after an 8-week open-label trial of methylphenidate (MPH). A network of white matter connections linking 18 different brain regions was significantly weakened in youth with ADHD who were COMT Met-carriers compared to those who were Val-homozygous (P?white matter integrity, fractional anisotropy, was correlated with impaired pretreatment performance in continuous performance test omission errors and response time variability, as well as with improvement in continuous performance test response time variability after MPH treatment. Altered white matter connectivity was exclusively based on COMT genotypes, and was not evident in DAT1 or DRD4. We demonstrated that white matter connectivity in youth with ADHD is associated with COMT Val158Met genotypes. The present findings suggest that different layers of dopamine-related genes and interindividual variability in the genetic polymorphisms should be taken into account when investigating the human connectome. PMID:25201318

  16. 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

  17. 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

  18. 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 ɛ-neighbor method for building a network graph and apply it to testing abnormal connectivity in autism.

  19. Cerebral white matter correlates of delay discounting in adolescents.

    PubMed

    Ho, Beng-Choon; Koeppel, Julie A; Barry, Amy B

    2016-05-15

    The adolescent brain undergoes extensive structural white matter (WM) changes. Adolescence is also a critical time period during which cognitive, emotional and social maturation occurs in transition into adulthood. Compared to adults, adolescents are generally more impulsive with increased risk-taking behaviors. The goal of this study is to examine whether adolescent impulsivity may be related to cerebral WM maturation. In 89 healthy adolescents, we assessed impulsivity using the delay discounting task, and MRI WM volumes in brain regions previously implicated in delay discounting behaviors. We found that smaller delay discounting AUC (area under the curve) was associated with larger WM volumes in orbitofrontal, dorsolateral and medial prefrontal cortices (PFC) and motor cortex. There were no significant effects of AUC on WM volumes within somatosensory brain regions. In our sample, younger age was significantly associated with greater WM volumes in orbitofrontal and dorsolateral PFC subregions. Even after accounting for age-related effects, preference for immediate rewards (or greater impulsivity) still correlated with larger WM volumes in prefrontal regions known to mediate cognitive control. Our findings lend further support to the notion that reduced brain WM maturity may limit the ability in adolescents to forgo immediate rewards leading to greater impulsivity. PMID:26946275

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

    PubMed Central

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

    2016-01-01

    Previous studies attempting to quantify white matter (WM) microstructure in individuals with fragile X syndrome (FXS) have produced inconsistent findings, most likely due to the various control groups employed, differing analysis methods, and failure to examine for potential motion artifact. In addition, analyses have heretofore lacked sufficient specificity to provide regional information. In this study, we used Automated Fiber-tract Quantification (AFQ) to identify specific regions of aberrant WM microstructure along WM tracts in patients with FXS that differed from controls who were matched on age, IQ and degree of autistic symptoms. Participants were 20 patients with FXS, aged 10 to 23 years, and 20 matched controls. Using Automated Fiber-tract Quantification (AFQ), we created Tract Profiles of fractional anisotropy and mean diffusivity along 18 major WM fascicles. We found that fractional anisotropy was significantly increased in the left and right inferior longitudinal fasciculus (ILF), right uncinate fasciculus, and left cingulum hippocampus in individuals with FXS compared to controls. Conversely, mean diffusivity was significantly decreased in the right ILF in patients with FXS compared to controls. Age was significantly negatively associated with MD values across both groups in 11 tracts. Taken together, these findings indicate that FXS results in abnormal WM microstructure in specific regions of the ILF and uncinate fasciculus, most likely caused by inefficient synaptic pruning as a result of decreased or absent Fragile X Mental Retardation Protein (FMRP). Longitudinal studies are needed to confirm these findings. PMID:26937381

  1. Astrocytic Hypertrophy in Anterior Cingulate White Matter of Depressed Suicides

    PubMed Central

    Torres-Platas, Susana G; Hercher, Christa; Davoli, Maria Antonietta; Maussion, Gilles; Labont, Benoit; Turecki, Gustavo; Mechawar, Naguib

    2011-01-01

    Increasing evidence suggests that cortical astrocytic function is disrupted in mood disorders and suicide. The fine neuroanatomy of astrocytes, however, remains to be investigated in these psychiatric conditions. In this study, we performed a detailed morphometric analysis of 3D-reconstructed gray and white matter astrocytes in Golgi-impregnated anterior cingulate cortex (ACC) samples from depressed suicides and matched controls. Postmortem ACC samples (BA24) from 10 well-characterized depressed suicides and 10 matched sudden-death controls were obtained from the Quebec Suicide Brain Bank. Golgi-impregnated protoplasmic astrocytes (gray matter, layer VI) and fibrous astrocytes (adjacent white matter) were reconstructed, and their morphometric features were analyzed using the Neurolucida software. For each cell, the soma size as well as the number, length, and branching of processes were determined. The densities of thorny protrusions found along the processes of both astrocytic subtypes were also determined. Protoplasmic astrocytes showed no significant difference between groups for any of the quantified parameters. However, fibrous astrocytes had significantly larger cell bodies, as well as longer, more ramified processes in depressed suicides, with values for these parameters being about twice as high as those measured in controls. These results provide the first evidence of altered cortical astrocytic morphology in mood disorders. The presence of hypertrophic astrocytes in BA24 white matter is consistent with reports suggesting white matter alterations in depression, and provides further support to the neuroinflammatory theory of depression. PMID:21814185

  2. 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=30.38.1 years) and healthy controls (n=24, age=27.46.3 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

  3. 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

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

    PubMed

    Valds Hernndez, Maria Del C; Gallacher, Peter J; Bastin, Mark E; Royle, Natalie A; Maniega, Susana Muoz; 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

  5. 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 915. 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

  6. Microstructural white matter changes are correlated with the stage of psychiatric illness

    PubMed Central

    Lagopoulos, J; Hermens, D F; Hatton, S N; Battisti, R A; Tobias-Webb, J; White, D; Naismith, S L; Scott, E M; Ryder, W J; Bennett, M R; Hickie, I B

    2013-01-01

    Microstructural white matter changes have been reported in the brains of patients across a range of psychiatric disorders. Evidence now demonstrates significant overlap in these regions in patients with affective and psychotic disorders, thus raising the possibility that these conditions share common neurobiological processes. If affective and psychotic disorders share these disruptions, it is unclear whether they occur early in the course or develop gradually with persistence or recurrence of illness. Utilisation of a clinical staging model, as an adjunct to traditional diagnostic practice, is a viable mechanism for measuring illness progression. It is particularly relevant in young people presenting early in their illness course. It also provides a suitable framework for determining the timing of emergent brain alterations, including disruptions of white matter tracts. Using diffusion tensor imaging, we investigated the integrity of white matter tracts in 74 patients with sub-syndromal psychiatric symptoms as well as in 69 patients diagnosed with established psychosis or affective disorder and contrasted these findings with those of 39 healthy controls. A significant disruption in white matter integrity was found in the left anterior corona radiata and in particular the anterior thalamic radiation for both the patients groups when separately contrasted with healthy controls. Our results suggest that patients with sub-syndromal symptoms exhibit discernable early white matter changes when compared with healthy control subjects and more significant disruptions are associated with clinical evidence of illness progression. PMID:23612047

  7. White matter microstructural differences linked to left perisylvian language network in children with dyslexia

    PubMed Central

    Rimrodt, Sheryl L.; Peterson, Daniel J.; Denckla, Martha B.; Kaufmann, Walter E.; Cutting, Laurie E.

    2009-01-01

    Studies of dyslexia using diffusion tensor imaging (DTI) have reported fractional anisotropy (FA) differences in left inferior frontal gyrus (LIFG) and left temporo-parietal white matter, suggesting that impaired reading is associated with atypical white matter microstructure in these regions. These anomalies might reflect abnormalities in the left perisylvian language network, long implicated in dyslexia. While DTI investigations frequently report analyses on multiple tensor-derived measures (e.g., FA, orientation, tractography), it is uncommon to integrate analyses to examine the relationships between atypical findings. For the present study, semi-automated techniques were applied to DTI data in an integrated fashion to examine white matter microstructure in 14 children with dyslexia and 17 typically developing readers (ages 7-16 years). Correlations of DTI metrics (FA and fiber orientation) to reading skill (accuracy and speed) and to probabilistic tractography maps of the left perisylvian language tracts were examined. Consistent with previous reports, our findings suggest FA decreases in dyslexia in LIFG and left temporo-parietal white matter. The LIFG FA finding overlaps an area showing differences in fiber orientation in an anterior left perisylvian language pathway. Additionally,a positive correlation of FA to reading speed was found in a posterior circuit previously associated with activation on functional imaging during reading tasks. Overall, integrating results from several complementary semi-automated analyses reveals evidence linking atypical white matter microstructure in dyslexia to atypical fiber orientation in circuits implicated in reading including the left perisylvian language network. PMID:19682675

  8. Maturation-dependent vulnerability of perinatal white matter in premature birth.

    PubMed

    Back, Stephen A; Riddle, Art; McClure, Melissa M

    2007-02-01

    Survivors of premature birth have a predilection for perinatal brain injury, especially to 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 cystic necrotic lesions (periventricular leukomalacia) and diffuse myelination disturbances. Recent neuroimaging studies support that the incidence of periventricular leukomalacia is declining, whereas focal or diffuse noncystic injury is emerging as the predominant lesion. In a significant number of infants, PWMI appears to be initiated by perturbations in cerebral blood flow that reflect anatomic and physiological immaturity of the vasculature. Ischemic cerebral white matter is susceptible to pronounced free radical-mediated injury that particularly targets immature stages of the oligodendrocyte lineage. Emerging experimental data supports that pronounced ischemia in the periventricular white matter is necessary but not sufficient to generate the initial injury that leads to PWMI. The developmental predilection for PWMI to occur during prematurity appears to be related to both the timing of appearance and regional distribution of susceptible oligodendrocyte progenitors. Injury to oligodendrocyte progenitors may contribute to the pathogenesis of PWMI by disrupting the maturation of myelin-forming oligodendrocytes. There has been substantial recent progress in the understanding of the cellular and molecular pathogenesis of PWMI. The oligodendrocyte progenitor is a key target for preventive strategies to reduce ischemic cerebral white matter injury in premature infants. PMID:17261726

  9. 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…

  10. 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

  11. 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

  12. Coronary Heart Disease and Cortical Thickness, Gray Matter and White Matter Lesion Volumes on MRI

    PubMed Central

    Vuorinen, Miika; Damangir, Soheil; Niskanen, Eini; Miralbell, Julia; Rusanen, Minna; Spulber, Gabriela; Soininen, Hilkka; Kivipelto, Miia; Solomon, Alina

    2014-01-01

    Coronary heart disease (CHD) has been linked with cognitive decline and dementia in several studies. CHD is strongly associated with blood pressure, but it is not clear how blood pressure levels or changes in blood pressure over time affect the relation between CHD and dementia-related pathology. The aim of this study was to investigate relations between CHD and cortical thickness, gray matter volume and white matter lesion (WML) volume on MRI, considering CHD duration and blood pressure levels from midlife to three decades later. The study population included 69 elderly at risk of dementia who participated in the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study. CAIDE participants were examined in midlife, re-examined 21 years later, and then after additionally 7 years (in total up to 30 years follow-up). MRIs from the second re-examination were used to calculate cortical thickness, gray matter and WML volume. CHD diagnoses were obtained from the Finnish Hospital Discharge Register. Linear regression analyses were adjusted for age, sex, follow-up time and scanner type, and additionally total intracranial volume in GM volume analyses. Adding diabetes, cholesterol or smoking to the models did not influence the results. CHD was associated with lower thickness in multiple regions, and lower total gray matter volume, particularly in people with longer disease duration (>10 years). Associations between CHD, cortical thickness and gray matter volume were strongest in people with CHD and hypertension in midlife, and those with CHD and declining blood pressure after midlife. No association was found between CHD and WML volumes. Based on these results, long-term CHD seems to have detrimental effects on brain gray matter tissue, and these effects are influenced by blood pressure levels and their changes over time. PMID:25302686

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

    PubMed Central

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

    2014-01-01

    Summary It is unknown if the white matter properties associated with specific visual networks selectively affect category-specific processing. In a novel protocol we combined measurements of white matter structure, functional selectivity, and behavior in the same subjects. We find two parallel white matter pathways along the ventral temporal lobe connecting to either face-selective or place-selective regions. Diffusion properties of portions of these tracts adjacent to face- and place-selective regions of ventral temporal cortex correlate with behavioral performance for face or place processing, respectively. Strikingly, adults with developmental prosopagnosia (face blindness) express an atypical structure-behavior relationship near face-selective cortex, suggesting that white matter atypicalities in this region may have behavioral consequences. These data suggest that examining the interplay between cortical function, anatomical connectivity, and visual behavior is integral to understanding functional networks and their role in producing visual abilities and deficits. PMID:25569351

  14. A Role for White Matter Abnormalities in the Pathophysiology of Bipolar Disorder

    PubMed Central

    Mahon, Katie; Burdick, Katherine E.; Szeszko, Philip R.

    2010-01-01

    Bipolar disorder is a chronically disabling psychiatric disorder characterized by manic states that is often interspersed with periods of depression whose neurobiology remains largely unknown. There is, however, increasing evidence that white matter (WM) abnormalities may play an important role in the neurobiology of the disorder. In this review we critically evaluate evidence for WM abnormalities in bipolar disorder obtained from neuroimaging, neuropathological, and genetic research. Increased rates of white matter hyperintensities, regional volumetric abnormalities, abnormal water diffusion along prefrontal-subcortical tracts, fewer oligodendrocytes in prefrontal WM, and alterations in the expression of myelin-and oligodendrocyte-related genes are among the most consistent findings. Abnormalities converge in the prefrontal WM and, in particular, tracts that connect prefrontal regions and subcortical gray matter structures known to be involved in emotion. Taken together, the evidence supports and clarifies a model of bipolar disorder that involves disconnectivity in regions implicated in emotion generation and regulation. PMID:19896972

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

    SciTech Connect

    Uh, Jinsoo; Merchant, Thomas E.; Li, Yimei; Li, Xingyu; Sabin, Noah D.; Indelicato, Daniel J.; Ogg, Robert J.; Boop, Frederick A.; Jane, John A.; Hua, Chiaho

    2015-09-01

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

  16. Quantifying the effects of normal ageing on white matter structure using unsupervised tract shape modelling.

    PubMed

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

    2010-05-15

    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 tract shape, tract integrity and age in a range of frontal and non-frontal tracts in 90 non-demented subjects aged over 65 years using an enhanced version of probabilistic neighbourhood tractography. This novel method for automatic single seed point placement employs unsupervised learning and streamline selection to provide reliable and accurate tract segmentation, whilst also indicating how the shape of an individual tract compares to that of a predefined reference tract. There were significant negative correlations between tract shape similarity to reference tracts derived from a young brain white matter atlas and age in genu and splenium of corpus callosum. Controlling for intracranial and lateral ventricle volume, the latter of which increased significantly with age, attenuated these correlations by 40% and 84%, respectively, indicating that this age-related change in callosal tract topology is significantly mediated by global atrophy and ventricular enlargement. In accordance with the "frontal ageing" hypothesis, there was a significant positive correlation between mean diffusivity (D) and age, and a significant negative correlation between fractional anisotropy (FA) and age in corpus callosum genu; correlations not seen in splenium. Significant positive correlations were also observed between D and age in bilateral cingulum cingulate gyri, uncinate fasciculi and right corticospinal tract. This pattern of correlations was not, however, reproduced when those subjects with significant white matter lesion load were analyzed separately from those without. These data therefore suggest that brain atrophy and white matter lesions play a significant role in driving regional patterns of age-related changes in white matter tract shape and integrity. PMID:20171285

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

    PubMed Central

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

    2013-01-01

    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 tract shape, tract integrity and age in a range of frontal and non-frontal tracts in 90 non-demented subjects aged over 65 years using an enhanced version of probabilistic neighbourhood tractography. This novel method for automatic single seed point placement employs unsupervised learning and streamline selection to provide reliable and accurate tract segmentation, whilst also indicating how the shape of an individual tract compares to that of a predefined reference tract. There were significant negative correlations between tract shape similarity to reference tracts derived from a young brain white matter atlas and age in genu and splenium of corpus callosum. Controlling for intracranial and lateral ventricle volume, the latter of which increased significantly with age, attenuated these correlations by 40 and 84 % respectively, indicating that this age-related change in callosal tract topology is significantly mediated by global atrophy and ventricular enlargement. In accordance with the frontal ageing hypothesis, there was a significant positive correlation between mean diffusivity (?D?) and age, and a significant negative correlation between fractional anisotropy (FA) and age in corpus callosum genu; correlations not seen in splenium. Significant positive correlations were also observed between ?D? and age in bilateral cingulum cingulate gyri, uncinate fasciculi and right corticospinal tract. This pattern of correlations was not, however, reproduced when those subjects with significant white matter lesion load were analyzed separately from those without. These data therefore suggest that brain atrophy and white matter lesions play a significant role in driving regional patterns of age-related changes in white matter tract shape and integrity. PMID:20171285

  18. 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,…

  19. 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,

  20. 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…

  1. Mechanisms of white matter changes induced by meditation

    PubMed Central

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

    2012-01-01

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

  2. 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...

  3. Impaired cerebrovascular hemodynamics are associated with cerebral white matter damage

    PubMed Central

    Purkayastha, Sushmita; Fadar, Otite; Mehregan, Aujan; Salat, David H; Moscufo, Nicola; Meier, Dominik S; Guttmann, Charles RG; Fisher, Naomi DL; Lipsitz, Lewis A; Sorond, Farzaneh A

    2014-01-01

    White matter hyperintensities (WMH) in elderly individuals with vascular diseases are presumed to be due to ischemic small vessel diseases; however, their etiology is unknown. We examined the cross-sectional relationship between cerebrovascular hemodynamics and white matter structural integrity in elderly individuals with vascular risk factors. White matter hyperintensity volumes, fractional anisotropy (FA), and mean diffusivity (MD) were obtained from MRI in 48 subjects (757years). Pulsatility index (PI) and dynamic cerebral autoregulation (dCA) was assessed using transcranial Doppler ultrasound of the middle cerebral artery. Dynamic cerebral autoregulation was calculated from transfer function analysis (phase and gain) of spontaneous blood pressure and flow velocity oscillations in the low (LF, 0.03 to 0.15?Hz) and high (HF, 0.16 to 0.5?Hz) frequency ranges. Higher PI was associated with greater WMH (P<0.005). Higher phase across all frequency ranges was associated with greater FA and lower MD (P<0.005). Lower gain was associated with higher FA in the LF range (P=0.001). These relationships between phase and FA were significant in the territories limited to the middle cerebral artery as well as across the entire brain. Our results show a strong relationship between impaired cerebrovascular hemodynamics (PI and dCA) and loss of cerebral white matter structural integrity (WMH and DTI metrics) in elderly individuals. PMID:24129749

  4. 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

  5. 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

  6. 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…

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

    PubMed Central

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

    2010-01-01

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

  8. White Matter Abnormalities in Schizophrenia and Schizotypal Personality Disorder

    PubMed Central

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

    2015-01-01

    Prior diffusion tensor imaging (DTI) studies examining schizotypal personality disorder (SPD) and schizophrenia, separately have shown that compared with healthy controls (HCs), patients show frontotemporal white matter (WM) abnormalities. This is the first DTI study to directly compare WM tract coherence with tractography and fractional anisotropy (FA) across the schizophrenia spectrum in a large sample of demographically matched HCs (n = 55), medication-naive SPD patients (n = 49), and unmedicated/never-medicated schizophrenia patients (n = 22) to determine whether (a) frontal-striatal-temporal WM tract abnormalities in schizophrenia are similar to, or distinct from those observed in SPD; and (b) WM tract abnormalities are associated with clinical symptom severity indicating a common underlying pathology across the spectrum. Compared with both the HC and SPD groups, schizophrenia patients showed WM abnormalities, as indexed by lower FA in the temporal lobe (inferior longitudinal fasciculus) and cingulum regions. SPD patients showed lower FA in the corpus callosum genu compared with the HC group, but this regional abnormality was more widespread in schizophrenia patients. Across the schizophrenia spectrum, greater WM disruptions were associated with greater symptom severity. Overall, frontal-striatal-temporal WM dysconnectivity is attenuated in SPD compared with schizophrenia patients and may mitigate the emergence of psychosis. PMID:24962608

  9. 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

  10. Susceptibility induced graywhite matter MRI contrast in the human brain

    PubMed Central

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

    2012-01-01

    MR phase images have shown significantly improved contrast between cortical gray and white matter regions compared to magnitude images obtained with gradient echo sequences. A variety of underlying biophysical mechanisms (including iron, blood, myelin content, macromolecular chemical exchange, and fiber orientation) have been suggested to account for this observation but assessing the individual contribution of these factors is limited in vivo. For a closer investigation of iron and myelin induced susceptibility changes, postmortem MRI of six human corpses (age range at death: 5680years) was acquired in situ. Following autopsy, the iron concentrations in the frontal and occipital cortex as well as in white matter regions were chemically determined. The magnetization transfer ratio (MTR) was used as an indirect measure for myelin content. Susceptibility effects were assessed separately by determining R2* relaxation rates and quantitative phase shifts. Contributions of myelin and iron to local variations of the susceptibility were assessed by univariate and multivariate linear regression analysis. Mean iron concentration was lower in the frontal cortex than in frontal white matter (266 vs. 456mg/kg wet tissue) while an inverse relation was found in the occipital lobe (cortical gray matter: 4110 vs. white matter: 3410mg/kg wet tissue). Multiple regression analysis revealed iron and MTR as independent predictors of the effective transverse relaxation rate R2* but solely MTR was identified as source of MR phase contrast. R2* was correlated with iron concentrations in cortical gray matter only (r=0.42, p<0.05). In conclusion, MR phase contrast between cortical gray and white matter can be mainly attributed to variations in myelin content, but not to iron concentration. Both, myelin and iron impact the effective transverse relaxation rate R2* significantly. Magnitude contrast is limited because it only reflects the extent but not the direction of the susceptibility shift. PMID:21893208

  11. 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 Brodmanns 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

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

    PubMed

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

    2014-01-01

    Spastic diplegic cerebral palsy (SDCP) is a common type of cerebral palsy (CP), which presents as a group of motor-impairment syndromes. Previous conventional MRI studies have reported abnormal structural changes in SDCP, such as periventricular leucomalacia. However, there are roughly 27.8% SDCP patients presenting normal appearance in conventional MRI, which were considered as occult SDCP. In this study, sixteen patients with occult SDCP and 16 age- and sex-matched healthy control subjects were collected and the data were acquired on a 3T MR system. We applied voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) analysis to investigate whole brain grey and white matter injury in occult SDCP. By using VBM method, the grey matter volume reduction was revealed in the bilateral basal ganglia regions, thalamus, insula, and left cerebral peduncle, whereas the white matter atrophy was found to be located in the posterior part of corpus callosum and right posterior corona radiata in the occult SDCP patients. By using TBSS, reduced fractional anisotropy (FA) values were detected in multiple white matter regions, including bilateral white matter tracts in prefrontal lobe, temporal lobe, internal and external capsule, corpus callosum, cingulum, thalamus, brainstem and cerebellum. Additionally, several regions of white matter tracts injury were found to be significantly correlated with motor dysfunction. These results collectively revealed the spatial patterns of whole brain grey and white matter injury in occult SDCP. PMID:24964139

  13. White matter alterations in temporal lobe epilepsy

    NASA Astrophysics Data System (ADS)

    Diniz, P. B.; Salmon, C. E.; Velasco, T. R.; Sakamoto, A. C.; Leite, J. P.; Santos, A. C.

    2011-03-01

    In This study, we used Fractional anisotropy (FA), mean diffusivity (D), parallel diffusivity (D//) and perpendicular diffusivity (D), to localize the regions where occur axonal lesion and demyelization. TBSS was applied to analyze the FA data. After, the regions with alteration were studied with D, D// and D maps. Patients exhibited widespread degradation of FA. With D, D// and D maps analysis we found alterations in corpus callosum, corticospinal tract, fornix, internal capsule, corona radiate, Sagittal stratum, cingulum, fronto-occipital fasciculus and uncinate fasciculus. Our results are consistent with the hypothesis that exist demyelization and axonal damage in patients with TLE.

  14. Aerobic fitness is associated with greater white matter integrity in children

    PubMed Central

    Chaddock-Heyman, Laura; Erickson, Kirk I.; Holtrop, Joseph L.; Voss, Michelle W.; Pontifex, Matthew B.; Raine, Lauren B.; Hillman, Charles H.; Kramer, Arthur F.

    2014-01-01

    Aerobic fitness has been found to play a positive role in brain and cognitive health of children. Yet, many of the neural biomarkers related to aerobic fitness remain unknown. Here, using diffusion tensor imaging, we demonstrated that higher aerobic fitness was related to greater estimates of white matter microstructure in children. Higher fit 9- and 10-year-old children showed greater fractional anisotropy (FA) in sections of the corpus callosum, corona radiata, and superior longitudinal fasciculus, compared to lower fit children. The FA effects were primarily characterized by aerobic fitness differences in radial diffusivity, thereby raising the possibility that estimates of myelination may vary as a function of individual differences in fitness during childhood. White matter structure may be another potential neural mechanism of aerobic fitness that assists in efficient communication between gray matter regions as well as the integration of regions into networks. PMID:25191243

  15. Gray and White Matter Distribution in Dyslexia: A VBM Study of Superior Temporal Gyrus Asymmetry

    PubMed Central

    Dole, Marjorie; Meunier, Fanny; Hoen, Michel

    2013-01-01

    In the present study, we investigated brain morphological signatures of dyslexia by using a voxel-based asymmetry analysis. Dyslexia is a developmental disorder that affects the acquisition of reading and spelling abilities and is associated with a phonological deficit. Speech perception disabilities have been associated with this deficit, particularly when listening conditions are challenging, such as in noisy environments. These deficits are associated with known neurophysiological correlates, such as a reduction in the functional activation or a modification of functional asymmetry in the cortical regions involved in speech processing, such as the bilateral superior temporal areas. These functional deficits have been associated with macroscopic morphological abnormalities, which potentially include a reduction in gray and white matter volumes, combined with modifications of the leftward asymmetry along the perisylvian areas. The purpose of this study was to investigate gray/white matter distribution asymmetries in dyslexic adults using automated image processing derived from the voxel-based morphometry technique. Correlations with speech-in-noise perception abilities were also investigated. The results confirmed the presence of gray matter distribution abnormalities in the superior temporal gyrus (STG) and the superior temporal Sulcus (STS) in individuals with dyslexia. Specifically, the gray matter of adults with dyslexia was symmetrically distributed over one particular region of the STS, the temporal voice area, whereas normal readers showed a clear rightward gray matter asymmetry in this area. We also identified a region in the left posterior STG in which the white matter distribution asymmetry was correlated to speech-in-noise comprehension abilities in dyslexic adults. These results provide further information concerning the morphological alterations observed in dyslexia, revealing the presence of both gray and white matter distribution anomalies and the potential involvement of these defects in speech-in-noise deficits. PMID:24098565

  16. 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.

  17. 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.…

  18. 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

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

    PubMed

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

    2014-11-01

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

  20. 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

  1. Serum S100B Protein is Specifically Related to White Matter Changes in Schizophrenia

    PubMed Central

    Milleit, Berko; Smesny, Stefan; Rothermundt, Matthias; Preul, Christoph; Schroeter, Matthias L.; von Eiff, Christof; Ponath, Gerald; Milleit, Christine; Sauer, Heinrich; Gaser, Christian

    2016-01-01

    Background: Schizophrenia can be conceptualized as a form of dysconnectivity between brain regions.To investigate the neurobiological foundation of dysconnectivity, one approach is to analyze white matter structures, such as the pathology of fiber tracks. S100B is considered a marker protein for glial cells, in particular oligodendrocytes and astroglia, that passes the blood brain barrier and is detectable in peripheral blood. Earlier Studies have consistently reported increased S100B levels in schizophrenia. In this study, we aim to investigate associations between S100B and structural white matter abnormalities. Methods: We analyzed data of 17 unmedicated schizophrenic patients (first and recurrent episode) and 22 controls. We used voxel based morphometry (VBM) to detect group differences of white matter structures as obtained from T1-weighted MR-images and considered S100B serum levels as a regressor in an age-corrected interaction analysis. Results: S100B was increased in both patient subgroups. Using VBM, we found clusters indicating significant differences of the association between S100B concentration and white matter. Involved anatomical structures are the posterior cingulate bundle and temporal white matter structures assigned to the superior longitudinal fasciculus. Conclusions: S100B-associated alterations of white matter are shown to be existent already at time of first manifestation of psychosis and are distinct from findings in recurrent episode patients. This suggests involvement of S100B in an ongoing and dynamic process associated with structural brain changes in schizophrenia. However, it remains elusive whether increased S100B serum concentrations in psychotic patients represent a protective response to a continuous pathogenic process or if elevated S100B levels are actively involved in promoting structural brain damage. PMID:27013967

  2. 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

  3. Voxel-based assessment of gray and white matter volumes in Alzheimer's disease.

    PubMed

    Guo, Xiaojuan; Wang, Zhiqun; Li, Kuncheng; Li, Ziyi; Qi, Zhigang; Jin, Zhen; Yao, Li; Chen, Kewei

    2010-01-01

    Using the study-specific templates and optimized voxel-based morphometry (VBM), this study investigated abnormalities in gray and white matter to provide depiction of the concurrent structural changes in 13 patients with Alzheimer's disease (AD) compared with 14 age- and sex-matched normal controls. Consistent with previous studies, patients with AD exhibited significant gray matter volume reductions mainly in the hippocampus, parahippocampal gyrus, insula, superior/middle temporal gyrus, thalamus, cingulate gyrus, and superior/inferior parietal lobule. In addition, white matter volume reductions were found predominately in the temporal lobe, corpus callosum, and inferior longitudinal fasciculus. Furthermore, a number of additional white matter regions such as precentral gyrus, cingulate fasciculus, superior and inferior frontal gyrus, and sub-gyral in parietal lobe were also affected. The pattern of gray and white matter volume reductions helps us understand the underlying pathologic mechanisms in AD and potentially can be used as an imaging marker for the studies of AD in the future. PMID:19879920

  4. Voxel-based assessment of gray and white matter volumes in Alzheimers disease

    PubMed Central

    Guo, Xiaojuan; Wang, Zhiqun; Li, Kuncheng; Li, Ziyi; Qi, Zhigang; Jin, Zhen; Yao, Li; Chen, Kewei

    2010-01-01

    Using the study-specific templates and optimized voxel-based morphometry (VBM), this study investigated abnormalities in gray and white matter to provide depiction of the concurrent structural changes in 13 patients with Alzheimers disease (AD) compared with 14 age- and sex-matched normal controls. Consistent with previous studies, patients with AD exhibited significant gray matter volume reductions mainly in the hippocampus, parahippocampal gyrus, insula, superior/middle temporal gyrus, thalamus, cingulate gyrus, and superior/inferior parietal lobule. In addition, white matter volume reductions were found predominately in the temporal lobe, corpus callosum, and inferior longitudinal fasciculus. Furthermore, a number of additional white matter regions such as precentral gyrus, cingulate fasciculus, superior and inferior frontal gyrus, and sub-gyral in parietal lobe were also affected. The pattern of gray and white matter volume reductions helps us understand the underlying pathologic mechanisms in AD and potentially can be used as an imaging marker for the studies of AD in the future. PMID:19879920

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

    PubMed

    Sigaard, Rasmus Krarup; Kjr, 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

  6. 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

  7. 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

  8. 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

  9. Conserved and variable architecture of human white matter connectivity.

    PubMed

    Bassett, Danielle S; Brown, Jesse A; Deshpande, Vibhas; Carlson, Jean M; Grafton, Scott T

    2011-01-15

    Whole-brain network analysis of diffusion imaging tractography data is an important new tool for quantification of differential connectivity patterns across individuals and between groups. Here we investigate both the conservation of network architectural properties across methodological variation and the reproducibility of individual architecture across multiple scanning sessions. Diffusion spectrum imaging (DSI) and diffusion tensor imaging (DTI) data were both acquired in triplicate from a cohort of healthy young adults. Deterministic tractography was performed on each dataset and inter-regional connectivity matrices were then derived by applying each of three widely used whole-brain parcellation schemes over a range of spatial resolutions. Across acquisitions and preprocessing streams, anatomical brain networks were found to be sparsely connected, hierarchical, and assortative. They also displayed signatures of topo-physical interdependence such as Rentian scaling. Basic connectivity properties and several graph metrics consistently displayed high reproducibility and low variability in both DSI and DTI networks. The relative increased sensitivity of DSI to complex fiber configurations was evident in increased tract counts and network density compared with DTI. In combination, this pattern of results shows that network analysis of human white matter connectivity provides sensitive and temporally stable topological and physical estimates of individual cortical structure across multiple spatial scales. PMID:20850551

  10. 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

  11. 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

  12. 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

  13. White Matter Disease Contributes to Apathy and Disinhibition in Behavioral Variant Frontotemporal Dementia

    PubMed Central

    Powers, John P.; Massimo, Lauren; McMillan, Corey T.; Yushkevich, Paul A.; Zhang, Hui; Gee, James C.; Grossman, Murray

    2015-01-01

    Objective To relate changes in fractional anisotropy associated with behavioral variant frontotemporal dementia to measures of apathy and disinhibition. Background Apathy and disinhibition are the 2 most common behavioral features of behavioral variant frontotemporal dementia, and these symptoms are associated with accelerated patient decline and caregiver stress. However, little is known about how white matter disease contributes to these symptoms. Methods We collected neuropsychiatric data, volumetric magnetic resonance imaging, and diffusion-weighted imaging in 11 patients who met published criteria for behavioral variant frontotemporal dementia and had an autopsy-validated cerebrospinal fluid profile consistent with frontotemporal lobar degeneration. We also collected imaging data on 34 healthy seniors for analyses defining regions of disease in the patients. We calculated and analyzed fractional anisotropy with a white matter tract-specific method. This approach uses anatomically guided data reduction to increase sensitivity, and localizes results within canonically defined tracts. We used nonparametric, cluster-based statistical analysis to relate fractional anisotropy to neuropsychiatric measures of apathy and disinhibition. Results The patients with behavioral variant frontotemporal dementia had widespread reductions in fractional anisotropy in anterior portions of frontal and temporal white matter, compared to the controls. Fractional anisotropy correlated with apathy in the left uncinate fasciculus and with disinhibition in the right corona radiata. Conclusions In patients with behavioral variant frontotemporal dementia, apathy and disinhibition are associated with distinct regions of white matter disease. The implicated fiber tracts likely support frontotemporal networks that are involved in goal-directed behavior. PMID:25539040

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

    PubMed

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

    2015-08-01

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

  15. Language-general and -specific white matter microstructural bases for reading

    PubMed Central

    Zhang, Mingxia; Chen, Chuansheng; Xue, Gui; Lu, Zhong-lin; Mei, Leilei; Xue, Hongli; Wei, Miao; He, Qinghua; Li, Jin; Dong, Qi

    2014-01-01

    In the past decade, several studies have investigated language-general and -specific brain regions for reading. However, very limited research has examined the white matter that connects these cortical regions. By using diffusion tensor imaging (DTI), the current study investigated the common and divergent relationship between white matter integrity indexed by fractional anisotropy (FA) and native language reading abilities in 89 Chinese and 93 English speakers. Conjunction analysis revealed that for both groups, reading ability was associated with the FA of seven white matter fiber bundles in two main anatomical locations in the left hemisphere: the dorsal corona radiate/corpus callosum/superior longitudinal fasciculus which might be for phonological access, and the ventral uncinate fasciculus/external capsule/inferior fronto-occipital fasciculus which might be for semantic processing. Contrast analysis showed that the FA of the left temporal part of superior longitudinal fasciculus contributed more to reading in English than in Chinese, which is consistent with the notion that this tract is involved in grapheme-to-phoneme conversion for alphabetic language reading. These results are the first evidence of language-general and specific white matter microstructural bases for reading. PMID:24814214

  16. White Matter Ischemic Changes in Hyperacute Ischemic Stroke

    PubMed Central

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

    2015-01-01

    Background and Purpose The purpose of this study was to evaluate changes in fractional anisotropy (FA), as measured by diffusion tensor imaging, of white matter (WM) infarction and hypoperfusion in patients with acute ischemic stroke using a quantitative voxel-based analysis. Methods In this prospective study, diffusion tensor imaging and dynamic susceptibility contrast perfusion sequences were acquired in 21 patients with acute ischemic stroke who presented within 6 hours of symptom onset. The coregistered FA, apparent diffusion coefficient, and dynamic susceptibility contrast time to maximum (Tmax) maps were used for voxel-based quantification using a region of interest approach in the ipsilateral affected side and in the homologous contralateral WM. The regions of WM infarction versus hypoperfusion were segmented using a threshold method. Data were analyzed by regression and ANOVA. Results There was an overall significant mean difference (P<0.001) for the apparent diffusion coefficient, Tmax, and FA values between the normal, hypoperfused, and infarcted WM. The meanSD of FA was significantly higher (P<0.001) in hypoperfused WM (0.3970.019) and lower (P<0.001) in infarcted WM (0.3130.037) when compared with normal WM (0.3600.020). Regression tree analysis of hypoperfused WM showed the largest mean FA difference at Tmax above versus below 5.4 s with a mean difference of 0.033 (P=0.0096). Conclusions Diffusion tensor imaging-FA was decreased in regions of WM infarction and increased in hypoperfused WM in patients with hyperacute acute ischemic stroke. The significantly increased FA values in the hypoperfused WM with Tmax?5.4 s are suggestive of early ischemic microstructural changes. PMID:25523053

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

    PubMed Central

    Borstad, Alexandra L.; Choi, Seongjin; Schmalbrock, Petra; Nichols-Larsen, Deborah S.

    2015-01-01

    Frontoparietal white matter supports information transfer between brain areas involved in complex haptic tasks such as somatosensory discrimination. The purpose of this study was to gain an understanding of the relationship between microstructural integrity of frontoparietal network white matter and haptic performance in persons with chronic stroke and to compare frontoparietal network integrity in participants with stroke and age matched control participants. Nineteen individuals with stroke and 16 controls participated. Haptic performance was quantified using the Hand Active Sensation Test (HASTe), an 18-item match-to-sample test of weight and texture discrimination. Three tesla MRI was used to obtain diffusion-weighted and high-resolution anatomical images of the whole brain. Probabilistic tractography was used to define 10 frontoparietal tracts total; Four intrahemispheric tracts measured bilaterally 1) thalamus to primary somatosensory cortex (TS1), 2) thalamus to primary motor cortex (TM1), 3) primary to secondary somatosensory cortex (S1 to SII) and 4) primary somatosensory cortex to middle frontal gyrus (S1 to MFG) and, 2 interhemispheric tracts; S1S1 and precuneus interhemispheric. A control tract outside the network, the cuneus interhemispheric tract, was also examined. The diffusion metrics fractional anisotropy (FA), mean diffusivity (MD), axial (AD) and radial diffusivity (RD) were quantified for each tract. Diminished FA and elevated MD values are associated with poorer white matter integrity in chronic stroke. Nine of 10 tracts quantified in the frontoparietal network had diminished structural integrity poststroke compared to the controls. The precuneus interhemispheric tract was not significantly different between groups. Principle component analysis across all frontoparietal white matter tract MD values indicated a single factor explained 47% and 57% of the variance in tract mean diffusivity in stroke and control groups respectively. Age strongly correlated with the shared variance across tracts in the control, but not in the poststroke participants. A moderate to good relationship was found between ipsilesional TM1 MD and affected hand HASTe score (r=?0.62, p=0.006) and less affected hand HASTe score (r=?0.53, p=0.022). Regression analysis revealed approximately 90% of the variance in affected hand HASTe score was predicted by the white matter integrity in the frontoparietal network (as indexed by MD) in poststroke participants while 87% of the variance in HASTe score was predicted in control participants. This study demonstrates the importance of frontoparietal white matter in mediating haptic performance and specifically identifies that TM1 and precuneus interhemispheric tracts may be appropriate targets for piloting rehabilitation interventions, such as noninvasive brain stimulation, when the goal is to improve poststroke haptic performance. PMID:26759788

  18. 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…

  19. 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

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

    PubMed Central

    Brouwer, Rachel M.; Mandl, Ren C. W.; Schnack, Hugo G.; van Soelen, Inge L. C.; van Baal, G. Caroline; Peper, Jiska S.; Kahn, Ren 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

  1. Visuotopic Cortical Connectivity Underlying Attention Revealed with White-Matter Tractography

    PubMed Central

    Greenberg, Adam S.; Verstynen, Timothy; Chiu, Yu-Chin; Yantis, Steven; Schneider, Walter; Behrmann, Marlene

    2012-01-01

    Visual attention selects behaviorally relevant information for detailed processing by resolving competition for representation among stimuli in retinotopically organized visual cortex. The signals that control this attentional biasing are thought to arise in a frontoparietal network of several brain regions, including posterior parietal cortex. Recent studies have revealed a topographic organization in the intraparietal sulcus (IPS) that mirrors the retinotopic organization in visual cortex, suggesting that connectivity between these regions might provide the mechanism by which attention acts on early cortical representations. Using white-matter imaging and functional MRI, we examined the connectivity between two topographic regions of IPS and six retinotopically defined areas in visual cortex. We observed a strong positive correlation between attention modulations in visual cortex and connectivity of posterior IPS, suggesting that these white-matter connections mediate the attention signals that resolve competition among stimuli for representation in visual cortex. Furthermore, we found that connectivity between IPS and V1 consistently respects visuotopic boundaries, whereas connections to V2 and V3/VP disperse by 60%. This pattern is consistent with changes in receptive field size across regions and suggests that a primary role of posterior IPS is to code spatially specific visual information. In summary, we have identified white-matter pathways that are ideally suited to carry attentional biasing signals in visuotopic coordinates from parietal control regions to sensory regions in humans. These results provide critical evidence for the biased competition theory of attention and specify neurobiological constraints on the functional brain organization of visual attention. PMID:22357860

  2. 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

  3. Differential developmental trajectories of magnetic susceptibility in human brain gray and white matter over the lifespan.

    PubMed

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

    2014-06-01

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

  4. Impaired small-world efficiency in structural cortical networks in multiple sclerosis associated with white matter lesion load

    PubMed Central

    He, Yong; Dagher, Alain; Chen, Zhang; Charil, Arnaud; Zijdenbos, Alex; Worsley, Keith

    2009-01-01

    White matter tracts, which play a crucial role in the coordination of information flow between different regions of grey matter, are particularly vulnerable to multiple sclerosis. Many studies have shown that the white matter lesions in multiple sclerosis are associated with focal abnormalities of grey matter, but little is known about the alterations in the coordinated patterns of cortical morphology among regions in the disease. Here, we used cortical thickness measurements from structural magnetic resonance imaging to investigate the relationship between the white matter lesion load and the topological efficiency of structural cortical networks in multiple sclerosis. Network efficiency was defined using a small-world network model that quantifies the effectiveness of information transfer within brain networks. In this study, we first classified patients (n = 330) into six subgroups according to their total white matter lesion loads, and identified structural brain networks for each multiple sclerosis group by thresholding the corresponding inter-regional cortical thickness correlation matrix, followed by a network efficiency analysis with graph theoretical approaches. The structural cortical networks in multiple sclerosis demonstrated efficient small-world architecture regardless of the lesion load, an organization that maximizes the information processing at a relatively low wiring cost. However, we found that the overall small-world network efficiency in multiple sclerosis was significantly disrupted in a manner proportional to the extent of total white matter lesions. Moreover, regional efficiency was also significantly decreased in specific brain regions, including the insula and precentral gyrus as well as regions of prefrontal and temporal association cortices. Finally, we showed that the lesions also altered many cortical thickness correlations in the frontal, temporal and parietal lobes. Our results suggest that the white matter lesions in multiple sclerosis might be associated with aberrant neuronal connectivity among widely distributed brain regions, and provide structural (morphological) evidence for the notion of multiple sclerosis as a disconnection syndrome. PMID:19439423

  5. 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 parietaltemporal 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

    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

  7. 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 785). 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

  8. [Hyperintense punctiform images in the white matter: a diagnostic approach].

    PubMed

    Medrano Martorell, S; Cuadrado Blázquez, M; García Figueredo, D; González Ortiz, S; Capellades Font, J

    2012-01-01

    The presence of hyperintense punctiform images in the white matter in T2 weighted magnetic resonance (MR) sequences is a very common finding and is occasionally a diagnostic challenge for the radiologist. The present article attempts, using an anatomical approach to the brain circulation, as well as from histopathology correlation studies, to simplify the task of interpreting these images from the description of the three main patterns of hyperintense punctiform images in the white matter: vascular pattern, which corresponds to microvascular lesions; perivascular pattern, which represents inflammatory disease of which the paradigm is multiple sclerosis; and a non-specific pattern, which has to be a microvascular disease. From the various semiological elements in the MR images, a predominant pattern can be determined in each case and, in this way, helps in the differential diagnosis. PMID:22284561

  9. 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

  10. 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

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

    PubMed

    Parra, Mario A; Saarimki, Heini; Bastin, Mark E; Londoo, 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

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

    PubMed

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

    2015-09-01

    Little is known about the emergence of structural asymmetry of white matter tracts during early brain development. We examined whether and when asymmetry in diffusion parameters of limbic and association white matter pathways emerged in humans in 23 brains ranging from 15 gestational weeks (GW) up to 3 years of age (11 ex vivo and 12 in vivo cases) using high-angular resolution diffusion imaging tractography. Age-related development of laterality was not observed in a limbic connectional pathway (cingulum bundle or fornix). Among the studied cortico-cortical association pathways (inferior longitudinal fasciculus [ILF], inferior fronto-occipital fasciculus, and arcuate fasciculus), only the ILF showed development of age-related laterality emerging as early as the second trimester. Comparisons of ages older and younger than 40 GW revealed a leftward asymmetry in the cingulum bundle volume and a rightward asymmetry in apparent diffusion coefficient and leftward asymmetry in fractional anisotropy in the ILF in ages older than 40 GW. These results suggest that morphometric asymmetry in cortical areas precedes the emergence of white matter pathway asymmetry. Future correlative studies will investigate whether such asymmetry is anatomically/genetically driven or associated with functional stimulation. PMID:24812082

  13. Longitudinal Characterization of White Matter Maturation During Adolescence

    PubMed Central

    Bava, Sunita; Thayer, Rachel; Jacobus, Joanna; Ward, Megan; Jernigan, Terry L.; Tapert, Susan F.

    2010-01-01

    Background: Late adolescence is comprised of considerable developmental transitions, though brain maturational changes during this period are subtle and difficult to quantitatively evaluate from standard brain imaging acquisitions. To date, primarily cross-sectional studies have characterized typical developmental changes during adolescence, but these processes need further description within a longitudinal framework. Method: To assess the developmental trajectory of typical white matter development, we examined 22 healthy adolescents with serial diffusion tensor images (DTI) collected at a mean age of 17.8 years and 16-months later. Diffusion parameters fractional anisotropy, and mean, radial, and axial diffusivity were subjected to whole-brain voxelwise time point comparisons using tract-based spatial statistics. Results: At follow-up, adolescents showed significant change (≥ 153 contiguous voxels each at p<.01) in diffusion properties, including in bilateral superior longitudinal fasciculi, superior corona radiata, anterior thalamic radiations, and posterior limb of the internal capsule. Overall, correlations with cognitive performances suggested behavioral improvement corresponding with white matter changes. Conclusion: These longitudinal DTI findings support continued microstructural change in white matter during late adolescence, and suggest ongoing refinement of projection and association fibers into early adulthood. PMID:20206151

  14. Pathogenesis of cerebral white matter injury of prematurity.

    PubMed

    Khwaja, O; Volpe, J J

    2008-03-01

    Cerebral white matter injury, characterised by loss of premyelinating oligodendrocytes (pre-OLs), is the most common form of injury to the preterm brain and is associated with a high risk of neurodevelopmental impairment. The unique cerebrovascular anatomy and physiology of the premature baby underlies the exquisite sensitivity of white matter to the abnormal milieu of preterm extrauterine life, in particular ischaemia and inflammation. These two upstream mechanisms can coexist and amplify their effects, leading to activation of two principal downstream mechanisms: excitotoxicity and free radical attack. Upstream mechanisms trigger generation of reactive oxygen and nitrogen species. The pre-OL is intrinsically vulnerable to free radical attack due to immaturity of antioxidant enzyme systems and iron accumulation. Ischaemia and inflammation trigger glutamate receptor-mediated injury leading to maturation-dependent cell death and loss of cellular processes. This review looks at recent evidence for pathogenetic mechanisms in white matter injury with emphasis on targets for prevention and treatment of injury. PMID:18296574

  15. Clinical associations of prenatal ischaemic white matter injury.

    PubMed Central

    Gaffney, G; Squier, M V; Johnson, A; Flavell, V; Sellers, S

    1994-01-01

    Neuropathological examinations were carried out at necropsy on 274 cases of intrauterine death or neonatal death at or before three days after birth. Fifty six (20.4%) subjects had evidence of prenatal ischaemic brain damage. On review of the maternal case notes to ascertain antenatal clinical associations there was an increased incidence of intrauterine growth retardation, either based on birth weight for gestational age (odds ratio (OR) 2.0; 95% confidence interval (CI) 1.1 to 3.7) or diagnosed antenatally (OR 2.7; 95% CI 1.3 to 5.6). Oligohydramnios was also more common (OR 2.9; 95% CI 1.2 to 7.0). The association of intrauterine growth retardation and white matter damage remained after excluding fetuses with a major congenital anomaly (OR 2.4; 95% CI 1.1 to 5.1). The findings suggest that chronic intrauterine hypoxia may be associated with damage to cerebral white matter among fetuses and infants who die. The relation between ischaemic white matter damage and cerebral palsy among survivors remains speculative. PMID:8154901

  16. 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 15 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

  17. White matter structure and clinical characteristics of stroke patients: A diffusion tensor MRI study.

    PubMed

    Ueda, Ryo; Yamada, Naoki; Kakuda, Wataru; Abo, Masahiro; Senoo, Atsushi

    2016-03-15

    Fractional anisotropy has been used in many studies that examined post-stroke changes in white matter. This study was performed to clarify cerebral white matter changes after stroke using generalized fractional anisotropy (GFA). White matter structure was visualized using diffusion tensor imaging in 72 patients with post-stroke arm paralysis. Exercise-related brain regions were examined in cerebral white matter using GFA. The relationship between GFA and clinical characteristics was examined. Overall, the mean GFA of the lesioned hemisphere was significantly lower than that of the non-lesioned hemisphere (P<0.05), the white matter of the lesioned side was severely affected by stroke. A weak negative correlation between GFA and time since stroke onset was found in Brodmann area 5 of the non-lesioned hemisphere. Age correlated negatively with GFA in Brodmann areas 5 and 7 of the lesioned hemisphere. Though these results may be due to a decrease in the frequency of use of the paralyzed limb over time, GFA overall was significantly and negatively affected by the subject's age. The GFA values of patients with paralysis of the dominant hand were significantly different from those of patients with paralysis of the nondominant hand in Brodmann areas 4 and 6 of the non-lesioned hemisphere and Brodmann area 4 of the lesioned hemisphere (P<0.05). The stroke size and location were not associated with GFA differences. Differences between the GFA of the lesioned and non-lesioned hemispheres varied depending on the affected brain region, age at onset of paralysis, and paralysis of the dominant or non-dominant hand. PMID:26783693

  18. 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 (1218) 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

  19. Gray and white matter degeneration revealed by diffusion in an Alzheimer mouse model.

    PubMed

    Zerbi, Valerio; Kleinnijenhuis, Michiel; Fang, Xiaotian; Jansen, Diane; Veltien, Andor; Van Asten, Jack; Timmer, Nienke; Dederen, Pieter J; Kiliaan, Amanda J; Heerschap, Arend

    2013-05-01

    In patients with Alzheimer's disease (AD) the severity of white matter degeneration correlates with the clinical symptoms of the disease. In this study, we performed diffusion-tensor magnetic resonance imaging at ultra-high field in a mouse model for AD (APP(swe)/PS1(dE9)) in combination with a voxel-based approach and tractography to detect changes in water diffusivity in white and gray matter, because these reflect structural alterations in neural tissue. We found substantial changes in water diffusion parallel and perpendicular to axonal tracts in several white matter regions like corpus callosum and fimbria of the hippocampus, that match with previous findings of axonal disconnection and myelin degradation in AD patients. Moreover, we found a significant increase in diffusivity in specific hippocampal subregions, which is supported by neuronal loss as visualized with Klver-Barrera staining. This work demonstrates the potential of ultra-high field diffusion-tensor magnetic resonance imaging as a noninvasive modality to describe white and gray matter structural changes in mouse models for neurodegenerative disorders, and provides valuable knowledge to assess future AD prevention strategies in translational research. PMID:23273575

  20. 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

  1. 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 cortexbrain 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

  2. Microstructural abnormalities of white matter differentiate pediatric and adult onset bipolar disorder

    PubMed Central

    Lu, Lisa H; Zhou, Xiaohong Joe; Fitzgerald, Jacklynn; Keedy, Sarah K; Reilly, James L; Passarotti, Alessandra M; Sweeney, John A; Pavuluri, Mani

    2012-01-01

    Background White matter microstructure, known to undergo significant developmental transformation, is abnormal in bipolar disorder (BD). Available evidence suggests that white matter deviation may be more pronounced in pediatric than adult onset BD. This study aimed to examine how white matter microstructure deviates from a typical maturational trajectory in BD. Methods Fractional anisotropy (FA) was measured in 35 individuals presenting with first episode BD (type I) and 46 healthy controls (HC) (aged 942) using diffusion tensor imaging (DTI). Patients were medication free and close to illness onset at the time of DTI scans. Tract based spatial statistics were used to examine the center of white matter tracts, and FA was extracted from nine tracts of interest. Axial, radial, and mean diffusivity were examined in post-hoc analyses. Results The left anterior limb of the internal capsule (ALIC) showed significantly lower FA in pediatric than adult onset BD. The lower FA in BD was due primarily to greater radial rather than a decrease in axial diffusivity. Conclusions ALIC connects the frontal lobes with archistriatum, thalamus, and medial temporal regions, and alteration in these pathways may contribute to mood dysregulation in BD. Abnormalities in this pathway appear to be associated with an earlier onset of illness and thus may reflect a greater liability for illness. PMID:22882719

  3. 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

  4. 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

  5. Effects of prenatal alcohol exposure on the development of white matter volume and change in executive function.

    PubMed

    Gautam, P; Nuez, S C; Narr, K L; Kan, E C; Sowell, E R

    2014-01-01

    Prenatal alcohol exposure can cause a wide range of deficits in executive function that persist throughout life, but little is known about how changes in brain structure relate to cognition in affected individuals. In the current study, we predicted that the rate of white matter volumetric development would be atypical in children with fetal alcohol spectrum disorders (FASD) when compared to typically developing children, and that the rate of change in cognitive function would relate to differential white matter development between groups. Data were available for 103 subjects [49 with FASD, 54 controls, age range 6-17, mean age=11.83] with 153 total observations. Groups were age-matched. Participants underwent structural magnetic resonance imaging (MRI) and an executive function (EF) battery. Using white matter volumes measured bilaterally for frontal and parietal regions and the corpus callosum, change was predicted by modeling the effects of age, intracranial volume, sex, and interactions with exposure status and EF measures. While both groups showed regional increases in white matter volumes and improvement in cognitive performance over time, there were significant effects of exposure status on age-related relationships between white matter increases and EF measures. Specifically, individuals with FASD consistently showed a positive relationship between improved cognitive function and increased white matter volume over time, while no such relationships were seen in controls. These novel results relating improved cognitive function with increased white matter volume in FASD suggest that better cognitive outcomes could be possible for FASD subjects through interventions that enhance white matter plasticity. PMID:24918069

  6. Testing the white matter retrogenesis hypothesis of cognitive aging

    PubMed Central

    Brickman, Adam M.; Meier, Irene B.; Korgaonkar, Mayuresh S.; Provenzano, Frank A.; Grieve, Stuart M.; Siedlecki, Karen L.; Wasserman, Ben T.; Williams, Leanne M.; Zimmerman, Molly E.

    2011-01-01

    Background The retrogenesis hypothesis postulates that late-myelinated white matter fibers are most vulnerable to age- and disease-related degeneration, which in turn mediate cognitive decline. While recent evidence supports this hypothesis in the context of Alzheimers disease, it has not been tested systematically in normal cognitive aging. Methods In the current study, we examined the retrogenesis hypothesis in a group (n=282) of cognitively normal individuals ranging in age from 7 to 87 years from the Brain Resource International Database. Participants were evaluated with a comprehensive neuropsychological battery and were imaged with diffusion tensor imaging. Fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (DA), measures of white matter coherence, were computed in two prototypical early-myelinated fiber tracts (posterior limb of the internal capsule, cerebral peduncles) and two prototypical late-myelinated fiber tracts (superior longitudinal fasciculus, inferior longitudinal fasciculus) chosen to parallel previous studies; mean summary values were also computed for other early- and late-myelinated fiber tracts. We examined age-associated differences in FA, RD, and DA in the developmental trajectory (ages 7 to 30 years) and degenerative trajectory (ages 31 to 87 years), and tested whether the measures of white matter coherence mediated age-related cognitive decline in the older group. Results FA and DA values were greater for early-myelinated fibers than for late-myelinated fibers, and RD values were lower for early-myelinated than late-myelinated fibers. There were age-associated differences in FA, RD, and DA across early- and late-myelinated fiber tracts in the younger group, but the magnitude of differences did not vary as a function of early or late myelinating status. FA and RD in most fiber tracts showed reliable age-associated differences in the older age group, but the magnitudes were greatest for the late-myelinated tract summary measure, inferior longitudinal fasciculus (late fiber tract), and cerebral peduncles (early fiber tract). Finally, FA in the inferior longitudinal fasciculus and cerebral peduncles and RD in the cerebral peduncles mediated age-associated differences in an executive functioning factor. Discussion Taken together, the findings highlight the importance of white matter coherence in cognitive aging and provide some, but not complete, support for the white matter retrogenesis hypothesis in normal cognitive aging. PMID:21783280

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

    SciTech Connect

    Qiu Deqiang; Kwong, Dora; Chan, Godfrey; Leung, Lucullus; Khong, P.-L.

    2007-11-01

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

  8. Spatial heterogeneity in oligodendrocyte lineage maturation and not cerebral blood flow predicts fetal ovine periventricular white matter injury.

    PubMed

    Riddle, Art; Luo, Ning Ling; Manese, Mario; Beardsley, Douglas J; Green, Lisa; Rorvik, Dawn A; Kelly, Katherine A; Barlow, Clyde H; Kelly, Jeffrey J; Hohimer, A Roger; Back, Stephen A

    2006-03-15

    Although periventricular white matter injury (PWMI) is the leading cause of chronic neurological disability and cerebral palsy in survivors of premature birth, the cellular-molecular mechanisms by which ischemia-reperfusion contributes to the pathogenesis of PWMI are not well defined. To define pathophysiologic relationships among ischemia, acute cerebral white matter damage, and vulnerable target populations, we used a global cerebral ischemia-reperfusion model in the instrumented 0.65 gestation fetal sheep. We developed a novel method to make repeated measurements of cerebral blood flow using fluorescently labeled microspheres to resolve the spatial heterogeneity of flow in situ in three-dimensional space. Basal flow in the periventricular white matter (PVWM) was significantly lower than in the cerebral cortex. During global cerebral ischemia induced by carotid occlusion, flow to all regions was reduced by nearly 90%. Ischemia of 30 or 37 min duration generated selective graded injury to frontal and parietal PVWM, two regions of predilection for human PWMI. Injury was proportional to the duration of ischemia and increased markedly with 45 min of ischemia to extensively damage cortical and subcortical gray matter. Surprisingly, the distribution of PVWM damage was not uniform and not explained by heterogeneity in the degree of white matter ischemia. Rather, the extent of white matter damage coincided with the presence of a susceptible population of late oligodendrocyte progenitors. These data support that although ischemia is necessary to generate PWMI, the presence of susceptible populations of oligodendrocyte progenitors underlies regional predilection to injury. PMID:16540583

  9. 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: 1.2814.32; 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

  10. Frontal white matter changes and aggression in methamphetamine dependence.

    PubMed

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

    2016-02-01

    Chronic methamphetamine (MA) use can lead to white matter (WM) changes and increased levels of aggression. While previous studies have examined WM abnormalities relating to cognitive impairment, associations between WM integrity and aggression in MA dependence remain unclear.Diffusion Tensor Imaging (DTI) was used to investigate WM changes in 40 individuals with MA dependence and 40 matched healthy controls. A region of interest (ROI) approach using tract based spatial statistics (TBSS) in FSL was performed. We compared fractional anisotropy (FA), mean diffusivity (MD), parallel diffusivity (??) and perpendicular diffusivity (??) in WM tracts of the frontal brain. A relationship of WM with aggression scores from the Buss & Perry Questionnaire was investigated. Mean scores for anger (p<0.001), physical aggression (p=0.032) and total aggression (p=0.021) were significantly higher in the MA group relative to controls. ROI analysis showed increased MD (U=439.5, p=0.001) and ?? (U=561.5, p=0.021) values in the genu of the corpus callosum, and increased MD (U=541.5, p=0.012) values in the right cingulum in MA dependence. None of the WM changes were significantly associated with aggression scores. This study provides evidence of frontal WM changes and increased levels of aggression in individuals with MA dependence. The lack of significant associations between WM and aggressive behaviour may reflect methodological issues in measuring such behaviour, or may indicate that the neurobiology of aggression is not simply correlated with WM damage but is more complex. PMID:26671551

  11. Q-ball imaging of macaque white matter architecture.

    PubMed

    Tuch, David S; Wisco, Jonathan J; Khachaturian, Mark H; Ekstrom, Leeland B; Ktter, Rolf; Vanduffel, Wim

    2005-05-29

    Diffusion-weighted magnetic resonance imaging holds substantial promise as a technique for non-invasive imaging of white matter (WM) axonal projections. For diffusion imaging to be capable of providing new insight into the connectional neuroanatomy of the human brain, it will be necessary to histologically validate the technique against established tracer methods such as horseradish peroxidase and biocytin histochemistry. The macaque monkey provides an ideal model for histological validation of the diffusion imaging method due to the phylogenetic proximity between humans and macaques, the gyrencephalic structure of the macaque cortex, the large body of knowledge on the neuroanatomic connectivity of the macaque brain and the ability to use comparable magnetic resonance acquisition protocols in both species. Recently, it has been shown that high angular resolution diffusion imaging (HARDI) can resolve multiple axon orientations within an individual imaging voxel in human WM. This capability promises to boost the accuracy of tract reconstructions from diffusion imaging. If the macaque is to serve as a model for histological validation of the diffusion tractography method, it will be necessary to show that HARDI can also resolve intravoxel architecture in macaque WM. The present study therefore sought to test whether the technique can resolve intravoxel structure in macaque WM. Using a HARDI method called q-ball imaging (QBI) it was possible to resolve composite intravoxel architecture in a number of anatomic regions. QBI resolved intravoxel structure in, for example, the dorsolateral convexity, the pontine decussation, the pulvinar and temporal subcortical WM. The paper concludes by reviewing remaining challenges for the diffusion tractography project. PMID:16087432

  12. Prefrontal cortex white matter tracts in prodromal Huntington disease.

    PubMed

    Matsui, Joy T; Vaidya, Jatin G; Wassermann, Demian; Kim, Regina Eunyoung; Magnotta, Vincent A; Johnson, Hans J; Paulsen, Jane S

    2015-10-01

    Huntington disease (HD) is most widely known for its selective degeneration of striatal neurons but there is also growing evidence for white matter (WM) deterioration. The primary objective of this research was to conduct a large-scale analysis using multisite diffusion-weighted imaging (DWI) tractography data to quantify diffusivity properties along major prefrontal cortex WM tracts in prodromal HD. Fifteen international sites participating in the PREDICT-HD study collected imaging and neuropsychological data on gene-positive HD participants without a clinical diagnosis (i.e., prodromal) and gene-negative control participants. The anatomical prefrontal WM tracts of the corpus callosum (PFCC), anterior thalamic radiations (ATRs), inferior fronto-occipital fasciculi (IFO), and uncinate fasciculi (UNC) were identified using streamline tractography of DWI. Within each of these tracts, tensor scalars for fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity coefficients were calculated. We divided prodromal HD subjects into three CAG-age product (CAP) groups having Low, Medium, or High probabilities of onset indexed by genetic exposure. We observed significant differences in WM properties for each of the four anatomical tracts for the High CAP group in comparison to controls. Additionally, the Medium CAP group presented differences in the ATR and IFO in comparison to controls. Furthermore, WM alterations in the PFCC, ATR, and IFO showed robust associations with neuropsychological measures of executive functioning. These results suggest long-range tracts essential for cross-region information transfer show early vulnerability in HD and may explain cognitive problems often present in the prodromal stage. Hum Brain Mapp 36:3717-3732, 2015. © 2015 Wiley Periodicals, Inc. PMID:26179962

  13. Perinatal Clinical Antecedents of White Matter Microstructural Abnormalities on Diffusion Tensor Imaging in Extremely Preterm Infants

    PubMed Central

    Pogribna, Ulana; Yu, Xintian; Burson, Katrina; Zhou, Yuxiang; Lasky, Robert E.; Narayana, Ponnada A.; Parikh, Nehal A.

    2013-01-01

    Objective To identify perinatal clinical antecedents of white matter microstructural abnormalities in extremely preterm infants. Methods A prospective cohort of extremely preterm infants (N = 86) and healthy term controls (N = 16) underwent diffusion tensor imaging (DTI) at term equivalent age. Region of interest-based measures of white matter microstructure - fractional anisotropy and mean diffusivity - were quantified in seven vulnerable cerebral regions and group differences assessed. In the preterm cohort, multivariable linear regression analyses were conducted to identify independent clinical factors associated with microstructural abnormalities. Results Preterm infants had a mean (standard deviation) gestational age of 26.1 (1.7) weeks and birth weight of 824 (182) grams. Compared to term controls, the preterm cohort exhibited widespread microstructural abnormalities in 9 of 14 regional measures. Chorioamnionitis, necrotizing enterocolitis, white matter injury on cranial ultrasound, and increasing duration of mechanical ventilation were adversely correlated with regional microstructure. Conversely, antenatal steroids, female sex, longer duration of caffeine therapy, and greater duration of human milk use were independent favorable factors. White matter injury on cranial ultrasound was associated with a five weeks or greater delayed maturation of the corpus callosum; every additional 10 days of human milk use were associated with a three weeks or greater advanced maturation of the corpus callosum. Conclusions Diffusion tensor imaging is sensitive in detecting the widespread cerebral delayed maturation and/or damage increasingly observed in extremely preterm infants. In our cohort, it also aided identification of several previously known or suspected perinatal clinical antecedents of brain injury, aberrant development, and neurodevelopmental impairments. PMID:24009724

  14. Meta-analytic investigations of structural grey matter, executive domain-related functional activations, and white matter diffusivity in obsessive compulsive disorder: an integrative review.

    PubMed

    Eng, Goi Khia; Sim, Kang; Chen, Shen-Hsing Annabel

    2015-05-01

    Obsessive-compulsive disorder (OCD) is a debilitating disorder. However, existing neuroimaging findings involving executive function and structural abnormalities in OCD have been mixed. Here we conducted meta-analyses to investigate differences in OCD samples and controls in: Study 1 - grey matter structure; Study 2 - executive function task-related activations during (i) response inhibition, (ii) interference, and (iii) switching tasks; and Study 3 - white matter diffusivity. Results showed grey matter differences in the frontal, striatal, thalamus, parietal and cerebellar regions; task domain-specific neural differences in similar regions; and abnormal diffusivity in major white matter regions in OCD samples compared to controls. Our results reported concurrence of abnormal white matter diffusivity with corresponding abnormalities in grey matter and task-related functional activations. Our findings suggested the involvement of other brain regions not included in the cortico-striato-thalamo-cortical network, such as the cerebellum and parietal cortex, and questioned the involvement of the orbitofrontal region in OCD pathophysiology. Future research is needed to clarify the roles of these brain regions in the disorder. PMID:25766413

  15. 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

  16. 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

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

    PubMed

    Borstad, Alexandra L; Choi, Seongjin; Schmalbrock, Petra; Nichols-Larsen, Deborah S

    2016-01-01

    Frontoparietal white matter supports information transfer between brain areas involved in complex haptic tasks such as somatosensory discrimination. The purpose of this study was to gain an understanding of the relationship between microstructural integrity of frontoparietal network white matter and haptic performance in persons with chronic stroke and to compare frontoparietal network integrity in participants with stroke and age matched control participants. Nineteen individuals with stroke and 16 controls participated. Haptic performance was quantified using the Hand Active Sensation Test (HASTe), an 18-item match-to-sample test of weight and texture discrimination. Three tesla MRI was used to obtain diffusion-weighted and high-resolution anatomical images of the whole brain. Probabilistic tractography was used to define 10 frontoparietal tracts total; Four intrahemispheric tracts measured bilaterally 1) thalamus to primary somatosensory cortex (T-S1), 2) thalamus to primary motor cortex (T-M1), 3) primary to secondary somatosensory cortex (S1 to SII) and 4) primary somatosensory cortex to middle frontal gyrus (S1 to MFG) and, 2 interhemispheric tracts; S1-S1 and precuneus interhemispheric. A control tract outside the network, the cuneus interhemispheric tract, was also examined. The diffusion metrics fractional anisotropy (FA), mean diffusivity (MD), axial (AD) and radial diffusivity (RD) were quantified for each tract. Diminished FA and elevated MD values are associated with poorer white matter integrity in chronic stroke. Nine of 10 tracts quantified in the frontoparietal network had diminished structural integrity poststroke compared to the controls. The precuneus interhemispheric tract was not significantly different between groups. Principle component analysis across all frontoparietal white matter tract MD values indicated a single factor explained 47% and 57% of the variance in tract mean diffusivity in stroke and control groups respectively. Age strongly correlated with the shared variance across tracts in the control, but not in the poststroke participants. A moderate to good relationship was found between ipsilesional T-M1 MD and affected hand HASTe score (r = - 0.62, p = 0.006) and less affected hand HASTe score (r = - 0.53, p = 0.022). Regression analysis revealed approximately 90% of the variance in affected hand HASTe score was predicted by the white matter integrity in the frontoparietal network (as indexed by MD) in poststroke participants while 87% of the variance in HASTe score was predicted in control participants. This study demonstrates the importance of frontoparietal white matter in mediating haptic performance and specifically identifies that T-M1 and precuneus interhemispheric tracts may be appropriate targets for piloting rehabilitation interventions, such as noninvasive brain stimulation, when the goal is to improve poststroke haptic performance. PMID:26759788

  18. White Matter Neuron Alterations in Schizophrenia and Related Disorders

    PubMed Central

    Connor, Caroline M; Crawford, Benjamin C; Akbarian, Schahram

    2010-01-01

    Increased density and altered spatial distribution of subcortical white matter neurons (WMN) represents one of the more well replicated cellular alterations found in schizophrenia and related disease. In many of the affected cases, the underlying genetic risk architecture for these WMN abnormalities remains unknown. Increased density of neurons immunoreactive for Microtubule-Associated Protein 2 (MAP2) and Neuronal Nuclear Antigen (NeuN) have been reported by independent studies, though there are negative reports as well; additionally, group differences in some of the studies appear to be driven by a small subset of cases. Alterations in markers for inhibitory (GABAergic) neurons have also been described. For example, downregulation of neuropeptide Y (NPY) and nitric oxide synthase (NOS1) in inhibitory WMN positioned at the gray/white matter border, as well as altered spatial distribution, have been reported. While increased density of WMN has been suggested to reflect disturbance of neurodevelopmental processes, including neuronal migration, neurogenesis, and cell death, alternative hypothesessuch as an adaptive response to microglial activation in mature CNS, as has been described in multiple sclerosisshould also be considered. We argue that larger scale studies involving hundreds of postmortem specimens will be necessary in order to clearly establish the subset of subjects affected. Additionally, these larger cohorts could make it feasible to connect the cellular pathology to environmental and genetic factors implicated in schizophrenia and some cases with bipolar disorder or autism. These could include the 22q11 deletion (Velocardiofacial/ DiGeorge) syndrome, which in some cases is associated with neuronal ectopias in white matter. PMID:20691252

  19. Temperature dependence of water diffusion pools in brain white matter.

    PubMed

    Dhital, Bibek; Labadie, Christian; Stallmach, Frank; Mller, Harald E; Turner, Robert

    2016-02-15

    Water diffusion in brain tissue can now be easily investigated using magnetic resonance (MR) techniques, providing unique insights into cellular level microstructure such as axonal orientation. The diffusive motion in white matter is known to be non-Gaussian, with increasing evidence for more than one water-containing tissue compartment. In this study, freshly excised porcine brain white matter was measured using a 125-MHz MR spectrometer (3T) equipped with gradient coils providing magnetic field gradients of up to 35,000mT/m. The sample temperature was varied between -14 and +19C. The hypothesis tested was that white matter contains two slowly exchanging pools of water molecules with different diffusion properties. A Stejskal-Tanner diffusion sequence with very short gradient pulses and b-factors up to 18.8ms/?m(2) was used. The dependence on b-factor of the attenuation due to diffusion was robustly fitted by a biexponential function, with comparable volume fractions for each component. The diffusion coefficient of each component follows Arrhenius behavior, with significantly different activation energies. The measured volume fractions are consistent with the existence of three water-containing compartments, the first comprising relatively free cytoplasmic and extracellular water molecules, the second of water molecules in glial processes, and the third comprising water molecules closely associated with membranes, as for example, in the myelin sheaths and elsewhere. The activation energy of the slow diffusion pool suggests proton hopping at the surface of membranes by a Grotthuss mechanism, mediated by hydrating water molecules. PMID:26658929

  20. White matter tractography in early psychosis: clinical and neurocognitive associations

    PubMed Central

    Hatton, Sean N.; Lagopoulos, Jim; Hermens, Daniel F.; Hickie, Ian B.; Scott, Elizabeth; Bennett, Maxwell R.

    2014-01-01

    Background While many diffusion tensor imaging (DTI) investigations have noted disruptions to white matter integrity in individuals with chronic psychotic disorders, fewer studies have been conducted in young people at the early stages of disease onset. Using whole tract reconstruction techniques, the aim of this study was to identify the white matter pathology associated with the common clinical symptoms and executive function impairments observed in young people with psychosis. Methods We obtained MRI scans from young people with psychosis and healthy controls. Eighteen major white matter tracts were reconstructed to determine group differences in fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) and then were subsequently correlated with symptomatology and neurocognitive performance. Results Our study included 42 young people with psychosis (mean age 23 yr) and 45 healthy controls (mean age 25 yr). Compared with the control group, the psychosis group had reduced FA and AD in the left inferior longitudinal fasciculus (ILF) and forceps major indicative of axonal disorganization, reduction and/or loss. These changes were associated with worse overall psychiatric symptom severity, increases in positive and negative symptoms, and worse current levels of depression. The psychosis group also showed FA reductions in the left superior longitudinal fasciculus that were associated with impaired neurocognitive performance in attention and semantic fluency. Limitations Our analysis grouped 4 subcategories of psychosis together, and a larger follow-up study comparing affective and nonaffective psychoses is warranted. Conclusion Our findings suggest that impaired axonal coherence in the left ILF and forceps major underpin psychiatric symptoms in young people in the early stages of psychosis. PMID:25111788

  1. 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

  2. Shared genetic variance between obesity and white matter integrity in Mexican Americans

    PubMed Central

    Spieker, Elena A.; Kochunov, Peter; Rowland, Laura M.; Sprooten, Emma; Winkler, Anderson M.; Olvera, Rene L.; Almasy, Laura; Duggirala, Ravi; Fox, Peter T.; Blangero, John; Glahn, David C.; Curran, Joanne E.

    2015-01-01

    Obesity is a chronic metabolic disorder that may also lead to reduced white matter integrity, potentially due to shared genetic risk factors. Genetic correlation analyses were conducted in a large cohort of Mexican American families in San Antonio (N = 761, 58% females, ages 1881 years; 41.3 14.5) from the Genetics of Brain Structure and Function Study. Shared genetic variance was calculated between measures of adiposity [(body mass index (BMI; kg/m2) and waist circumference (WC; in)] and whole-brain and regional measurements of cerebral white matter integrity (fractional anisotropy). Whole-brain average and regional fractional anisotropy values for 10 major white matter tracts were calculated from high angular resolution diffusion tensor imaging data (DTI; 1.7 1.7 3 mm; 55 directions). Additive genetic factors explained intersubject variance in BMI (heritability, h2 = 0.58), WC (h2 = 0.57), and FA (h2 = 0.49). FA shared significant portions of genetic variance with BMI in the genu (?G = ?0.25), body (?G = ?0.30), and splenium (?G = ?0.26) of the corpus callosum, internal capsule (?G = ?0.29), and thalamic radiation (?G = ?0.31) (all p's = 0.043). The strongest evidence of shared variance was between BMI/WC and FA in the superior fronto-occipital fasciculus (?G = ?0.39, p = 0.020; ?G = ?0.39, p = 0.030), which highlights region-specific variation in neural correlates of obesity. This may suggest that increase in obesity and reduced white matter integrity share common genetic risk factors. PMID:25763009

  3. Imaging Small Vessel-Associated White Matter Changes in Aging

    PubMed Central

    Salat, David H.

    2014-01-01

    Alterations in cerebrovascular structure and function may underlie the most common age-associated cognitive, psychiatric, and neurological conditions presented by older adults. Although much remains to understand, existing research suggests several age-associated detrimental conditions may be mediated through sometimes subtle small vessel-induced damage to the cerebral white matter. Here we review a selected portion of the vast work that demonstrates links between changes in vascular and neural health as a function of advancing age, and how even changes in low-to-moderate risk individuals, potentially beginning early in the adult age-span, may have an important impact on functional status in late life. PMID:24316059

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

    PubMed Central

    2014-01-01

    Background Incidental white matter hyperintensities (WMHs) are common findings on T2-weighted magnetic resonance images of the aged brain and have been associated with cognitive decline. While a variety of pathogenic mechanisms have been proposed, the origin of WMHs and the extent to which lesions in the deep and periventricular white matter reflect distinct etiologies remains unclear. Our aim was to quantify the fractional blood volume (vb) of small WMHs in vivo using a novel magnetic resonance imaging (MRI) approach and examine the contribution of bloodbrain barrier disturbances to WMH formation in the deep and periventricular white matter. Methods Twenty-three elderly volunteers (aged 5982 years) underwent 7 Tesla relaxographic imaging and fluid-attenuated inversion recovery (FLAIR) MRI. Maps of longitudinal relaxation rate constant (R1) were prepared before contrast reagent (CR) injection and throughout CR washout. Voxelwise estimates of vb were determined by fitting temporal changes in R1 values to a two-site model that incorporates the effects of transendothelial water exchange. Average vb values in deep and periventricular WMHs were determined after semi-automated segmentation of FLAIR images. Ventricular permeability was estimated from the change in CSF R1 values during CR washout. Results In the absence of CR, the total water fraction in both deep and periventricular WMHs was increased compared to normal appearing white matter (NAWM). The vb of deep WMHs was 1.8??0.6mL/100g and was significantly reduced compared to NAWM (2.4??0.8mL/100g). In contrast, the vb of periventricular WMHs was unchanged compared to NAWM, decreased with ventricular volume and showed a positive association with ventricular permeability. Conclusions Hyperintensities in the deep WM appear to be driven by vascular compromise, while those in the periventricular WM are most likely the result of a compromised ependyma in which the small vessels remain relatively intact. These findings support varying contributions of bloodbrain barrier and brain-CSF interface disturbances in the pathophysiology of deep and periventricular WMHs in the aged human brain. PMID:25379172

  5. 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

  6. 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

  7. Acute cerebral white matter damage in lethal salicylate intoxication.

    PubMed

    Rauschka, Helmut; Aboul-Enein, Fahmy; Bauer, Jan; Nobis, Hans; Lassmann, Hans; Schmidbauer, Manfred

    2007-01-01

    A 34-year-old oligophrenic woman was admitted in comatose state with marked tachypnea. History revealed the oral ingestion of a large amount of acetylsalicylate to attenuate ear pain within the preceding 3 days. Laboratory investigations showed a toxic concentration of serum salicylate (668 mg/l, toxic range above 200 mg/l) and metabolic acidosis. Oxygenation, blood pressure, electrocardiography, echocardiography and CT of thorax and brain were normal. The patient was intubated, fluid and bicarbonate was given intravenously. Six hours after admission asystolia refractory to resuscitation led to death. Autopsy showed venous congestion of the brain, cardiac dilatation and pulmonary edema. Brain histopathology showed myelin disintegration and caspase-3 activation in glial cells, whereas, grey matter changes were sparse. Acute white matter damage is suggested to be the substrate of cerebral dysfunction in salicylate intoxication and possible mechanisms are discussed. PMID:16930716

  8. Altered Cerebellar White Matter Integrity in Patients with Mild Traumatic Brain Injury in the Acute Stage

    PubMed Central

    Wang, Zhongqiu; Wu, Wenzhong; Liu, Yongkang; Wang, Tianyao; Chen, Xiao; Zhang, Jianhua; Zhou, Guoxing; Chen, Rong

    2016-01-01

    Background and Purpose Imaging studies of traumatic brain injury demonstrate that the cerebellum is often affected. We aim to examine fractional anisotropy alteration in acute-phase mild traumatic brain injury patients in cerebellum-related white matter tracts. Materials and Methods This prospective study included 47 mild traumatic brain injury patients in the acute stage and 37 controls. MR imaging and neurocognitive tests were performed in patients within 7 days of injury. White matter integrity was examined by using diffusion tensor imaging. We used three approaches, tract-based spatial statistics, graphical-model-based multivariate analysis, and region-of-interest analysis, to detect altered cerebellar white matter integrity in mild traumatic brain injury patients. Results Results from three analysis methods were in accordance with each other, and suggested fractional anisotropy in the middle cerebellar peduncle and the pontine crossing tract was changed in the acute-phase mild traumatic brain injury patients, relative to controls (adjusted p-value < 0.05). Higher fractional anisotropy in the middle cerebellar peduncle was associated with worse performance in the fluid cognition composite (r = -0.289, p-value = 0.037). Conclusion Altered cerebellar fractional anisotropy in acute-phase mild traumatic brain injury patients is localized in specific regions and statistically associated with cognitive deficits detectable on neurocognitive testing. PMID:26967320

  9. 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.

  10. Early-Stage Psychotherapy Produces Elevated Frontal White Matter Integrity in Adult Major Depressive Disorder

    PubMed Central

    Lv, Fajin; Zhang, Yong; Zhou, Linke; Yang, Deyu; Xie, Peng

    2013-01-01

    Background Psychotherapy has demonstrated comparable efficacy to antidepressant medication in the treatment of major depressive disorder. Metabolic alterations in the MDD state and in response to treatment have been detected by functional imaging methods, but the underlying white matter microstructural changes remain unknown. The goal of this study is to apply diffusion tensor imaging techniques to investigate psychotherapy-specific responses in the white matter. Methods Twenty-one of forty-five outpatients diagnosed with major depression underwent diffusion tensor imaging before and after a four-week course of guided imagery psychotherapy. We compared fractional anisotropy in depressed patients (n = 21) with healthy controls (n = 22), and before-after treatment, using whole brain voxel-wise analysis. Results Post-treatment, depressed subjects showed a significant reduction in the 17-item Hamilton Depression Rating Scale. As compared to healthy controls, depressed subjects demonstrated significantly increased fractional anisotropy in the right thalamus. Psychopathological changes did not recover post-treatment, but a novel region of increased fractional anisotropy was discovered in the frontal lobe. Conclusions At an early stage of psychotherapy, higher fractional anisotropy was detected in the frontal emotional regulation-associated region. This finding reveals that psychotherapy may induce white matter changes in the frontal lobe. This remodeling of frontal connections within mood regulation networks positively contributes to the “top-down” mechanism of psychotherapy. PMID:23646178

  11. White matter apoptosis is increased by delayed hypothermia and rewarming in a neonatal piglet model of hypoxic ischemic encephalopathy.

    PubMed

    Wang, B; Armstrong, J S; Reyes, M; Kulikowicz, E; Lee, J-H; Spicer, D; Bhalala, U; Yang, Z-J; Koehler, R C; Martin, L J; Lee, J K

    2016-03-01

    Therapeutic hypothermia is widely used to treat neonatal hypoxic ischemic (HI) brain injuries. However, potentially deleterious effects of delaying the induction of hypothermia and of rewarming on white matter injury remain unclear. We used a piglet model of HI to assess the effects of delayed hypothermia and rewarming on white matter apoptosis. Piglets underwent HI injury or sham surgery followed by normothermic or hypothermic recovery at 2h. Hypothermic groups were divided into those with no rewarming, slow rewarming at 0.5C/h, or rapid rewarming at 4C/h. Apoptotic cells in the subcortical white matter of the motor gyrus, corpus callosum, lateral olfactory tract, and internal capsule at 29h were identified morphologically and counted by hematoxylin & eosin staining. Cell death was verified by terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL) assay. White matter neurons were also counted, and apoptotic cells were immunophenotyped with the oligodendrocyte marker 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase). Hypothermia, slow rewarming, and rapid rewarming increased apoptosis in the subcortical white matter relative to normothermia (p<0.05). The number of white matter neurons was not lower in groups with more apoptosis after hypothermia or rapid rewarming, indicating that the apoptosis occurred among glial cells. Hypothermic piglets had more apoptosis in the lateral olfactory tract than those that were rewarmed (p<0.05). The promotion of apoptosis by hypothermia and rewarming in these regions was independent of HI. In the corpus callosum, HI piglets had more apoptosis than shams after normothermia, slow rewarming, and rapid rewarming (p<0.05). Many apoptotic cells were myelinating oligodendrocytes identified by CNPase positivity. Our results indicate that delaying the induction of hypothermia and rewarming are associated with white matter apoptosis in a piglet model of HI; in some regions these temperature effects are independent of HI. Vulnerable cells include myelinating oligodendrocytes. This study identifies a deleterious effect of therapeutic hypothermia in the developing brain. PMID:26739327

  12. 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

  13. 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.

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

    PubMed Central

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

    2015-01-01

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

  15. White Matter Integrity is Reduced in Bulimia Nervosa

    PubMed Central

    Mettler, Lisa N.; Shott, Megan E.; Pryor, Tamara; Yang, Tony T.; Frank, Guido K.W.

    2013-01-01

    Objective To investigate brain white matter (WM) functionality in bulimia nervosa (BN) in relation to anxiety. Method Twenty-one control (CW, mean age 277 years) and 20 BN women (mean age 255 years) underwent brain diffusion tensor imaging (DTI) to measure fractional anisotropy (FA; an indication of WM axon integrity) and the apparent diffusion coefficient (ADC; reflecting WM cell damage). Results FA was decreased in BN in the bilateral corona radiata extending into the posterior limb of the internal capsule, the corpus callosum, the right sub-insular white matter and right fornix. In CW but not BN trait anxiety correlated negatively with fornix, corpus callosum and left corona radiata FA. ADC was increased in BN compared to CW in the bilateral corona radiata, corpus callosum, inferior fronto-occipital and uncinate fasciculus. Alterations in BN WM functionality were not due to structural brain alterations. Discussion WM integrity is disturbed in BN, especially in the corona radiate, which has been associated with taste and brain reward processing. Whether this is a premorbid condition or an effect from the illness is yet uncertain. The relationships between WM FA and trait anxiety in CW but not BN may suggest that altered WM functionality contributes to high anxious traits in BN. PMID:23354827

  16. Apcdd1 stimulates oligodendrocyte differentiation after white matter injury.

    PubMed

    Lee, Hyun Kyoung; Laug, Dylan; Zhu, Wenyi; Patel, Jay M; Ung, Kevin; Arenkiel, Benjamin R; Fancy, Stephen P J; Mohila, Carrie; Deneen, Benjamin

    2015-10-01

    Wnt signaling plays an essential role in developmental and regenerative myelination of the CNS, therefore it is critical to understand how the factors associated with the various regulatory layers of this complex pathway contribute to these processes. Recently, Apcdd1 was identified as a negative regulator of proximal Wnt signaling, however its role in oligodendrocyte (OL) differentiation and reymelination in the CNS remain undefined. Analysis of Apcdd1 expression revealed dynamic expression during OL development, where its expression is upregulated during differentiation. Functional studies using ex vivo and in vitro OL systems revealed that Apcdd1 promotes OL differentiation, suppresses Wnt signaling, and associates with ?-catenin. Application of these findings to white matter injury (WMI) models revealed that Apcdd1 similarly promotes OL differentiation after gliotoxic injury in vivo and acute hypoxia ex vivo. Examination of Apcdd1 expression in white matter lesions from neonatal WMI and adult multiple sclerosis revealed its expression in subsets of oligodendrocyte (OL) precursors. These studies describe, for the first time, the role of Apcdd1 in OLs after WMI and reveal that negative regulators of the proximal Wnt pathway can influence regenerative myelination, suggesting a new therapeutic strategy for modulating Wnt signaling and stimulating repair after WMI. PMID:25946682

  17. Targeting of White Matter Tracts With Transcranial Magnetic Stimulation

    PubMed Central

    Nummenmaa, Aapo; McNab, Jennifer A.; Savadjiev, Peter; Okada, Yoshio; Hmlinen, Matti S.; Wang, Ruopeng; Wald, Lawrence L.; Pascual-Leone, Alvaro; Wedeen, Van J.; Raij, Tommi

    2014-01-01

    Background TMS activations of white matter depend not only on the distance from the coil, but also on the orientation of the axons relative to the TMS-induced electric field, and especially on axonal bends that create strong local field gradient maxima. Therefore, tractography contains potentially useful information for TMS targeting. Objective/methods Here, we utilized 1-mm resolution diffusion and structural T1-weighted MRI to construct large-scale tractography models, and localized TMS white matter activations in motor cortex using electromagnetic forward modeling in a boundary element model (BEM). Results As expected, in sulcal walls, pyramidal cell axonal bends created preferred sites of activation that were not found in gyral crowns. The model agreed with the well-known coil orientation sensitivity of motor cortex, and also suggested unexpected activation distributions emerging from the E-field and tract configurations. We further propose a novel method for computing the optimal coil location and orientation to maximally stimulate a pre-determined axonal bundle. Conclusions Diffusion MRI tractography with electromagnetic modeling may improve spatial specificity and efficacy of TMS. PMID:24220599

  18. A Combined Measure of Vascular Risk for White Matter Lesions

    PubMed Central

    Watts, Amber; Honea, Robyn A.; Billinger, Sandra A.; Rhyner, Kathleen T.; Hutfles, Lewis; Vidoni, Eric D.; Burns, Jeffrey M.

    2015-01-01

    Background Though hypertension is a commonly studied risk factor for white matter lesions (WMLs), measures of blood pressure may fluctuate depending on external conditions resulting in measurement error. Indicators of arterial stiffening and reduced elasticity may be more sensitive indicators of risk for WMLs in aging; however the interdependent nature of vascular indicators creates statistical complications. Objective The purpose of the study was to determine whether a factor score comprised of multiple vascular indicators would be a stronger predictor of WMLs than traditional measures of blood pressure. Methods In a sample of well-characterized nondemented older adults, we used a factor analytic approach to account for variance common across multiple vascular measures while reducing measurement error. The result was a single factor score reflecting arterial stiffness and reduced elasticity. We used this factor score to predict white matter lesion volumes acquired via fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging. Results The combined vascular factor score was a stronger predictor of deep WML (? = 0.42, p < 0.001) and periventricular WML volumes (? = 0.49, p < 0.001). After accounting for the vascular factor, systolic and diastolic blood pressure measurements were not significant predictors. Conclusions This suggests that a combined measure of arterial elasticity and stiffening may be a stronger predictor of WMLs than systolic and diastolic blood pressure accounting for the multicollinearity associated with a variety of interrelated vascular measures. PMID:25690663

  19. 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

  20. Disruption of brain white matter microstructure in women with anorexia nervosa

    PubMed Central

    Via, Esther; Zalesky, Andrew; Snchez, Isabel; Forcano, Laura; Harrison, Ben J.; Pujol, Jess; Fernndez-Aranda, Fernando; Menchn, Jos Manuel; Soriano-Mas, Carles; Cardoner, Narcs; Fornito, Alex

    2014-01-01

    Background The etiology of anorexia nervosa is still unknown. Multiple and distributed brain regions have been implicated in its pathophysiology, implying a dysfunction of connected neural circuits. Despite these findings, the role of white matter in anorexia nervosa has been rarely assessed. In this study, we used diffusion tensor imaging (DTI) to characterize alterations of white matter microstructure in a clinically homogeneous sample of patients with anorexia nervosa. Methods Women with anorexia nervosa (restricting subtype) and healthy controls underwent brain DTI. We used tract-based spatial statistics to compare fractional anisotropy (FA) and mean diffusivity (MD) maps between the groups. Furthermore, axial (AD) and radial diffusivity (RD) measures were extracted from regions showing group differences in either FA or MD. Results We enrolled 19 women with anorexia nervosa and 19 healthy controls in our study. Patients with anorexia nervosa showed significant FA decreases in the parietal part of the left superior longitudinal fasciculus (SLF; pFWE < 0.05), with increased MD and RD but no differences in AD. Patients with anorexia nervosa also showed significantly increased MD in the fornix (pFWE < 0.05), accompanied by decreased FA and increased RD and AD. Limitations Limitations include our modest sample size and cross-sectional design. Conclusion Our findings support the presence of white matter pathology in patients with anorexia nervosa. Alterations in the SLF and fornix might be relevant to key symptoms of anorexia nervosa, such as body image distortion or impairments in bodyenergybalance and reward processes. The differences found in both areas replicate those found in previous DTI studies and support a role for white matter pathology of specific neural circuits in individuals with anorexia nervosa. PMID:24913136

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

    PubMed Central

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

    2015-01-01

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

  2. 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

  3. Oligodendroglial alterations and the role of microglia in white matter injury: relevance to schizophrenia.

    PubMed

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

    2013-01-01

    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

  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. A magnetization transfer study of white matter in siblings of multiple sclerosis patients.

    PubMed

    Filippi, M; Campi, A; Martino, G; Colombo, B; Comi, G

    1997-04-15

    In this study, we evaluated magnetization transfer ratio values in the brain white matter of siblings of multiple sclerosis (MS) patients and compared them to those obtained in sex- and age-matched normal controls. No statistically significant difference was found between the two groups for all the white matter areas studied (frontal and occipital lobes, centrum semiovale, periventricular white matter, internal capsule, genu and splenium of the corpus callosum). PMID:9106120

  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. 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

  8. 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

  9. 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

  10. 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, Ren 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

  11. Differential White Matter Connectivity in Early Mild Cognitive Impairment According to CSF Biomarkers

    PubMed Central

    Lim, Jae-Sung; Park, Young Ho; Jang, Jae-Won; Park, So Yong; Kim, SangYun

    2014-01-01

    Mild cognitive impairment (MCI) is a heterogeneous group and certain MCI subsets eventually convert to dementia. Cerebrospinal fluid (CSF) biomarkers are known to predict this conversion. We sought evidence for the differences in white matter connectivity between early amnestic MCI (EMCI) subgroups according to a CSF phosphorylated tau181p/amyloid beta142 ratio of 0.10. From the Alzheimer's Disease Neuroimaging Initiative database, 16 high-ratio, 25 low-ratio EMCI patients, and 20 normal controls with diffusion tensor images and CSF profiles were included. Compared to the high-ratio group, radial diffusivity significantly increased in both sides of the corpus callosum and the superior and inferior longitudinal fasciculus in the low-ratio group. In widespread white matter skeleton regions, the low-ratio group showed significantly increased mean, axial, and radial diffusivity compared to normal controls. However, the high-ratio group showed no differences when compared to the normal group. In conclusion, our study revealed that there were significant differences in white matter connectivity between EMCI subgroups according to CSF phosphorylated tau181p/amyloid beta142ratios. PMID:24614676

  12. White Matter Microstructure in Attention-Deficit/Hyperactivity Disorder Subjects and Their Siblings

    PubMed Central

    Lawrence, Katherine E.; Levitt, Jennifer G.; Loo, Sandra K.; Ly, Ronald; Yee, Victor; ONeill, Joseph; Alger, Jeffry; Narr, Katherine L.

    2013-01-01

    Objective Previous voxel-based and regions-of-interest (ROI)-based diffusion tensor imaging (DTI) studies have found above-normal mean diffusivity (MD) and below-normal fractional anisotropy (FA) in subjects with attention-deficit/hyperactivity disorder (ADHD). However, findings remain mixed and few studies have examined the contribution of ADHD familial liability to white matter microstructure. Method We used refined DTI tractography methods to examine MD, FA, axial diffusivity (AD) and radial diffusivity (RD) of the anterior thalamic radiation, cingulum, corticospinal tract, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, forceps major, forceps minor, superior longitudinal fasciculus and uncinate fasciculus in children and adolescents with ADHD (n = 56), unaffected siblings of ADHD probands (n = 31) and healthy controls (n = 17). Results Subjects with ADHD showed significantly higher MD than controls in the anterior thalamic radiation, forceps minor, and superior longitudinal fasciculus. Unaffected siblings of subjects with ADHD displayed similar differences in MD as subjects with ADHD. While none of the tested tracts showed a significant effect of FA, the tracts with elevated MD likewise displayed elevated AD in both subjects with ADHD and unaffected siblings. Differences in RD between subjects with ADHD, unaffected siblings and controls were not as widespread as differences in MD and AD. Conclusion Our findings suggest that disruptions in white matter microstructure occur in several large white matter pathways in association with ADHD and indicate a familial liability for the disorder. Furthermore, MD may reflect these abnormalities more sensitively than FA. PMID:23582873

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

    PubMed Central

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

    2013-01-01

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

  14. The effects of a neuregulin 1 variant on white matter density and integrity.

    PubMed

    McIntosh, A M; Moorhead, T W J; Job, D; Lymer, G K S; Muoz Maniega, S; McKirdy, J; Sussmann, J E D; Baig, B J; Bastin, M E; Porteous, D; Evans, K L; Johnstone, E C; Lawrie, S M; Hall, J

    2008-11-01

    Theories of abnormal anatomical and functional connectivity in schizophrenia and bipolar disorder are supported by evidence from functional magnetic resonance imaging (MRI), structural MRI and diffusion tensor imaging (DTI). The presence of similar abnormalities in unaffected relatives suggests such disconnectivity is genetically mediated, albeit through unspecified loci. Neuregulin 1 (NRG1) is a psychosis susceptibility gene with effects on neuronal migration, axon guidance and myelination that could potentially explain these findings. In the current study, unaffected subjects were genotyped at the NRG1 single nucleotide polymorphism (SNP) rs6994992 (SNP8NRG243177) locus, previously associated with increased risk for psychosis, and the effect of genetic variation at this locus on white matter density (T(1)-weighted MRI) and integrity (DTI) was ascertained. Subjects with the risk-associated TT genotype had reduced white matter density in the anterior limb of the internal capsule and evidence of reduced structural connectivity in the same region using DTI. We therefore provide the first imaging evidence that genetic variation in NRG1 is associated with reduced white matter density and integrity in human subjects. This finding is discussed in the context of NRG1 effects on neuronal migration, axon guidance and myelination. PMID:17925794

  15. Fractional anisotropy of water diffusion in cerebral white matter across the lifespan

    PubMed Central

    Kochunov, P.; Williamson, D.E.; Lancaster, J.; Fox, P.; Cornell, J; Blangero, J.; Glahn, DC

    2010-01-01

    Determining the time of peak of cerebral maturation is vital for our understanding of when cerebral maturation ceases and the cerebral degeneration in healthy aging begins. We carefully mapped changes in fractional anisotropy (FA) of water diffusion for eleven major cerebral white matter tracts in a large group (831) of healthy human subjects aged 1190. FA is a neuroimaging index of micro-structural white matter integrity, sensitive to age-related changes in cerebral myelin levels, measured using diffusion tensor imaging. The average FA values of cerebral white matter (WM) reached peak at the age 326 years. FA measurements for all but one major cortical white matter tract (cortico-spinal) reached peaks between 23 and 39 years of age. The maturation rates, prior to age-of-peak were significantly correlated (r=0.74; p=.01) with the rates of decline, past age-of-peak. Regional analysis of corpus callosum (CC) showed that thinly-myelinated, densely packed fibers in the genu, that connect pre-frontal areas, maturated later and showed higher decline in aging than the more thickly myelinated motor and sensory areas in the body and splenium of CC. Our findings can be summarized as: associative, cerebral WM tracts that reach their peak FA values later in life also show progressively higher age-related decline than earlier maturing motor and sensory tracts. These findings carry multiple and diverse implications for both theoretical studies of the neurobiology of maturation and aging and for the clinical studies of neuropsychiatric disorders. PMID:20122755

  16. 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

  17. White matter correlates of cognitive inhibition during development: a diffusion tensor imaging study.

    PubMed

    Treit, S; Chen, Z; Rasmussen, C; Beaulieu, C

    2014-09-12

    Inhibitory control and cognitive flexibility are two key executive functions that develop in childhood and adolescence, increasing one's capacity to respond dynamically to changing external demands and refrain from impulsive behaviors. These gains evolve in concert with significant brain development. Magnetic resonance imaging studies have identified numerous frontal and cingulate cortical areas associated with performance on inhibition tasks, but less is known about the involvement of the underlying anatomical connectivity, namely white matter. Here we used diffusion tensor imaging (DTI) to examine correlations between a DTI-derived parameter, fractional anisotropy (FA) of white matter, and performance on the NEPSY-II Inhibition test (Naming, Inhibition and Switching conditions) in 49 healthy children aged 5-16years (20 females; 29 males). First, whole brain voxel-based analysis revealed several clusters in the frontal projections of the corpus callosum, where higher FA was associated with worse inhibitory performance, as well as several clusters in posterior brain regions and one in the brainstem where higher FA was associated with better cognitive flexibility (in the Switching task), suggesting a dichotomous relationship between FA and these two aspects of cognitive control. Tractography through these clusters identified several white matter tracts, which were then manual traced in native space. Pearson's correlations confirmed associations between higher FA of frontal projections of the corpus callosum with poorer inhibitory performance (independent of age), though associations with Switching were not significant. Post-hoc evaluation suggested that FA of orbital and anterior frontal projections of the corpus callosum also mediated performance differences across conditions, which may reflect differences in self-monitoring or strategy use. These findings suggest a link between the development of inhibition and cognitive control with that of the underlying white matter, and may help to identify deviations of neurobiology in adolescent psychopathology. PMID:24355493

  18. White matter tract and glial-associated changes in 5-hydroxymethylcytosine following chronic cerebral hypoperfusion.

    PubMed

    Tsenkina, Yanina; Ruzov, Alexey; Gliddon, Catherine; Horsburgh, Karen; De Sousa, Paul A

    2014-12-10

    White matter abnormalities due to age-related cerebrovascular alterations is a common pathological hallmark associated with functional impairment in the elderly which has been modeled in chronically hypoperfused mice. 5-Methylcytosine (5mC) and its oxidized derivative 5-hydroxymethylcytosine (5hmC) are DNA modifications that have been recently linked with age-related neurodegeneration and cerebrovascular pathology. Here we conducted a pilot investigation of whether chronic cerebral hypoperfusion might affect genomic distribution of these modifications and/ or a Ten-Eleven Translocation protein 2 (TET2) which catalyses hydroxymethylation in white and grey matter regions of this animal model. Immunohistochemical evaluation of sham and chronically hypoperfused mice a month after surgery revealed significant (p<0.05) increases in the proportion of 5hmC positive cells, Iba1 positive inflammatory microglia, and NG2 positive oligodendroglial progenitors in the hypoperfused corpus callosum. In the same white matter tract there was an absence of hypoperfusion-induced alterations in the proportion of 5mC, TET2 positive cells and CC1 positive mature oligodrendrocytes. Correlation analysis across animals within both treatment groups demonstrated a significant association of the elevated 5hmC levels with increases in the proportion of inflammatory microglia only (p=0.01) in the corpus callosum. In vitro studies revealed that 5hmC is lost during oligodendroglial maturation but not microglial activation. Additionally, TET1, TET2, and TET3 protein levels showed dynamic alterations during oligodendroglial development and following oxidative stress in vitro. Our study suggests that 5hmC exhibits white matter tract and cell type specific dynamics following chronic cerebral hypoperfusion in mice. PMID:25305569

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

    PubMed

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

    2013-01-01

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

  20. Spasticity and white matter abnormalities in adult phenylketonuria.

    PubMed Central

    McCombe, P A; McLaughlin, D B; Chalk, J B; Brown, N N; McGill, J J; Pender, M P

    1992-01-01

    A 19 year old male with phenylketonuria (PKU) developed a spastic paparesis 8 months after stopping his restricted phenylalanine diet. CT and MRI showed abnormalities of the deep cerebral white matter, and visual evoked response latencies were prolonged. The spasticity gradually improved over several months after resuming the PKU diet. A repeat MRI scan was unchanged. His brother also had PKU and ceased dietary restrictions, but his only neurological abnormality was a slight increase in the deep tendon reflexes of the lower limbs. CT and MRI of his brain was normal. DNA analysis showed that both brothers were homozygous for the same PKU mutation. These patients demonstrate that reversible neurological signs may develop in patients with classic PKU after ceasing dietary restrictions and that these may be associated with abnormalities seen on neuro-imaging. Images PMID:1602307

  1. 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

  2. The corpus callosum: white matter or terra incognita

    PubMed Central

    Fitsiori, A; Nguyen, D; Karentzos, A; Delavelle, J; Vargas, M I

    2011-01-01

    The corpus callosum is the largest white matter structure in the brain, consisting of 200250 million contralateral axonal projections and the major commissural pathway connecting the hemispheres of the human brain. The pathology of the corpus callosum includes a wide variety of entities that arise from different causes such as congenital, inflammatory, tumoural, degenerative, infectious, metabolic, traumatic, vascular and toxic agents. The corpus callosum, or a specific part of it, can be affected selectively. Numerous pathologies of the corpus callosum are encountered during CT and MRI. The aim of this study is to facilitate a better understanding and thus treatment of the pathological entities of the corpus callosum by categorising them according to their causes and their manifestations in MR and CT imaging. Familiarity with its anatomy and pathology is important to the radiologist in order to recognise its disease at an early stage and help the clinician establish the optimal therapeutic approach. PMID:21172964

  3. 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

  4. Relationship Between White Matter Hyperintensities Penumbra and Cavity Formation

    PubMed Central

    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/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

  5. 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=72.25.3yrs, endurance training>15yrs) and 10 sedentary older adults similar in age and educational level (2 females, age=74.54.3yrs) 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

  6. 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.

  7. White Matter Correlates of Neuropsychological Dysfunction in Systemic Lupus Erythematosus

    PubMed Central

    Jung, Rex E.; Chavez, Robert S.; Flores, Ranee A.; Qualls, Clifford; Sibbitt, Wilmer L.; Roldan, Carlos A.

    2012-01-01

    Patients diagnosed with Systemic Lupus Erythematosus have similar levels of neuropsychological dysfunction (i.e., 2050%) as those with Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). We hypothesized a gradient between cognition and white matter integrity, such that strongest brain-behavior relationships would emerge in NPSLE, intermediate in non-NPSLE, and minimal in controls. We studied thirty-one patients (16 non-NPSLE; 15 NPSLE), ranging in age from 18 to 59 years old (100% female), and eighteen age and gender matched healthy controls. DTI examinations were performed on a 1.5T scanner. A broad neuropsychological battery was administered, tapping attention, memory, processing speed, and executive functioning. The Total z-score consisted of the combined sum of all neuropsychological measures. In control subjects, we found no significant FA-Total z-score correlations. NPSLE, non-NPSLE, and control subjects differed significantly in terms of Total z-score (NPSLE?=??2.25+/?1.77, non-NPSLE?=??1.22+/?1.03, Controls?=??0.10+/?.57; F?=?13.2, p<.001). In non-NPSLE subjects, FA within the right external capsule was significantly correlated with Total z-score. In NPSLE subjects, the largest FA-Total z-score clusters were observed within the left anterior thalamic radiation and right superior longitudinal fasciculus. In subsequent analyses the largest number of significant voxels linked FA with the Processing Speed z-score in NPSLE. The current results reflect objective white matter correlates of neuropsychological dysfunction in both NPSLE and (to a lesser degree) in non-NPSLE. non-NPSLE and NPSLE subjects did not differ significantly in terms of depression, as measured by the GDI; thus, previous hypotheses suggesting moderating effects of depression upon neuropsychological performance do not impact the current FA results. PMID:22291880

  8. 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

  9. Imaging evidence of early brain tissue degeneration in patients with vanishing white matter disease: a multimodal MR study.

    PubMed

    Ding, Xiao-Qi; Bley, Annette; Ohlenbusch, Andreas; Kohlschtter, Alfried; Fiehler, Jens; Zhu, Wenzhen; Lanfermann, Heinrich

    2012-04-01

    To find imaging signs of active degenerative processes in vanishing white matter disease (VWM), six VWM patients and six matched controls underwent MR examinations. The data were analyzed with modified Scheltens scales for morphological findings and determined quantitatively for apparent diffusion coefficient (ADC). Single-voxel MR spectra were acquired at the parietal white matter and analyzed with LCModel. Typical VWM brain lesions were found in all patients accompanied by proton diffusion abnormalities: Increased ADC appeared in brain regions with severe myelin destruction in all patients, and reduced ADC in two of six younger patients in remaining white matter adjacent to the lesions or at the borders around the lesions, who had a short history of the disease (? 1 year). The MR spectroscopy revealed reductions of NAA, Cho, and Cr, which correlate to the grade of white matter abnormalities. An increase of myo-inositol as marker of reactive gliosis was missing. Thus, restricted proton diffusion was evident in younger VWM patients with short history of disease, which in combination with lack of reactive gliosis may reflect early white matter degeneration in VWM. The multimodal MR methods are useful for characterizing such tissue degeneration in brain in vivo. PMID:22128017

  10. 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

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

    PubMed

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

    2015-11-01

    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

  12. BRAIN ACTIVITY DURING BLADDER FILLING IS RELATED TO WHITE MATTER STRUCTURAL CHANGES IN OLDER WOMEN WITH URINARY INCONTINENCE

    PubMed Central

    Tadic, Stasa D.; Griffiths, Derek; Murrin, Andrew; Schaefer, Werner; Aizenstein, Howard J.; Resnick, Neil M.

    2010-01-01

    Evidence from longitudinal studies in community-dwelling elderly links complaints of urgency and urinary incontinence with structural white matter changes known as white matter hyperintensities (WMH). How WMH might lead to incontinence remains unknown, since information about how they relate to neural circuits involved in continence control is lacking. The aim of this study was to investigate the role of WMH in altered brain activity in older women with urgency incontinence. In a cross-sectional study, we measured WMH, globally and in specific white matter tracts, and correlated them with regional brain activity measured by fMRI (combined with simultaneous urodynamic monitoring) during bladder filling and reported 'urgency'. We postulated that increase in global WMH burden would be associated with changes (either attenuation or reinforcement) in responses to bladder filling in brain regions involved in bladder control. Secondly, we proposed that such apparent effects of global WMH burden might be specifically related to the burden in a few critical white matter pathways. The results showed that regional activations (e.g. medial/superior frontal gyrus adjacent to dorsal ACG) and deactivations (e.g. perigenual ACG adjacent to ventromedial prefrontal cortex) became more prominent with increased global WMH burden, suggesting that activity aimed at suppressing urgency was augmented. Secondary analyses confirmed that the apparent effect of global WMH burden might reflect the presence of WMH in specific pathways (anterior thalamic radiation and superior longitudinal fasciculus), thus affecting connections between key regions and suggesting possible mechanisms involved in continence control. PMID:20302947

  13. 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

  14. 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…

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

    PubMed

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

    2016-03-01

    Elevated reaction time (RT) is common in brain disorders. We studied three forms of RT in a neurodevelopmental disorder, spina bifida myelomeningocele (SBM), characterized by regional alterations of both white and grey matter, and typically developing individuals aged 8 to 48 years, in order to establish the nature of the lifespan-relations of RT and brain variables. Cognitive accuracy and RT speed and variability were all impaired in SBM relative to the typically developing group, but the most important effects of SBM on RT are seen on tasks that require a cognitive decision rule. Individuals with SBM are impaired not only in speeded performance, but also in the consistency of their performance on tasks that extend over time, which may contribute to poor performance on a range of cognitive tasks. The group with SBM showed smaller corrected corpus callosum proportions, larger corrected cerebellar white matter proportions, and larger corrected proportions for grey matter in the Central Executive and Salience networks. There were clear negative relations between RT measures and corpus callosum, Central Executive, and Default Mode networks in the group with SBM; relations were not observed in typically developing age peers. Statistical mediation analyses indicated that corpus callosum and Central Executive Network were important mediators. While RT is known to rely heavily on white matter under conditions of typical development and in individuals with adult-onset brain injury, we add the new information that additional involvement of grey matter may be important for a key neuropsychological function in a common neurodevelopmental disorder. PMID:26040977

  16. 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.

  17. Quantitative diffusion tensor imaging in cerebral palsy due to periventricular white matter injury.

    PubMed

    Thomas, Bejoy; Eyssen, Maria; Peeters, Ronald; Molenaers, Guy; Van Hecke, Paul; De Cock, Paul; Sunaert, Stefan

    2005-11-01

    Periventricular white matter injury (PWI) is a major form of brain injury observed in congenital hemiparesis. The aim of this study is to determine the usefulness of diffusion tensor imaging (DTI) and fibre tracking in delineating the primary and secondary degenerative changes in cerebral white matter and deep grey matter in patients with spastic cerebral palsy due to PWI and to look for any possible reorganization of the axonal architecture. Five hemiparetic cerebral palsy patients (median age 14 years) with known PWI were prospectively studied with DTI of the brain at 1.5T and quantitatively compared with five age and sex matched controls. Fibre tracts for various corticofugal, thalamocortical and association tracts were generated and analysed for the DTI fibre count and for diffusion parameters. A region of interest based analysis was performed for the directionally averaged mean diffusivity (D(av)) and fractional anisotropy (FA) values in various white matter locations in the brain and the brainstem and in the deep grey matter nuclei. Group statistics were performed for these parameters using Mann-Whitney U-test comparing the affected sides in patients with either side in controls and the unaffected side in hemiparetics. There was significant reduction in DTI fibre count on the lesional side involving corticospinal tract (CST), corticobulbar tract (CBT) and superior thalamic radiation in the patient group compared with controls. Also there was an increase in DTI fibre count in the unaffected side of the hemiparetic patients in CST and CBT, which reached statistical significance only in CBT. The corpus callosum, cingulum, superior longitudinal fasciculus and middle cerebellar peduncle failed to show any significant change. ROI measurements on the primary site of white matter lesion and the thalamus revealed a significant increase in D(av) and decrease in FA, suggesting primary degeneration. The CST in the brainstem, the body of corpus callosum and the head of caudate and lentiform nuclei showed features of secondary degeneration on the affected side. The CST on the unaffected side of hemiparetics was found to have a significant decrease in D(av) and an increase in FA. Thus the degeneration of various motor and sensory pathways, as well as deep grey matter structures, appears to be important in determining the pathophysiological mechanisms in patients with congenital PWI. Also evidence suggesting the reorganization of sensorimotor tracts in the unaffected side of spastic hemiparetic patients was noted. PMID:16049045

  18. 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

  19. 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…

  20. 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…

  1. 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…

  2. 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…

  3. 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…

  4. 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...

  5. 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

  6. 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

  7. 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…

  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. 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

  11. 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

  12. Early detection of microstructural white matter changes associated with arterial pulsatility

    PubMed Central

    Jolly, Todd A. D.; Bateman, Grant A.; Levi, Christopher R.; Parsons, Mark W.; Michie, Patricia T.; Karayanidis, Frini

    2013-01-01

    Increased cerebral blood flow pulsatility is common in vascular dementia and is associated with macrostructural damage to cerebral white matter or leukoaraiosis (LA). In this study, we examine whether cerebral blood flow pulsatility is associated with macrostructural and microstructural changes in cerebral white matter in older adults with no or mild LA and no evidence of dementia. Diffusion Tensor Imaging was used to measure fractional anisotropy (FA), an index of the microstructural integrity of white matter, and radial diffusivity (RaD), a measure sensitive to the integrity of myelin. When controlling for age, increased arterial pulsation was associated with deterioration in both measures of white matter microstructure but not LA severity. A stepwise multiple linear regression model revealed that arterial pulsatility index was the strongest predictor of FA (R = 0.483, adjusted R2 = 0.220), followed by LA severity, but not age. These findings suggest that arterial pulsatility may provide insight into age-related reduction in white matter FA. Specifically, increased arterial pulsatility may increase perivascular shear stress and lead to accumulation of damage to perivascular oligodendrocytes, resulting in microstructural changes in white matter and contributing to proliferation of LA over time. Changes in cerebral blood flow pulsatility may therefore provide a sensitive index of white matter health that could facilitate the early detection of risk for perivascular white matter damage and the assessment of the effectiveness of preventative treatment targeted at reducing pulsatility. PMID:24302906

  13. Abnormal White Matter Integrity in Adolescents with Internet Addiction Disorder: A Tract-Based Spatial Statistics Study

    PubMed Central

    Qin, Lindi; Zhao, Zhimin; Xu, Jianrong; Lei, Hao

    2012-01-01

    Background Internet addiction disorder (IAD) is currently becoming a serious mental health issue around the globe. Previous studies regarding IAD were mainly focused on associated psychological examinations. However, there are few studies on brain structure and function about IAD. In this study, we used diffusion tensor imaging (DTI) to investigate white matter integrity in adolescents with IAD. Methodology/Principal Findings Seventeen IAD subjects and sixteen healthy controls without IAD participated in this study. Whole brain voxel-wise analysis of fractional anisotropy (FA) was performed by tract-based spatial statistics (TBSS) to localize abnormal white matter regions between groups. TBSS demonstrated that IAD had significantly lower FA than controls throughout the brain, including the orbito-frontal white matter, corpus callosum, cingulum, inferior fronto-occipital fasciculus, and corona radiation, internal and external capsules, while exhibiting no areas of higher FA. Volume-of-interest (VOI) analysis was used to detect changes of diffusivity indices in the regions showing FA abnormalities. In most VOIs, FA reductions were caused by an increase in radial diffusivity while no changes in axial diffusivity. Correlation analysis was performed to assess the relationship between FA and behavioral measures within the IAD group. Significantly negative correlations were found between FA values in the left genu of the corpus callosum and the Screen for Child Anxiety Related Emotional Disorders, and between FA values in the left external capsule and the Young's Internet addiction scale. Conclusions Our findings suggest that IAD demonstrated widespread reductions of FA in major white matter pathways and such abnormal white matter structure may be linked to some behavioral impairments. In addition, white matter integrity may serve as a potential new treatment target and FA may be as a qualified biomarker to understand the underlying neural mechanisms of injury or to assess the effectiveness of specific early interventions in IAD. PMID:22253926

  14. Improved Sensitivity to Cerebral White Matter Abnormalities in Alzheimers Disease with Spherical Deconvolution Based Tractography

    PubMed Central

    Reijmer, Yael D.; Leemans, Alexander; Heringa, Sophie M.; Wielaard, Ilse; Jeurissen, Ben; Koek, Huiberdina L.; Biessels, Geert Jan

    2012-01-01

    Diffusion tensor imaging (DTI) based fiber tractography (FT) is the most popular approach for investigating white matter tracts in vivo, despite its inability to reconstruct fiber pathways in regions with crossing fibers. Recently, constrained spherical deconvolution (CSD) has been developed to mitigate the adverse effects of crossing fibers on DTI based FT. Notwithstanding the methodological benefit, the clinical relevance of CSD based FT for the assessment of white matter abnormalities remains unclear. In this work, we evaluated the applicability of a hybrid framework, in which CSD based FT is combined with conventional DTI metrics to assess white matter abnormalities in 25 patients with early Alzheimers disease. Both CSD and DTI based FT were used to reconstruct two white matter tracts: one with regions of crossing fibers, i.e., the superior longitudinal fasciculus (SLF) and one which contains only one fiber orientation, i.e. the midsagittal section of the corpus callosum (CC). The DTI metrics, fractional anisotropy (FA) and mean diffusivity (MD), obtained from these tracts were related to memory function. Our results show that in the tract with crossing fibers the relation between FA/MD and memory was stronger with CSD than with DTI based FT. By contrast, in the fiber bundle where one fiber population predominates, the relation between FA/MD and memory was comparable between both tractography methods. Importantly, these associations were most pronounced after adjustment for the planar diffusion coefficient, a measure reflecting the degree of fiber organization complexity. These findings indicate that compared to conventionally applied DTI based FT, CSD based FT combined with DTI metrics can increase the sensitivity to detect functionally significant white matter abnormalities in tracts with complex white matter architecture. PMID:22952880

  15. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    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

  18. Attention-network specific alterations of structural connectivity in the undamaged white matter in acute neglect.

    PubMed

    Umarova, Roza M; Reisert, Marco; Beier, Tanja-Ute; Kiselev, Valerij G; Klppel, Stefan; Kaller, Christoph P; Glauche, Volkmar; Mader, Irina; Beume, Lena; Hennig, Jrgen; Weiller, Cornelius

    2014-09-01

    Visual neglect results from dysfunction within the spatial attention network. The structural connectivity in undamaged brain tissue in neglect has barely been investigated until now. In the present study, we explored the microstructural white matter characteristics of the contralesional hemisphere in relation to neglect severity and recovery in acute stroke patients. We compared age-matched healthy subjects and three groups of acute stroke patients (9??0.5 days after stroke): (i) patients with nonrecovered neglect (n?=?12); (ii) patients with rapid recovery from initial neglect (within the first week post-stroke, n?=?7), (iii) stroke patients without neglect (n?=?17). We analyzed the differences between groups in grey and white matter density and fractional anisotropy (FA) and used fiber tracking to identify the affected fibers. Patients with nonrecovered neglect differed from those with rapid recovery by FA-reduction in the left inferior parietal lobe. Fibers passing through this region connect the left-hemispheric analogues of the ventral attention system. Compared with healthy subjects, neglect patients with persisting neglect had FA-reduction in the left superior parietal lobe, optic radiation, and left corpus callosum/cingulum. Fibers passing through these regions connect centers of the left dorsal attention system. FA-reduction in the identified regions correlated with neglect severity. The study shows for the first time white matter changes within the spatial attention system remote from the lesion and correlating with the extent and persistence of neglect. The data support the concept of neglect as disintegration within the whole attention system and illustrate the dynamics of structural-functional correlates in acute stroke. PMID:24668692

  19. White Matter Atrophy and Cognitive Dysfunctions in Neuromyelitis Optica

    PubMed Central

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

    2012-01-01

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

  20. CHARACTERIZING WHITE MATTER CONNECTIVITY IN MAJOR DEPRESSIVE DISORDER: AUTOMATED FIBER QUANTIFICATION AND MAXIMUM DENSITY PATHS

    PubMed Central

    Sacchet, Matthew D.; Prasad, Gautam; Foland-Ross, Lara C.; Joshi, Shantanu H.; Hamilton, J. Paul; Thompson, Paul M.; Gotlib, Ian H.

    2014-01-01

    Diffusion-weighted imaging allows for in vivo assessment of white matter structure, which can be used to assess aberrations associated with disease. Several new methods permit the automated assessment of important white matter characteristics. In the current study we used Automated Fiber Quantification (AFQ) to assess differences between depressed and nondepressed individuals in 18 major white matter tracts. We then used the Maximum Density Path (MDP) method to further characterize group differences identified with AFQ. The results of the AFQ analyses indicated that fractional anisotropy (FA; an index of white matter integrity) along bilateral corticospinal tracts (CST) was higher in depressed than in nondepressed individuals. MDP analyses revealed that white matter anomalies were restricted to four subregions that included the corona radiata and the internal and external capsules. These results provide further evidence that MDD is associated with abnormalities in cortical-to-subcortical connectivity. PMID:25540677

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

    PubMed Central

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

    2012-01-01

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

  2. 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

  3. Individual Differences in Distinct Components of Attention are Linked to Anatomical Variations in Distinct White Matter Tracts

    PubMed Central

    Niogi, Sumit; Mukherjee, Pratik; Ghajar, Jamshid; McCandliss, Bruce D.

    2009-01-01

    Inter-subject variations in white matter tract properties are known to correlate with individual differences in performance in cognitive domains such as attention. The specificity of such linkages, however, is largely unexplored at the level of specific component operations of attention associated with distinct anatomical networks. This study examines individual performance variation within three functional components of attention alerting, orienting, and conflict processing identified by the Attention Network Task (ANT), and relates each to inter-subject variation in a distinct set of white matter tract regions. Diffusion tensor imaging data collected at 3T was used to calculate average fractional anisotropy within a set of individualized a priori defined regions of interest using the Reproducible Objective Quantification Scheme (ROQS) (Niogi and McCandliss, 2006; Niogi et al., 2007). Results demonstrate three functionally distinct components of attention that each correlate distinctly with three white matter tract regions. Structurefunction correlations were found between alerting and the anterior limb of the internal capsule, orienting and the splenium of the corpus callosum, and conflict and the anterior corona radiata. A multiple regression/dissociation analysis demonstrated a triple dissociation between these three structure-function relationships that provided evidence of three anatomically and functionally separable networks. These results extend previous findings from functional imaging and lesion studies that suggest these three components of attention are subserved by dissociable networks, and suggest that variations in white matter tract microstructure may modulate the efficiency of these cognitive processes in highly specific ways. PMID:20204143

  4. White Matter Hemodynamic Abnormalities precede Sub-cortical Gray Matter Changes in Multiple Sclerosis

    PubMed Central

    Varga, Andrew W.; Johnson, Glyn; Babb, James S.; Herbert, Joseph; Grossman, Robert I.; Inglese, Matilde

    2009-01-01

    Background Hypoperfusion has been reported in lesions, normal-appearing white (NAWM) and gray matter (NAGM) of patients with clinically definite multiple sclerosis (MS) by using perfusion MRI. However, it is still unknown how early such changes in perfusion occur. The aim of our study was to assess the presence of hemodynamic changes in the NAWM and subcortical NAGM of patients with clinically isolated syndrome (CIS) in comparison to healthy controls and to patients with early relapsing-remitting (RR) MS. Methods Absolute cerebral blood flow (CBF), blood volume (CBV) and mean transit time (MTT) were measured in the periventricular and frontal NAWM, thalamus and putamen nuclei of 12 patients with CIS, 12 with early RR-MS and 12 healthy controls using dynamic susceptibility contrast enhanced (DSC) T2*-weighted MRI. Results Compared to controls, CBF was significantly decreased in the periventricular NAWM of CIS patients and in the periventricular NAWM and putamen of RR-MS patients. Compared to CIS, RR-MS patients showed a significant CBF decrease in the putamen. Conclusions CBF was decreased in the NAWM of both CIS and RR-MS patients and in the subcortical NAGM of RR-MS patients suggesting a continuum of tissue perfusion decreases beginning in white matter and spreading to gray matter, as the disease progresses. PMID:19181347

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

    PubMed Central

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

    2014-01-01

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

  6. [White matter fiber tractography and quantitative analysis of diffusion tensor imaging].

    PubMed

    Shimoji, Keigo; Tokumaru, Aya M

    2015-04-01

    Magnetic resonance diffusion tensor imaging (DTI) is a noninvasive technique that can identify and quantify white matter tracts by evaluating the diffusion of water in biological tissues. While association fibers are bundles of axons within the brain that unite different parts of the same cerebral hemisphere, projection fibers are bundles of axons that unite the cortex with lower parts of the brain and the spinal cord. The commissural fibers are axon bundles that connect the two hemispheres of the brain. Quantitative analysis of DTI can be roughly classified into three types: region of interest analysis, tract-specific analysis, and fully automated hypothesis free whole brain analysis. PMID:25846596

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

    PubMed Central

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

    2015-01-01

    Objective Protracted, systemic inflammation has been associated with adverse effects on cognition and brain structure, and may accelerate neurodegenerative disease processes; however, it is less clear whether changes in inflammation are associated with brain structure. Methods We studied 276 black and white older adults (mean age=83 years at time of imaging) enrolled in a prospective study of aging. Inflammation (measured with CRP) was assessed repeatedly over 6 years (i.e. Year 2, 4, 6, & 8). Brain MRIs were obtained at years 1011 with DTI; regions of interest included late-myelinating areas vulnerable to aging, including frontal-parietal [superior longitudinal fasciculus (SLF)-dorsal] and temporal (SLF-temporal; uncinate) white matter tracts. Results Mean CRP values significantly declined (t=?5.54, p<.0001) over 6 years, and subject-specific slopes (BLUPs) all showed a decline (mean=?.57, SD=.53) for our participant sample. More than 50% of study participants were still in the moderate to high cardiovascular risk range based on CRP values at Year 8. After controlling for demographics, vascular risk factors and MRI white matter hyperintensities, larger decreases in CRP values over time were significantly associated with higher fractional anisotropy in the SLF-dorsal [Beta=?0.0052, standard error (SE)=0.003; 95% confidence interval (CI)= ?0.0103 to ?0.0025, p=.04], SLF-temporal (Beta=?0.0109, SE=0.004; 95%CI=?0.0189 to ?0.0029, p=.008), and uncinate (Beta=?0.0067, SE=0.003; 95%CI=?0.0132 to ?0.0001, p=.05) fasciculi. Conclusions Results suggest that in a prospective cohort of older individuals, faster declines in inflammation over time are related to indicators of white matter health, even after accounting for vascular risk factors. PMID:25554492

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

    PubMed

    Ratnarajah, Nagulan; Qiu, Anqi

    2014-11-15

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

  9. 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

  10. Thalamo-frontal white matter alterations in chronic schizophrenia: a quantitative diffusion tractography study.

    PubMed

    Oh, Jungsu S; Kubicki, Marek; Rosenberger, Gudrun; Bouix, Sylvain; Levitt, James J; McCarley, Robert W; Westin, Carl-Fredrik; Shenton, Martha E

    2009-11-01

    Diffusion tensor imaging (DTI) and fiber tractography are useful tools for reconstructing white matter tracts (WMT) in the brain. Previous tractography studies have sought to segment reconstructed WMT into anatomical structures using several approaches, but quantification has been limited to extracting mean values of diffusion indices. Delineating WMT in schizophrenia is of particular interest because schizophrenia has been hypothesized to be a disorder of disrupted connectivity, especially between frontal and temporal regions of the brain. In this study, we aim to differentiate diffusion properties of thalamo-frontal pathways in schizophrenia from normal controls. We present a quantitative group comparison method, which combines the strengths of both tractography-based and voxel-based studies. Our algorithm extracts white matter pathways using whole brain tractography. Functionally relevant bundles are selected and parsed from the resulting set of tracts, using an internal capsule (IC) region of interest (ROI) as "source", and different Brodmann area (BA) ROIs as "targets". The resulting bundles are then longitudinally parameterized so that diffusion properties can be measured and compared along the WMT. Using this processing pipeline, we were able to find altered diffusion properties in male patients with chronic schizophrenia in terms of fractional anisotropy (FA) decreases and mean diffusivity (MD) increases in precise and functionally relevant locations. These findings suggest that our method can enhance the regional and functional specificity of DTI group studies, thus improving our understanding of brain function. PMID:19449328

  11. Role of white-matter pathways in coordinating alpha oscillations in resting visual cortex.

    PubMed

    Hindriks, R; Woolrich, M; Luckhoo, H; Joensson, M; Mohseni, H; Kringelbach, M L; Deco, G

    2015-02-01

    In the absence of cognitive tasks and external stimuli, strong rhythmic fluctuations with a frequency ? 10 Hz emerge from posterior regions of human neocortex. These posterior ?-oscillations can be recorded throughout the visual cortex and are particularly strong in the calcarine sulcus, where the primary visual cortex is located. The mechanisms and anatomical pathways through which local \\alpha-oscillations are coordinated however, are not fully understood. In this study, we used a combination of magnetoencephalography (MEG), diffusion tensor imaging (DTI), and biophysical modeling to assess the role of white-matter pathways in coordinating cortical ?-oscillations. Our findings suggest that primary visual cortex plays a special role in coordinating ?-oscillations in higher-order visual regions. Specifically, the amplitudes of ?-sources throughout visual cortex could be explained by propagation of ?-oscillations from primary visual cortex through white-matter pathways. In particular, ?-amplitudes within visual cortex correlated with both the anatomical and functional connection strengths to primary visual cortex. These findings reinforce the notion of posterior ?-oscillations as intrinsic oscillations of the visual system. We speculate that they might reflect a default-mode of the visual system during which higher-order visual regions are rhythmically primed for expected visual stimuli by ?-oscillations in primary visual cortex. PMID:25449741

  12. Human adult white matter progenitor cells are multipotent neuroprogenitors similar to adult hippocampal progenitors.

    PubMed

    Lojewski, Xenia; Hermann, Andreas; Wegner, Florian; Arazo-Bravo, Marcos J; Hallmeyer-Elgner, Susanne; Kirsch, Matthias; Schwarz, Johannes; Schler, Hans R; Storch, Alexander

    2014-04-01

    Adult neural progenitor cells (aNPC) are a potential autologous cell source for cell replacement in neurologic diseases or for cell-based gene therapy of neurometabolic diseases. Easy accessibility, long-term expandability, and detailed characterization of neural progenitor cell (NPC) properties are important requisites for their future translational/clinical applications. aNPC can be isolated from different regions of the adult human brain, including the accessible subcortical white matter (aNPCWM), but systematic studies comparing long-term expanded aNPCWM with aNPC from neurogenic brain regions are not available. Freshly isolated cells from subcortical white matter and hippocampus expressed oligodendrocyte progenitor cell markers such as A2B5, neuron-glial antigen 2 (NG2), and oligodendrocyte transcription factor 2 (OLIG2) in ?20% of cells but no neural stem cell (NSC) markers such as CD133 (Prominin1), Nestin, SOX2, or PAX6. The epidermal growth factor receptor protein was expressed in 18% of aNPCWM and 7% of hippocampal aNPC (aNPCHIP), but only a small fraction of cells, 1 of 694 cells from white matter and 1 of 1,331 hippocampal cells, was able to generate neurospheres. Studies comparing subcortical aNPCWM with their hippocampal counterparts showed that both NPC types expressed mainly markers of glial origin such as NG2, A2B5, and OLIG2, and the NSC/NPC marker Nestin, but no pericyte markers. Both NPC types were able to produce neurons, astrocytes, and oligodendrocytes in amounts comparable to fetal NSC. Whole transcriptome analyses confirmed the strong similarity of aNPCWM to aNPCHIP. Our data show that aNPCWM are multipotent NPC with long-term expandability similar to NPC from hippocampus, making them a more easily accessible source for possible autologous NPC-based treatment strategies. PMID:24558163

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

    PubMed Central

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

    2014-01-01

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

  14. 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

  15. The value of T1-weighted images in the differentiation between MS, white matter lesions, and subcortical arteriosclerotic encephalopathy (SAE).

    PubMed

    Uhlenbrock, D; Sehlen, S

    1989-01-01

    The aim of the study was to define reliable criteria for the differentiation of MR imaging between patients with MS and with "vascular" white matter lesions/SAE. We examined 35 patients with proven MS according to the Poser criteria and 35 patients with other white matter lesions and/or SAE. The result is that with MR a differentiation can be achieved provided that T1-weighted spin-echo sequences are included and the different pattern of distribution is considered. MS plaques are predominantly located in the subependymal region, vascular white matter lesions are mainly located in the water-shed of the superficial middle cerebral branches and the deep perforating long medullary vessels in the centrum semiovale. Infratentorial lesions are more often seen in MS. Confluence at the lateral ventricles is frequently accompanied by confluent abnormalities around the third ventricle, Sylvian aqueduct, and fourth ventricle, which is uncommon in SAE. In MS many lesions visible on T2-weighted images have a cellular or intracellular composition that renders them visible also on T1-weighted ones as regions with low signal intensity and more or less distinct boundary. "Vascular" white matter lesions and SAE mainly represent demyelination and can therefore be seen on T2-weighted images, but corresponding low signal intensity lesions on T1-weighted images are uncommon. In some exceptions there are such lesions with low signal representing lacunar infarcts or widened Virchow-Robin-spaces. PMID:2674767

  16. 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

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

    PubMed

    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

  18. 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.

  19. 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

  20. Modeling blast induced neurotrauma in isolated spinal cord white matter.

    PubMed

    Connell, Sean; Ouyang, Hui; Shi, Riyi

    2011-10-01

    Blast-induced neurotrauma (BINT) is a common injury associated with the present military conflicts. Exposure to the shock-wave produced from exploding ordnances leads to significant neurological deficits throughout the brain and spinal cord. Prevention and treatment of this injury requires an appropriate understanding of the mechanisms governing the neurological response. Here, we present a novel ex-vivo BINT model where an isolated section of guinea pig spinal cord white matter is exposed to the shock-wave produced from a small scale explosive event. Additionally, we define the relationship between shock-wave impact, tissue deformation and resulting anatomical and functional deficits associated with BINT. Our findings suggest an inverse relationship between the magnitude of the shock-wave overpressure and the degree of functional deficits using a double sucrose gap recording chamber. Similar correlations are drawn between overpressure and degree of anatomical damage of neuronal processes using a dye-exclusion assay. The following approach is expected to significantly contribute to the detection, mitigation and eventual treatment of BINT. PMID:20703730

  1. Social Reward Dependence and Brain White Matter Microstructure

    PubMed Central

    Westlye, Lars T.; Fjell, Anders M.; Grydeland, Hkon; Walhovd, Kristine B.

    2012-01-01

    People show consistent differences in their cognitive and emotional responses to environmental cues, manifesting, for example, as variability in social reward processing and novelty-seeking behavior. However, the neurobiological foundation of human temperament and personality is poorly understood. A likely hypothesis is that personality traits rely on the integrity and function of distributed neurocircuitry. In this diffusion tensor imaging (DTI) study, this hypothesis was tested by examining the associations between reward dependence (RD) and novelty seeking (NS), as measured by Cloningers Temperament and Character Inventory, and fractional anisotropy (FA) and mean diffusivity (MD) as DTI-derived indices of white matter (WM) microstructure across the brain. The results supported the hypothesis. RD was associated with WM architecture coherence as indicated by a negative correlation between RD and FA in frontally distributed areas including pathways connecting important constituents of reward-related neurocircuitry. The associations between RD and FA could not be explained by age, sex, alcohol consumption, or trait anxiety. In contrast, no effects were observed for NS. These findings support the theory that WM fiber tract properties modulate individual differences in social reward processing. PMID:22156472

  2. White matter hyperintensities predict low frequency hearing in older adults.

    PubMed

    Eckert, Mark A; Kuchinsky, Stefanie E; Vaden, Kenneth I; Cute, Stephanie L; Spampinato, Maria V; Dubno, Judy R

    2013-06-01

    Vascular disease has been proposed as a contributing factor for presbyacusis (age-related hearing loss). While this hypothesis is supported by pathological evidence of vascular decline in post-mortem human and animal studies, evidence in human subjects has been mixed with associations typically reported between a measure of vascular health and low frequency hearing in older women. Given the difficulty of characterizing the in vivo health of the cochlear artery in humans, an estimate of cerebral small vessel disease was used to test the prediction that age-related change in low frequency hearing and not high frequency hearing is related to a global decline in vascular health. We examined the extent to which these associations were specific to women and influenced by a history of high blood pressure in 72 older adults (mean age 67.12 years, SD = 8.79). Probability estimates of periventricular white matter hyperintensities (WMH) from T1- and fluid attenuated T2-weighted magnetic resonance images were significantly associated with a low frequency hearing metric across the sample, which were independent of age, but driven by women and people with a history of high blood pressure. These results support the premise that vascular declines are one mechanism underlying age-related changes in low frequency hearing. PMID:23512682

  3. 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

  4. White-matter lesions without lacunar infarcts in CADASIL.

    PubMed

    Benisty, Sarah; Reyes, Sonia; Godin, Ophelia; Hervé, Dominique; Zieren, Nikola; Jouvent, Eric; Zhu, Yicheng; During, Marco; Dichgans, Martin; Chabriat, Hugues

    2012-01-01

    To better characterize the clinical spectrum related to white-matter hyperintensities (WMH) in small vessel disease, 66 patients with WMH but without any lacunar infarct were selected out of a cohort of 248 CADASIL individuals. Characteristics of these patients were compared to those of patients with lacunar infarcts. Relationships between the normalized volume of WMH (nWMH), presence of microhemorrhages, brain parenchymal fraction (BPF). and cognitive performances were assessed. The Trail Making Test (TMT) A and B times, Mattis Dementia Rating Scale (MDRS) total score, attention subscore, verbal fluency score and delayed memory recall were significantly correlated with nWMH but not with BPF. Presence of microhemorrhages was associated with worse TMT B time and attention MDRS subscore after adjustment for WMH. All subjects had Mini-Mental Status Examination scores ≥24 and presented with no or only mild disability. These results suggest that CADASIL patients with isolated WMH can present with executive and attention deficit but not with severe disability and that additional lesions are needed to cause significant disability and/or dementia. PMID:22330818

  5. Mapping White Matter Integrity in Elderly People with HIV

    PubMed Central

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

    2013-01-01

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

  6. Social reward dependence and brain white matter microstructure.

    PubMed

    Bjrnebekk, Astrid; Westlye, Lars T; Fjell, Anders M; Grydeland, Hkon; Walhovd, Kristine B

    2012-11-01

    People show consistent differences in their cognitive and emotional responses to environmental cues, manifesting, for example, as variability in social reward processing and novelty-seeking behavior. However, the neurobiological foundation of human temperament and personality is poorly understood. A likely hypothesis is that personality traits rely on the integrity and function of distributed neurocircuitry. In this diffusion tensor imaging (DTI) study, this hypothesis was tested by examining the associations between reward dependence (RD) and novelty seeking (NS), as measured by Cloninger's Temperament and Character Inventory, and fractional anisotropy (FA) and mean diffusivity (MD) as DTI-derived indices of white matter (WM) microstructure across the brain. The results supported the hypothesis. RD was associated with WM architecture coherence as indicated by a negative correlation between RD and FA in frontally distributed areas including pathways connecting important constituents of reward-related neurocircuitry. The associations between RD and FA could not be explained by age, sex, alcohol consumption, or trait anxiety. In contrast, no effects were observed for NS. These findings support the theory that WM fiber tract properties modulate individual differences in social reward processing. PMID:22156472

  7. 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

  8. 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.

  9. 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

  10. 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

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

    PubMed

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

    2015-10-01

    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 (18months old) had either an intracaudate injection of 100?l 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 be at more than 10mg/kg for a therapeutic duration more than 2days with a therapeutic time window of 12h to reduce ICH-induced white matter loss at 2months. 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

  12. 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 l 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

  13. 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

  14. Maturational differences in thalamocortical white matter microstructure and auditory evoked response latencies in autism spectrum disorders.

    PubMed

    Roberts, Timothy P L; Lanza, Matthew R; Dell, John; Qasmieh, Saba; Hines, Katherine; Blaskey, Lisa; Zarnow, Deborah M; Levy, Susan E; Edgar, J Christopher; Berman, Jeffrey I

    2013-11-01

    White matter diffusion anisotropy in the acoustic radiations was characterized as a function of development in autistic and typically developing children. Auditory-evoked neuromagnetic fields were also recorded from the same individuals and the latency of the left and right middle latency superior temporal gyrus auditory ~50ms response (M50)(1) was measured. Group differences in structural and functional auditory measures were examined, as were group differences in associations between white matter pathways, M50 latency, and age. Acoustic radiation white matter fractional anisotropy did not differ between groups. Individuals with autism displayed a significant M50 latency delay. Only in typically developing controls, white matter fractional anisotropy increased with age and increased white matter anisotropy was associated with earlier M50 responses. M50 latency, however, decreased with age in both groups. Present findings thus indicate that although there is loss of a relationship between white matter structure and auditory cortex function in autism spectrum disorders, and although there are delayed auditory responses in individuals with autism than compared with age-matched controls, M50 latency nevertheless decreases as a function of age in autism, parallel to the observation in typically developing controls (although with an overall latency delay). To understand auditory latency delays in autism and changes in auditory responses as a function of age in controls and autism, studies examining white matter as well as other factors that influence auditory latency, such as synaptic transmission, are of interest. PMID:24055954

  15. Frontal White Matter Volume Is Associated with Brain Enlargement and Higher Structural Connectivity in Anthropoid Primates

    PubMed Central

    Smaers, Jeroen Bert; Schleicher, Axel; Zilles, Karl; Vinicius, Lucio

    2010-01-01

    Previous research has indicated the importance of the frontal lobe and its ‘executive’ connections to other brain structures as crucial in explaining primate neocortical adaptations. However, a representative sample of volumetric measurements of frontal connective tissue (white matter) has not been available. In this study, we present new volumetric measurements of white and grey matter in the frontal and non-frontal neocortical lobes from 18 anthropoid species. We analyze this data in the context of existing theories of neocortex, frontal lobe and white versus grey matter hyperscaling. Results indicate that the ‘universal scaling law’ of neocortical white to grey matter applies separately for frontal and non-frontal lobes; that hyperscaling of both neocortex and frontal lobe to rest of brain is mainly due to frontal white matter; and that changes in frontal (but not non-frontal) white matter volume are associated with changes in rest of brain and basal ganglia, a group of subcortical nuclei functionally linked to ‘executive control’. Results suggest a central role for frontal white matter in explaining neocortex and frontal lobe hyperscaling, brain size variation and higher neural structural connectivity in anthropoids. PMID:20161758

  16. Altered tract-specific white matter microstructure is related to poorer cognitive performance: The Rotterdam Study.

    PubMed

    Cremers, Lotte G M; de Groot, Marius; Hofman, Albert; Krestin, Gabriel P; van der Lugt, Aad; Niessen, Wiro J; Vernooij, Meike W; Ikram, M Arfan

    2016-03-01

    White matter microstructural integrity has been related to cognition. Yet, the potential role of specific white matter tracts on top of a global white matter effect remains unclear, especially when considering specific cognitive domains. Therefore, we determined the tract-specific effect of white matter microstructure on global cognition and specific cognitive domains. In 4400 nondemented and stroke-free participants (mean age 63.7 years, 55.5% women), we obtained diffusion magnetic resonance imaging parameters (fractional anisotropy and mean diffusivity) in 14 white matter tracts using probabilistic tractography and assessed cognitive performance with a cognitive test battery. Tract-specific white matter microstructure in all supratentorial tracts was associated with poorer global cognition. Lower fractional anisotropy in association tracts, primarily the inferior fronto-occipital fasciculus, and higher mean diffusivity in projection tracts, in particular the posterior thalamic radiation, most strongly related to poorer cognition. Altered white matter microstructure related to poorer information processing speed, executive functioning, and motor speed, but not to memory. Tract-specific microstructural changes may aid in better understanding the mechanism of cognitive impairment and neurodegenerative diseases. PMID:26923407

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

    PubMed

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

    2012-12-01

    In recent years, there has been a renewed interest in the study of white matter anatomy, both with the use of postmortem dissections and diffusion tensor imaging tractography. One of the precursors in the study of white matter anatomy was Raymond de Vieussens (1641-1716), a French anatomist born in Le Vigan. He studied medicine at the University of Montpellier in southern France, one of the most ancient and lively schools of medicine in Europe. In 1684 Vieussens published his masterpiece, the Neurographia Universalis, which is still considered one of the most complete and accurate descriptions of the nervous system provided in the 17th century. He described the white matter of the centrum ovale and was the first to demonstrate the continuity of the white matter fibers from the centrum ovale to the brainstem. He also described the dentate nuclei, the pyramids, and the olivary nuclei. According to the theory of Galen, Vieussens considered that the function of the white matter was to convey the "animal spirit" from the centrum ovale to the spinal cord. Although neglected, Vieussens' contribution to the study of white matter is relevant. His pioneering work showed that the white matter is not a homogeneous substance, but rather a complex structure rich in fibers that are interconnected with different parts of the brain. These initial results paved the way to advancements observed in later centuries that eventually led to modern hodology. PMID:22998052

  18. Neurocircuitry of emotion and cognition in alcoholism: contributions from white matter fiber tractography

    PubMed Central

    Schulte, Tilman; Mller-Oehring, Eva M.; Pfefferbaum, Adolf; Sullivan, Edith V.

    2010-01-01

    Chronic alcoholism is characterized by impaired control over emotionally motivated actions towards alcohol use. Neuropathologically, it is associated with widespread brain structural compromise marked by gray matter shrinkage, ventricular enlargement, and white matter degradation. The extent to which cortical damage itself or cortical disconnection by white matter fiber pathway disruption contribute to deficits in emotion, cognition, and behavior can be investigated with in vivo structural neuroimaging and diffusion tensor imaging (DTI)-based quantitative fiber tracking. Tractography in alcoholism has revealed abnormalities in selective white matter fiber bundles involving limbic fiber tracts (fornix and cingulum) that connect cortico-limbic-striatal nodes of emotion and reward circuits. Studies documenting brain-behavior relationships support the role of alcoholism-related white matter fiber degradation as a substrate of clinical impairment. An understanding of the role of cortico-limbic fiber degradation in emotional dysregulation in alcoholism is now emerging. PMID:21319499

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

    PubMed Central

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

    2011-01-01

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

  20. Reading performance correlates with white-matter properties in preterm and term children

    PubMed Central

    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 females; mean age 12y 8mo [SD 2y 5mo], mean gestational age 39.6 weeks (SD 1.2), and mean birthweight 3877g [SD 473]). Method We tested whether fractional anisotropy in a left hemisphere temporoparietal region and in the corpus callosum correlates with birthweight and scores on the following three subtests of the Woodcock-Johnson III Tests of Achievement: word identification, word attack, and passage comprehension. Results Preterm children had lower reading scores than a comparison group for all reading subtests (p<0.05). We found significant correlations between birthweight and fractional anisotropy in the whole corpus callosum (p=0.001), and between fractional anisotropy and reading skill in the genu (p=0.001) and body (p=0.001) of the corpus callosum. The correlation between reading skill and fractional anisotropy in a left temporoparietal region previously associated with reading disability was not significant (p=0.095). Interpretation We conclude that perinatal white-matter injury of the central corpus callosum may have long-term developmental implications for reading performance. PMID:19747208

  1. 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

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

    PubMed Central

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

    2013-01-01

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

  3. Diffusion Tensor Imaging in PSEN1-Related Spastic Paraparesis Reveals Widespread White Matter Abnormalities

    PubMed Central

    Braskie, Meredith N; Alger, Jeffry; Bordelon, Yvette M; Wharton, David; Ringman, John M

    2014-01-01

    Objective: To investigate white matter changes in familial Alzheimer's disease (FAD) patients with spastic paraparesis (SP) using diffusion tensor imaging (DTI). Background: Though FAD due to PSEN1 mutations typically recapitulates late onset AD, it can have unusual clinical features including SP. SP is seen with specific PSEN1 mutations and is frequently associated with “cotton wool” amyloid plaques. The pathophysiology underlying SP in FAD is not well understood, though disproportionate degeneration of the corticospinal tracts has been implicated. Design/Methods: We compared white matter integrity in two persons with the A431E PSEN1 mutation with early and severe SP to that of 8 symptomatic PSEN1 mutation carriers without SP from DTI images obtained on a 3T Siemens Trio scanner using 64 direction EPI sequence. Fractional Anisotropy (FA) images were generated using FSL Diffusion Toolbox. FA images were then processed using FSL Tract Based Spatial Statistics toolbox to obtain group level voxel-based statistical maps. Results: The patients with SP were men, mean age of 48, duration of illness of 5.5 years, and CDR SOB scores of 8.5. The 8 subjects without SP (5 men) had various PSEN1 mutations, mean age of 54 years, illness duration of 4.6 years, and CDR SOB scores of 6.1 (all P-values > .05). Using the false discovery rate to correct for multiple comparisons, significantly lower FA were seen in subjects with SP in widespread areas including in the orbitofrontal region, corpus callosum, bilateral precentral gyri, and the anterior limb of the right internal capsule. The reverse contrast revealed no areas in which persons without SP had lower FA relative to those with SP. Conclusions: SP is the most evident clinical manifestation of widespread FA decreases in persons with the A431E PSEN1 mutation, suggesting it may be mediated by a generalized effect of this mutation on white matter.

  4. 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

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

    PubMed Central

    Li, Lei; Lei, Du; Li, Lingjiang; Huang, Xiaoqi; Suo, Xueling; Xiao, Fenglai; Kuang, Weihong; Li, Jin; Bi, Feng; Lui, Su; Kemp, Graham J.; Sweeney, John A.; Gong, Qiyong

    2016-01-01

    Studies of posttraumatic stress disorder (PTSD) are complicated by wide variability in the intensity and duration of prior stressors in patient participants, secondary effects of chronic psychiatric illness, and a variable history of treatment with psychiatric medications. In magnetic resonance imaging (MRI) studies, patient samples have often been small, and they were not often compared to similarly stressed patients without PTSD in order to control for general stress effects. Findings from these studies have been inconsistent. The present study investigated whole-brain microstructural alterations of white matter in a large drug-naive population who survived a specific, severe traumatic event (a major 8.0-magnitude earthquake). Using diffusion tensor imaging (DTI), we explored group differences between 88 PTSD patients and 91 matched traumatized non-PTSD controls in fractional anisotropy (FA), as well as its component elements axial diffusivity (AD) and radial diffusivity (RD), and examined these findings in relation to findings from deterministic DTI tractography. Relations between white matter alterations and psychiatric symptom severity were examined. PTSD patients, relative to similarly stressed controls, showed an FA increase as well as AD and RD changes in the white matter beneath left dorsolateral prefrontal cortex and forceps major. The observation of increased FA in the PTSD group suggests that the pathophysiology of PTSD after a specific acute traumatic event is distinct from what has been reported in patients with several years duration of illness. Alterations in dorsolateral prefrontal cortex may be an important aspect of illness pathophysiology, possibly via the region's established role in fear extinction circuitry. Use-dependent myelination or other secondary compensatory changes in response to heightened demands for threat appraisal and emotion regulation may be involved. PMID:26981581

  6. Accelerated Changes in White Matter Microstructure during Aging: A Longitudinal Diffusion Tensor Imaging Study

    PubMed Central

    Walhovd, Kristine B.; Storsve, Andreas B.; Tamnes, Christian K.; Westlye, Lars T.; Johansen-Berg, Heidi; Fjell, Anders M.

    2014-01-01

    It is well established that human brain white matter structure changes with aging, but the timescale and spatial distribution of this change remain uncertain. Cross-sectional diffusion tensor imaging (DTI) studies indicate that, after a period of relative stability during adulthood, there is an accelerated decline in anisotropy and increase in diffusivity values during senescence; and, spatially, results have been discussed within the context of several anatomical frameworks. However, inferring trajectories of change from cross-sectional data can be challenging; and, as yet, there have been no longitudinal reports of the timescale and spatial distribution of age-related white matter change in healthy adults across the adult lifespan. In a longitudinal DTI study of 203 adults between 20 and 84 years of age, we used tract-based spatial statistics to characterize the pattern of annual change in fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity and examined whether there was an acceleration of change with age. We found extensive and overlapping significant annual decreases in fractional anisotropy, and increases in axial diffusivity, radial diffusivity, and mean diffusivity. Spatially, results were consistent with inferior-to-superior gradients of lesser-to-greater vulnerability. Annual change increased with age, particularly within superior regions, with age-related decline estimated to begin in the fifth decade. Charting white matter microstructural changes in healthy aging provides essential context to clinical studies, and future studies should compare age trajectories between healthy participants and at-risk populations and also explore the relationship between DTI rates of change and cognitive decline. PMID:25392509

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

    Li, Lei; Lei, Du; Li, Lingjiang; Huang, Xiaoqi; Suo, Xueling; Xiao, Fenglai; Kuang, Weihong; Li, Jin; Bi, Feng; Lui, Su; Kemp, Graham J; Sweeney, John A; Gong, Qiyong

    2016-02-01

    Studies of posttraumatic stress disorder (PTSD) are complicated by wide variability in the intensity and duration of prior stressors in patient participants, secondary effects of chronic psychiatric illness, and a variable history of treatment with psychiatric medications. In magnetic resonance imaging (MRI) studies, patient samples have often been small, and they were not often compared to similarly stressed patients without PTSD in order to control for general stress effects. Findings from these studies have been inconsistent. The present study investigated whole-brain microstructural alterations of white matter in a large drug-naive population who survived a specific, severe traumatic event (a major 8.0-magnitude earthquake). Using diffusion tensor imaging (DTI), we explored group differences between 88 PTSD patients and 91 matched traumatized non-PTSD controls in fractional anisotropy (FA), as well as its component elements axial diffusivity (AD) and radial diffusivity (RD), and examined these findings in relation to findings from deterministic DTI tractography. Relations between white matter alterations and psychiatric symptom severity were examined. PTSD patients, relative to similarly stressed controls, showed an FA increase as well as AD and RD changes in the white matter beneath left dorsolateral prefrontal cortex and forceps major. The observation of increased FA in the PTSD group suggests that the pathophysiology of PTSD after a specific acute traumatic event is distinct from what has been reported in patients with several years duration of illness. Alterations in dorsolateral prefrontal cortex may be an important aspect of illness pathophysiology, possibly via the region's established role in fear extinction circuitry. Use-dependent myelination or other secondary compensatory changes in response to heightened demands for threat appraisal and emotion regulation may be involved. PMID:26981581

  9. Unsupervised White Matter Fiber Clustering and Tract Probability Map Generation: Applications of a Gaussian Process framework for white matter fibers

    PubMed Central

    Wassermann, D.; Bloy, L.; Kanterakis, E.; Verma, R.; Deriche, R.

    2010-01-01

    With the increasing importance of fiber tracking in diffusion tensor images for clinical needs, there has been a growing demand for an objective mathematical framework to perform quantitative analysis of white matter fiber bundles incorporating their underlying physical significance. This paper presents such a novel mathematical framework that facilitates mathematical operations between tracts using an inner product based on Gaussian processes, between fibers which span a metric space. This metric facilitates combination of fiber tracts, rendering operations like tract membership to a bundle or bundle similarity simple. Based on this framework, we have designed an automated unsupervised atlas-based clustering method that does not require manual initialization nor an a priori knowledge of the number of clusters. Quantitative analysis can now be performed on the clustered tract volumes across subjects thereby avoiding the need for point parametrization of these fibers, or the use of medial or envelope representations as in previous work. Experiments on synthetic data demonstrate the mathematical operations. Subsequently, the applicability of the unsupervised clustering framework has been demonstrated on a 21 subject dataset. PMID:20079439

  10. 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, Jos 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

  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 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

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

    PubMed

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

    2015-06-01

    Children with prenatal alcohol exposure (PAE) may have cognitive, behavioral and brain abnormalities. Here, we compare rates of white matter and subcortical gray matter volume change in PAE and control children, and examine relationships between annual volume change and arithmetic ability, behavior, and executive function. Participants (n = 75 PAE/64 control; age: 7.1-15.9 years) each received two structural magnetic resonance scans, ~2 years apart. Assessments included Wechsler Intelligence Scale for Children (WISC-IV), the Child Behavior Checklist and the Behavior Rating Inventory of Executive Function. Subcortical white and gray volumes were extracted for each hemisphere. Group volume differences were tested using false discovery rate (q < 0.05). Analyses examined group-by-age interactions and group-score interactions for correlations between change in volume and raw behavioral scores. Results showed that subjects with PAE had smaller volumes than control subjects across the brain. Significant group-score interactions were found in temporal and parietal regions for WISC arithmetic scores and in frontal and parietal regions for behavioral measures. Poorer cognitive/ behavioral outcomes were associated with larger volume increases in PAE, while control subjects generally showed no significant correlations. In contrast with previous results demonstrating different trajectories of cortical volume change in PAE, our results show similar rates of subcortical volume growth in subjects with PAE and control subjects. We also demonstrate abnormal brain-behavior relationships in subjects with PAE, suggesting different use of brain resources. Our results are encouraging in that, due to the stable volume differences, there may be an extended window of opportunity for intervention in children with PAE. PMID:25711175

  13. 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

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

    PubMed

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

    2012-12-01

    The white racial category in the U.S. encompasses persons who have Arab ancestry. Arab Americans, however, have always occupied a precarious position in relationship to Whiteness. This study examined differences in reporting racial/ethnic discrimination among Arab Americans. It also investigated whether and how the association between discrimination and psychological distress varies by characteristics that capture an Arab American's proximity to/distance from Whiteness. We used data from the Detroit Arab American Study (2003; n = 1016), which includes measures of discrimination and the Kessler-10 scale of psychological distress. A series of logistic regression models were specified to test the discrimination-psychological distress association, stratified by five measures that capture Whiteness--subjective racial identification, religion, skin color, ethnic centrality, and residence in the ethnic enclave. Discrimination was more frequently reported by Muslim Arab Americans, those who racially identify as non-white, and who live in the ethnic enclave. Conversely, the association between discrimination and psychological distress was stronger for Christian Arab Americans, those who racially identify as white, who have dark skin color, and who live outside the ethnic enclave. Even though Arab Americans who occupy an identity location close to Whiteness are less subjected to discrimination, they are more negatively affected by it. The findings illuminate the complex pathways through which discrimination associates with psychological distress among 'white' immigrants. Further research on discrimination and health among Arab Americans can help unpack the white racial category and deconstruct Whiteness. PMID:22901668

  15. Candidate-gene analysis of white matter hyperintensities on neuroimaging

    PubMed Central

    Tran, Theresa; Cotlarciuc, Ioana; Yadav, Sunaina; Hasan, Nazeeha; Bentley, Paul; Levi, Christopher; Worrall, Bradford B; Meschia, James F; Rost, Natalia; Sharma, Pankaj

    2016-01-01

    Background White matter hyperintensities (WMH) are a common radiographic finding and may be a useful endophenotype for small vessel diseases. Given high heritability of WMH, we hypothesised that certain genotypes may predispose individuals to these lesions and consequently, to an increased risk of stroke, dementia and death. We performed a meta-analysis of studies investigating candidate genes and WMH to elucidate the genetic susceptibility to WMH and tested associated variants in a new independent WMH cohort. We assessed a causal relationship of WMH to methylene tetrahydrofolate reductase (MTHFR). Methods Database searches through March 2014 were undertaken and studies investigating candidate genes in WMH were assessed. Associated variants were tested in a new independent ischaemic cohort of 1202 WMH patients. Mendelian randomization was undertaken to assess a causal relationship between WMH and MTHFR. Results We identified 43 case-control studies interrogating eight polymorphisms in seven genes covering 6,314 WMH cases and 15,461 controls. Fixed-effects meta-analysis found that the C-allele containing genotypes of the aldosterone synthase CYP11B2 T(−344)C gene polymorphism were associated with a decreased risk of WMH (OR=0.61; 95% CI, 0.44 to 0.84; p=0.003). Using mendelian randomisation the association among MTHFR C677T, homocysteine levels and WMH, approached, but did not reach, significance (expected OR=1.75; 95% CI, 0.90−3.41; observed OR=1.68; 95% CI, 0.97−2.94). Neither CYP11B2 T(−344)C nor MTHFR C677T were significantly associated when tested in a new independent cohort of 1202 patients with WMH. Conclusions There is a genetic basis to WMH but anonymous genome wide and exome studies are more likely to provide novel loci of interest. PMID:25835038

  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. Probing dark matter crests with white dwarfs and IMBHs

    NASA Astrophysics Data System (ADS)

    Amaro-Seoane, P.; Casanellas, J.; Schödel, R.; Davidson, E.; Cuadra, J.

    2016-03-01

    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 makes it impossible to detect the potential associated luminosities, contrary to smaller stellar systems which are close enough to us and not heavily extincted, such as -Cen. We investigate the prospects of detection of DM-burning WDs in a stellar cluster harbouring an intermediate-mass black hole (IMBH), which leads to higher densities of DM at the centre. We calculate the capture rate and estimate the luminosity that a WD would emit depending on its distance to the centre of the cluster. Direct-summation N-body simulations of -Cen yield a non-negligible number of WDs in the range of radii of interest. We apply our assumption to published HST/ACS observations of stars in the center of -Cen and, although we are not able to identify any evident candidate, we proof that their bunching up at high luminosities would be unique. We predict that DM burning will lead to a truncation of the cooling sequence at the faint end. The detection of DM burning in future observations of dense stellar clusters could allow us to probe different models of DM distributions and characteristics. On the other hand, if DM-burning WDs really exist, their number and properties could give hints to the existence of IMBHs.

  18. Clinical Prediction of Fall Risk and White Matter Abnormalities

    PubMed Central

    Koo, Bang-Bon; Bergethon, Peter; Qiu, Wei Qiao; Scott, Tammy; Hussain, Mohammed; Rosenberg, Irwin; Caplan, Louis R.; Bhadelia, Rafeeque A.

    2015-01-01

    Background 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 determined by the Tinetti scale, have specific patterns of WM abnormalities on diffusion tensor imaging. Design, Setting, and Patients Community-based cohort of 125 homebound elderly individuals. Main Outcome Measures Diffusion tensor imaging scans were analyzed using tract-based spatial statistics analysis to determine the location of WM abnormalities in subjects with Tinetti scale scores of 25 or higher (without risk of falls) and lower than 25 (with risk of falls). Multivariate linear least squares correlation analysis was performed to determine the association between Tinetti scale scores and local fractional anisotropy values on each skeletal voxel controlling for possible confounders. Results In subjects with risk of falls (Tinetti scale score <25), clusters of abnormal WM were seen in the medial frontal and parietal subcortical pathways, genu and splenium of corpus callosum, posterior cingulum, prefrontal and orbitofrontal pathways, and longitudinal pathways that connect frontal-parietal-temporal lobes. Among these abnormalities, those in medial frontal and parietal subcortical pathways correlated with Mini-Mental State Examination scores, while the other locations were unrelated to these scores. Conclusions Elderly individuals at risk for falls as determined by the Tinetti scale have WM abnormalities in specific locations on diffusion tensor imaging, some of which correlate with cognitive function scores. PMID:22332181

  19. 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

  20. Rethinking the standard trans-cortical approaches in the light of superficial white matter anatomy

    PubMed Central

    Latini, Francesco; Ryttlefors, Mats

    2015-01-01

    A better comprehension of the superficial white matter organization is important in order to minimize potential and avoidable damage to long or intermediate association fibre bundles during every step of a surgical approach. We recently proposed a technique for cadaver specimen preparation, which seems able to identify a more systematic organization of the superficial white matter terminations. Moreover, the use of the physiological intracranial vascular network for the fixation process allowed us to constantly show main vascular landmarks associated with white matter structures. Hence three examples of standard approaches to eloquent areas are herein reanalyzed starting from the first superficial layer. New insights into the possible surgical trajectories and subsequent quantitative damages of both vessels and white matter fibres can help readapt even the most standard and widely accepted approach trough the brain cortex. A more detailed study of these fine anatomical details may become in the near future a fundamental part of the neurosurgical training and the preoperative planning. PMID:26889162

  1. Effects of cholinesterase inhibition on brain white matter volume in Alzheimer's disease.

    PubMed

    Venneri, Annalena; Lane, Roger

    2009-02-18

    Brain white matter volume changes were quantified by using voxel-based morphometry in 26 minimal-to-mild Alzheimer's disease patients receiving cholinesterase inhibitors over 20 weeks. Patients treated with rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase, did not show those reductions in white matter volume that were observed in patients treated with acetylcholinesterase-selective agents, donepezil and galantamine. This is the first time that dual cholinesterase inhibition has been shown to influence white matter volume specifically. The findings are consistent with a thesis that dual cholinesterase inhibition may have neuroprotective potential. Attenuated loss of brain volumes and delayed/slower long-term clinical decline in patients treated with agents such as rivastigmine may be due to less extensive white matter damage and loss of corticosubcortical connectivity. PMID:19444953

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

    PubMed

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

    2014-01-01

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

  3. 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

    2010-07-0