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Sample records for white matter region

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

    PubMed Central

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

    2013-01-01

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

  2. Regional white matter hyperintensities: aging, AD risk, and cognitive function

    PubMed Central

    Birdsill, Alex C; Koscik, Rebecca L; Jonaitis, Erin M; Johnson, Sterling C; Okonkwo, Ozioma C; Hermann, Bruce P; LaRue, Asenath; Sager, Mark A; Bendlin, Barbara B

    2013-01-01

    White matter hyperintensities (WMH) of presumed vascular origin as seen on T2-weighted fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI), are known to increase with age and are elevated in Alzheimer’s disease (AD). The cognitive implications of these common markers are not well understood. Previous research has primarily focused on global measures of WMH burden and broad localizations that contain multiple white matter tracts. The aims of this study were to determine the pattern of WMH accumulation with age, risk for AD, and the relationship with cognitive function utilizing a voxel-wise analysis capable of identifying specific white matter regions. Three hundred and forty-nine participants underwent T1-weighted and high-resolution T2FLAIR MRI and neuropsychological testing. Increasing age and lower cognitive speed and flexibility (a component of executive function), were both significantly associated with regional WMH throughout the brain. When age was controlled, lower cognitive speed and flexibility was independently associated with WMH in the superior corona radiata. APOE4 and parental family history of AD were not associated with higher burden of WMH. The results contribute to a larger body of literature suggesting that white matter measures are linked with processing speed, and illustrate the utility of voxel-wise analysis in understanding the effect of lesion location on cognitive function. PMID:24199958

  3. A volumetric approach to quantifying region-to-region white matter connectivity in diffusion tensor MRI.

    PubMed

    Fletcher, P Thomas; Tao, Ran; Jeong, Won-Ki; Whitaker, Ross T

    2007-01-01

    In this paper we present a volumetric approach for quantitatively studying white matter connectivity from diffusion tensor magnetic resonance imaging (DT-MRI). The proposed method is based on a minimization of path cost between two regions, defined as the integral of local costs that are derived from the full tensor data along the path. We solve the minimal path problem using a Hamilton-Jacobi formulation of the problem and a new, fast iterative method that computes updates on the propagating front of the cost function at every point. The solutions for the fronts emanating from the two initial regions are combined, giving a voxel-wise connectivity measurement of the optimal paths between the regions that pass through those voxels. The resulting high-connectivity voxels provide a volumetric representation of the white matter pathway between the terminal regions. We quantify the tensor data along these pathways using nonparametric regression of the tensors and of derived measures as a function of path length. In this way we can obtain volumetric measures on white-matter tracts between regions without any explicit integration of tracts. We demonstrate the proposed method on several fiber tracts from DT-MRI data of the normal human brain. PMID:17633712

  4. 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…

  5. Regional Gray Matter Atrophy Coexistent with Occipital Periventricular White Matter Hyper Intensities.

    PubMed

    Duan, Dazhi; Li, Congyang; Shen, Lin; Cui, Chun; Shu, Tongsheng; Zheng, Jian

    2016-01-01

    White matter hyperintensities (WMHs) and brain atrophy often coexist in the elderly. Additionally, WMH is often observed as occipital periventricular hyperintensities (OPVHs) with low-grade periventricular (PV) white matter (WM) lesions and is usually confined within an anatomical structure. However, the effects of OPVHs on gray matter (GM) atrophy remain largely unknown. In this study, we investigated GM atrophy in OPVHs patients and explored the relationship between such atrophy and clinical risk factors. T1-weighted and T2-weighted Magnetic resonance imaging (MRI) were acquired, and voxel-based morphometry (VBM) analysis was applied. The clinical (demographic and cardiovascular) risk factors of the OPVHs patients and healthy controls were then compared. Lastly, scatter plots and correlation analysis were applied to explore the relationship between the MRI results and clinical risk factors in the OPVHs patients. OPVHs patients had significantly reduced GM in the right supramarginal gyrus, right angular gyrus, right middle temporal gyrus, right anterior cingulum and left insula compared to healthy controls. Additionally, OPVHs patients had GM atrophy in the left precentral gyrus and left insula cortex, and such atrophy is associated with a reduction in low-density lipoprotein cholesterol (LDL-C) and apolipoprotein-B (Apo-B). PMID:27656141

  6. Regional Gray Matter Atrophy Coexistent with Occipital Periventricular White Matter Hyper Intensities

    PubMed Central

    Duan, Dazhi; Li, Congyang; Shen, Lin; Cui, Chun; Shu, Tongsheng; Zheng, Jian

    2016-01-01

    White matter hyperintensities (WMHs) and brain atrophy often coexist in the elderly. Additionally, WMH is often observed as occipital periventricular hyperintensities (OPVHs) with low-grade periventricular (PV) white matter (WM) lesions and is usually confined within an anatomical structure. However, the effects of OPVHs on gray matter (GM) atrophy remain largely unknown. In this study, we investigated GM atrophy in OPVHs patients and explored the relationship between such atrophy and clinical risk factors. T1-weighted and T2-weighted Magnetic resonance imaging (MRI) were acquired, and voxel-based morphometry (VBM) analysis was applied. The clinical (demographic and cardiovascular) risk factors of the OPVHs patients and healthy controls were then compared. Lastly, scatter plots and correlation analysis were applied to explore the relationship between the MRI results and clinical risk factors in the OPVHs patients. OPVHs patients had significantly reduced GM in the right supramarginal gyrus, right angular gyrus, right middle temporal gyrus, right anterior cingulum and left insula compared to healthy controls. Additionally, OPVHs patients had GM atrophy in the left precentral gyrus and left insula cortex, and such atrophy is associated with a reduction in low-density lipoprotein cholesterol (LDL-C) and apolipoprotein-B (Apo-B).

  7. Regional Gray Matter Atrophy Coexistent with Occipital Periventricular White Matter Hyper Intensities

    PubMed Central

    Duan, Dazhi; Li, Congyang; Shen, Lin; Cui, Chun; Shu, Tongsheng; Zheng, Jian

    2016-01-01

    White matter hyperintensities (WMHs) and brain atrophy often coexist in the elderly. Additionally, WMH is often observed as occipital periventricular hyperintensities (OPVHs) with low-grade periventricular (PV) white matter (WM) lesions and is usually confined within an anatomical structure. However, the effects of OPVHs on gray matter (GM) atrophy remain largely unknown. In this study, we investigated GM atrophy in OPVHs patients and explored the relationship between such atrophy and clinical risk factors. T1-weighted and T2-weighted Magnetic resonance imaging (MRI) were acquired, and voxel-based morphometry (VBM) analysis was applied. The clinical (demographic and cardiovascular) risk factors of the OPVHs patients and healthy controls were then compared. Lastly, scatter plots and correlation analysis were applied to explore the relationship between the MRI results and clinical risk factors in the OPVHs patients. OPVHs patients had significantly reduced GM in the right supramarginal gyrus, right angular gyrus, right middle temporal gyrus, right anterior cingulum and left insula compared to healthy controls. Additionally, OPVHs patients had GM atrophy in the left precentral gyrus and left insula cortex, and such atrophy is associated with a reduction in low-density lipoprotein cholesterol (LDL-C) and apolipoprotein-B (Apo-B). PMID:27656141

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

    PubMed

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

    2016-08-01

    Establishing the neural bases of individual differences in personality has been an enduring topic of interest. However, while a growing literature has sought to characterize grey matter correlates of personality traits, little attention to date has been focused on regional white matter correlates of personality, especially for the personality traits agreeableness, conscientiousness and openness. To rectify this gap in knowledge we used a large sample (n > 550) of older adults who provided data on both personality (International Personality Item Pool) and white matter tract-specific fractional anisotropy (FA) from diffusion tensor MRI. Results indicated that conscientiousness was associated with greater FA in the left uncinate fasciculus (β = 0.17, P < 0.001). We also examined links between FA and the personality meta-trait 'stability', which is defined as the common variance underlying agreeableness, conscientiousness, and neuroticism/emotional stability. We observed an association between left uncinate fasciculus FA and stability (β = 0.27, P < 0.001), which fully accounted for the link between left uncinate fasciculus FA and conscientiousness. In sum, these results provide novel evidence for links between regional white matter microstructure and key traits of human personality, specifically conscientiousness and the meta-trait, stability. Future research is recommended to replicate and address the causal directions of these associations. PMID:27013101

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

    PubMed Central

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

    2016-01-01

    Establishing the neural bases of individual differences in personality has been an enduring topic of interest. However, while a growing literature has sought to characterize grey matter correlates of personality traits, little attention to date has been focused on regional white matter correlates of personality, especially for the personality traits agreeableness, conscientiousness and openness. To rectify this gap in knowledge we used a large sample (n > 550) of older adults who provided data on both personality (International Personality Item Pool) and white matter tract-specific fractional anisotropy (FA) from diffusion tensor MRI. Results indicated that conscientiousness was associated with greater FA in the left uncinate fasciculus (β = 0.17, P < 0.001). We also examined links between FA and the personality meta-trait ‘stability’, which is defined as the common variance underlying agreeableness, conscientiousness, and neuroticism/emotional stability. We observed an association between left uncinate fasciculus FA and stability (β = 0.27, P < 0.001), which fully accounted for the link between left uncinate fasciculus FA and conscientiousness. In sum, these results provide novel evidence for links between regional white matter microstructure and key traits of human personality, specifically conscientiousness and the meta-trait, stability. Future research is recommended to replicate and address the causal directions of these associations. PMID:27013101

  10. Age related changes in microglial phenotype vary between CNS regions: grey versus white matter differences.

    PubMed

    Hart, Adam D; Wyttenbach, Andreas; Perry, V Hugh; Teeling, Jessica L

    2012-07-01

    Subtle regional differences in microglial phenotype exist in the adult mouse brain. We investigated whether these differences were amplified during ageing and following systemic challenge with lipopolysaccharide (LPS). We studied microglial morphology and phenotype in young (4mo) and aged (21mo) C57/BL6 mice using immunohistochemistry and quantified the expression levels of surface molecules on microglia in white and grey matter along the rostral-caudal neuraxis. We detected significant regional, age dependent differences in microglial phenotypes, with the microglia of white matter and caudal areas of the CNS exhibiting greater upregulation of CD11b, CD68, CD11c, F4/80 and FcγRI than grey matter and rostral CNS areas. Upregulation of CD11c with age was restricted to the white matter, as was the appearance of multinucleated giant cells. Systemic LPS caused a subtle upregulation of FcγRI after 24 h, but the other markers examined were not affected. Burrowing behaviour and static rod assays were used to assess hippocampal and cerebellar integrity. Aged mice exhibited exaggerated and prolonged burrowing deficits following systemic LPS injection, while in the absence of an inflammatory challenge aged mice performed significantly worse than young mice in the static rod test. Taken together, these findings show that the effects of age on microglial phenotype and functional integrity vary significantly between CNS compartments, as do, albeit to a lesser extent, the effects of systemic LPS.

  11. Skeleton-based region competition for automated gray matter and white matter segmentation of human brain MR images

    NASA Astrophysics Data System (ADS)

    Chu, Yong; Chen, Ya-Fang; Su, Min-Ying; Nalcioglu, Orhan

    2005-04-01

    Image segmentation is an essential process for quantitative analysis. Segmentation of brain tissues in magnetic resonance (MR) images is very important for understanding the structural-functional relationship for various pathological conditions, such as dementia vs. normal brain aging. Different brain regions are responsible for certain functions and may have specific implication for diagnosis. Segmentation may facilitate the analysis of different brain regions to aid in early diagnosis. Region competition has been recently proposed as an effective method for image segmentation by minimizing a generalized Bayes/MDL criterion. However, it is sensitive to initial conditions - the "seeds", therefore an optimal choice of "seeds" is necessary for accurate segmentation. In this paper, we present a new skeleton-based region competition algorithm for automated gray and white matter segmentation. Skeletons can be considered as good "seed regions" since they provide the morphological a priori information, thus guarantee a correct initial condition. Intensity gradient information is also added to the global energy function to achieve a precise boundary localization. This algorithm was applied to perform gray and white matter segmentation using simulated MRI images from a realistic digital brain phantom. Nine different brain regions were manually outlined for evaluation of the performance in these separate regions. The results were compared to the gold-standard measure to calculate the true positive and true negative percentages. In general, this method worked well with a 96% accuracy, although the performance varied in different regions. We conclude that the skeleton-based region competition is an effective method for gray and white matter segmentation.

  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

  13. 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

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

    PubMed Central

    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

    2015-01-01

    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

  15. 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 17.0 ± 2.9 years) compared with age-matched 14 healthy controls (age 16.3 ± 2.3 years) using magnetic resonance imaging (MRI)-based high-resolution T1-weighted images with voxel based morphometry (VBM) analyses. White matter atrophy appeared in perinatally HIV-infected youths in brain areas including the bilateral posterior corpus callosum (CC), bilateral external capsule, bilateral ventral temporal WM, mid cerebral peduncles, and basal pons over controls. Gray matter volume increase was observed in HIV-infected youths for several regions including the left superior frontal gyrus, inferior occipital gyrus, gyrus rectus, right mid cingulum, parahippocampal gyrus, bilateral inferior temporal gyrus, and middle temporal gyrus compared with controls. Global WM and GM volumes did not differ significantly between groups. These results indicate WM injury in perinatally HIV-infected youths, but the interpretation of the GM results, which appeared as increased regional volumes, is not clear. Further longitudinal studies are needed to clarify if our results represent active ongoing brain infection or toxicity from HIV treatment resulting in neuronal cell swelling and regional increased GM volume. Our findings suggest that assessment of regional GM and WM volume changes, based on VBM procedures, may be an additional measure to assess brain integrity in HIV-infected youths and to evaluate success of current ART therapy for efficacy in the brain.

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

    PubMed

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

    2015-01-01

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

  18. Reduced glucose uptake and Aβ in brain regions with hyperintensities in connected white matter

    PubMed Central

    Rusinek, H.; Tsui, W.; Mosconi, L.; Li, Y.; Osorio, R.S.; Williams, S.; Randall, C.; Spector, N.; McHugh, P.; Murray, J.; Pirraglia, E.; Vallabhajosula, S.; Raj, A.; de Leon, M.J.

    2014-01-01

    Interstitial concentration of amyloid beta (Aß) is positively related to synaptic activity in animal experiments. In humans, Aß deposition in Alzheimer's disease overlaps with cortical regions highly active earlier in life. White matter lesions (WML) disrupt connections between gray matter (GM) regions which in turn changes their activation patterns. Here, we tested if WML are related to Aß accumulation (measured with PiB-PET) and glucose uptake (measured with FDGPET) in connected GM. WML masks from 72 cognitively normal (age 61.7±9.6 years, 71% women) individuals were obtained from T2-FLAIR. MRI and PET images were normalized into common space, segmented and parcellated into gray matter (GM) regions. The effects of WML on connected GM regions were assessed using the Change in Connectivity (ChaCo) score. Defined for each GM region, ChaCo is the percentage of WM tracts connecting to that region that pass through the WML mask. The regional relationship between ChaCo, glucose uptake and Aß was explored via linear regression. Subcortical regions of the bilateral caudate, putamen, calcarine, insula, thalamus and anterior cingulum had WM connections with the most lesions, followed by frontal, occipital, temporal, parietal and cerebellar regions. Regional analysis revealed that GM with more lesions in connecting WM and thus impaired connectivity had lower FDG-PET (r=0.20, p<0.05 corrected) and lower PiB uptake (r=0.28, p<0.05 corrected). Regional regression also revealed that both ChaCo (β=0.045) and FDG-PET (β=0.089) were significant predictors of PiB. In conclusion, brain regions with more lesions in connecting WM had lower glucose metabolism and lower Aß deposition. PMID:24999038

  19. Reduced glucose uptake and Aβ in brain regions with hyperintensities in connected white matter.

    PubMed

    Glodzik, L; Kuceyeski, A; Rusinek, H; Tsui, W; Mosconi, L; Li, Y; Osorio, R S; Williams, S; Randall, C; Spector, N; McHugh, P; Murray, J; Pirraglia, E; Vallabhajosula, S; Raj, A; de Leon, M J

    2014-10-15

    Interstitial concentration of amyloid beta (Aß) is positively related to synaptic activity in animal experiments. In humans, Aß deposition in Alzheimer's disease overlaps with cortical regions highly active earlier in life. White matter lesions (WML) disrupt connections between gray matter (GM) regions which in turn changes their activation patterns. Here, we tested if WML are related to Aß accumulation (measured with PiB-PET) and glucose uptake (measured with FDG-PET) in connected GM. WML masks from 72 cognitively normal (age 61.7 ± 9.6 years, 71% women) individuals were obtained from T2-FLAIR. MRI and PET images were normalized into common space, segmented and parcellated into gray matter (GM) regions. The effects of WML on connected GM regions were assessed using the Change in Connectivity (ChaCo) score. Defined for each GM region, ChaCo is the percentage of WM tracts connecting to that region that pass through the WML mask. The regional relationship between ChaCo, glucose uptake and Aß was explored via linear regression. Subcortical regions of the bilateral caudate, putamen, calcarine, insula, thalamus and anterior cingulum had WM connections with the most lesions, followed by frontal, occipital, temporal, parietal and cerebellar regions. Regional analysis revealed that GM with more lesions in connecting WM and thus impaired connectivity had lower FDG-PET (r = 0.20, p<0.05 corrected) and lower PiB uptake (r = 0.28, p<0.05 corrected). Regional regression also revealed that both ChaCo (β = 0.045) and FDG-PET (β = 0.089) were significant predictors of PiB. In conclusion, brain regions with more lesions in connecting WM had lower glucose metabolism and lower Aß deposition.

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

    PubMed

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

    2012-12-01

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

  1. Regional MRI Diffusion, White-Matter Hyperintensities, and Cognitive Function in Alzheimer's Disease and Vascular Dementia

    PubMed Central

    Scrascia, Federica; Quattrocchi, Carlo Cosimo; Errante, Yuri; Gangemi, Emma; Curcio, Giuseppe; Ursini, Francesca; Silvestrini, Mauro; Maggio, Paola; Beomonte Zobel, Bruno; Rossini, Paolo Maria; Pasqualetti, Patrizio; Falsetti, Lorenzo; Vernieri, Fabrizio

    2016-01-01

    Background and Purpose An increase in brain water diffusivity as measured using magnetic resonance imaging (MRI) has been recently reported in normal-appearing white matter (NAWM) in patients affected by cognitive impairment. However, it remains to be clarified if this reflects an overt neuronal tissue disruption that leads to degenerative or microvascular lesions. This question was addressed by comparing the regional MRI apparent diffusion coefficients (ADCs) of NAWM in patients affected by Alzheimer's disease (AD) or vascular dementia (VaD). The relationships of ADCs with the white-matter hyperintensity (WMH) burden, carotid atherosclerosis, and cognitive performance were also investigated. Methods Forty-nine AD and 31 VaD patients underwent brain MRI to assess the WMH volume and regional NAWM ADCs, neuropsychological evaluations, and carotid ultrasound to assess the plaque severity and intima-media thickness (IMT). Results Regional ADCs in NAWM did not differ between VaD and AD patients, while the WMH volume was greater in VaD than in AD patients. The ADC in the anterior corpus callosum was related to the WMH volume, while a greater carotid IMT was positively correlated with the temporal ADC and WMH volume. The memory performance was worse in patients with higher temporal ADCs. Constructional praxis scores were related to ADCs in the frontal, and occipital lobes, in the anterior and posterior corpus callosum as well as to the WMH volume. Abstract reasoning was related to frontal, parietal, and temporal ADCs. Conclusions Our data show that higher regional ADCs in NAWM are associated with microcirculatory impairment, as depicted by the WMH volume. Moreover, regional ADCs in NAWM are differently associated with the neuropsychological performances in memory, constructional praxia, and abstract reasoning domains. PMID:27074295

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

    PubMed Central

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

    2015-01-01

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

  3. Individual Differences in Verbal Abilities Associated with Regional Blurring of the Left Gray and White Matter Boundary

    PubMed Central

    Blackmon, Karen; Halgren, Eric; Barr, William B.; Carlson, Chad; Devinsky, Orrin; DuBois, Jonathan; Quinn, Brian T.; French, Jacqueline; Kuzniecky, Ruben

    2011-01-01

    Blurring of the cortical gray and white matter border on MRI is associated with normal aging, pathological aging, and the presence of focal cortical dysplasia. However, it remains unclear whether normal variations in signal intensity contrast at the gray and white matter junction reflect the functional integrity of subjacent tissue. This study explores the relationship between verbal abilities and gray and white matter contrast (GWC) in healthy human adults. Participants were scanned at 3 T MRI and administered standardized measures of verbal expression and verbal working memory. GWC was estimated by calculating the non-normalized T1 image intensity contrast above and below the cortical gray/white matter interface. Spherical averaging and whole-brain correlational analyses were performed. Sulcal regions exhibited higher contrast compared to gyral regions. We found a strongly lateralized and regionally specific profile with reduced verbal expression abilities associated with blurring in left hemisphere inferior frontal cortex and temporal pole. Reduced verbal working memory was associated with blurring in widespread left frontal and temporal cortices. Such lateralized and focal results provide support for GWC as a measure of regional functional integrity and highlight its potential role in probing the neuroanatomical substrates of cognition in healthy and diseased populations. PMID:22031871

  4. Gray and White Matter Structures in the Midcingulate Cortex Region Contribute to Body Mass Index in Chinese Young Adults

    PubMed Central

    He, Qinghua; Chen, Chuansheng; Dong, Qi; Xue, Gui; Chen, Chunhui; Lu, Zhong-Lin; Bechara, Antoine

    2014-01-01

    Overweight and obesity are rapidly becoming a central public health challenge around the world. Previous studies have suggested that elevated Body Mass Index (BMI) might be associated with structural changes in both gray and white matter, but this association is still not well understood. The present study aimed to investigate the relationship between BMI and brain structure with a relatively large sample of young adults (N = 336) in a small age range (20 ± 1 years). VBM results showed significant negative correlations between BMI and Gray Matter Volumes (GMV) in the MCC, left OFC, and left VMPFC. There was also a significant negative correlation between BMI and white matter integrity as indexed by fractional anisotropy (FA) in bilateral cingulum. Further tractography analysis showed a significant negative correlation between BMI and the number of fibers passing the MCC region. Regression analysis showed that gray matter and white matter in these regions both contributed to the variance of BMI. These results remained significant even when analysis was restricted to the subjects with normal-weights. Finally, we found that decision making ability (as assessed by the Iowa Gambling Task) mediated the association between the structure of the MCC (a region responsible for impulse control and decision making) and BMI. These results shed light on the structural neural basis of weight variations. PMID:24146133

  5. 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…

  6. 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 ...

  7. White matter injury in ischemic stroke.

    PubMed

    Wang, Yuan; Liu, Gang; Hong, Dandan; Chen, Fenghua; Ji, Xunming; Cao, Guodong

    2016-06-01

    Stroke is one of the major causes of disability and mortality worldwide. It is well known that ischemic stroke can cause gray matter injury. However, stroke also elicits profound white matter injury, a risk factor for higher stroke incidence and poor neurological outcomes. The majority of damage caused by stroke is located in subcortical regions and, remarkably, white matter occupies nearly half of the average infarct volume. Indeed, white matter is exquisitely vulnerable to ischemia and is often injured more severely than gray matter. Clinical symptoms related to white matter injury include cognitive dysfunction, emotional disorders, sensorimotor impairments, as well as urinary incontinence and pain, all of which are closely associated with destruction and remodeling of white matter connectivity. White matter injury can be noninvasively detected by MRI, which provides a three-dimensional assessment of its morphology, metabolism, and function. There is an urgent need for novel white matter therapies, as currently available strategies are limited to preclinical animal studies. Optimal protection against ischemic stroke will need to encompass the fortification of both gray and white matter. In this review, we discuss white matter injury after ischemic stroke, focusing on clinical features and tools, such as imaging, manifestation, and potential treatments. We also briefly discuss the pathophysiology of WMI and future research directions. PMID:27090751

  8. White matter injury in ischemic stroke.

    PubMed

    Wang, Yuan; Liu, Gang; Hong, Dandan; Chen, Fenghua; Ji, Xunming; Cao, Guodong

    2016-06-01

    Stroke is one of the major causes of disability and mortality worldwide. It is well known that ischemic stroke can cause gray matter injury. However, stroke also elicits profound white matter injury, a risk factor for higher stroke incidence and poor neurological outcomes. The majority of damage caused by stroke is located in subcortical regions and, remarkably, white matter occupies nearly half of the average infarct volume. Indeed, white matter is exquisitely vulnerable to ischemia and is often injured more severely than gray matter. Clinical symptoms related to white matter injury include cognitive dysfunction, emotional disorders, sensorimotor impairments, as well as urinary incontinence and pain, all of which are closely associated with destruction and remodeling of white matter connectivity. White matter injury can be noninvasively detected by MRI, which provides a three-dimensional assessment of its morphology, metabolism, and function. There is an urgent need for novel white matter therapies, as currently available strategies are limited to preclinical animal studies. Optimal protection against ischemic stroke will need to encompass the fortification of both gray and white matter. In this review, we discuss white matter injury after ischemic stroke, focusing on clinical features and tools, such as imaging, manifestation, and potential treatments. We also briefly discuss the pathophysiology of WMI and future research directions.

  9. Human Brain White Matter Atlas: Identification and Assignment of Common Anatomical Structures in Superficial White Matter

    PubMed Central

    Oishi, Kenichi; Zilles, Karl; Amunts, Katrin; Faria, Andreia; Jiang, Hangyi; Li, Xin; Akhter, Kazi; Hua, Kegang; Woods, Roger; Toga, Arthur W.; Pike, G. Bruce; Rosa-Neto, Pedro; Evans, Alan; Zhang, Jiangyang; Huang, Hao; Miller, Michael I.; van Zijl, Peter C.M.; Mazziotta, John; Mori, Susumu

    2008-01-01

    Structural delineation and assignment are the fundamental steps in understanding the anatomy of the human brain. The white matter has been structurally defined in the past only at its core regions (deep white matter). However, the most peripheral white matter areas, which are interleaved between the cortex and the deep white matter, have lacked clear anatomical definitions and parcellations. We used axonal fiber alignment information from diffusion tensor imaging (DTI) to delineate the peripheral white matter, and investigated its relationship with the cortex and the deep white matter. Using DTI data from 81 healthy subjects, we identified nine common, blade-like anatomical regions, which were further parcellated into 21 subregions based on the cortical anatomy. Four short association fiber tracts connecting adjacent gyri (U-fibers) were also identified reproducibly among the healthy population. We anticipate that this atlas will be useful resource for atlas-based white matter anatomical studies. PMID:18692144

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

    PubMed

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

    2011-12-01

    The technique of diffusion tensor imaging (DTI) has been used to investigate alterations in white matter architecture following long-term training and expertise. Professional simultaneous interpreters (SI) provide an ideal model for the investigation of training-induced plasticity due to the high demands placed on sound to motor mapping mechanisms, which are vital for executing fast interpretations. In line with our hypothesis, we found clusters with decreased fractional anisotropy (FA) in the SI group in brain regions previously shown to support sensory-motor coupling mechanisms and speech articulation (cluster extent family-wise error corrected, P < 0.01). Furthermore, we found an altered white matter architecture indicated by lower FA values in the SI group in the most anterior and posterior parts of the corpus callosum. Our results suggest that language expertise is accompanied by plastic adaptations in regions strongly involved in motor aspects of speech and in interhemispheric information transfer. These results have implications for our understanding of language expertise in relation to white matter adaptations.

  11. 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

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

    PubMed

    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

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

    PubMed

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

    2015-11-01

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

  14. 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.

  15. Diffusion tensor imaging of white and grey matter within the spinal cord of normal Beagle dogs: Sub-regional differences of the various diffusion parameters.

    PubMed

    Yoon, Hakyoung; Park, Noh-Won; Ha, Yun-Mi; Kim, Jaehwan; Moon, Won-Jin; Eom, Kidong

    2016-09-01

    Diffusion tensor imaging (DTI) is an advanced diffusion weighted imaging technique that can identify early stage lesions and Wallerian degeneration within the spinal cord; these changes are difficult to recognise on conventional magnetic resonance imaging (MRI). The only DTI parameters previously investigated in dogs are fractional anisotropy and mean diffusivity (MD). The aim of this study was to evaluate multiple DTI parameters in sub-regional areas of the spinal cord in normal Beagles. All imaging data were obtained from the lumbar spinal cord (L1-L3) of ten normal dogs using a 3 Tesla MRI scanner. Transverse multi-shot echo planar imaging sequences (b values = 0 and 800 s/mm(2); 12 directions) were used for DTI. Regions of interest were selected from sub-regions of the white and grey matter, and from the whole spinal cord, in the transverse plane in all DTI maps. The DTI parameters in spinal cord sub-regions in the transverse plane were significantly different amongst the white matter, grey matter and whole spinal cord (P < 0.05 for all DTI parameters except MD), as well as between white matter sub-regions (P < 0.05 for most DTI parameters except radial diffusivity, MD and planar index). DTI-based sub-regional analysis of white and grey matter may be useful for regional evaluation of the dog spinal cord.

  16. White Matter Microstructure and Cognitive Function

    PubMed Central

    Anderson, Elaine J.; Husain, Masud

    2013-01-01

    In recent years, diffusion-weighted magnetic resonance imaging (DW-MRI) has been increasingly used to explore the relationship between white matter structure and cognitive function. This technique uses the passive diffusion of water molecules to infer properties of the surrounding tissue. DW-MRI has been extensively employed to investigate how individual differences in behavior are related to variability in white matter microstructure on a range of different cognitive tasks and also to examine the effect experiential learning might have on brain structural connectivity. Using diffusion tensor tractography, large white matter pathways have been traced in vivo and used to explore patterns of white matter projections between different brain regions. Recent findings suggest that diffusion-weighted imaging might even be used to measure functional differences in water diffusion during task performance. This review describes some research highlights in diffusion-weighted imaging and how this technique can be employed to further our understanding of cognitive function. PMID:22020545

  17. 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 domains—WM dementia—occurs 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

  18. 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.

  19. 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. PMID:26801955

  20. 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.

  1. 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.

  2. Regional Variation of White Matter Development in the Cat Brain Revealed by Ex Vivo Diffusion MR Tractography

    PubMed Central

    Dai, Guangping; Das, Avilash; Hayashi, Emiko; Chen, Qin; Takahashi, Emi

    2016-01-01

    Three-dimensional reconstruction of developing fiber pathways is essential to assessing the developmental course of fiber pathways in the whole brain. We applied diffusion spectrum imaging (DSI) tractography to five juvenile ex vivo cat brains at postnatal day (P) 35, when the degree of myelination varies across brain regions. We quantified diffusion properties (fractional anisotropy [FA] and apparent diffusion coefficient [ADC]) and other measurements (number, volume, and voxel count) on reconstructed pathways for projection (cortico-spinal and thalamo-cortical), corpus callosal, limbic (cingulum and fornix), and association (cortico-cortical) pathways, and characterized regional differences in maturation patterns by assessing diffusion properties. FA values were significantly higher in cortico-cortical pathways within the right hemisphere compared to those within the left hemisphere, while the other measurements for the cortico-cortical pathways within the hemisphere did not show asymmetry. ADC values were not asymmetric in both types of pathways. Interestingly, tract count and volume were significantly larger in the left thalamo-cortical pathways compared to the right thalamo-cortical pathways. The bilateral thalamo-cortical pathways showed high FA values compared to the other fiber pathways. On the other hand, ADC values did not show any differences across pathways studied. These results demonstrate that DSI tractography successfully depicted regional variations of white matter tracts during development when myelination is incomplete. Low FA and high ADC values in the cingulum bundle suggest that the cingulum bundle is less mature than the others at this developmental stage. PMID:27568056

  3. On describing human white matter anatomy: the white matter query language.

    PubMed

    Wassermann, Demian; Makris, Nikos; Rathi, Yogesh; Shenton, Martha; Kikinis, Ron; Kubicki, Marek; Westin, Carl-Fredrik

    2013-01-01

    The main contribution of this work is the careful syntactical definition of major white matter tracts in the human brain based on a neuroanatomist's expert knowledge. We present a technique to formally describe white matter tracts and to automatically extract them from diffusion MRI data. The framework is based on a novel query language with a near-to-English textual syntax. This query language allows us to construct a dictionary of anatomical definitions describing white matter tracts. The definitions include adjacent gray and white matter regions, and rules for spatial relations. This enables automated coherent labeling of white matter anatomy across subjects. We use our method to encode anatomical knowledge in human white matter describing 10 association and 8 projection tracts per hemisphere and 7 commissural tracts. The technique is shown to be comparable in accuracy to manual labeling. We present results applying this framework to create a white matter atlas from 77 healthy subjects, and we use this atlas in a proof-of-concept study to detect tract changes specific to schizophrenia. PMID:24505722

  4. On describing human white matter anatomy: the white matter query language.

    PubMed

    Wassermann, Demian; Makris, Nikos; Rathi, Yogesh; Shenton, Martha; Kikinis, Ron; Kubicki, Marek; Westin, Carl-Fredrik

    2013-01-01

    The main contribution of this work is the careful syntactical definition of major white matter tracts in the human brain based on a neuroanatomist's expert knowledge. We present a technique to formally describe white matter tracts and to automatically extract them from diffusion MRI data. The framework is based on a novel query language with a near-to-English textual syntax. This query language allows us to construct a dictionary of anatomical definitions describing white matter tracts. The definitions include adjacent gray and white matter regions, and rules for spatial relations. This enables automated coherent labeling of white matter anatomy across subjects. We use our method to encode anatomical knowledge in human white matter describing 10 association and 8 projection tracts per hemisphere and 7 commissural tracts. The technique is shown to be comparable in accuracy to manual labeling. We present results applying this framework to create a white matter atlas from 77 healthy subjects, and we use this atlas in a proof-of-concept study to detect tract changes specific to schizophrenia.

  5. Biofidelic white matter heterogeneity decreases computational model predictions of white matter strains during rapid head rotations.

    PubMed

    Maltese, Matthew R; Margulies, Susan S

    2016-11-01

    The finite element (FE) brain model is used increasingly as a design tool for developing technology to mitigate traumatic brain injury. We developed an ultra high-definition FE brain model (>4 million elements) from CT and MRI scans of a 2-month-old pre-adolescent piglet brain, and simulated rapid head rotations. Strain distributions in the thalamus, coronal radiata, corpus callosum, cerebral cortex gray matter, brainstem and cerebellum were evaluated to determine the influence of employing homogeneous brain moduli, or distinct experimentally derived gray and white matter property representations, where some white matter regions are stiffer and others less stiff than gray matter. We find that constitutive heterogeneity significantly lowers white matter deformations in all regions compared with homogeneous properties, and should be incorporated in FE model injury prediction.

  6. 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.…

  7. Excitotoxic damage to white matter

    PubMed Central

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

    2007-01-01

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

  8. 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

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

    PubMed

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

    2015-12-01

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

  10. White Matter Alteration in Metabolic Syndrome

    PubMed Central

    Shimoji, Keigo; Abe, Osamu; Uka, Takanori; Yasmin, Hasina; Kamagata, Koji; Asahi, Kouichi; Hori, Masaaki; Nakanishi, Atsushi; Tamura, Yoshifumi; Watada, Hirotaka; Kawamori, Ryuzo; Aoki, Shigeki

    2013-01-01

    OBJECTIVE We explored the regional pattern of white matter alteration in subjects with metabolic syndrome. We also investigated whether white matter alteration was correlated with BMI. RESEARCH DESIGN AND METHODS Seven middle-aged men with metabolic syndrome and seven without metabolic syndrome underwent diffusion tensor imaging with a 3T magnetic resonance imaging imager. We analyzed the fractional anisotropy (FA) values by using a tract-based spatial statistics technique (whole-brain analysis). We subsequently focused on measuring the mean FA values of the right inferior fronto-occipital fasciculus (IFOF) of all subjects by tract-specific analysis (regional brain analysis). We used a Pearson correlation coefficient to evaluate the relationship between BMI and mean FA values of the right IFOF. RESULTS In the whole-brain analysis, subjects with metabolic syndrome had significantly lower FA values than control subjects in part of the right external capsule (part of the right IFOF), the entire corpus callosum, and part of the deep white matter of the right frontal lobe. In the regional brain analysis, the mean FA value of the right IFOF was 0.41 ± 0.03 for subjects with metabolic syndrome and 0.44 ± 0.05 for control subjects. A significant negative correlation was observed between BMI and FA values in the right IFOF (r = −0.56, P < 0.04). CONCLUSIONS Our results show that microstructural white matter changes occur in patients with metabolic syndrome. FA values may be useful indices of white matter alterations in patients with metabolic syndrome. PMID:23172976

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

    PubMed

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

    2012-02-01

    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

  12. Higher Adolescent Body Mass Index Is Associated with Lower Regional Gray and White Matter Volumes and Lower Levels of Positive Emotionality

    PubMed Central

    Kennedy, James T.; Collins, Paul F.; Luciana, Monica

    2016-01-01

    Adolescent obesity is associated with an increased chance of developing serious health risks later in life. Identifying the neurobiological and personality factors related to increases in adiposity is important to understanding what drives maladaptive consummatory and exercise behaviors that result in obesity. Previous research has largely focused on adults with few findings published on interactions among adiposity, brain structure, and personality. In this study, Voxel Based Morphometry (VBM) was used to identify associations between gray and white matter volumes and increasing adiposity, as measured by Body Mass Index percentile (BMI%), in 137 adolescents (age range: 9–20 years, BMI% range: 5.16–99.56). Variations in gray and white matter volume and BMI% were then linked to individual differences in personality measures from the Multidimensional Personality Questionnaire (MPQ). After controlling for age and other covariates, BMI% correlated negatively with gray matter volume in the bilateral caudate (right: partial r = −0.338, left: r = −0.404), medial prefrontal cortex (partial r = −0.339), anterior cingulate (partial r = −0.312), bilateral frontal pole (right: partial r = −0.368, left: r = −0.316), and uncus (partial r = −0.475) as well as white matter volume bilaterally in the anterior limb of the internal capsule (right: partial r = −0.34, left: r = −0.386), extending to the left middle frontal subgyral white matter. Agentic Positive Emotionality (PEM-AG) was correlated negatively with BMI% (partial r = −0.384). PEM-AG was correlated positively with gray matter volume in the right uncus (partial r = 0.329). These results suggest that higher levels of adiposity in adolescents are associated with lower trait levels in reward-related personality domains, as well as structural variations in brain regions associated with reward processing, control, and sensory integration.

  13. Higher Adolescent Body Mass Index Is Associated with Lower Regional Gray and White Matter Volumes and Lower Levels of Positive Emotionality.

    PubMed

    Kennedy, James T; Collins, Paul F; Luciana, Monica

    2016-01-01

    Adolescent obesity is associated with an increased chance of developing serious health risks later in life. Identifying the neurobiological and personality factors related to increases in adiposity is important to understanding what drives maladaptive consummatory and exercise behaviors that result in obesity. Previous research has largely focused on adults with few findings published on interactions among adiposity, brain structure, and personality. In this study, Voxel Based Morphometry (VBM) was used to identify associations between gray and white matter volumes and increasing adiposity, as measured by Body Mass Index percentile (BMI%), in 137 adolescents (age range: 9-20 years, BMI% range: 5.16-99.56). Variations in gray and white matter volume and BMI% were then linked to individual differences in personality measures from the Multidimensional Personality Questionnaire (MPQ). After controlling for age and other covariates, BMI% correlated negatively with gray matter volume in the bilateral caudate (right: partial r = -0.338, left: r = -0.404), medial prefrontal cortex (partial r = -0.339), anterior cingulate (partial r = -0.312), bilateral frontal pole (right: partial r = -0.368, left: r = -0.316), and uncus (partial r = -0.475) as well as white matter volume bilaterally in the anterior limb of the internal capsule (right: partial r = -0.34, left: r = -0.386), extending to the left middle frontal subgyral white matter. Agentic Positive Emotionality (PEM-AG) was correlated negatively with BMI% (partial r = -0.384). PEM-AG was correlated positively with gray matter volume in the right uncus (partial r = 0.329). These results suggest that higher levels of adiposity in adolescents are associated with lower trait levels in reward-related personality domains, as well as structural variations in brain regions associated with reward processing, control, and sensory integration. PMID:27660604

  14. Higher Adolescent Body Mass Index Is Associated with Lower Regional Gray and White Matter Volumes and Lower Levels of Positive Emotionality

    PubMed Central

    Kennedy, James T.; Collins, Paul F.; Luciana, Monica

    2016-01-01

    Adolescent obesity is associated with an increased chance of developing serious health risks later in life. Identifying the neurobiological and personality factors related to increases in adiposity is important to understanding what drives maladaptive consummatory and exercise behaviors that result in obesity. Previous research has largely focused on adults with few findings published on interactions among adiposity, brain structure, and personality. In this study, Voxel Based Morphometry (VBM) was used to identify associations between gray and white matter volumes and increasing adiposity, as measured by Body Mass Index percentile (BMI%), in 137 adolescents (age range: 9–20 years, BMI% range: 5.16–99.56). Variations in gray and white matter volume and BMI% were then linked to individual differences in personality measures from the Multidimensional Personality Questionnaire (MPQ). After controlling for age and other covariates, BMI% correlated negatively with gray matter volume in the bilateral caudate (right: partial r = −0.338, left: r = −0.404), medial prefrontal cortex (partial r = −0.339), anterior cingulate (partial r = −0.312), bilateral frontal pole (right: partial r = −0.368, left: r = −0.316), and uncus (partial r = −0.475) as well as white matter volume bilaterally in the anterior limb of the internal capsule (right: partial r = −0.34, left: r = −0.386), extending to the left middle frontal subgyral white matter. Agentic Positive Emotionality (PEM-AG) was correlated negatively with BMI% (partial r = −0.384). PEM-AG was correlated positively with gray matter volume in the right uncus (partial r = 0.329). These results suggest that higher levels of adiposity in adolescents are associated with lower trait levels in reward-related personality domains, as well as structural variations in brain regions associated with reward processing, control, and sensory integration. PMID:27660604

  15. 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

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

    PubMed

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

    2014-12-01

    Sporadic Creutzfeldt-Jakob disease is considered primarily a disease of grey matter, although the extent of white matter involvement has not been well described. We used diffusion tensor imaging to study the white matter in sporadic Creutzfeldt-Jakob disease compared to healthy control subjects and to correlated magnetic resonance imaging findings with histopathology. Twenty-six patients with sporadic Creutzfeldt-Jakob disease and nine age- and gender-matched healthy control subjects underwent volumetric T1-weighted and diffusion tensor imaging. Six patients had post-mortem brain analysis available for assessment of neuropathological findings associated with prion disease. Parcellation of the subcortical white matter was performed on 3D T1-weighted volumes using Freesurfer. Diffusion tensor imaging maps were calculated and transformed to the 3D-T1 space; the average value for each diffusion metric was calculated in the total white matter and in regional volumes of interest. Tract-based spatial statistics analysis was also performed to investigate the deeper white matter tracts. There was a significant reduction of mean (P=0.002), axial (P=0.0003) and radial (P=0.0134) diffusivities in the total white matter in sporadic Creutzfeldt-Jakob disease. Mean diffusivity was significantly lower in most white matter volumes of interest (P<0.05, corrected for multiple comparisons), with a generally symmetric pattern of involvement in sporadic Creutzfeldt-Jakob disease. Mean diffusivity reduction reflected concomitant decrease of both axial and radial diffusivity, without appreciable changes in white matter anisotropy. Tract-based spatial statistics analysis showed significant reductions of mean diffusivity within the white matter of patients with sporadic Creutzfeldt-Jakob disease, mainly in the left hemisphere, with a strong trend (P=0.06) towards reduced mean diffusivity in most of the white matter bilaterally. In contrast, by visual assessment there was no white matter

  17. White matter changes in patients with hypoxic amnesia.

    PubMed

    Di Paola, M; Moscatelli, A; Bigler, E D; Caltagirone, C; Carlesimo, G A

    2011-02-01

    A deficit of declarative memory is a common sequela after a hypoxic episode. While the role of gray matter changes (i.e., atrophy of hippocampal formation) as mainly responsible for memory loss has been emphasized, the role of the white matter damage has so far been neglected. The present study was aimed at evaluating whether white matter damage, within the neural circuitry responsible for declarative memory functioning, is present in anoxic patients. We assessed, by means of voxel-based morphometry, the integrity of white matter regions in five patients with hypoxic amnesia. When anoxic patients were compared to healthy controls, significantly less white matter density was detected in the fornix, anterior portion of the cingulum bundle and uncinate fasciculus bilaterally. We conclude that cerebral hypoxia may alter, together with the hippocampi, the integrity of white matter fibers throughout the memory-limbic system.

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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…

  3. Traumatic white matter injury and toxic leukoencephalopathies.

    PubMed

    Al-Hasani, Omer Hussain; Smith, Colin

    2011-09-01

    White matter injury may be secondary to a range of neurodegenerative disorders, such as the common dementing disorders of the elderly, or may be a consequence of specific white matter disorders, such as multiple sclerosis and the rare leukodystrophies. This article will focus on two relatively common primary groups of disorders of the white matter, traumatic white matter injury and toxic leukoencephalopathies. Traumatic axonal injury may be focal or diffuse, and is associated with a clinical spectrum ranging from concussion through to coma and death. The molecular mechanisms underlying axonal degeneration secondary to traumatic axonal degeneration are being elucidated and may give an insight into potential therapeutic targets. Toxic leukoencephalopathy may be secondary to exposure to a wide range of compounds, including chemotherapeutic drugs. These toxins may produce white matter injury through a range of mechanisms, and the potential toxic effects of compounds need to be considered when assessing a patient with a nonspecific leukoencephalopathy.

  4. Dark-matter admixed white dwarfs

    NASA Astrophysics Data System (ADS)

    Leung, S.-C.; Chu, M.-C.; Lin, L.-M.; Wong, K.-W.

    2013-06-01

    We study the equilibrium structures of white dwarfs with dark matter cores formed by non-self-annihilating dark matter (DM) particles with masses ranging from 1 GeV to 100 GeV, which are assumed to form an ideal degenerate Fermi gas inside the stars. For DM particles of mass 10 GeV and 100 GeV, we find that stable stellar models exist only if the mass of the DM core inside the star is less than O(10-3)M⊙ and O(10-6)M⊙, respectively. The global properties of these stars, and in particular the corresponding Chandrasekhar mass limits, are essentially the same as those of traditional white dwarf models without DM. Nevertheless, in the 10 GeV case, the gravitational attraction of the DM core is strong enough to squeeze the normal matter in the core region to densities above neutron drip, far above those in traditional white dwarfs. For DM with a particle mass of 1 GeV, the DM core inside the star can be as massive as ˜0.1M⊙ and affects the global structure of the star significantly. In this case, the radius of a stellar model with DM can be about two times smaller than that of a traditional white dwarf. Furthermore, the Chandrasekhar mass limit can also be decreased by as much as 40%. Our results may have implications on the extent to which type Ia supernovae can be regarded as standard candles—a key assumption in the discovery of dark energy.

  5. 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.

  6. Interactive effects of apolipoprotein E4 and diabetes risk on later myelinating white matter regions in neurologically healthy older aged adults.

    PubMed

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

    2014-05-01

    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 individuals at risk of AD. A sample of 107 healthy elderly (80 APOE4-/27 APOE4+) individuals underwent structural magnetic resonance imaging/diffusion tensor imaging (DTI). Data were prepared using Tract-Based Spatial Statistics, and a priori regions of interest (ROIs) were extracted from T1-based WM parcellations. Regions of interest included later myelinating frontal/temporal/parietal WM regions and control regions measured by fractional anisotropy (FA). There were no APOE group differences in DTI for any ROI. Within the APOE4 group, we found negative relationships between hemoglobin A1c/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.

  7. 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

  8. Development of white matter and reading skills.

    PubMed

    Yeatman, Jason D; Dougherty, Robert F; Ben-Shachar, Michal; Wandell, Brian A

    2012-10-30

    White matter tissue properties are highly correlated with reading proficiency; we would like to have a model that relates the dynamics of an individual's white matter development to their acquisition of skilled reading. The development of cerebral white matter involves multiple biological processes, and the balance between these processes differs between individuals. Cross-sectional measures of white matter mask the interplay between these processes and their connection to an individual's cognitive development. Hence, we performed a longitudinal study to measure white-matter development (diffusion-weighted imaging) and reading development (behavioral testing) in individual children (age 7-15 y). The pattern of white-matter development differed significantly among children. In the left arcuate and left inferior longitudinal fasciculus, children with above-average reading skills initially had low fractional anisotropy (FA) that increased over the 3-y period, whereas children with below-average reading skills had higher initial FA that declined over time. We describe a dual-process model of white matter development comprising biological processes with opposing effects on FA, such as axonal myelination and pruning, to explain the pattern of results.

  9. 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.

  10. 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 T₁-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.

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

    NASA Astrophysics Data System (ADS)

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

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

  12. White Matter Development in Adolescence: A DTI Study

    PubMed Central

    Terwilliger, R.; Woo, J.; Luna, B.

    2010-01-01

    Adolescence is a unique period of physical and cognitive development that includes concurrent pubertal changes and sex-based vulnerabilities. While diffusion tensor imaging (DTI) studies show white matter maturation throughout the lifespan, the state of white matter integrity specific to adolescence is not well understood as are the contributions of puberty and sex. We performed whole-brain DTI studies of 114 children, adolescents, and adults to identify age-related changes in white matter integrity that characterize adolescence. A distinct set of regions across the brain were found to have decreasing radial diffusivity across age groups. Region of interest analyses revealed that maturation was attained by adolescence in broadly distributed association and projection fibers, including those supporting cortical and brain stem integration that may underlie known enhancements in reaction time during this period. Maturation after adolescence included association and projection tracts, including prefrontal–striatal connections, known to support top-down executive control of behavior and interhemispheric connectivity. Maturation proceeded in parallel with pubertal changes to the postpubertal stage, suggesting hormonal influences on white matter development. Females showed earlier maturation of white matter integrity compared with males. Together, these findings suggest that white matter connectivity supporting executive control of behavior is still immature in adolescence. PMID:20051363

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

    PubMed

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

    2015-06-01

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

  14. 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

  15. White matter tracts of speech and language.

    PubMed

    Smits, Marion; Jiskoot, Lize C; Papma, Janne M

    2014-10-01

    Diffusion tensor imaging (DTI) has been used to investigate the white matter (WM) tracts underlying the perisylvian cortical regions known to be associated with language function. The arcuate fasciculus is composed of 3 segments (1 long and 2 short) whose separate functions correlate with traditional models of conductive and transcortical motor or sensory aphasia, respectively. DTI mapping of language fibers is useful in presurgical planning for patients with dominant hemisphere tumors, particularly when combined with functional magnetic resonance imaging. DTI has found damage to language networks in stroke patients and has the potential to influence poststroke rehabilitation and treatment. Assessment of the WM tracts involved in the default mode network has been found to correlate with mild cognitive impairment, potentially explaining language deficits in patients with apparently mild small vessel ischemic disease. Different patterns of involvement of language-related WM structures appear to correlate with different clinical subtypes of primary progressive aphasias.

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

    PubMed Central

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

    2012-01-01

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

  17. Vesicular release of glutamate from unmyelinated axons in white matter

    PubMed Central

    Ziskin, Jennifer L; Nishiyama, Akiko; Rubio, Maria; Fukaya, Masahiro; Bergles, Dwight E

    2007-01-01

    Directed fusion of transmitter-laden vesicles enables rapid intercellular signaling in the central nervous system and occurs at synapses within gray matter. Here we show that action potentials also induce the release of glutamate from axons in the corpus callosum, a white matter region responsible for interhemispheric communication. Callosal axons release glutamate by vesicular fusion, which induces quantal AMPA receptor–mediated currents in NG2+ glial progenitors at anatomically distinct axo–glial synaptic junctions. Glutamate release from axons was facilitated by repetitive stimulation and could be inhibited through activation of metabotropic autoreceptors. Although NG2+ cells form associations with nodes of Ranvier in white matter, measurements of conduction velocity indicated that unmyelinated fibers are responsible for glutamatergic signaling with NG2+ glia. This activity-dependent secretion of glutamate was prevalent in the developing and mature mouse corpus callosum, indicating that axons within white matter both conduct action potentials and engage in rapid neuron-glia communication. PMID:17293857

  18. Cerebral white matter in early puberty is associated with luteinizing hormone concentrations.

    PubMed

    Peper, Jiska S; Brouwer, Rachel M; Schnack, Hugo G; van Baal, G Caroline M; van Leeuwen, Marieke; van den Berg, Stéphanie M; Delemarre-Van de Waal, Henriëtte A; Janke, Andrew L; Collins, D Louis; Evans, Alan C; Boomsma, Dorret I; Kahn, René S; Hulshoff Pol, Hilleke E

    2008-08-01

    Puberty is a period in which cerebral white matter grows considerably, whereas gray matter decreases. The first endocrinological marker of puberty in both boys and girls is an increased secretion of luteinizing hormone (LH). Here we investigated the phenotypic association between LH, global and focal gray and white matter in 104 healthy nine-year-old monozygotic and dizygotic twins. Volumetric MRI and voxel-based morphometry were applied to measure global gray and white matter and to estimate relative concentrations of regional cerebral gray and white matter, respectively. A possible common genetic origin of this association (genetic correlation) was examined. Results showed that higher LH levels are associated with a larger global white matter proportion and with higher regional white matter density. Areas of increased white matter density included the cingulum, middle temporal gyrus and splenium of the corpus callosum. No association between LH and global gray matter proportion or regional gray matter density was found. Our data indicate that a common genetic factor underlies the association between LH level and regional white matter density. We suggest that the increase of white matter growth during puberty reported earlier might be directly or indirectly mediated by LH production. In addition, genes involved in LH production may be promising candidate genes in neuropsychiatric illnesses with an onset in early adolescence.

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

    PubMed

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

    2014-01-01

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

  20. Alterations in white matter microstructure in neurofibromatosis-1.

    PubMed

    Karlsgodt, Katherine H; Rosser, Tena; Lutkenhoff, Evan S; Cannon, Tyrone D; Silva, Alcino; Bearden, Carrie E

    2012-01-01

    Neurofibromatosis (NF1) represents the most common single gene cause of learning disabilities. NF1 patients have impairments in frontal lobe based cognitive functions such as attention, working memory, and inhibition. Due to its well-characterized genetic etiology, investigations of NF1 may shed light on neural mechanisms underlying such difficulties in the general population or other patient groups. Prior neuroimaging findings indicate global brain volume increases, consistent with neural over-proliferation. However, little is known about alterations in white matter microstructure in NF1. We performed diffusion tensor imaging (DTI) analyses using tract-based spatial statistics (TBSS) in 14 young adult NF1 patients and 12 healthy controls. We also examined brain volumetric measures in the same subjects. Consistent with prior studies, we found significantly increased overall gray and white matter volume in NF1 patients. Relative to healthy controls, NF1 patients showed widespread reductions in white matter integrity across the entire brain as reflected by decreased fractional anisotropy (FA) and significantly increased absolute diffusion (ADC). When radial and axial diffusion were examined we found pronounced differences in radial diffusion in NF1 patients, indicative of either decreased myelination or increased space between axons. Secondary analyses revealed that FA and radial diffusion effects were of greatest magnitude in the frontal lobe. Such alterations of white matter tracts connecting frontal regions could contribute to the observed cognitive deficits. Furthermore, although the cellular basis of these white matter microstructural alterations remains to be determined, our findings of disproportionately increased radial diffusion against a background of increased white matter volume suggest the novel hypothesis that one potential alteration contributing to increased cortical white matter in NF1 may be looser packing of axons, with or without myelination

  1. 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.

  2. 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.

  3. 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

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

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

    PubMed

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

    2012-08-29

    Although reading skill remains relatively stable with advancing age in humans, neurophysiological measures suggest potential reductions in efficiency of lexical information processing. It is unclear whether these age-related changes are secondary to decreases in regional cortical thickness and/or microstructure of fiber tracts essential to language. Magnetoencephalography, volumetric MRI, and diffusion tensor imaging were performed in 10 young (18-33 years) and 10 middle-aged (42-64 years) human individuals to evaluate the spatiotemporal dynamics and structural correlates of age-related changes in lexical-semantic processing. Increasing age was associated with reduced activity in left temporal lobe regions from 250 to 350 ms and in left inferior prefrontal cortex from 350 to 450 ms (i.e., N400). Hierarchical regression indicated that age no longer predicted left inferior prefrontal activity after cortical thickness and fractional anisotropy (FA) of the uncinate fasciculus (UF) were considered. Interestingly, FA of the UF was a stronger predictor of the N400 response than cortical thickness. Age-related reductions in left-lateralization of language responses were observed between 250 and 350 ms, 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.

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

    PubMed

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

    2016-01-15

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

  7. Diffusion tensor imaging findings of white matter changes in first episode schizophrenia: a systematic review.

    PubMed

    Kuswanto, Carissa Nadia; Teh, Irvin; Lee, Tih-Shih; Sim, Kang

    2012-04-01

    Earlier structural magnetic resonance imaging in schizophrenia have noted smaller white matter volumes in diverse brain regions and recent diffusion tensor imaging (DTI) studies have allowed better elucidation of changes in brain white matter integrity within the illness. As white matter abnormalities have been reported to occur early in the course of schizophrenia, we systematically review extant DTI studies of anomalies of white matter integrity in first episode schizophrenia (FES) up till October 2011. Overall, disruptions of white matter integrity were found in the cortical, subcortical brain regions and white matter associative and commissural tracts, suggesting that changes of cortical-subcortical white matter integrity were found at an early stage of the disorder. These changes in white matter integrity were correlated with specific cognitive deficits (verbal and spatial working memory) as well as psychopathology (positive more than negative symptoms) in patients with FES. The correlation of these white matter integrity changes with cognitive and phenomenological factors may shed light on neurobiological substrates underlying these clinical manifestations. Future studies need to validate these findings in larger samples of subjects and in different populations as well as chart the progress of these cerebral white matter changes over time so as to better appreciate their trajectory with illness course, treatment and chronicity.

  8. 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.

  9. 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 35:4475–4487, 2014. PMID:24578096

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  12. Maternal Adiposity Negatively Influences Infant Brain White Matter Development

    PubMed Central

    Ou, Xiawei; Thakali, Keshari M.; Shankar, Kartik; Andres, Aline; Badger, Thomas M.

    2015-01-01

    Objective To study potential effects of maternal body composition on central nervous system (CNS) development of newborn infants. Methods Diffusion tensor imaging (DTI) was used to evaluate brain white matter development in 2 week old, full-term, appropriate for gestational age (AGA) infants from uncomplicated pregnancies of normal-weight (BMI<25 at conception) or obese (BMI ≥30 at conception) and otherwise healthy mothers. Tract-based spatial statistics (TBSS) analyses were used for voxel-wise group comparison of fractional anisotropy (FA), a sensitive measure of white matter integrity. DNA methylation analyses of umbilical cord tissue focused on genes known to be important in CNS development were also performed. Results Newborns from obese women had significantly lower FA values in multiple white matter regions than those born of normal-weight mothers. Global and regional FA values negatively correlated (P<0.05) with maternal fat mass percentage. Linear regression analysis followed by gene ontology enrichment showed that methylation status of 68 CpG sites representing 57 genes with GO terms related to CNS development was significantly associated with maternal adiposity status. Conclusions These results suggest a negative association between maternal adiposity and white matter development in offspring. PMID:25919924

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

    PubMed

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

    2014-06-01

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

  14. 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 approaches—region-of-interest and voxelwise tract-based spatial statistics—to 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

  15. 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 30–50 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

  16. Cognitive correlates of white matter lesion load and brain atrophy

    PubMed Central

    Dong, Chuanhui; Nabizadeh, Nooshin; Caunca, Michelle; Cheung, Ying Kuen; Rundek, Tatjana; Elkind, Mitchell S.V.; DeCarli, Charles; Sacco, Ralph L.; Stern, Yaakov

    2015-01-01

    Objective: We investigated white matter lesion load and global and regional brain volumes in relation to domain-specific cognitive performance in the stroke-free Northern Manhattan Study (NOMAS) population. Methods: We quantified white matter hyperintensity volume (WMHV), total cerebral volume (TCV), and total lateral ventricular (TLV) volume, as well as hippocampal and cortical gray matter (GM) lobar volumes in a subgroup. We used general linear models to examine MRI markers in relation to domain-specific cognitive performance, adjusting for key covariates. Results: MRI and cognitive data were available for 1,163 participants (mean age 70 ± 9 years; 60% women; 66% Hispanic, 17% black, 15% white). Across the entire sample, those with greater WMHV had worse processing speed. Those with larger TLV volume did worse on episodic memory, processing speed, and semantic memory tasks, and TCV did not explain domain-specific variability in cognitive performance independent of other measures. Age was an effect modifier, and stratified analysis showed that TCV and WMHV explained variability in some domains above age 70. Smaller hippocampal volume was associated with worse performance across domains, even after adjusting for APOE ε4 and vascular risk factors, whereas smaller frontal lobe volumes were only associated with worse executive function. Conclusions: In this racially/ethnically diverse, community-based sample, white matter lesion load was inversely associated with cognitive performance, independent of brain atrophy. Lateral ventricular, hippocampal, and lobar GM volumes explained domain-specific variability in cognitive performance. PMID:26156514

  17. Inflammatory pathways link socioeconomic inequalities to white matter architecture.

    PubMed

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

    2013-09-01

    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 30-50 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

  18. Improved Segmentation of White Matter Tracts with Adaptive Riemannian Metrics

    PubMed Central

    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

  19. Periventricular White Matter Is a Nexus for Network Connectivity in the Human Brain.

    PubMed

    Owen, Julia P; Wang, Maxwell B; Mukherjee, Pratik

    2016-09-01

    The edges of the structural connectome traverse the white matter to connect cortical and subcortical nodes, although the anatomic embedding of these edges is generally overlooked in the literature. Characterization of the geometry of the structural connectome could provide an improved understanding of the relative importance of various white matter regions to the network architecture of the human brain in normal development and aging, as well as in white matter diseases with regionally specific patterns of vulnerability. Edge density imaging (EDI) has previously been used to show that the posterior periventricular white matter contains a disproportionately large number of connectome edges. In this study, the regional distribution of connectome edges within cerebral white matter, including the importance of posterior periventricular white matter, is further investigated and demonstrated to be invariant to different gray matter parcellations and different diffusion MRI acquisition and postprocessing/tractography methods. An examination of the highest k-core edges and a virtual lesion analysis illuminate hemispheric asymmetries (left>right) in the embedding of connectome edges. Therefore, EDI reveals specific areas of vulnerability within the white matter connectivity of the human brain, especially in the periventricular white matter. The idea of a periventricular nexus fits with the known neurobiology of brain development and may result from simple geometrical considerations in minimizing wiring cost in structural brain connectivity. PMID:27345586

  20. Periventricular White Matter Is a Nexus for Network Connectivity in the Human Brain.

    PubMed

    Owen, Julia P; Wang, Maxwell B; Mukherjee, Pratik

    2016-09-01

    The edges of the structural connectome traverse the white matter to connect cortical and subcortical nodes, although the anatomic embedding of these edges is generally overlooked in the literature. Characterization of the geometry of the structural connectome could provide an improved understanding of the relative importance of various white matter regions to the network architecture of the human brain in normal development and aging, as well as in white matter diseases with regionally specific patterns of vulnerability. Edge density imaging (EDI) has previously been used to show that the posterior periventricular white matter contains a disproportionately large number of connectome edges. In this study, the regional distribution of connectome edges within cerebral white matter, including the importance of posterior periventricular white matter, is further investigated and demonstrated to be invariant to different gray matter parcellations and different diffusion MRI acquisition and postprocessing/tractography methods. An examination of the highest k-core edges and a virtual lesion analysis illuminate hemispheric asymmetries (left>right) in the embedding of connectome edges. Therefore, EDI reveals specific areas of vulnerability within the white matter connectivity of the human brain, especially in the periventricular white matter. The idea of a periventricular nexus fits with the known neurobiology of brain development and may result from simple geometrical considerations in minimizing wiring cost in structural brain connectivity.

  1. 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…

  2. White Matter Integrity Reductions in Intermittent Explosive Disorder.

    PubMed

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

    2016-10-01

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

  3. 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

  4. White Matter Integrity Reductions in Intermittent Explosive Disorder.

    PubMed

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

    2016-10-01

    Intermittent explosive disorder (IED), as described in DSM-5, is the categorical expression of pathological impulsive aggression. Previous work has identified neurobiological correlates of the disorder in patterns of frontal-limbic brain activity and dysregulation of serotonergic neurotransmission. Given the importance of short- and-long range white matter connections of the brain in social and emotional behavior, studies of white matter connectivity in impulsive aggression are warranted. Diffusion tensor imaging (DTI) studies in the related conditions of antisocial and borderline personality disorder have produced preliminary evidence of disturbed white matter connectivity in these disorders, but to date there have been no DTI studies in IED. A total of 132 male and female adults between the ages of 18 and 55 years underwent Turboprop-DTI on a 3-Tesla MRI scanner. Of these, 42 subjects had IED, 40 were normal controls, and 50 were clinical psychiatric controls with psychiatric disorders without IED. All subjects were free of alcohol, psychotropic medications, or drugs of abuse. The diffusion tensor was calculated in each voxel and maps of fractional anisotropy (FA) were generated. Tract-based spatial statistics (TBSS) were used to compare FA along the white matter skeleton among the three subject groups. IED was associated with lower FA in two clusters located in the superior longitudinal fasciculus (SLF) when compared with the psychiatric and healthy controls. Impulsive aggression and borderline personality disorder, but not psychopathy or antisocial personality disorder, was associated with lower FA in the two clusters within the SLF. In conclusion, IED was associated with lower white matter integrity in long-range connections between the frontal and temporoparietal regions. PMID:27206265

  5. 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.

  6. EEG functional connectivity, axon delays and white matter disease

    PubMed Central

    Nunez, Paul L.; Srinivasan, Ramesh; Fields, R. Douglas

    2016-01-01

    Objective Both structural and functional brain connectivities are closely linked to white matter disease. We discuss several such links of potential interest to neurologists, neurosurgeons, radiologists, and non-clinical neuroscientists. Methods Treatment of brains as genuine complex systems suggests major emphasis on the multi-scale nature of brain connectivity and dynamic behavior. Cross-scale interactions of local, regional, and global networks are apparently responsible for much of EEG's oscillatory behaviors. Finite axon propagation speed, often assumed to be infinite in local network models, is central to our conceptual framework. Results Myelin controls axon speed, and the synchrony of impulse traffic between distant cortical regions appears to be critical for optimal mental performance and learning. Results Several experiments suggest that axon conduction speed is plastic, thereby altering the regional and global white matter connections that facilitate binding of remote local networks. Conclusions Combined EEG and high resolution EEG can provide distinct multi-scale estimates of functional connectivity in both healthy and diseased brains with measures like frequency and phase spectra, covariance, and coherence. Significance White matter disease may profoundly disrupt normal EEG coherence patterns, but currently these kinds of studies are rare in scientific labs and essentially missing from clinical environments. PMID:24815984

  7. Plasticity of white matter connectivity in phonetics experts.

    PubMed

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

    2016-09-01

    Phonetics experts are highly trained to analyze and transcribe speech, both with respect to faster changing, phonetic features, and to more slowly changing, prosodic features. Previously we reported that, compared to non-phoneticians, phoneticians had greater local brain volume in bilateral auditory cortices and the left pars opercularis of Broca's area, with training-related differences in the grey-matter volume of the left pars opercularis in the phoneticians group (Golestani et al. 2011). In the present study, we used diffusion MRI to examine white matter microstructure, indexed by fractional anisotropy, in (1) the long segment of arcuate fasciculus (AF_long), which is a well-known language tract that connects Broca's area, including left pars opercularis, to the temporal cortex, and in (2) the fibers arising from the auditory cortices. Most of these auditory fibers belong to three validated language tracts, namely to the AF_long, the posterior segment of the arcuate fasciculus and the middle longitudinal fasciculus. We found training-related differences in phoneticians in left AF_long, as well as group differences relative to non-experts in the auditory fibers (including the auditory fibers belonging to the left AF_long). Taken together, the results of both studies suggest that grey matter structural plasticity arising from phonetic transcription training in Broca's area is accompanied by changes to the white matter fibers connecting this very region to the temporal cortex. Our findings suggest expertise-related changes in white matter fibers connecting fronto-temporal functional hubs that are important for phonetic processing. Further studies can pursue this hypothesis by examining the dynamics of these expertise related grey and white matter changes as they arise during phonetic training. PMID:26386692

  8. Plasticity of white matter connectivity in phonetics experts.

    PubMed

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

    2016-09-01

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

  9. Developmental regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor subunit expression in forebrain and relationship to regional susceptibility to hypoxic/ischemic injury. I. Rodent cerebral white matter and cortex.

    PubMed

    Talos, Delia M; Fishman, Rachel E; Park, Hyunkyung; Folkerth, Rebecca D; Follett, Pamela L; Volpe, Joseph J; Jensen, Frances E

    2006-07-01

    This is the first part of a two-part study to investigate the cellular distribution and temporal regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) subunits in the developing white matter and cortex in rat (part I) and human (part II). Western blot and immunocytochemistry were used to evaluate the differential expression of AMPAR subunits on glial and neuronal subtypes during the first 3 postnatal weeks in the Long Evans and Sprague Dawley rat strains. In Long Evans rats during the first postnatal week, GluR2-lacking AMPARs were expressed predominantly on white matter cells, including radial glia, premyelinating oligodendrocytes, and subplate neurons, whereas, during the second postnatal week, these AMPARs were highly expressed on cortical neurons, coincident with decreased expression on white matter cells. Immunocytochemical analysis revealed that cell-specific developmental changes in AMPAR expression occurred 2-3 days earlier by chronological age in Sprague Dawley rats compared with Long Evans rats, despite overall similar temporal sequencing. In both white and gray matter, the periods of high GluR2 deficiency correspond to those of regional susceptibility to hypoxic/ischemic injury in each of the two rat strains, supporting prior studies suggesting a critical role for Ca2+-permeable AMPARs in excitotoxic cellular injury and epileptogenesis. The developmental regulation of these receptor subunits strongly suggests that Ca2+ influx through GluR2-lacking AMPARs may play an important role in neuronal and glial development and injury in the immature brain. Moreover, as demonstrated in part II, there are striking similarities between rat and human in the regional and temporal maturational regulation of neuronal and glial AMPAR expression.

  10. White matter connectivity and Internet gaming disorder.

    PubMed

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

    2016-05-01

    Internet use and on-line game play stimulate corticostriatal-limbic circuitry in both healthy subjects and subjects with Internet gaming disorder (IGD). We hypothesized that increased fractional anisotropy (FA) with decreased radial diffusivity (RD) would be observed in IGD subjects, compared with healthy control subjects, and that these white matter indices would be associated with clinical variables including duration of illness and executive function. We screened 181 male patients in order to recruit a large number (n = 58) of IGD subjects without psychiatric co-morbidity as well as 26 male healthy comparison subjects. Multiple diffusion-weighted images were acquired using a 3.0 Tesla magnetic resonance imaging scanner. Tract-based spatial statistics was applied to compare group differences in diffusion tensor imaging (DTI) metrics between IGD and healthy comparison subjects. IGD subjects had increased FA values within forceps minor, right anterior thalamic radiation, right corticospinal tract, right inferior longitudinal fasciculus, right cingulum to hippocampus and right inferior fronto-occipital fasciculus (IFOF) as well as parallel decreases in RD value within forceps minor, right anterior thalamic radiation and IFOF relative to healthy control subjects. In addition, the duration of illness in IGD subjects was positively correlated with the FA values (integrity of white matter fibers) and negatively correlated with RD scores (diffusivity of axonal density) of whole brain white matter. In IGD subjects without psychiatric co-morbidity, our DTI results suggest that increased myelination (increased FA and decreased RD values) in right-sided frontal fiber tracts may be the result of extended game play. PMID:25899390

  11. Aging in deep gray matter and white matter revealed by diffusional kurtosis imaging.

    PubMed

    Gong, Nan-Jie; Wong, Chun-Sing; Chan, Chun-Chung; Leung, Lam-Ming; Chu, Yiu-Ching

    2014-10-01

    Diffusion tensor imaging has already been extensively used to probe microstructural alterations in white matter tracts, and scarcely, in deep gray matter. However, results in literature regarding age-related degenerative mechanisms in white matter tracts and parametric changes in the putamen are inconsistent. Diffusional kurtosis imaging is a mathematical extension of diffusion tensor imaging, which could more comprehensively mirror microstructure, particularly in isotropic tissues such as gray matter. In this study, we used the diffusional kurtosis imaging method and a white-matter model that provided metrics of explicit neurobiological interpretations in healthy participants (58 in total, aged from 25 to 84 years). Tract-based whole-brain analyses and regions-of-interest (anterior and posterior limbs of the internal capsule, cerebral peduncle, fornix, genu and splenium of corpus callosum, globus pallidus, substantia nigra, red nucleus, putamen, caudate nucleus, and thalamus) analyses were performed to examine parametric differences across regions and correlations with age. In white matter tracts, evidence was found supportive for anterior-posterior gradient and not completely supportive for retrogenesis theory. Age-related degenerations appeared to be broadly driven by axonal loss. Demyelination may also be a major driving mechanism, although confined to the anterior brain. In terms of deep gray matter, higher mean kurtosis and fractional anisotropy in the globus pallidus, substantia nigra, and red nucleus reflected higher microstructural complexity and directionality compared with the putamen, caudate nucleus, and thalamus. In particular, the unique age-related positive correlations for fractional anisotropy, mean kurtosis, and radial kurtosis in the putamen opposite to those in other regions call for further investigation of exact underlying mechanisms. In summary, the results suggested that diffusional kurtosis can provide measurements in a new dimension that

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

    PubMed

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

    2012-08-01

    occurred in frontal lobe tracts crossing the genu of the corpus callosum-a region not generally included in current neural models of language processing. These results indicate that plasticity of white matter plays an important role in adult language learning and additionally demonstrate the potential of longitudinal diffusion tensor imaging as a new tool to yield insights into cognitive processes. PMID:22571459

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

    PubMed

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

    2012-08-01

    occurred in frontal lobe tracts crossing the genu of the corpus callosum-a region not generally included in current neural models of language processing. These results indicate that plasticity of white matter plays an important role in adult language learning and additionally demonstrate the potential of longitudinal diffusion tensor imaging as a new tool to yield insights into cognitive processes.

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

    PubMed

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

    2015-02-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

    Wilson's disease is a metabolic disorder which presents with hepatitis or hepatic decompensation commonly. Neurologic manifestations are late and include movement disorders, personality changes, and seizures. Magnetic resonance imaging (MRI) brain shows high signal changes in putamen, lentiform nucleus, thalamus, and brainstem. White matter lesions are rare. We report a child of Wilson's disease who presented to us with dystonia, rigidity, myoclonus and had symmetrical white matter changes in the fronto-parietooccipital region. Diffusion restriction in bilateral frontoparietal areas was also seen which is rare in chronic cases like ours. Atypical MRI characteristics should be considered in patients with clinical signs of neurological involvement in Wilson's disease as it is a devastating but treatable disease. PMID:27365966

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

    PubMed

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

    2016-01-01

    Wilson's disease is a metabolic disorder which presents with hepatitis or hepatic decompensation commonly. Neurologic manifestations are late and include movement disorders, personality changes, and seizures. Magnetic resonance imaging (MRI) brain shows high signal changes in putamen, lentiform nucleus, thalamus, and brainstem. White matter lesions are rare. We report a child of Wilson's disease who presented to us with dystonia, rigidity, myoclonus and had symmetrical white matter changes in the fronto-parietooccipital region. Diffusion restriction in bilateral frontoparietal areas was also seen which is rare in chronic cases like ours. Atypical MRI characteristics should be considered in patients with clinical signs of neurological involvement in Wilson's disease as it is a devastating but treatable disease. PMID:27365966

  18. 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

  19. 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

  20. 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

  1. 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.

  2. Understanding Neuronal Architecture in Obesity through Analysis of White Matter Connection Strength

    PubMed Central

    Riederer, Justin W.; Shott, Megan E.; Deguzman, Marisa; Pryor, Tamara L.; Frank, Guido K. W.

    2016-01-01

    Despite the prevalence of obesity, our understanding of its neurobiological underpinnings is insufficient. Diffusion weighted imaging and calculation of white matter connection strength are methods to describe the architecture of anatomical white matter tracts. This study is aimed to characterize white matter architecture within taste-reward circuitry in a population of obese individuals. Obese (n = 18, age = 28.7 ± 8.3 years) and healthy control (n = 24, age = 27.4 ± 6.3 years) women underwent diffusion weighted imaging. Using probabilistic fiber tractography (FSL PROBTRACKX2 toolbox) we calculated connection strength within 138 anatomical white matter tracts. Obese women (OB) displayed lower and greater connectivity within taste-reward circuitry compared to controls (Wilks’ λ < 0.001; p < 0.001). Connectivity was lower in white matter tracts connecting insula, amygdala, prefrontal cortex (PFC), orbitofrontal cortex (OFC) and striatum. Connectivity was greater between the amygdala and anterior cingulate cortex (ACC). This study indicates that lower white matter connectivity within white matter tracts of insula-fronto-striatal taste-reward circuitry are associated with obesity as well as greater connectivity within white matter tracts connecting the amygdala and ACC. The specificity of regions suggests sensory integration and reward processing are key associations that are altered in and might contribute to obesity. PMID:27375463

  3. Understanding Neuronal Architecture in Obesity through Analysis of White Matter Connection Strength.

    PubMed

    Riederer, Justin W; Shott, Megan E; Deguzman, Marisa; Pryor, Tamara L; Frank, Guido K W

    2016-01-01

    Despite the prevalence of obesity, our understanding of its neurobiological underpinnings is insufficient. Diffusion weighted imaging and calculation of white matter connection strength are methods to describe the architecture of anatomical white matter tracts. This study is aimed to characterize white matter architecture within taste-reward circuitry in a population of obese individuals. Obese (n = 18, age = 28.7 ± 8.3 years) and healthy control (n = 24, age = 27.4 ± 6.3 years) women underwent diffusion weighted imaging. Using probabilistic fiber tractography (FSL PROBTRACKX2 toolbox) we calculated connection strength within 138 anatomical white matter tracts. Obese women (OB) displayed lower and greater connectivity within taste-reward circuitry compared to controls (Wilks' λ < 0.001; p < 0.001). Connectivity was lower in white matter tracts connecting insula, amygdala, prefrontal cortex (PFC), orbitofrontal cortex (OFC) and striatum. Connectivity was greater between the amygdala and anterior cingulate cortex (ACC). This study indicates that lower white matter connectivity within white matter tracts of insula-fronto-striatal taste-reward circuitry are associated with obesity as well as greater connectivity within white matter tracts connecting the amygdala and ACC. The specificity of regions suggests sensory integration and reward processing are key associations that are altered in and might contribute to obesity.

  4. 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 T1 W 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

  5. 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.

  6. 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

  7. 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.

  8. Clinical correlates of MRI white matter abnormalities in schizophrenia.

    PubMed

    Hoptman, J Matthew

    2010-01-01

    Schizophrenia is a severe psychiatric illness that can be accompanied by positive symptoms, negative symptoms, and cognitive dysfunctions in most cognitive domains. Neuroimaging studies have focused on understanding the relationship between schizophrenia and brain abnormalities. Most of these have focused on the well-documented gray matter abnormalities. However, emphasis has recently been placed on white matter abnormalities associated with the disorder. A number of studies have found reduced white matter volumes in schizophrenia and abnormalities in genes associated with white matter. The clinical significance of these abnormalities is just beginning to be understood. The advent of diffusion tensor imaging (DTI) has been particularly important in this regard, as it allows us to draw inferences regarding the organization of white matter in the brain. In this article, I will review recent work showing clinical correlates of neuroimaging-based white matter abnormalities in schizophrenia.

  9. White matter microstructure mediates the relationship between cardiorespiratory fitness and spatial working memory in older adults.

    PubMed

    Oberlin, Lauren E; Verstynen, Timothy D; Burzynska, Agnieszka Z; Voss, Michelle W; Prakash, Ruchika Shaurya; Chaddock-Heyman, Laura; Wong, Chelsea; Fanning, Jason; Awick, Elizabeth; Gothe, Neha; Phillips, Siobhan M; Mailey, Emily; Ehlers, Diane; Olson, Erin; Wojcicki, Thomas; McAuley, Edward; Kramer, Arthur F; Erickson, Kirk I

    2016-05-01

    White matter structure declines with advancing age and has been associated with a decline in memory and executive processes in older adulthood. Yet, recent research suggests that higher physical activity and fitness levels may be associated with less white matter degeneration in late life, although the tract-specificity of this relationship is not well understood. In addition, these prior studies infrequently associate measures of white matter microstructure to cognitive outcomes, so the behavioral importance of higher levels of white matter microstructural organization with greater fitness levels remains a matter of speculation. Here we tested whether cardiorespiratory fitness (VO2max) levels were associated with white matter microstructure and whether this relationship constituted an indirect pathway between cardiorespiratory fitness and spatial working memory in two large, cognitively and neurologically healthy older adult samples. Diffusion tensor imaging was used to determine white matter microstructure in two separate groups: Experiment 1, N=113 (mean age=66.61) and Experiment 2, N=154 (mean age=65.66). Using a voxel-based regression approach, we found that higher VO2max was associated with higher fractional anisotropy (FA), a measure of white matter microstructure, in a diverse network of white matter tracts, including the anterior corona radiata, anterior internal capsule, fornix, cingulum, and corpus callosum (PFDR-corrected<.05). This effect was consistent across both samples even after controlling for age, gender, and education. Further, a statistical mediation analysis revealed that white matter microstructure within these regions, among others, constituted a significant indirect path between VO2max and spatial working memory performance. These results suggest that greater aerobic fitness levels are associated with higher levels of white matter microstructural organization, which may, in turn, preserve spatial memory performance in older adulthood.

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

    PubMed Central

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

    2015-01-01

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

  11. Developmental regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor subunit expression in forebrain and relationship to regional susceptibility to hypoxic/ischemic injury. II. Human cerebral white matter and cortex.

    PubMed

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

    2006-07-01

    This report is the second of a two-part evaluation of developmental differences in alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) subunit expression in cell populations within white matter and cortex. In part I, we reported 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. Similarly to the case in the rodent, there is a direct correlation between selective vulnerability to H/I and expression of GluR2-lacking AMPARs in human brain. For midgestational cases aged 20-24 postconceptional weeks (PCW) and for 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 postterm 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 nonpyramidal 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 to validate specific rodent maturational stages as appropriate models for evaluation of H/I pathophysiology.

  12. 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…

  13. 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…

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

    PubMed

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

    2016-06-01

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

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

    PubMed

    Takao, H; Hayashi, N; Ohtomo, K

    2013-02-12

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

  16. 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.

  17. Imaging of Cortical and White Matter Language Processing.

    PubMed

    Klein, Andrew P; Sabsevitz, David S; Ulmer, John L; Mark, Leighton P

    2015-06-01

    Although investigations into the functional and anatomical organization of language within the human brain began centuries ago, it is recent advanced imaging techniques including functional magnetic resonance imaging and diffusion tensor imaging that have helped propel our understanding forward at an unprecedented rate. Important cortical brain regions and white matter tracts in language processing subsystems including semantic, phonological, and orthographic functions have been identified. An understanding of functional and dysfunctional language anatomy is critical for practicing radiologists. This knowledge can be applied to routine neuroimaging examinations as well as to more advanced examinations such as presurgical brain mapping.

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2015-09-01

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

  20. Relationship between age and white matter integrity in children with phenylketonuria.

    PubMed

    Wesonga, Erika; Shimony, Joshua S; Rutlin, Jerrel; Grange, Dorothy K; White, Desiree A

    2016-06-01

    Diffusion tensor imaging (DTI) has shown poorer microstructural white matter integrity in children with phenylketonuria (PKU), specifically decreases in mean diffusivity (MD), in comparison with healthy children. However, little research has been conducted to investigate the relationship between age and white matter integrity in this population. The present study examined group differences in the relationship between age and MD across a range of brain regions in 31 children with early- and continuously-treated PKU and 51 healthy control children. Relationships among MD, age, and group were explored using hierarchical linear regression and Pearson correlation. Results indicated a stronger age-related decrease in MD for children with PKU in comparison with healthy children in 4 of the 10 brain regions examined, suggesting that the trajectory of white matter development is abnormal in children with PKU. Further research using longitudinal methodology is needed to fully elucidate our understanding of white matter development in children with PKU.

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

    PubMed

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

    2011-01-01

    Experts of abacus, who have the skills of abacus-based mental calculation (AMC), are able to manipulate numbers via an imagined abacus in mind and demonstrate extraordinary ability in mental calculation. Behavioral studies indicated that abacus experts utilize visual strategy in solving numerical problems, and fMRI studies confirmed the enhanced involvement of visuospatial-related neural resources in AMC. This study aims to explore the possible changes in brain white matter induced by long-term training of AMC. Two matched groups participated: the abacus group consisting of 25 children with over 3-year training in abacus calculation and AMC, the controls including 25 children without any abacus experience. We found that the abacus group showed higher average fractional anisotropy (FA) in whole-brain fiber tracts, and the regions with increased FA were found in corpus callosum, left occipitotemporal junction and right premotor projection. No regions, however, showed decreased FA in the abacus group. Further analysis revealed that the differences in FA values were mainly driven by the alternation of radial rather than axial diffusivities. Furthermore, in forward digit and letter memory span tests, AMC group showed larger digit/letter memory spans. Interestingly, individual differences in white matter tracts were found positively correlated with the memory spans, indicating that the widespread increase of FA in the abacus group result possibly from the AMC training. In conclusion, our findings suggested that long-term AMC training from an early age may improve the memory capacity and enhance the integrity in white matter tracts related to motor and visuospatial processes. PMID:20235096

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

    PubMed

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

    2011-01-01

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

  3. 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

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

    PubMed

    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.

  5. [Volumetry of cerebral gray and white matter using VSRAD®].

    PubMed

    Matsuda, Hiroshi

    2015-04-01

    Voxel-based morphometry (VBM) using structural brain MRI has been widely used for the early and differential diagnosis and evaluation of disease progression in neuropsychiatric diseases. VBM of MRI data comprises segmentation into gray matter, white matter, and cerebrospinal fluid partitions; anatomical standardization of all the images to the same stereotactic space using linear affine transformation and further non-linear warping and smoothing; and finally performing statistical analysis. Stand-alone VBM software using SPM8 plus DARTEL running on Windows (Voxel-based Specific Regional analysis system for Alzheimer's disease, VSRAD®) has been developed as an adjunct to the clinical assessment. This software provides a Z-score map as a result of the comparison of the patient's MRI with a normal database.

  6. 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

  7. Altered Superficial White Matter on Tractography MRI in Alzheimer's Disease

    PubMed Central

    Reginold, William; Luedke, Angela C.; Itorralba, Justine; Fernandez-Ruiz, Juan; Islam, Omar; Garcia, Angeles

    2016-01-01

    Background/Aims Superficial white matter provides extensive cortico-cortical connections. This tractography study aimed to assess the diffusion characteristics of superficial white matter tracts in Alzheimer's disease. Methods Diffusion tensor 3T magnetic resonance imaging scans were acquired in 24 controls and 16 participants with Alzheimer's disease. Neuropsychological test scores were available in some participants. Tractography was performed by the Fiber Assignment by Continuous Tracking (FACT) method. The superficial white matter was manually segmented and divided into frontal, parietal, temporal and occipital lobes. The mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AxD) and fractional anisotropy (FA) of these tracts were compared between controls and participants with Alzheimer's disease and correlated with available cognitive tests while adjusting for age and white matter hyperintensity volume. Results Alzheimer's disease was associated with increased MD (p = 0.0011), increased RD (p = 0.0019) and increased AxD (p = 0.0017) in temporal superficial white matter. In controls, superficial white matter was associated with the performance on the Montreal Cognitive Assessment, Stroop and Trail Making Test B tests, whereas in Alzheimer's disease patients, it was not associated with the performance on cognitive tests. Conclusion Temporal lobe superficial white matter appears to be disrupted in Alzheimer's disease. PMID:27489557

  8. Tryptophan Metabolism and White Matter Integrity in Schizophrenia.

    PubMed

    Chiappelli, Joshua; Postolache, Teodor T; Kochunov, Peter; Rowland, Laura M; Wijtenburg, S Andrea; Shukla, Dinesh K; Tagamets, Malle; Du, Xiaoming; Savransky, Anya; Lowry, Christopher A; Can, Adem; Fuchs, Dietmar; Hong, L Elliot

    2016-09-01

    Schizophrenia is associated with abnormalities in the structure and functioning of white matter, but the underlying neuropathology is unclear. We hypothesized that increased tryptophan degradation in the kynurenine pathway could be associated with white matter microstructure and biochemistry, potentially contributing to white matter abnormalities in schizophrenia. To test this, fasting plasma samples were obtained from 37 schizophrenia patients and 38 healthy controls and levels of total tryptophan and its metabolite kynurenine were assessed. The ratio of kynurenine to tryptophan was used as an index of tryptophan catabolic activity in this pathway. White matter structure and function were assessed by diffusion tensor imaging (DTI) and (1)H magnetic resonance spectroscopy (MRS). Tryptophan levels were significantly lower (p<0.001), and kynurenine/tryptophan ratios were correspondingly higher (p=0.018) in patients compared with controls. In patients, lower plasma tryptophan levels corresponded to lower structural integrity (DTI fractional anisotropy) (r=0.347, p=0.038). In both patients and controls, the kynurenine/tryptophan ratio was inversely correlated with frontal white matter glutamate level (r=-0.391 and -0.350 respectively, p=0.024 and 0.036). These results provide initial evidence implicating abnormal tryptophan/kynurenine pathway activity in changes to white matter integrity and white matter glutamate in schizophrenia.

  9. Molecular Probes for Imaging Myelinated White Matter in CNS

    PubMed Central

    Wu, Chunying; Wei, Jinjun; Tian, Donghua; Feng, Yue; Miller, Robert H.; Wang, Yanming

    2009-01-01

    Abnormalities and changes in myelination in the brain are seen in many neurodegenerative disorders such as multiple sclerosis (MS). Direct detection and quantification of myelin content in vivo is desired to facilitate diagnosis and therapeutic treatments of myelin-related diseases. The imaging studies require use of myelin-imaging agents that readily enter the brain and selectively bind to myelinated regions. For this purpose, we have systematically evaluated a series of stilbene derivatives as myelin imaging agents. Spectrophotometry-based and radioligand-based binding assays showed that these stilbene derivatives exhibited relatively high myelin-binding affinities. In vitro myelin staining exhibited that the compounds selectively stained intact myelinated regions in wild type mouse brain. In situ tissue staining demonstrated that the compounds readily entered the mouse brain and selectively labeled myelinated white matter regions. These studies suggested that these stilbene derivatives can be used as myelin-imaging probes to monitor myelin pathology in vivo. PMID:18844339

  10. Heterogeneity in age-related white matter changes.

    PubMed

    Schmidt, Reinhold; Schmidt, Helena; Haybaeck, Johannes; Loitfelder, Marisa; Weis, Serge; Cavalieri, Margherita; Seiler, Stephan; Enzinger, Christian; Ropele, Stefan; Erkinjuntti, Timo; Pantoni, Leonardo; Scheltens, Philip; Fazekas, Franz; Jellinger, Kurt

    2011-08-01

    White matter changes occur endemically in routine magnetic resonance imaging (MRI) scans of elderly persons. MRI appearance and histopathological correlates of white matter changes are heterogeneous. Smooth periventricular hyperintensities, including caps around the ventricular horns, periventricular lining and halos are likely to be of non-vascular origin. They relate to a disruption of the ependymal lining with subependymal widening of the extracellular space and have to be differentiated from subcortical and deep white matter abnormalities. For the latter a distinction needs to be made between punctate, early confluent and confluent types. Although punctate white matter lesions often represent widened perivascular spaces without substantial ischemic tissue damage, early confluent and confluent lesions correspond to incomplete ischemic destruction. Punctate abnormalities on MRI show a low tendency for progression, while early confluent and confluent changes progress rapidly. The causative and modifying pathways involved in the occurrence of sporadic age-related white matter changes are still incompletely understood, but recent microarray and genome-wide association approaches increased the notion of pathways that might be considered as targets for therapeutic intervention. The majority of differentially regulated transcripts in white matter lesions encode genes associated with immune function, cell cycle, proteolysis, and ion transport. Genome-wide association studies identified six SNPs mapping to a locus on chromosome 17q25 to be related to white matter lesion load in the general population. We also report first and preliminary data that demonstrate apolipoprotein E (ApoE) immunoreactivity in white matter lesions and support epidemiological findings indicating that ApoE is another factor possibly related to white matter lesion occurrence. Further insights come from modern MRI techniques, such as diffusion tensor and magnetization transfer imaging, as they

  11. 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.

  12. 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

  13. 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

  14. 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

  15. Cortical Gray and Adjacent White Matter Demonstrate Synchronous Maturation in Very Preterm Infants.

    PubMed

    Smyser, Tara A; Smyser, Christopher D; Rogers, Cynthia E; Gillespie, Sarah K; Inder, Terrie E; Neil, Jeffrey J

    2016-08-01

    Spatial and functional gradients of development have been described for the maturation of cerebral gray and white matter using histological and radiological approaches. We evaluated these patterns in very preterm (VPT) infants using diffusion tensor imaging. Data were obtained from 3 groups: 1) 22 VPT infants without white matter injury (WMI), of whom all had serial MRI studies during the neonatal period, 2) 19 VPT infants with WMI, of whom 3 had serial MRI studies and 3) 12 healthy, term-born infants. Regions of interest were placed in the cortical gray and adjacent white matter in primary motor, primary visual, visual association, and prefrontal regions. From the MRI data at term-equivalent postmenstrual age, differences in mean diffusivity were found in all areas between VPT infants with WMI and the other 2 groups. In contrast, minimal differences in fractional anisotropy were found between the 3 groups. These findings suggest that cortical maturation is delayed in VPT infants with WMI when compared with term control infants and VPT infants without WMI. From the serial MRI data from VPT infants, synchronous development between gray and white matter was evident in all areas and all groups, with maturation in primary motor and sensory regions preceding that of association areas. This finding highlights the regionally varying but locally synchronous nature of the development of cortical gray matter and its adjacent white matter.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-01-01

    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.

  18. 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

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

    PubMed

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

    2013-02-01

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

  20. White matter integrity associated with volitional motor activity.

    PubMed

    Walther, Sebastian; Federspiel, Andrea; Horn, Helge; Wiest, Roland; Dierks, Thomas; Strik, Werner; Müller, Thomas J

    2010-03-31

    Variations of white matter integrity have been associated with interindividual differences in brain function. Still, little is known about the impact of white matter integrity on quantitative motor behaviour. Diffusion tensor imaging and continuous wrist actigraphy were measured on the same day in 12 individuals. Fractional anisotropy as measure of white matter integrity was correlated with the motor activity level. Positive correlations of fractional anisotropy and activity level were detected in the cingulum and the right superior longitudinal fasciculus underneath the precentral gyrus. Negative correlations were found in the left corticobulbar tract, in the right posterior corpus callosum and in the left superior longitudinal fasciculus. Volitional motor activity was associated with white matter integrity in motor relevant fiber tracts.

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

    PubMed

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

    2009-06-15

    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 subcortical 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. Diffusion Tensor Imaging for Assessing Brain Gray and White Matter Abnormalities in a Feline Model of α-Mannosidosis.

    PubMed

    Kumar, Manoj; Duda, Jeff T; Yoon, Sea Young; Bagel, Jessica; O'Donnell, Patricia; Vite, Charles; Pickup, Stephen; Gee, James C; Wolfe, John H; Poptani, Harish

    2016-01-01

    α-Mannosidosis (AMD) is an autosomal recessively inherited lysosomal storage disorder affecting brain function and structure. We performed ex vivo and in vivo diffusion tensor imaging (DTI) on the brains of AMD-affected cats to assess gray and white matter abnormalities. A multi-atlas approach was used to generate a brain template to process the ex vivo DTI data. The probabilistic label method was used to measure fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity values from gray and white matter regions from ex vivo DTI. Regional analysis from various regions of the gray matter (frontal cortex, cingulate gyrus, caudate nucleus, hippocampus, thalamus, and occipital cortex), and white matter (corpus callosum, corticospinal tract, cerebral peduncle, external and internal capsule) was also performed on both ex vivo and in vivo DTI. Ex vivo DTI revealed significantly reduced FA from both gray and white matter regions in AMD-affected cats compared to controls. Significantly reduced FA was also observed from in vivo DTI of AMD-affected cats compared to controls, with lower FA values observed in all white matter regions. We also observed significantly increased axial and radial diffusivity values in various gray and white matter regions in AMD cats from both ex vivo and in vivo DTI data. Imaging findings were correlated with histopathologic analyses suggesting that DTI studies can further aid in the characterization of AMD by assessing the microstructural abnormalities in both white and gray matter.

  3. 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.

  4. Cardiorespiratory fitness and white matter integrity in Alzheimer's disease.

    PubMed

    Perea, R D; Vidoni, E D; Morris, J K; Graves, R S; Burns, J M; Honea, R A

    2016-09-01

    The objective of this study was to investigate the relationship between cardiorespiratory (CR) fitness and the brain's white matter tract integrity using diffusion tensor imaging (DTI) in the Alzheimer's disease (AD) population. We recruited older adults in the early stages of AD (n = 37; CDR = 0.5 and 1) and collected cross-sectional fitness and diffusion imaging data. We examined the association between CR fitness (peak oxygen consumption [VO2peak]) and fractional anisotropy (FA) in AD-related white matter tracts using two processing methodologies: a tract-of-interest approach and tract-based spatial statistic (TBSS). Subsequent diffusivity metrics (radial diffusivity [RD], mean diffusivity [MD], and axial diffusivity [A × D]) were also correlated with VO2peak. The tract-of-interest approach showed that higher VO2peak was associated with preserved white matter integrity as measured by increased FA in the right inferior fronto-occipital fasciculus (p = 0.035, r = 0.36). We did not find a significant correlation using TBSS, though there was a trend for a positive association between white matter integrity and higher VO2peak measures (p < 0.01 uncorrected). Our findings indicate that higher CR fitness levels in early AD participants may be related to preserved white matter integrity. However to draw stronger conclusions, further study on the relationship between fitness and white matter deterioration in AD is necessary.

  5. 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...

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

    PubMed Central

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

    2015-01-01

    The mammalian brain is composed of an outer layer of gray matter, consisting of cell bodies, dendrites, and unmyelinated axons, and an inner core of white matter, consisting primarily of myelinated axons. Recent evidence suggests that microstructural differences between gray and white matter play an important role during neurodevelopment. While brain tissue as a whole is rheologically well characterized, the individual features of gray and white matter remain poorly understood. Here we quantify the mechanical properties of gray and white matter using a robust, reliable, and repeatable method, flat-punch indentation. To systematically characterize gray and white matter moduli for varying indenter diameters, loading rates, holding times, post-mortem times, and locations we performed a series of n=192 indentation tests. We found that indenting thick, intact coronal slices eliminates the common challenges associated with small specimens: it naturally minimizes boundary effects, dehydration, swelling, and structural degradation. When kept intact and hydrated, brain slices maintained their mechanical characteristics with standard deviations as low as 5% throughout the entire testing period of five days post mortem. White matter, with an average modulus of 1.895kPa±0.592kPa, was on average 39% stiffer than gray matter, p<0.01, with an average modulus of 1.389kPa±0.289kPa, and displayed larger regional variations. It was also more viscous than gray matter and responded less rapidly to mechanical loading. Understanding the rheological differences between gray and white matter may have direct implications on diagnosing and understanding the mechanical environment in neurodevelopment and neurological disorders. PMID:25819199

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

    PubMed

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

    2015-06-01

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

  8. 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: 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

  9. 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.

  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. 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

  12. 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

  13. Military blast exposure, ageing and white matter integrity

    PubMed Central

    Trotter, Benjamin B.; Robinson, Meghan E.; Milberg, William P.; McGlinchey, Regina E.

    2015-01-01

    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

  14. 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

  15. 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

  16. 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.

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

    PubMed

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

    2016-08-30

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

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

    PubMed

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

    2016-08-30

    Several authors have proposed that schizophrenia is the result of impaired connectivity between specific brain regions rather than differences in local brain activity. White matter abnormalities have been suggested as the anatomical substrate for this dysconnectivity hypothesis. Information processing speed may act as a key cognitive resource facilitating higher order cognition by allowing multiple cognitive processes to be simultaneously available. However, there is a lack of established associations between these variables in schizophrenia. We hypothesised that the relationship between white matter and general intelligence would be mediated by processing speed. White matter water diffusion parameters were studied using Tract-based Spatial Statistics and computed within 46 regions-of-interest (ROI). Principal component analysis was conducted on these white matter ROI for fractional anisotropy (FA) and mean diffusivity, and on neurocognitive subtests to extract general factors of white mater structure (gFA, gMD), general intelligence (g) and processing speed (gspeed). There was a positive correlation between g and gFA (r= 0.67, p =0.001) that was partially and significantly mediated by gspeed (56.22% CI: 0.10-0.62). These findings suggest a plausible model of structure-function relations in schizophrenia, whereby white matter structure may provide a neuroanatomical substrate for general intelligence, which is partly supported by speed of information processing. PMID:27308721

  19. White and gray matter contributions to executive function recovery after traumatic brain injury

    PubMed Central

    Zhong, Wanting; Chau, Aileen; Solomon, Jeffrey; Krueger, Frank; Grafman, Jordan

    2015-01-01

    Objective: We investigated the association between regional white and gray matter volume loss and performance on executive functions (EFs) in patients with penetrating traumatic brain injury (pTBI). Methods: We studied 164 pTBI patients and 43 healthy controls from the Vietnam Head Injury Study. We acquired CT scans for pTBI patients and divided them according to lesion localization (left and right prefrontal cortex [PFC]). We administered EF tests (Verbal Fluency, Trail Making, Twenty Questions) and used voxel-based lesion symptom mapping (VLSM) and group-based correlational and multiple regression analyses to examine the relative influence of gray and white matter lesions on EF recovery. Results: The VLSM analysis revealed that white and gray white matter lesions were associated with impaired EFs. In the left PFC lesion group, damage to the PFC gray matter, anterior corona radiata, and superior longitudinal fasciculus (SLF) were most correlated with functional recovery. Verbal Fluency, which involves a broad fronto-temporo-parietal network, was best predicted by SLF lesion volume. Trail Making and Twenty Questions, which is associated with more focal left frontal damage, was better predicted by PFC lesions. Conclusions: Our results indicated that white matter volume loss can be a superior predictor of recovery and a crucial factor driving clinical outcome in functions involving a broad network such as Verbal Fluency. White matter damage may place additional burden on recovery by deteriorating signal transmission between cortical areas within a functional network. PMID:25746558

  20. White Matter Abnormalities in Patients with Treatment-Resistant Genetic Generalized Epilepsies.

    PubMed

    Szaflarski, Jerzy P; Lee, Seongtaek; Allendorfer, Jane B; Gaston, Tyler E; Knowlton, Robert C; Pati, Sandipan; Ver Hoef, Lawrence W; Deutsch, Georg

    2016-06-10

    BACKGROUND Genetic generalized epilepsies (GGEs) are associated with microstructural brain abnormalities that can be evaluated with diffusion tensor imaging (DTI). Available studies on GGEs have conflicting results. Our primary goal was to compare the white matter structure in a cohort of patients with video/EEG-confirmed GGEs to healthy controls (HCs). Our secondary goal was to assess the potential effect of age at GGE onset on the white matter structure. MATERIAL AND METHODS A convenience sample of 23 patients with well-characterized treatment-resistant GGEs (13 female) was compared to 23 HCs. All participants received MRI at 3T. DTI indices, including fractional anisotropy (FA) and mean diffusivity (MD), were compared between groups using Tract-Based Spatial Statistics (TBSS). RESULTS After controlling for differences between groups, abnormalities in DTI parameters were observed in patients with GGEs, including decreases in functional anisotropy (FA) in the hemispheric (left>right) and brain stem white matter. The examination of the effect of age at GGE onset on the white matter integrity revealed a significant negative correlation in the left parietal white matter region FA (R=-0.504; p=0.017); similar trends were observed in the white matter underlying left motor cortex (R=-0.357; p=0.103) and left posterior limb of the internal capsule (R=-0.319; p=0.148). CONCLUSIONS Our study confirms the presence of widespread white matter abnormalities in patients with GGEs and provides evidence that the age at GGE onset may have an important effect on white matter integrity.

  1. White Matter Abnormalities in Patients with Treatment-Resistant Genetic Generalized Epilepsies

    PubMed Central

    Szaflarski, Jerzy P.; Lee, Seongtaek; Allendorfer, Jane B.; Gaston, Tyler E.; Knowlton, Robert C.; Pati, Sandipan; Ver Hoef, Lawrence W.; Deutsch, Georg

    2016-01-01

    Background Genetic generalized epilepsies (GGEs) are associated with microstructural brain abnormalities that can be evaluated with diffusion tensor imaging (DTI). Available studies on GGEs have conflicting results. Our primary goal was to compare the white matter structure in a cohort of patients with video/EEG-confirmed GGEs to healthy controls (HCs). Our secondary goal was to assess the potential effect of age at GGE onset on the white matter structure. Material/Methods A convenience sample of 23 patients with well-characterized treatment-resistant GGEs (13 female) was compared to 23 HCs. All participants received MRI at 3T. DTI indices, including fractional anisotropy (FA) and mean diffusivity (MD), were compared between groups using Tract-Based Spatial Statistics (TBSS). Results After controlling for differences between groups, abnormalities in DTI parameters were observed in patients with GGEs, including decreases in functional anisotropy (FA) in the hemispheric (left>right) and brain stem white matter. The examination of the effect of age at GGE onset on the white matter integrity revealed a significant negative correlation in the left parietal white matter region FA (R=−0.504; p=0.017); similar trends were observed in the white matter underlying left motor cortex (R=−0.357; p=0.103) and left posterior limb of the internal capsule (R=−0.319; p=0.148). Conclusions Our study confirms the presence of widespread white matter abnormalities in patients with GGEs and provides evidence that the age at GGE onset may have an important effect on white matter integrity. PMID:27283395

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

    PubMed Central

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

    2012-01-01

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

  3. Alterations in white matter volume and integrity in obesity and type 2 diabetes.

    PubMed

    van Bloemendaal, Liselotte; Ijzerman, Richard G; Ten Kulve, Jennifer S; Barkhof, Frederik; Diamant, Michaela; Veltman, Dick J; van Duinkerken, Eelco

    2016-06-01

    Type 2 diabetes mellitus (T2DM) is characterized by obesity, hyperglycemia and insulin resistance. Both T2DM and obesity are associated with cerebral complications, including an increased risk of cognitive impairment and dementia, however the underlying mechanisms are largely unknown. In the current study, we aimed to determine the relative contributions of obesity and the presence of T2DM to altered white matter structure. We used diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) to measure white matter integrity and volume in obese T2DM patients without micro- or macrovascular complications, age- gender- and BMI-matched normoglycemic obese subjects and age- and gender-matched normoglycemic lean subjects. We found that obese T2DM patients compared with lean subjects had lower axial diffusivity (in the right corticospinal tract, right inferior fronto-occipital tract, right superior longitudinal fasciculus and right forceps major) and reduced white matter volume (in the right inferior parietal lobe and the left external capsule region). In normoglycemic obese compared with lean subjects axial diffusivity as well as white matter volume tended to be reduced, whereas there were no significant differences between normoglycemic obese subjects and T2DM patients. Decreased white matter integrity and volume were univariately related to higher age, being male, higher BMI, HbA1C and fasting glucose and insulin levels. However, multivariate analyses demonstrated that only BMI was independently related to white matter integrity, and age, gender and BMI to white matter volume loss. Our data indicate that obese T2DM patients have reduced white matter integrity and volume, but that this is largely explained by BMI, rather than T2DM per se.

  4. Fusion of white and gray matter geometry: a framework for investigating brain development.

    PubMed

    Savadjiev, Peter; Rathi, Yogesh; Bouix, Sylvain; Smith, Alex R; Schultz, Robert T; Verma, Ragini; Westin, Carl-Fredrik

    2014-12-01

    Current neuroimaging investigation of the white matter typically focuses on measurements derived from diffusion tensor imaging, such as fractional anisotropy (FA). In contrast, imaging studies of the gray matter oftentimes focus on morphological features such as cortical thickness, folding and surface curvature. As a result, it is not clear how to combine findings from these two types of approaches in order to obtain a consistent picture of morphological changes in both gray and white matter. In this paper, we propose a joint investigation of gray and white matter morphology by combining geometrical information from white and the gray matter. To achieve this, we first introduce a novel method for computing multi-scale white matter tract geometry. Its formulation is based on the differential geometry of curve sets and is easily incorporated into a continuous scale-space framework. We then incorporate this method into a novel framework for "fusing" white and gray matter geometrical information. Given a set of fiber tracts originating in a particular cortical region, the key idea is to compute two scalar fields that represent geometrical characteristics of the white matter and of the surface of the cortical region. A quantitative marker is created by combining the distributions of these scalar values using Mutual Information. This marker can be then used in the study of normal and pathological brain structure and development. We apply this framework to a study on autism spectrum disorder in children. Our preliminary results support the view that autism may be characterized by early brain overgrowth, followed by reduced or arrested growth (Courchesne, 2004).

  5. Cardiorespiratory fitness and brain volume and white matter integrity

    PubMed Central

    Zhu, Na; Schreiner, Pamela J.; Launer, Lenore J.; Whitmer, Rachel A.; Sidney, Stephen; Demerath, Ellen; Thomas, William; Bouchard, Claude; He, Ka; Erus, Guray; Battapady, Harsha; Bryan, R. Nick

    2015-01-01

    Objective: We hypothesized that greater cardiorespiratory fitness is associated with lower odds of having unfavorable brain MRI findings. Methods: We studied 565 healthy, middle-aged, black and white men and women in the CARDIA (Coronary Artery Risk Development in Young Adults) Study. The fitness measure was symptom-limited maximal treadmill test duration (Maxdur); brain MRI was measured 5 years later. Brain MRI measures were analyzed as means and as proportions below the 15th percentile (above the 85th percentile for white matter abnormal tissue volume). Results: Per 1-minute-higher Maxdur, the odds ratio for having less whole brain volume was 0.85 (p = 0.04) and for having low white matter integrity was 0.80 (p = 0.02), adjusted for age, race, sex, clinic, body mass index, smoking, alcohol, diet, physical activity, education, blood pressure, diabetes, total cholesterol, and lung function (plus intracranial volume for white matter integrity). No significant associations were observed between Maxdur and abnormal tissue volume or blood flow in white matter. Findings were similar for associations with continuous brain MRI measures. Conclusions: Greater physical fitness was associated with more brain volume and greater white matter integrity measured 5 years later in middle-aged adults. PMID:25957331

  6. 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

  7. Prolonged Cortisol Reactivity to Stress and White Matter in Schizophrenia

    PubMed Central

    Nugent, Katie L.; Chiappelli, Joshua; Sampath, Hemalatha; Rowland, Laura M.; Thangavelu, Kavita; Davis, Beshaun; Du, Xiaoming; Muellerklein, Florian; Daughters, Stacey; Kochunov, Peter; Hong, L. Elliot

    2015-01-01

    Objective While acute hypothalamic-pituitary-adrenal axis response to stress is often adaptive, prolonged responses may have detrimental effects. Many components of white matter structures are sensitive to prolonged cortisol exposure. We aimed to identify a behavioral laboratory assay for which cortisol response related to brain pathophysiology in schizophrenia. We hypothesized that an abnormally prolonged cortisol response to stress may be linked to abnormal white matter integrity in patients with schizophrenia. Methods Acute and prolonged salivary cortisol response was measured outside the scanner at pre-test and then at 0, 20, and 40 minutes after a psychological stress task in patients with schizophrenia (n=45) and controls (n=53). Tract-averaged white matter was measured by 64-direction diffusion tensor imaging in a subset of patients (n=30) and controls (n=33). Results Patients who did not tolerate and quit the psychological stress task had greater acute (t=2.52, p=0.016; t=3.51, p=0.001 at zero and 20 minutes) and prolonged (t=3.62, p=0.001 at 40 minutes) cortisol reactivity compared with patients who finished the task. Abnormally prolonged cortisol reactivity in patients was significantly associated with reduced white matter integrity (r=−0.468, p=0.009). Regardless of task completion status, acute cortisol response was not related to the white matter measures in patients or controls. Conclusions This paradigm was successful at identifying a subset of patients whose cortisol response was associated with brain pathophysiology. Abnormal cortisol response may adversely affect white matter integrity, partly explaining this pathology observed in schizophrenia. Prolonged stress responses may be targeted for intervention to test for protective effects against white matter damages. PMID:26186431

  8. Clinical characteristics of children with cerebral white matter abnormalities.

    PubMed

    Kristjánsdóttir, R; Uvebrant, P; Wiklund, L M

    2000-01-01

    The rapidly expanding use of magnetic resonance imaging (MRI) in children with neurological impairments of unknown aetiology has revealed a large number of children with abnormalities of the cerebral white matter, some with leukodystrophy-like white matter abnormalities on MRI, but non-progressive in clinical presentation and course. The aim of this study was to investigate the clinical and neuroradiological characteristics of 26 children with white matter abnormalities of unknown origin and to find diagnostic clues or indicators of progressive versus nonprogressive disease. The typical child with white matter abnormalities was characterized by onset of symptoms within the first year of life, most often presenting as general developmental delay and hypotonia. Later-appearing signs were spasticity and ataxia and as a rule severe learning and motor disabilities. Serious ophthalmological signs were frequently seen. Perinatal adverse events were rare, infectious aetiologies not indicated but prenatal stigmata relatively common. The clinical course was progressive in 11 children and non-progressive in 15. Late onset presentation was associated with a progressive course whereas prenatal stigmata and asymmetrical white matter lesions only were found in children with a non-progressive disorder. The MRI showed three main patterns: a) a generalized increase of the T2 signal of the white matter in 12 children, b) a bilateral, symmetric but not generalized abnormality in nine and c) asymmetric, focal or multifocal pathology in five. Useful information as to clinical entities and course was obtained from the combined clinical and radiological assessment. A precise nosological diagnosis could be made in six cases. The study showed that white matter abnormalities in children constitute a heterogeneous group of rare and 'anonymous' conditions, motivating collaborative studies for further clarification of background and management. PMID:10701100

  9. 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

  10. Neuroblast Distribution after Cortical Impact Is Influenced by White Matter Injury in the Immature Gyrencephalic Brain

    PubMed Central

    Taylor, Sabrina R.; Smith, Colin M.; Keeley, Kristen L.; McGuone, Declan; Dodge, Carter P.; Duhaime, Ann-Christine; Costine, Beth A.

    2016-01-01

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

  11. Neuroblast Distribution after Cortical Impact Is Influenced by White Matter Injury in the Immature Gyrencephalic Brain

    PubMed Central

    Taylor, Sabrina R.; Smith, Colin M.; Keeley, Kristen L.; McGuone, Declan; Dodge, Carter P.; Duhaime, Ann-Christine; Costine, Beth A.

    2016-01-01

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

  12. Neuroblast Distribution after Cortical Impact Is Influenced by White Matter Injury in the Immature Gyrencephalic Brain.

    PubMed

    Taylor, Sabrina R; Smith, Colin M; Keeley, Kristen L; McGuone, Declan; Dodge, Carter P; Duhaime, Ann-Christine; Costine, Beth A

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

    Subcortical white matter builds neural connections between cortical and subcortical regions and constitutes the basis of neural networks. It plays a very important role in normal brain function. Various studies have shown that white matter deteriorates with aging. However, due to the limited spatial resolution provided by traditional diffusion imaging techniques, microstructural information from subcortical white matter with normal aging has not been comprehensively assessed. This study aims to investigate the deterioration effect with aging in the subcortical white matter and provide a baseline standard for pathological disorder diagnosis. We apply our newly developed multi-shot high resolution diffusion tensor imaging, using self-feeding multiplexed sensitivity-encoding, to measure subcortical white matter changes in regions of interest of healthy persons with a wide age range. Results show significant fractional anisotropy decline and radial diffusivity increasing with age, especially in the anterior part of the brain. We also find that subcortical white matter has more prominent changes than white matter close to the central brain. The observed changes in the subcortical white matter may be indicative of a mild demyelination and a loss of myelinated axons, which may contribute to normal age-related functional decline. PMID:27332713

  15. 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

  16. White matter lateralization and interhemispheric coherence to auditory modulations in normal reading and dyslexic adults.

    PubMed

    Vandermosten, Maaike; Poelmans, Hanne; Sunaert, Stefan; Ghesquière, Pol; Wouters, Jan

    2013-09-01

    Neural activation of slow acoustic variations that are important for syllable identification is more lateralized to the right hemisphere than activation of fast acoustic changes that are important for phoneme identification. It has been suggested that this complementary function at different hemispheres is rooted in a different degree of white matter myelination in the left versus right hemisphere. The present study will investigate this structure-function relationship with Diffusion Tensor Imaging (DTI) and Auditory Steady-State Responses (ASSR), respectively. With DTI we examined white matter lateralization in the cortical auditory and language regions (i.e. posterior region of the superior temporal gyrus and the arcuate fasciculus) and white matter integrity in the splenium of the corpus callosum. With ASSR we examined interhemispheric coherence to slow, syllabic-rate (i.e. 4 Hz) and fast, phonemic-rate (i.e. 20 Hz) modulations. These structural and functional techniques were applied in a group of normal reading adults and a group of dyslexic adults for whom previously reduced functional interhemispheric connectivity at 20 Hz has been reported (Poelmans et al. (2012). Ear and Hearing, 33, 134-143). This sample was chosen since it is hypothesized that in dyslexic readers insufficient hemispheric asymmetry in myelination might relate to their auditory and phonological problems. Results demonstrate reduced white matter lateralization in the posterior superior temporal gyrus and the arcuate fasciculus in the dyslexic readers. Additionally, white matter lateralization in the posterior superior temporal gyrus and white matter integrity in the splenium of the corpus callosum related to interhemispheric coherence to phonemic-rate modulations (i.e. 20 Hz). Interestingly, this correlation pattern was opposite in normal versus dyslexic readers. These results might imply that less pronounced left white matter dominance in dyslexic adults might relate to their problems to

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

    PubMed

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

    2015-02-28

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

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

    PubMed

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

    2015-02-28

    Grey matter volume and cortical thickness are the two most widely used measures for detecting grey matter morphometric changes in various diseases such as schizophrenia. However, these two measures only share partial overlapping regions in identifying morphometric changes. Few studies have investigated the contributions of the potential factors to the differences of grey matter volume and cortical thickness. To investigate this question, 3T magnetic resonance images from 22 patients with schizophrenia and 20 well-matched healthy controls were chosen for analyses. Grey matter volume and cortical thickness were measured by VBM and Freesurfer. Grey matter volume results were then rendered onto the surface template of Freesurfer to compare the differences from cortical thickness in anatomical locations. Discrepancy regions of the grey matter volume and thickness where grey matter volume significantly decreased but without corresponding evidence of cortical thinning involved the rostral middle frontal, precentral, lateral occipital and superior frontal gyri. Subsequent region-of-interest analysis demonstrated that changes in surface area, grey/white matter intensity contrast and curvature accounted for the discrepancies. Our results suggest that the differences between grey matter volume and thickness could be jointly driven by surface area, grey/white matter intensity contrast and curvature. PMID:25595222

  19. WHITE MATTER DEVELOPMENT IN THE EARLY STAGES OF PSYCHOSIS

    PubMed Central

    Peters, Bart D.; Karlsgodt, Katherine H.

    2014-01-01

    Schizophrenia has been conceptualized as a disorder of both neurodevelopment and a disorder of connectivity. One important aspect of the neurodevelopmental hypothesis is that schizophrenia is no longer thought to have discrete illness time points, but rather a long trajectory of brain changes, spanning many years, across a series of stages of the disease including the prodrome, first episode, and chronic period. As the disease progresses, there is a complex relationship between age related changes and disease related changes. Therefore, neural changes, and specifically white matter based connectivity changes, in schizophrenia may be best conceptualized based on a lifespan trajectory. In this selective review, we discuss healthy changes in white matter integrity that occur with age, as well as changes that occur across illness stages. We further propose a set of models that might explain lifespan changes in white matter integrity in schizophrenia, with the conclusion that the evidence most strongly supports a pattern of disrupted maturation during adolescence, with the potential for later changes that may be a result of disease neurotoxicity, abnormal or excessive aging effects, as well as medication, cohort or other effects. Thus, when considering white matter integrity in psychosis, it is critical to consider age in addition to other contributing factors including disease specific effects. Discovery of the factors driving healthy white matter development across the lifespan and deviations from the normal developmental trajectory may provide insights relevant to the discovery of early treatment interventions. PMID:24893908

  20. NMDA receptor antibodies associated with distinct white matter syndromes

    PubMed Central

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

    2014-01-01

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

  1. Astrocytes in Oligodendrocyte Lineage Development and White Matter Pathology

    PubMed Central

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

    2016-01-01

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

  2. Astrocytes in Oligodendrocyte Lineage Development and White Matter Pathology.

    PubMed

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

    2016-01-01

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

  3. Astrocytes in Oligodendrocyte Lineage Development and White Matter Pathology.

    PubMed

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

    2016-01-01

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

  4. 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

  5. Characterizing white matter health and organization in atherosclerotic vascular disease: a diffusion tensor imaging study.

    PubMed

    Rowe Bijanki, Kelly; Arndt, Stephan; Magnotta, Vincent A; Nopoulos, Peg; Paradiso, Sergio; Matsui, Joy T; Johnson, Hans J; Moser, David J

    2013-12-30

    Atherosclerotic vascular disease (AVD) is endemic to the developed world, with known negative outcomes for cognition and brain health. The effects of AVD on the white matter fibers of the brain have not yet been studied using diffusion tensor imaging (DTI). This study examined differences in fractional anisotropy (FA) between AVD and healthy comparison (HC) participants, and described the regional patterns of FA in each group. AVD participants were hypothesized to have lower FA than HC participants, indicating abnormalities in white matter health or organization. 1.5 T diffusion tensor imaging was performed in 35 AVD and 22 HC participants. Mean FA measures were calculated for the white matter of the whole brain, as well for individual lobes. Globally and in every brain region measured except the temporal lobes, there were significant effects of group where AVD participants had lower FA values than their HC counterparts. Group differences in FA remained significant when controlled for white matter hyperintensity (WMH) volume, suggesting that FA detects white matter abnormality above and beyond what is measurable using the older WMH technique. These findings suggest a likely neural substrate underlying the changes in cognition and mood reported in atherosclerotic vascular disease patients.

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

    PubMed

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

    2016-01-01

    Fractional anisotropy (FA) and mean diffusivity (MD) are the most frequently used metrics to investigate white matter impairments in mental disorders. However, these two metrics are derived from intra-voxel analyses and only reflect the diffusion properties solely within the voxel unit. Local diffusion homogeneity (LDH) is a newly developed inter-voxel metric which quantifies the local coherence of water molecule diffusion in a model-free manner. In this study, 94 schizophrenia patients and 91 sex- and age-matched healthy controls underwent diffusion tensor imaging (DTI) examinations. White matter integrity was assessed by FA, MD and LDH. Group differences in these metrics were compared using tract-based spatial statistics (TBSS). Compared with healthy controls, schizophrenia patients exhibited reduced FA and increased MD in the corpus callosum, cingulum, internal capsule, fornix and widespread superficial white matter in the frontal, parietal, occipital and temporal lobes. We also found decreased LDH in the corpus callosum, cingulum, internal capsule and fornix in schizophrenia. Our findings suggest that both intra-voxel and inter-voxel diffusion metrics are able to detect impairments in the anisotropic white matter regions, and intra-voxel diffusion metrics could detect additional impairments in the widespread isotropic white matter regions in schizophrenia. PMID:27618693

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

    Wang, Lina; Jia, Feng; Wang, Chunli

    2016-01-01

    Fractional anisotropy (FA) and mean diffusivity (MD) are the most frequently used metrics to investigate white matter impairments in mental disorders. However, these two metrics are derived from intra-voxel analyses and only reflect the diffusion properties solely within the voxel unit. Local diffusion homogeneity (LDH) is a newly developed inter-voxel metric which quantifies the local coherence of water molecule diffusion in a model-free manner. In this study, 94 schizophrenia patients and 91 sex- and age-matched healthy controls underwent diffusion tensor imaging (DTI) examinations. White matter integrity was assessed by FA, MD and LDH. Group differences in these metrics were compared using tract-based spatial statistics (TBSS). Compared with healthy controls, schizophrenia patients exhibited reduced FA and increased MD in the corpus callosum, cingulum, internal capsule, fornix and widespread superficial white matter in the frontal, parietal, occipital and temporal lobes. We also found decreased LDH in the corpus callosum, cingulum, internal capsule and fornix in schizophrenia. Our findings suggest that both intra-voxel and inter-voxel diffusion metrics are able to detect impairments in the anisotropic white matter regions, and intra-voxel diffusion metrics could detect additional impairments in the widespread isotropic white matter regions in schizophrenia. PMID:27618693

  9. 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 interest–based 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

  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.

  11. Plasticity of left perisylvian white-matter tracts is associated with individual differences in math learning.

    PubMed

    Jolles, Dietsje; Wassermann, Demian; Chokhani, Ritika; Richardson, Jennifer; Tenison, Caitlin; Bammer, Roland; Fuchs, Lynn; Supekar, Kaustubh; Menon, Vinod

    2016-04-01

    Plasticity of white matter tracts is thought to be essential for cognitive development and academic skill acquisition in children. However, a dearth of high-quality diffusion tensor imaging (DTI) data measuring longitudinal changes with learning, as well as methodological difficulties in multi-time point tract identification have limited our ability to investigate plasticity of specific white matter tracts. Here, we examine learning-related changes of white matter tracts innervating inferior parietal, prefrontal and temporal regions following an intense 2-month math tutoring program. DTI data were acquired from 18 third grade children, both before and after tutoring. A novel fiber tracking algorithm based on a White Matter Query Language (WMQL) was used to identify three sections of the superior longitudinal fasciculus (SLF) linking frontal and parietal (SLF-FP), parietal and temporal (SLF-PT) and frontal and temporal (SLF-FT) cortices, from which we created child-specific probabilistic maps. The SLF-FP, SLF-FT, and SLF-PT tracts identified with the WMQL method were highly reliable across the two time points and showed close correspondence to tracts previously described in adults. Notably, individual differences in behavioral gains after 2 months of tutoring were specifically correlated with plasticity in the left SLF-FT tract. Our results extend previous findings of individual differences in white matter integrity, and provide important new insights into white matter plasticity related to math learning in childhood. More generally, our quantitative approach will be useful for future studies examining longitudinal changes in white matter integrity associated with cognitive skill development.

  12. Whole exome sequencing in patients with white matter abnormalities.

    PubMed

    Vanderver, Adeline; Simons, Cas; Helman, Guy; Crawford, Joanna; Wolf, Nicole I; Bernard, Geneviève; Pizzino, Amy; Schmidt, Johanna L; Takanohashi, Asako; Miller, David; Khouzam, Amirah; Rajan, Vani; Ramos, Erica; Chowdhury, Shimul; Hambuch, Tina; Ru, Kelin; Baillie, Gregory J; Grimmond, Sean M; Caldovic, Ljubica; Devaney, Joseph; Bloom, Miriam; Evans, Sarah H; Murphy, Jennifer L P; McNeill, Nathan; Fogel, Brent L; Schiffmann, Raphael; van der Knaap, Marjo S; Taft, Ryan J

    2016-06-01

    Here we report whole exome sequencing (WES) on a cohort of 71 patients with persistently unresolved white matter abnormalities with a suspected diagnosis of leukodystrophy or genetic leukoencephalopathy. WES analyses were performed on trio, or greater, family groups. Diagnostic pathogenic variants were identified in 35% (25 of 71) of patients. Potentially pathogenic variants were identified in clinically relevant genes in a further 7% (5 of 71) of cases, giving a total yield of clinical diagnoses in 42% of individuals. These findings provide evidence that WES can substantially decrease the number of unresolved white matter cases. Ann Neurol 2016;79:1031-1037.

  13. 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

    2016-01-01

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

  14. 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.

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

    PubMed

    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.

  16. Cerebral White Matter Correlates of Delay Discounting in Adolescents

    PubMed Central

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

    2016-01-01

    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

  17. 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

  18. Tissue plasminogen activator prevents white matter damage following stroke

    PubMed Central

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

    2011-01-01

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

  19. Infrared spectroscopic characterization of human white matter, grey matter, and multiple sclerosis lesions

    NASA Astrophysics Data System (ADS)

    Choo, Lin-P'ing; Jackson, Michael; Halliday, William C.; Mantsch, Henry H.

    1994-01-01

    FT-IR spectroscopy has been used to characterize white matter, grey matter, and multiple sclerosis (MS) plaques from human central nervous system (CNS) tissue. Discrimination among these three tissue types is possible due to variations in composition. Spectra of white matter exhibit strong lipid absorptions. In contrast, spectra of grey matter reveal a reduced lipid contribution and a significant absorption from water. MS plaques exhibit spectra indicative of lipid loss and, depending upon whether the plaques are chronic or acute, changes in the protein and/or water content.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

    Shira, Rosenzweig; Thomas, Carmichael S.

    2015-01-01

    Approximately one quarter of all strokes in humans occur in white matter, and the progressive nature of white matter lesions often results in severe physical and mental disability. Unlike cortical grey matter stroke, the pathology of white matter stroke revolves around disrupted connectivity and injured axons and glial cells, rather than neuronal cell bodies. Consequently, the mechanisms behind ischemic damage to white matter elements, the regenerative responses of glial cells and their signaling pathways, all differ significantly from those in grey matter. Development of effective therapies for white matter stroke would require an enhanced understanding of the complex cellular and molecular interactions within the white matter, leading to the identification of new therapeutic targets. This review will address the unique properties of the axon-glia unit during white matter stroke, describe the challenging process of promoting effective white matter repair, and discuss recently-identified signaling pathways which may hold potential targets for repair in this disease. PMID:25704204

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

    PubMed

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

    2011-03-15

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

  3. 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

  4. 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…

  5. 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…

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

    PubMed Central

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

    2012-01-01

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

  7. 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,…

  8. Tract-specific white matter microstructure and gait in humans.

    PubMed

    Verlinden, Vincentius J A; de Groot, Marius; Cremers, Lotte G M; van der Geest, Jos N; Hofman, Albert; Niessen, Wiro J; van der Lugt, Aad; Vernooij, Meike W; Ikram, M Arfan

    2016-07-01

    Gait is a complex sequence of movements, requiring cooperation of many brain areas, such as the motor cortex, somatosensory cortex, and cerebellum. However, it is unclear which connecting white matter tracts are essential for communication across brain areas to facilitate proper gait. Using diffusion tensor imaging, we investigated associations of microstructural organization in 14 brain white matter tracts with gait, among 2330 dementia- and stroke-free community-dwelling individuals. Gait was assessed by electronic walkway and summarized into Global Gait, and 7 gait domains. Higher white matter microstructure associated with higher Global Gait, Phases, Variability, Pace, and Turning. Microstructure in thalamic radiations, followed by association tracts and the forceps major, associated most strongly with gait. Hence, in community-dwelling individuals, higher white matter microstructure associated with better gait, including larger strides, more single support, less stride-to-stride variability, and less turning steps. Our findings suggest that intact thalamocortical communication, cortex-to-cortex communication, and interhemispheric visuospatial integration are most essential in human gait. PMID:27255826

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  10. Genetics Home Reference: leukoencephalopathy with vanishing white matter

    MedlinePlus

    ... the unfolded protein response in vanishing white matter disease. J Neuropathol Exp Neurol. 2006 Jul;65(7):707-15. Citation on PubMed van der Voorn JP, van Kollenburg B, Bertrand G, Van Haren K, Scheper GC, Powers JM, van der Knaap MS. The unfolded protein ...

  11. 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…

  12. White Matter Diseases with Radiologic-Pathologic Correlation.

    PubMed

    Sarbu, Nicolae; Shih, Robert Y; Jones, Robert V; Horkayne-Szakaly, Iren; Oleaga, Laura; Smirniotopoulos, James G

    2016-01-01

    White matter diseases include a wide spectrum of disorders that have in common impairment of normal myelination, either by secondary destruction of previously myelinated structures (demyelinating processes) or by primary abnormalities of myelin formation (dysmyelinating processes). The pathogenesis of many white matter diseases remains poorly understood. Demyelinating disorders are the object of this review and will be further divided into autoimmune, infectious, vascular, and toxic-metabolic processes. Autoimmune processes include multiple sclerosis and related diseases: tumefactive demyelinating lesions, Balo concentric sclerosis, Marburg and Schilder variants, neuromyelitis optica (Devic disease), acute disseminated encephalomyelitis, and acute hemorrhagic leukoencephalopathy (Hurst disease). Infectious processes include Lyme disease (neuroborreliosis), progressive multifocal leukoencephalopathy, and human immunodeficiency virus (HIV) encephalopathy. Vascular processes include different types of small-vessel disease: arteriolosclerosis, cerebral amyloid angiopathy, cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), primary angiitis of the central nervous system, Susac syndrome, and neurolupus. Toxic-metabolic processes include osmotic myelinolysis, methotrexate leukoencephalopathy, and posterior reversible encephalopathy syndrome. The imaging spectrum can vary widely from small multifocal white matter lesions to confluent or extensive white matter involvement. Understanding the pathologic substrate is fundamental for understanding the radiologic manifestations, and a systematic approach to the radiologic findings, in correlation with clinical and laboratory data, is crucial for narrowing the differential diagnosis. (©)RSNA, 2016. PMID:27618323

  13. 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...

  14. Astrocytes are central in the pathomechanisms of vanishing white matter

    PubMed Central

    Dooves, Stephanie; Bugiani, Marianna; Postma, Nienke L.; Polder, Emiel; Land, Niels; Horan, Stephen T.; van Deijk, Anne-Lieke F.; van de Kreeke, Aleid; Jacobs, Gerbren; Vuong, Caroline; Klooster, Jan; Kamermans, Maarten; Wortel, Joke; Wisse, Lisanne E.; Scheper, Gert C.; Abbink, Truus E.M.; Heine, Vivi M.; van der Knaap, Marjo S.

    2016-01-01

    Vanishing white matter (VWM) is a fatal leukodystrophy that is caused by mutations in genes encoding subunits of eukaryotic translation initiation factor 2B (eIF2B). Disease onset and severity are codetermined by genotype. White matter astrocytes and oligodendrocytes are almost exclusively affected; however, the mechanisms of VWM development remain unclear. Here, we used VWM mouse models, patients’ tissue, and cell cultures to investigate whether astrocytes or oligodendrocytes are the primary affected cell type. We generated 2 mouse models with mutations (Eif2b5Arg191His/Arg191His and Eif2b4Arg484Trp/Arg484Trp) that cause severe VWM in humans and then crossed these strains to develop mice with various mutation combinations. Phenotypic severity was highly variable and dependent on genotype, reproducing the clinical spectrum of human VWM. In all mutant strains, impaired maturation of white matter astrocytes preceded onset and paralleled disease severity and progression. Bergmann glia and retinal Müller cells, nonforebrain astrocytes that have not been associated with VWM, were also affected, and involvement of these cells was confirmed in VWM patients. In coculture, VWM astrocytes secreted factors that inhibited oligodendrocyte maturation, whereas WT astrocytes allowed normal maturation of VWM oligodendrocytes. These studies demonstrate that astrocytes are central in VWM pathomechanisms and constitute potential therapeutic targets. Importantly, astrocytes should also be considered in the pathophysiology of other white matter disorders. PMID:26974157

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

    PubMed Central

    Cătălin, B.; Mitran, Smaranda; Albu, Carmen; Iancău, Maria

    2013-01-01

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

  16. White matter abnormalities in schizophrenia and schizotypal personality disorder.

    PubMed

    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.

  17. White matter hyperintensity volume and impaired mobility among older adults

    PubMed Central

    Willey, Joshua Z.; Scarmeas, Nikolaos; Provenzano, Frank A.; Luchsinger, José A.; Mayeux, Richard; Brickman, Adam M.

    2012-01-01

    Gait speed is associated with multiple adverse outcomes of aging. White matter hyperintensities (WMH) on magnetic resonance imaging (MRI) have been associated with gait speed, though few studies have examined changes in gait speed over time in population-based studies comprising participants from diverse cultural backgrounds. The purpose of this study was to examine the association between a decline in gait speed and total and regional WMH volumes in a community-based study of aging. Participants (n=701) in a community-based study of older adults underwent gait speed measurement via a 4-meter walk test at the time of initial enrollment and MRI at a second time interval (mean 4.7[SD=0.5] years apart). Logistic regression was used to examine the association between large WMH volume and regional WMH volume with gait speed < 0.5 m/s (abnormal speed), and a transition to abnormal gait speed. Analyses were adjusted for demographic and clinical factors. Large WMH volume was associated with a transition to abnormal gait speed between the two visits, but not after adjustment for modifiable vascular disease risk factors. In adjusted models increased frontal lobe WMH volume was not associated with a transition to abnormal gait speed. WMH are associated with slowing of gait over time. Prevention of WMH presents a potential strategy for the prevention of gait speed decline. PMID:23128969

  18. 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

  19. Increased integrity of white matter pathways after dual n-back training.

    PubMed

    Salminen, Tiina; Mårtensson, Johan; Schubert, Torsten; Kühn, Simone

    2016-06-01

    Dual n-back WM training has been shown to produce broad transfer effects to different untrained cognitive functions. The task is demanding to the cognitive system because it includes a bi-modal (auditory and visual) dual-task component. A previous WM training study showed increased white matter integrity in the parietal lobe as well as the anterior part of the corpus callosum after visual n-back training. We investigated dual n-back training-related changes in white matter pathways. We anticipated dual n-back training to increase white matter integrity in pathways that connect brain regions related to WM processes. Additionally, we hypothesized that dual n-back training would produce more brain-wide white matter changes than single n-back training because of the involvement of two modalities and the additional dual-task coordination component of the task. The dual n-back training group showed increased white matter integrity (reflected as increased fractional anisotropy, FA) after training. The effects were mostly left lateralized as compared with changes from pretest to posttest in the passive and active control groups. Additionally, significant effects were observed in the anterior part of the corpus callosum, when the training group was compared with the passive control group. There were no changes in pretest to posttest FA changes between the passive and active control groups. The results therefore show that dual n-back training produces increased integrity in white matter pathways connecting different brain regions. The results are discussed in reference to the bi-modal dual-task component of the training task.

  20. 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

  1. Multimodal neuroimaging of frontal white matter microstructure in early phase schizophrenia: the impact of early adolescent cannabis use

    PubMed Central

    2013-01-01

    Background A disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, could be responsible for the clinical symptoms and cognitive dysfunctions observed in schizophrenia. White matter, which comprises axons and their myelin sheaths, provides the physical foundation for functional connectivity in the brain. Myelin sheaths are located around the axons and provide insulation through the lipid membranes of oligodendrocytes. Empirical data suggests oligodendroglial dysfunction in schizophrenia, based on findings of abnormal myelin maintenance and repair in regions of deep white matter. The aim of this in vivo neuroimaging project is to assess the impact of early adolescent onset of regular cannabis use on brain white matter tissue integrity, and to differentiate this impact from the white matter abnormalities associated with schizophrenia. The ultimate goal is to determine the liability of early adolescent use of cannabis on brain white matter, in a vulnerable brain. Methods/Design Young adults with schizophrenia at the early stage of the illness (less than 5 years since diagnosis) will be the focus of this project. Four magnetic resonance imaging measurements will be used to assess different cellular aspects of white matter: a) diffusion tensor imaging, b) localized proton magnetic resonance spectroscopy with a focus on the neurochemical N-acetylaspartate, c) the transverse relaxation time constants of regional tissue water, d) and of N-acetylaspartate. These four neuroimaging indices will be assessed within the same brain region of interest, that is, a large white matter fibre bundle located in the frontal region, the left superior longitudinal fasciculus. Discussion We will expand our knowledge regarding current theoretical models of schizophrenia with a more comprehensive multimodal neuroimaging approach to studying the underlying cellular abnormalities of white matter, while taking into

  2. 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

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

    PubMed

    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

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

    PubMed Central

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

    2007-01-01

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

  5. 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.

  6. Early gray-matter and white-matter concentration in infancy predict later language skills: A whole brain voxel-based morphometry study

    PubMed Central

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

    2012-01-01

    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. Early gray-matter concentration in the right cerebellum, early white-matter concentration in the right cerebellum, and early white-matter concentration in the left posterior limb of the internal capsule (PLIC)/cerebral peduncle were positively and strongly associated with infants’ receptive language ability at 12 months. Early gray-matter concentration in the right hippocampus was positively and strongly correlated with infants’ expressive language ability at 12 months. Our results suggest that the cerebellum, PLIC/cerebral peduncle, and the hippocampus may be associated with early language development. Potential links between these structural predictors and infants’ linguistic functions are discussed. PMID:23274797

  7. 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.

  8. Associations between brain white matter integrity and disease severity in obstructive sleep apnea.

    PubMed

    Tummala, Sudhakar; Roy, Bhaswati; Park, Bumhee; Kang, Daniel W; Woo, Mary A; Harper, Ronald M; Kumar, Rajesh

    2016-10-01

    Obstructive sleep apnea (OSA) is characterized by recurrent upper airway blockage, with continued diaphragmatic efforts to breathe during sleep. Brain structural changes in OSA appear in various regions, including white matter sites that mediate autonomic, mood, cognitive, and respiratory control. However, the relationships between brain white matter changes and disease severity in OSA are unclear. This study examines associations between an index of tissue integrity, magnetization transfer (MT) ratio values (which show MT between free and proton pools associated with tissue membranes and macromolecules), and disease severity (apnea-hypopnea index [AHI]) in OSA subjects. We collected whole-brain MT imaging data from 19 newly diagnosed, treatment-naïve OSA subjects (50.4 ± 8.6 years of age, 13 males, AHI 39.7 ± 24.3 events/hr], using a 3.0-Tesla MRI scanner. With these data, whole-brain MT ratio maps were calculated, normalized to common space, smoothed, and correlated with AHI scores by using partial correlation analyses (covariates, age and gender; P < 0.005). Multiple brain sites in OSA subjects, including superior and inferior frontal regions, ventral medial prefrontal cortex and nearby white matter, midfrontal white matter, insula, cingulate and cingulum bundle, internal and external capsules, caudate nuclei and putamen, basal forebrain, hypothalamus, corpus callosum, and temporal regions, showed principally lateralized negative correlations (P < 0.005). These regions showed significant correlations even with correction for multiple comparisons (cluster-level, family-wise error, P < 0.05), except for a few superior frontal areas. Predominantly negative correlations emerged between local MT values and OSA disease severity, indicating potential usefulness of MT imaging for examining the OSA condition. These findings indicate that OSA severity plays a significant role in white matter injury. © 2016 Wiley Periodicals, Inc.

  9. 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

  10. 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.…

  11. Gray and white matter distribution in dyslexia: a VBM study of superior temporal gyrus asymmetry.

    PubMed

    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

  12. Edge Density Imaging: Mapping the Anatomic Embedding of the Structural Connectome Within the White Matter of the Human Brain

    PubMed Central

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

    2015-01-01

    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

  13. 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

  14. 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

  15. 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

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

    PubMed

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

    2016-01-01

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

  17. Can arterial spin labeling detect white matter perfusion signal?

    PubMed

    van Osch, Matthias J P; Teeuwisse, Wouter M; van Walderveen, Marianne A A; Hendrikse, Jeroen; Kies, Dennis A; van Buchem, Mark A

    2009-07-01

    Since the invention of arterial spin labeling (ASL) it has been acknowledged that ASL does not allow reliable detection of a white matter (WM) perfusion signal. However, recent developments such as pseudo-continuous labeling and background suppression have improved the quality. The goal of this research was to study the ability of these newer ASL sequences to detect WM perfusion signal. Background suppressed pseudo-continuous ASL was implemented at 3T with multislice 2D readout after 1525 ms. In five volunteers it was shown that 10 min scanning resulted in significant perfusion signal in 70% of WM voxels. Increasing the labeling and delay time did not lead to a higher percentage. In 27 normal volunteers it was found that 35 averages are necessary to detect significant WM signal, but 150 averages are needed to detect signal in the deep WM. Finally, it was shown in a patient with a cerebral arteriovenous malformation that pseudo-continuous ASL enabled the depiction of hypointense WM perfusion signal, although dynamic susceptibility contrast MRI showed that this region was merely showing delayed arrival of contrast agent than hypoperfusion. It can be concluded that, except within the deep WM, ASL is sensitive enough to detect WM perfusion signal and perfusion deficits. PMID:19365865

  18. 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

  19. Automated localization of periventricular and subcortical white matter lesions

    NASA Astrophysics Data System (ADS)

    van der Lijn, Fedde; Vernooij, Meike W.; Ikram, M. Arfan; Vrooman, Henri A.; Rueckert, Daniel; Hammers, Alexander; Breteler, Monique M. B.; Niessen, Wiro J.

    2007-03-01

    It is still unclear whether periventricular and subcortical white matter lesions (WMLs) differ in etiology or clinical consequences. Studies addressing this issue would benefit from automated segmentation and localization of WMLs. Several papers have been published on WML segmentation in MR images. Automated localization however, has not been investigated as much. This work presents and evaluates a novel method to label segmented WMLs as periventricular and subcortical. The proposed technique combines tissue classification and registration-based segmentation to outline the ventricles in MRI brain data. The segmented lesions can then be labeled into periventricular WMLs and subcortical WMLs by applying region growing and morphological operations. The technique was tested on scans of 20 elderly subjects in which neuro-anatomy experts manually segmented WMLs. Localization accuracy was evaluated by comparing the results of the automated method with a manual localization. Similarity indices and volumetric intraclass correlations between the automated and the manual localization were 0.89 and 0.95 for periventricular WMLs and 0.64 and 0.89 for subcortical WMLs, respectively. We conclude that this automated method for WML localization performs well to excellent in comparison to the gold standard.

  20. 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

  1. 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

    2015-11-20

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

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

    PubMed

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

    2011-11-16

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

  3. White Matter Ischemic Changes in Hyperacute Ischemic Stroke

    PubMed Central

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

    2015-01-01

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

  4. 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.

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

    PubMed

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

    2014-10-01

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

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

    PubMed

    Welcome, Suzanne E; Joanisse, Marc F

    2014-08-01

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

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

    PubMed

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

    2014-09-01

    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.

  8. Cerebral white matter recovery in abstinent alcoholics—a multimodality magnetic resonance study

    PubMed Central

    Durazzo, Timothy C.; Mon, Anderson; Yeh, Ping-Hong; Meyerhoff, Dieter J.

    2010-01-01

    Most previous neuroimaging studies of alcohol-induced brain injury and recovery thereof during abstinence from alcohol used a single imaging modality. They have demonstrated widespread microstructural, macrostructural or metabolite abnormalities that were partially reversible with abstinence, with the cigarette smoking potentially modulating these processes. The goals of this study were to evaluate white matter injury and recovery thereof, simultaneously with diffusion tensor imaging, magnetic resonance imaging and spectroscopy in the same cohort; and to evaluate the relationships between outcome measures of similar regions. We scanned 16 non-smoking and 20 smoking alcohol-dependent individuals at 1 week of abstinence from alcohol and 22 non-smoking light drinkers using a 1.5 T magnetic resonance scanner. Ten non-smoking alcohol-dependent individuals and 11 smoking alcohol-dependent individuals were re-scanned at 1 month of abstinence. All regional diffusion tensor imaging, magnetic resonance imaging and spectroscopic outcome measures were calculated over comparable volumes of frontal, temporal, parietal and occipital white matter. At 1 week of abstinence and relative to non-smoking light drinkers, non-smoking alcohol-dependent individuals had higher mean diffusivity in frontal, temporal and parietal white matter (all P < 0.008), whereas smoking alcohol-dependent individuals had elevated mean diffusivity only in frontal white matter (P = 0.03). Smoking alcohol-dependent individuals demonstrated lower concentrations of N-acetyl-aspartate (a marker of neuronal viability) in frontal white matter (P = 0.03), whereas non-smoking alcohol-dependent individuals had lower N-acetyl-aspartate in parietal white matter (P = 0.05). These abnormalities were not accompanied by detectable white matter atrophy. However, the patterns of white matter recovery were different between non-smoking alcohol-dependent individuals and smoking alcohol-dependent individuals. In non

  9. 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…

  10. White matter development in early puberty: a longitudinal volumetric and diffusion tensor imaging twin study.

    PubMed

    Brouwer, Rachel M; Mandl, René C W; Schnack, Hugo G; van Soelen, Inge L C; van Baal, G Caroline; Peper, Jiska S; Kahn, René S; Boomsma, Dorret I; Hulshoff Pol, H E

    2012-01-01

    White matter microstructure and volume show synchronous developmental patterns in children. White matter volume increases considerably during development. Fractional anisotropy, a measure for white matter microstructural directionality, also increases with age. Development of white matter volume and development of white matter microstructure seem to go hand in hand. The extent to which the same or different genetic and/or environmental factors drive these two aspects of white matter maturation is currently unknown. We mapped changes in white matter volume, surface area and diffusion parameters in mono- and dizygotic twins who were scanned at age 9 (203 individuals) and again at age 12 (126 individuals). Over the three-year interval, white matter volume (+6.0%) and surface area (+1.7%) increased, fiber bundles expanded (most pronounced in the left arcuate fasciculus and splenium), and fractional anisotropy increased (+3.0%). Genes influenced white matter volume (heritability ~85%), surface area (~85%), and fractional anisotropy (locally 7% to 50%) at both ages. Finally, volumetric white matter growth was negatively correlated with fractional anisotropy increase (r = -0.62) and this relationship was driven by environmental factors. In children who showed the most pronounced white matter growth, fractional anisotropy increased the least and vice-versa. Thus, white matter development in childhood may reflect a process of both expansion and fiber optimization.

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

    PubMed Central

    Brouwer, Rachel M.; Mandl, René C. W.; Schnack, Hugo G.; van Soelen, Inge L. C.; van Baal, G. Caroline; Peper, Jiska S.; Kahn, René S.; Boomsma, Dorret I.; Pol, H. E. Hulshoff

    2012-01-01

    White matter microstructure and volume show synchronous developmental patterns in children. White matter volume increases considerably during development. Fractional anisotropy, a measure for white matter microstructural directionality, also increases with age. Development of white matter volume and development of white matter microstructure seem to go hand in hand. The extent to which the same or different genetic and/or environmental factors drive these two aspects of white matter maturation is currently unknown. We mapped changes in white matter volume, surface area and diffusion parameters in mono- and dizygotic twins who were scanned at age 9 (203 individuals) and again at age 12 (126 individuals). Over the three-year interval, white matter volume (+6.0%) and surface area (+1.7%) increased, fiber bundles expanded (most pronounced in the left arcuate fasciculus and splenium), and fractional anisotropy increased (+3.0%). Genes influenced white matter volume (heritability ∼85%), surface area (∼85%), and fractional anisotropy (locally 7% to 50%) at both ages. Finally, volumetric white matter growth was negatively correlated with fractional anisotropy increase (r = –0.62) and this relationship was driven by environmental factors. In children who showed the most pronounced white matter growth, fractional anisotropy increased the least and vice-versa. Thus, white matter development in childhood may reflect a process of both expansion and fiber optimization. PMID:22514599

  12. Clinical Dementia Rating Scale Detects White Matter Changes in Older Adults at Risk for Alzheimer's Disease.

    PubMed

    Chang, Yu-Ling; Yen, Yu-Shiuan; Chen, Ta-Fu; Yan, Sui-Hing; Tseng, Wen-Yih Isaac

    2015-01-01

    This study investigated the putative changes in regional gray matter and cingulum bundle segments in mild cognitive impairment (MCI) by using two diagnostic criteria. Participants comprised 50 older adults with MCI and 22 healthy older controls (HC). The older adults with MCI were further divided into two groups defined by a global Clinical Dementia Rating (CDR) score of 0.5 and with (the CDR/NPT MCI group) or without (the CDR MCI group) objective cognitive impairments determined using neuropsychological tests (NPTs). Comparable regional gray matter integrity was observed among the three groups. However, the integrity of the right inferior segment of the cingulum bundle in the two MCI groups was more reduced than that in the HC group, and the CDR/NPT MCI group exhibited additional disruption in the left inferior cingulum bundle. The results also demonstrated that neuropsychological measures have greater predictive value for changes in white matter beyond the contribution of an informant-based instrument alone. Overall, the findings confirm the utility of informant-based assessment in detecting microstructural brain changes in high-risk older adults, even before objective cognitive impairment is evident. The findings also suggest that combining the neuropsychological measures with the informant-based assessment provided the greatest predictive value in assessing white matter disruption. The essential role of the white matter measurement as a biomarker for detecting individuals at a high risk of developing dementia was highlighted.

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

    PubMed Central

    DeRamus, Thomas P.; Kana, Rajesh K.

    2014-01-01

    Autism spectrum disorders (ASD) are characterized by impairments in social communication and restrictive, repetitive behaviors. While behavioral symptoms are well-documented, investigations into the neurobiological underpinnings of ASD have not resulted in firm biomarkers. Variability in findings across structural neuroimaging studies has contributed to difficulty in reliably characterizing the brain morphology of individuals with ASD. These inconsistencies may also arise from the heterogeneity of ASD, and wider age-range of participants included in MRI studies and in previous meta-analyses. To address this, the current study used coordinate-based anatomical likelihood estimation (ALE) analysis of 21 voxel-based morphometry (VBM) studies examining high-functioning individuals with ASD, resulting in a meta-analysis of 1055 participants (506 ASD, and 549 typically developing individuals). Results consisted of grey, white, and global differences in cortical matter between the groups. Modeled anatomical maps consisting of concentration, thickness, and volume metrics of grey and white matter revealed clusters suggesting age-related decreases in grey and white matter in parietal and inferior temporal regions of the brain in ASD, and age-related increases in grey matter in frontal and anterior-temporal regions. White matter alterations included fiber tracts thought to play key roles in information processing and sensory integration. Many current theories of pathobiology ASD suggest that the brains of individuals with ASD may have less-functional long-range (anterior-to-posterior) connections. Our findings of decreased cortical matter in parietal–temporal and occipital regions, and thickening in frontal cortices in older adults with ASD may entail altered cortical anatomy, and neurodevelopmental adaptations. PMID:25844306

  14. Patchy white matter hyperintensity in ring chromosome 18 syndrome.

    PubMed

    Anzai, Mai; Arai-Ichinoi, Natsuko; Takezawa, Yusuke; Endo, Wakaba; Inui, Takehiko; Sato, Ryo; Kikuchi, Atsuo; Uematsu, Mitsugu; Kure, Shigeo; Haginoya, Kazuhiro

    2016-09-01

    Ring chromosome 18 syndrome is a chromosomal abnormality in which partial deletions occur at both ends of chromosome 18, that is, distally on the short and long arms. Previously reported brain magnetic resonance imaging (MRI) abnormalities include diffuse hyperintensity in the white matter, which has been regarded as hypomyelination because the gene for myelin basic protein production is located on the long arm of chromosome 18. We report the case of a 14-year-old boy with ring chromosome 18 syndrome, whose MRI showed patchy asymmetrical T2 and fluid-attenuated inversion-recovery hyperintensities in the deep white matter as well as diffuse hypomyelination. These patchy lesions may indicate demyelination or gliosis rather than hypomyelination. This result differs from previous reports. PMID:27577543

  15. Lifespan maturation and degeneration of human brain white matter

    PubMed Central

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

    2014-01-01

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

  16. Longitudinal Changes in White Matter Integrity Among Adolescent Substance Users

    PubMed Central

    Bava, Sunita; Jacobus, Joanna; Thayer, Rachel E.; Tapert, Susan F.

    2012-01-01

    Background The influence of repeated substance use during adolescent neurodevelopment remains unclear as there have been few prospective investigations. The aims of this study were to identify longitudinal changes in fiber tract integrity associated with alcohol and marijuana use severity over the course of 1.5 years. Method Adolescents with extensive marijuana and alcohol use histories by mid-adolescence (n = 41) and youth with consistently minimal if any substance use (n = 51) were followed over 18 months. Teens received diffusion tensor imaging and detailed substance use assessments with toxicology screening at baseline and 18-month follow-ups (i.e., 182 scans in all), as well as interim substance use interviews each 6 months. Results At 18-month follow-up, substance users showed poorer white matter integrity in seven tracts: (1) right superior longitudinal fasciculus, (2) left superior longitudinal fasciculus, (3) right posterior thalamic radiations, (4) right prefrontal thalamic fibers, (5) right superior temporal gyrus white matter, (6) right inferior longitudinal fasciculus, and (7) left posterior corona radiata (ps< .01). More alcohol use during the interscan interval predicted higher mean diffusivity (i.e., worsened integrity) in right (p<.05) and left (p=.06) superior longitudinal fasciculi, above and beyond baseline values in these bundles. Marijuana use during the interscan interval did not predict change over time. More externalizing behaviors at Time 1 predicted lower fractional anisotropy and higher radial diffusivity (i.e., poorer integrity) of the right prefrontal thalamic fibers (p<.025). Conclusion Findings add to previous cross sectional studies reporting white matter disadvantages in youth with substance use histories. In particular, alcohol use during adolescent neurodevelopment may be linked to reductions in white matter quality in association fiber tracts with frontal connections. In contrast, youth who engage in a variety of risk taking

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

    PubMed

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

    2015-05-01

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

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

    PubMed

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

    2015-05-01

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

  19. Predicting White Matter Integrity from Multiple Common Genetic Variants

    PubMed Central

    Kohannim, Omid; Jahanshad, Neda; Braskie, Meredith N; Stein, Jason L; Chiang, Ming-Chang; Reese, April H; Hibar, Derrek P; Toga, Arthur W; McMahon, Katie L; de Zubicaray, Greig I; Medland, Sarah E; Montgomery, Grant W; Martin, Nicholas G; Wright, Margaret J; Thompson, Paul M

    2012-01-01

    Several common genetic variants have recently been discovered that appear to influence white matter microstructure, as measured by diffusion tensor imaging (DTI). Each genetic variant explains only a small proportion of the variance in brain microstructure, so we set out to explore their combined effect on the white matter integrity of the corpus callosum. We measured six common candidate single-nucleotide polymorphisms (SNPs) in the COMT, NTRK1, BDNF, ErbB4, CLU, and HFE genes, and investigated their individual and aggregate effects on white matter structure in 395 healthy adult twins and siblings (age: 20–30 years). All subjects were scanned with 4-tesla 94-direction high angular resolution diffusion imaging. When combined using mixed-effects linear regression, a joint model based on five of the candidate SNPs (COMT, NTRK1, ErbB4, CLU, and HFE) explained ∼6% of the variance in the average fractional anisotropy (FA) of the corpus callosum. This predictive model had detectable effects on FA at 82% of the corpus callosum voxels, including the genu, body, and splenium. Predicting the brain's fiber microstructure from genotypes may ultimately help in early risk assessment, and eventually, in personalized treatment for neuropsychiatric disorders in which brain integrity and connectivity are affected. PMID:22510721

  20. 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.

  1. Pathogenesis of cerebral white matter injury of prematurity

    PubMed Central

    Khwaja, O; Volpe, J J

    2008-01-01

    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

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

    PubMed

    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

  3. 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

  4. White matter integrity, creativity, and psychopathology: disentangling constructs with diffusion tensor imaging.

    PubMed

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

    2010-01-01

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

  5. 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

  6. 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.

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

    PubMed

    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

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

    PubMed

    Gautam, P; Nuñez, 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

  9. Brain metabolite abnormalities in the white matter of elderly schizophrenic subjects: implication for glial dysfunction

    PubMed Central

    Chang, Linda; Friedman, Joseph; Ernst, Thomas; Zhong, Kai; Tsopelas, Nicholas D.; Davis, Kenneth

    2008-01-01

    Background Abnormalities in the white matter of the brain may occur in individuals with schizophrenia as well as with normal aging. Therefore, elderly schizophrenic patients may suffer further cognitive decline as they age. This study determined whether elderly schizophrenia participants, especially those with declined cognitive function (CDR>1), show white matter metabolite abnormalities on proton magnetic resonance spectroscopy (1H MRS), and whether there are group differences in age-dependent changes in these brain metabolites. Method 23 elderly schizophrenic and 22 comparison participants fulfilling study criteria were enrolled. Localized, short echo-time 1H MRS at 4 Tesla was used to assess neurometabolite concentrations in several white matter regions. Results Compared to healthy subjects, schizophrenic participants had lower N-acetyl compounds (NA, −12.6%, p=0.0008), lower myoinositol (MI, −16.4%, p=0.026) and higher glutamate+glutamine (GLX, +28.7%, p=0.0016) concentrations across brain regions. Schizophrenic participants with CDR≥1 showed the lowest NA in the frontal and temporal regions compared to controls. Interactions between age and schizophrenia status on total creatine (CR) and choline-containing compounds (CHO) were observed; only schizophrenic participants showed age-related decreases of these two metabolites in the right frontal region. Conclusion Decreased NA in these white matter brain regions likely reflects reduced neuronal content associated with decreased synapses and neuronal cell volumes. The elevated GLX, if reflecting elevated glutamate, could result from excess neuronal glutamate release or glial dysfunction in glutamate re-uptake. The decreased MI in participants with schizophrenia suggests decreased glial content or dysfunctional glia, which might result from glutamate-mediated toxicity. PMID:17693392

  10. 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.

  11. Prefrontal cortex white matter tracts in prodromal Huntington disease

    PubMed Central

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

    2015-01-01

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

  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.

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

    PubMed

    Tuch, David S; Wisco, Jonathan J; Khachaturian, Mark H; Ekstrom, Leeland B; Kötter, 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.

  14. White Matter Microstructural Integrity and Neurobehavioral Outcome of HIV-Exposed Uninfected Neonates.

    PubMed

    Tran, Linh T; Roos, Annerine; Fouche, Jean-Paul; Koen, Nastassja; Woods, Roger P; Zar, Heather J; Narr, Katherine L; Stein, Dan J; Donald, Kirsten A

    2016-01-01

    The successful implementation of prevention programs for mother-to-child human immunodeficiency virus (HIV) transmission has dramatically reduced the prevalence of infants infected with HIV while increasing that of HIV-exposed uninfected (HEU) children. Neuropsychological assessments indicate that HEU children may exhibit differences in neurodevelopment compared to unexposed children (HUU). Pathological mechanisms leading to such neurodevelopmental delays are not clear. In this observational birth cohort study we explored the integrity of regional white matter microstructure in HEU infants, shortly after birth. Microstructural changes in white matter associated with prenatal HIV exposure were evaluated in HEU infants (n = 15) and matched controls (n = 22) using diffusion tensor imaging and tract-based spatial statistics. Additionally, diffusion values were extracted and compared for white matter tracts of interest, and associations with clinical outcomes from the Dubowitz neonatal neurobehavioral tool were investigated. Higher fractional anisotropy in the middle cerebellar peduncles of HEU compared to HUU neonates was found after correction for age and gender. Scores on the Dubowitz abnormal neurological signs subscale were positively correlated with FA (r = 0.58, P = 0.038) in the left uncinate fasciculus in HEU infants. This is the first study to present data suggesting that prenatal HIV exposure without infection is associated with altered white matter microstructural integrity in the neonatal period. Longitudinal studies of HEU infants as their brains mature are necessary to understand further the significance of prenatal HIV and antiretroviral treatment exposure on white matter integrity and neurodevelopmental outcomes.

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

    PubMed Central

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

    2014-01-01

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

  16. Altered Gray Matter Volume and White Matter Integrity in College Students with Mobile Phone Dependence

    PubMed Central

    Wang, Yongming; Zou, Zhiling; Song, Hongwen; Xu, Xiaodan; Wang, Huijun; d’Oleire Uquillas, Federico; Huang, Xiting

    2016-01-01

    Mobile phone dependence (MPD) is a behavioral addiction that has become an increasing public mental health issue. While previous research has explored some of the factors that may predict MPD, the underlying neural mechanisms of MPD have not been investigated yet. The current study aimed to explore the microstructural variations associated with MPD as measured with functional Magnetic Resonance Imaging (fMRI). Gray matter volume (GMV) and white matter (WM) integrity [four indices: fractional anisotropy (FA); mean diffusivity (MD); axial diffusivity (AD); and radial diffusivity (RD)] were calculated via voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) analysis, respectively. Sixty-eight college students (42 female) were enrolled and separated into two groups [MPD group, N = 34; control group (CG), N = 34] based on Mobile Phone Addiction Index (MPAI) scale score. Trait impulsivity was also measured using the Barratt Impulsiveness Scale (BIS-11). In light of underlying trait impulsivity, results revealed decreased GMV in the MPD group relative to controls in regions such as the right superior frontal gyrus (sFG), right inferior frontal gyrus (iFG), and bilateral thalamus (Thal). In the MPD group, GMV in the above mentioned regions was negatively correlated with scores on the MPAI. Results also showed significantly less FA and AD measures of WM integrity in the MPD group relative to controls in bilateral hippocampal cingulum bundle fibers (CgH). Additionally, in the MPD group, FA of the CgH was also negatively correlated with scores on the MPAI. These findings provide the first morphological evidence of altered brain structure with mobile phone overuse, and may help to better understand the neural mechanisms of MPD in relation to other behavioral and substance addiction disorders. PMID:27199831

  17. Altered Gray Matter Volume and White Matter Integrity in College Students with Mobile Phone Dependence.

    PubMed

    Wang, Yongming; Zou, Zhiling; Song, Hongwen; Xu, Xiaodan; Wang, Huijun; d'Oleire Uquillas, Federico; Huang, Xiting

    2016-01-01

    Mobile phone dependence (MPD) is a behavioral addiction that has become an increasing public mental health issue. While previous research has explored some of the factors that may predict MPD, the underlying neural mechanisms of MPD have not been investigated yet. The current study aimed to explore the microstructural variations associated with MPD as measured with functional Magnetic Resonance Imaging (fMRI). Gray matter volume (GMV) and white matter (WM) integrity [four indices: fractional anisotropy (FA); mean diffusivity (MD); axial diffusivity (AD); and radial diffusivity (RD)] were calculated via voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) analysis, respectively. Sixty-eight college students (42 female) were enrolled and separated into two groups [MPD group, N = 34; control group (CG), N = 34] based on Mobile Phone Addiction Index (MPAI) scale score. Trait impulsivity was also measured using the Barratt Impulsiveness Scale (BIS-11). In light of underlying trait impulsivity, results revealed decreased GMV in the MPD group relative to controls in regions such as the right superior frontal gyrus (sFG), right inferior frontal gyrus (iFG), and bilateral thalamus (Thal). In the MPD group, GMV in the above mentioned regions was negatively correlated with scores on the MPAI. Results also showed significantly less FA and AD measures of WM integrity in the MPD group relative to controls in bilateral hippocampal cingulum bundle fibers (CgH). Additionally, in the MPD group, FA of the CgH was also negatively correlated with scores on the MPAI. These findings provide the first morphological evidence of altered brain structure with mobile phone overuse, and may help to better understand the neural mechanisms of MPD in relation to other behavioral and substance addiction disorders. PMID:27199831

  18. Altered Gray Matter Volume and White Matter Integrity in College Students with Mobile Phone Dependence.

    PubMed

    Wang, Yongming; Zou, Zhiling; Song, Hongwen; Xu, Xiaodan; Wang, Huijun; d'Oleire Uquillas, Federico; Huang, Xiting

    2016-01-01

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

  19. Neurofeedback training induces changes in white and gray matter.

    PubMed

    Ghaziri, Jimmy; Tucholka, Alan; Larue, Vanessa; Blanchette-Sylvestre, Myriam; Reyburn, Gabrielle; Gilbert, Guillaume; Lévesque, Johanne; Beauregard, Mario

    2013-10-01

    The main objective of this structural magnetic resonance imaging (MRI) study was to investigate, using diffusion tensor imaging, whether a neurofeedback training (NFT) protocol designed to improve sustained attention might induce structural changes in white matter (WM) pathways, purportedly implicated in this cognitive ability. Another goal was to examine whether gray matter (GM) volume (GMV) might be altered following NFT in frontal and parietal cortical areas connected by these WM fiber pathways. Healthy university students were randomly assigned to an experimental group (EXP), a sham group, or a control group. Participants in the EXP group were trained to enhance the amplitude of their β1 waves at F4 and P4. Measures of attentional performance and MRI data were acquired one week before (Time 1) and one week after (Time 2) NFT. Higher scores on visual and auditory sustained attention were noted in the EXP group at Time 2 (relative to Time 1). As for structural MRI data, increased fractional anisotropy was measured in WM pathways implicated in sustained attention, and GMV increases were detected in cerebral structures involved in this type of attention. After 50 years of research in the field of neurofeedback, our study constitutes the first empirical demonstration that NFT can lead to microstructural changes in white and gray matter.

  20. Automated Detection of Lupus White Matter Lesions in MRI.

    PubMed

    Roura, Eloy; Sarbu, Nicolae; Oliver, Arnau; Valverde, Sergi; González-Villà, Sandra; Cervera, Ricard; Bargalló, Núria; Lladó, Xavier

    2016-01-01

    Brain magnetic resonance imaging provides detailed information which can be used to detect and segment white matter lesions (WML). In this work we propose an approach to automatically segment WML in Lupus patients by using T1w and fluid-attenuated inversion recovery (FLAIR) images. Lupus WML appear as small focal abnormal tissue observed as hyperintensities in the FLAIR images. The quantification of these WML is a key factor for the stratification of lupus patients and therefore both lesion detection and segmentation play an important role. In our approach, the T1w image is first used to classify the three main tissues of the brain, white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF), while the FLAIR image is then used to detect focal WML as outliers of its GM intensity distribution. A set of post-processing steps based on lesion size, tissue neighborhood, and location are used to refine the lesion candidates. The proposal is evaluated on 20 patients, presenting qualitative, and quantitative results in terms of precision and sensitivity of lesion detection [True Positive Rate (62%) and Positive Prediction Value (80%), respectively] as well as segmentation accuracy [Dice Similarity Coefficient (72%)]. Obtained results illustrate the validity of the approach to automatically detect and segment lupus lesions. Besides, our approach is publicly available as a SPM8/12 toolbox extension with a simple parameter configuration. PMID:27570507

  1. Automated Detection of Lupus White Matter Lesions in MRI

    PubMed Central

    Roura, Eloy; Sarbu, Nicolae; Oliver, Arnau; Valverde, Sergi; González-Villà, Sandra; Cervera, Ricard; Bargalló, Núria; Lladó, Xavier

    2016-01-01

    Brain magnetic resonance imaging provides detailed information which can be used to detect and segment white matter lesions (WML). In this work we propose an approach to automatically segment WML in Lupus patients by using T1w and fluid-attenuated inversion recovery (FLAIR) images. Lupus WML appear as small focal abnormal tissue observed as hyperintensities in the FLAIR images. The quantification of these WML is a key factor for the stratification of lupus patients and therefore both lesion detection and segmentation play an important role. In our approach, the T1w image is first used to classify the three main tissues of the brain, white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF), while the FLAIR image is then used to detect focal WML as outliers of its GM intensity distribution. A set of post-processing steps based on lesion size, tissue neighborhood, and location are used to refine the lesion candidates. The proposal is evaluated on 20 patients, presenting qualitative, and quantitative results in terms of precision and sensitivity of lesion detection [True Positive Rate (62%) and Positive Prediction Value (80%), respectively] as well as segmentation accuracy [Dice Similarity Coefficient (72%)]. Obtained results illustrate the validity of the approach to automatically detect and segment lupus lesions. Besides, our approach is publicly available as a SPM8/12 toolbox extension with a simple parameter configuration. PMID:27570507

  2. Proton magnetic resonance spectroscopy of periventricular white matter and hippocampus in obstructive sleep apnea patients

    PubMed Central

    Kızılgöz, Volkan; Aydın, Hasan; Tatar, İdil Güneş; Hekimoğlu, Baki; Ardıç, Sadık; Fırat, Hikmet; Dönmez, Cem

    2013-01-01

    Summary Background The purpose of this study was to diagnose the hypoxic impairment by Magnetic resonance spectroscopy (MRS), an advanced MR imaging technique, which could not be visualised by routine imaging methods in patients with obstructive sleep apnea (OSA). Material/Methods 20 OSA patients and 5 controls were included in this prospective research. MRS was performed on these 25 subjects to examine cerebral hypoxemia in specific regions (periventricular white matter and both hippocampi). Polysomnography was assumed as the gold standard. Statistical analysis was assessed by Mann-Whitney U test and Receiver operating characteristics (ROC) curve for NAA/Cho, NAA/Cr and Cho/Cr ratios. Results In the periventricular white matter, NAA/Cho ratio in OSA patients was significantly lower than in the control group (p<0.05). There were no statistical differences between the OSA and the control group for NAA/Cho, NAA/Cr and Cho/Cr ratios for both hippocampal regions. Additionally, Cho/Cr ratio in the periventricular white matter region of OSA group was higher than in the control group (p<0.05). Conclusions Hypoxic impairment induced by repeated episodes of apnea leads to significant neuronal damage in OSA patients. MRS provides valuable information in the assessment of hypoxic ischemic impairment by revealing important metabolite ratios for the specific areas of the brain. PMID:24505219

  3. COGNITIVE PROCESSING SPEED AND THE STRUCTURE OF WHITE MATTER PATHWAYS: CONVERGENT EVIDENCE FROM NORMAL VARIATION AND LESION STUDIES

    PubMed Central

    Turken, And U.; Whitfield-Gabrieli, Susan; Bammer, Roland; Baldo, Juliana; Dronkers, Nina F.; Gabrieli, John D. E.

    2008-01-01

    We investigated the relation between cognitive processing speed and structural properties of white matter pathways via convergent imaging studies in healthy and brain-injured groups. Voxel-based morphometry (VBM) was applied to diffusion tensor imaging data from thirty-nine young healthy subjects in order to investigate the relation between processing speed, as assessed with the Digit-Symbol subtest from WAIS-III, and fractional anisotropy, an index of microstructural organization of white matter. Digit-Symbol performance was positively correlated with fractional anisotropy of white matter in the parietal and temporal lobes bilaterally and in the left middle frontal gyrus. Fiber tractography indicated that these regions are consistent with the trajectories of the superior and inferior longitudinal fasciculi. In a second investigation, we assessed the effect of white matter damage on processing speed using voxel-based lesion symptom mapping (VLSM) analysis of data from seventy-two patients with left hemisphere strokes. Lesions in left parietal white matter, together with cortical lesions in supramarginal and angular gyri were associated with impaired performance. These findings suggest that cognitive processing speed, as assessed by the Digit-Symbol test, is closely related to the structural integrity of white matter tracts associated with parietal and temporal cortices and left middle frontal gyrus. Further, fiber tractography applied to VBM results and the patient findings suggest that the superior longitudinal fasciculus, a major tract subserving fronto-parietal integration, makes a prominent contribution to processing speed. PMID:18602840

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

    PubMed Central

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

    2013-01-01

    , posterior cingulate and frontal regions only in the Alzheimer’s group. The severity of white matter degeneration appears to be higher in advanced clinical stages, supporting the construct that these abnormalities are part of the pathophysiological processes of Alzheimer’s disease. PMID:24086371

  5. 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

  6. 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

  7. Alterations in white matter pathways in Angelman syndrome

    PubMed Central

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

    2010-01-01

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

  8. 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 18–81 years; 41.3 ± 14.5) from the Genetics of Brain Structure and Function Study. Shared genetic variance was calculated between measures of adiposity [(body mass index (BMI; kg/m2) and waist circumference (WC; in)] and whole-brain and regional measurements of cerebral white matter integrity (fractional anisotropy). Whole-brain average and regional fractional anisotropy values for 10 major white matter tracts were calculated from high angular resolution diffusion tensor imaging data (DTI; 1.7 × 1.7 × 3 mm; 55 directions). Additive genetic factors explained intersubject variance in BMI (heritability, h2 = 0.58), WC (h2 = 0.57), and FA (h2 = 0.49). FA shared significant portions of genetic variance with BMI in the genu (ρG = −0.25), body (ρG = −0.30), and splenium (ρG = −0.26) of the corpus callosum, internal capsule (ρG = −0.29), and thalamic radiation (ρG = −0.31) (all p's = 0.043). The strongest evidence of shared variance was between BMI/WC and FA in the superior fronto-occipital fasciculus (ρG = −0.39, p = 0.020; ρG = −0.39, p = 0.030), which highlights region-specific variation in neural correlates of obesity. This may suggest that increase in obesity and reduced white matter integrity share common genetic risk factors. PMID:25763009

  9. 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 [β=-0.05 (p=0.005) in univariate and β=-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 [β=0.11 (p=0.007) and β=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

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

    PubMed

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

    2014-03-01

    Brain development occurs rapidly during the first few years of life involving region-specific changes in both gray matter 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=35months) 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.

  11. Different scaling of white matter volume, cortical connectivity, and gyrification across rodent and primate brains

    PubMed Central

    Ventura-Antunes, Lissa; Mota, Bruno; Herculano-Houzel, Suzana

    2013-01-01

    Expansion of the cortical gray matter in evolution has been accompanied by an even faster expansion of the subcortical white matter volume and by folding of the gray matter surface, events traditionally considered to occur homogeneously across mammalian species. Here we investigate how white matter expansion and cortical folding scale across species of rodents and primates as the gray matter gains neurons. We find very different scaling rules of white matter expansion across the two orders, favoring volume conservation and smaller propagation times in primates. For a similar number of cortical neurons, primates have a smaller connectivity fraction and less white matter volume than rodents; moreover, as the cortex gains neurons, there is a much faster increase in white matter volume and in its ratio to gray matter volume in rodents than in primates. Order-specific scaling of the white matter can be attributed to different scaling of average fiber caliber and neuronal connectivity in rodents and primates. Finally, cortical folding increases as different functions of the number of cortical neurons in rodents and primates, scaling faster in the latter than in the former. While the neuronal rules that govern gray and white matter scaling are different across rodents and primates, we find that they can be explained by the same unifying model, with order-specific exponents. The different scaling of the white matter has implications for the scaling of propagation time and computational capacity in evolution, and calls for a reappraisal of developmental models of cortical expansion in evolution. PMID:23576961

  12. 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

  13. Higher diffusion in striatum and lower fractional anisotropy in white matter of methamphetamine users

    PubMed Central

    Alicata, Daniel; Chang, Linda; Cloak, Christine; Abe, Kylie; Ernst, Thomas

    2010-01-01

    Methamphetamine (METH) users showed structural and chemical abnormalities on magnetic resonance (MRI) studies, particularly in the frontal and basal ganglia brain regions. Diffusion tensor imaging (DTI) may provide further insights regarding the microstructural changes in METH users. We investigated diffusion tensor measures in frontal white matter and basal ganglia of 30 adult METH users and 30 control subjects using a 3 T MR scanner. Compared with healthy control subjects, METH users showed lower fractional anisotropy (FA) in right frontal white matter, and higher apparent diffusion coefficient (ADC) in left caudate and bilateral putamen. Higher left putamen ADC was associated with earlier initiation of METH use, greater daily amounts, and a higher cumulative lifetime dose. Similarly, higher right putamen ADC was associated with greater daily amounts and a higher cumulative lifetime dose. The lower FA in the right frontal white matter suggests axonal injury in these METH users. The higher ADC in the basal ganglia suggests greater inflammation or less myelination in these brain regions of those with younger age of first METH use and greater METH usage. PMID:19782540

  14. 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 0.5°C/h, or rapid rewarming at 4°C/h. Apoptotic cells in the subcortical white matter of the motor gyrus, corpus callosum, lateral olfactory tract, and internal capsule at 29h were identified morphologically and counted by hematoxylin & eosin staining. Cell death was verified by terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL) assay. White matter neurons were also counted, and apoptotic cells were immunophenotyped with the oligodendrocyte marker 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase). Hypothermia, slow rewarming, and rapid rewarming increased apoptosis in the subcortical white matter relative to normothermia (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

  15. Frontal White Matter Integrity Predictors of Adult Alcohol Treatment Outcome

    PubMed Central

    Sorg, Scott F.; Taylor, Michael J.; Alhassoon, Omar M.; Gongvatana, Assawin; Theilmann, Rebecca J.; Frank, Lawrence R.; Grant, Igor

    2013-01-01

    Background Previous research has associated abnormalities in frontal lobe functioning with alcohol relapse. In this study, we used diffusion tensor imaging to investigate whether frontal white matter integrity measured at the start of treatment differs between persons with alcohol use disorders (AUD) who sustain treatment gains and those who return to heavy use after treatment. Methods Forty-five treatment-seeking AUD inpatients and 30 healthy control subjects were included in the study. Six months after completing treatment, 16 of the AUD participants had resumed heavy use (RHU) and 29 others remained abstinent or drank minimally (treatment sustainers [TS]). Voxel-wise group comparisons (TS vs. RHU) were performed on fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity maps generated from each subject’s diffusion tensor imaging scan at the start of treatment. Results We found significantly lower FA and significantly higher RD in the frontal lobes of the RHU group, relative to the TS group. The RHU group data are consistent with previous reports of abnormal frontal white matter tract abnormalities in persons with AUD. Conclusions It is possible that the lower FA and higher RD in the RHU group reflect microstructural injury to frontal circuitries, and these may underlie the reduced cognitive control amid heightened reward sensitivity associated with resumption of heavy drinking. PMID:22047719

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

    PubMed

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

    2012-08-21

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

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

    PubMed

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

    2015-04-01

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

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

    PubMed

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

    2012-08-21

    Ischemic insults affecting the internal capsule result in sensory-motor disabilities which adversely affect the patient's life. Cerebral endothelial cells have been reported to exert a protective effect against brain damage, so the transplantation of healthy endothelial cells might have a beneficial effect on the outcome of ischemic brain damage. In this study, endothelin-1 (ET-1) was injected into the rat internal capsule to induce lacunar infarction. Seven days after ET-1 injection, microvascular endothelial cells (MVECs) were transplanted into the internal capsule. Meningeal cells or 0.2% bovine serum albumin-Hank's balanced salt solution were injected as controls. Two weeks later, the footprint test and histochemical analysis were performed. We found that MVEC transplantation improved the behavioral outcome based on recovery of hind-limb rotation angle (P<0.01) and induced remyelination (P<0.01) compared with the control groups. Also the inflammatory response was repressed by MVEC transplantation, judging from fewer ED-1-positive activated microglial cells in the MVEC-transplanted group than in the other groups. Elucidation of the mechanisms by which MVECs ameliorate ischemic damage of the white matter may provide important information for the development of effective therapies for white matter ischemia. PMID:22771710

  19. 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 β-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.

  20. Vanishing White Matter Disease in a Spanish Population

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    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

  2. fMRI Correlates of White Matter Hyperintensities in Late-Life Depression

    PubMed Central

    Aizenstein, Howard J.; Andreescu, Carmen; Edelman, Kathryn L.; Cochran, Jennifer L.; Price, Julie; Butters, Meryl A.; Karp, Jordan; Patel, Meenal; Reynolds, Charles F.

    2013-01-01

    Objective This study tests whether or not the structural white matter lesions that are characteristic of late-life depression are associated with alterations in the functional affective circuits of late-life depression. This study used an emotional faces paradigm that has been shown to engage the affective limbic brain regions. Method Thirty-three elderly depressed patients and 27 nondepressed comparison subjects participated in this study. The patients were recruited through the NIMH-sponsored Advanced Center for Interventions and Services Research for the Study of Late-Life Mood Disorders at the University of Pittsburgh Center for Bioethics and Health Law. Structural and functional MRI was used to assess white matter hyperintensity (WMH) burden and functional magnetic resonance imaging (fMRI) blood-oxygen-level-dependent (BOLD) response on a facial expression affective-reactivity task in both elderly participants with nonpsychotic and non-bipolar major depression (unmedicated) and nondepressed elderly comparison subjects. Results As expected, greater subgenual cingulate activity was observed in the depressed patients relative to the nondepressed comparison subjects. This same region showed greater task-related activity associated with a greater burden of cerebrovascular white matter change in the depressed group. Moreover, the depressed group showed a significantly greater interaction of WMH by fMRI activity effect than the nondepressed group. Conclusions The observation that high WMH burden in late-life depression is associated with greater BOLD response on the affective-reactivity task supports the model that white matter ischemia in elderly depressed patients disrupts brain mechanisms of affective regulation and leads to limbic hyperactivation. PMID:21799066

  3. Quantitative Tract-Based White Matter Development from Birth to Age Two Years

    PubMed Central

    Geng, Xiujuan; Gouttard, Sylvain; Sharma, Anuja; Gu, Hongbin; Styner, Martin; Lin, Weili; Gerig, Guido; Gilmore, John H

    2012-01-01

    Few large-scale studies have been done to characterize the normal human brain white matter growth in the first years of life. We investigated white matter maturation patterns in major fiber pathways in a large cohort of healthy young children from birth to age two using diffusion parameters fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (RD). Ten fiber pathways, including commissural, association and projection tracts, were examined with tract-based analysis, providing more detailed and continuous spatial developmental patterns compared to conventional ROI based methods. All DTI data sets were transformed to a population specific atlas with a group-wise longitudinal large deformation diffeomorphic registration approach. Diffusion measurements were analyzed along the major fiber tracts obtained in the atlas space. All fiber bundles show increasing FA values and decreasing radial and axial diffusivities during the development in the first two years of life. The changing rates of the diffusion indices are faster in the first year than the second year for all tracts. RD and FA show larger percentage changes in the first and second years than AD. The gender effects on the diffusion measures are small. Along different spatial locations of fiber tracts, maturation does not always follow the same speed. Temporal and spatial diffusion changes near cortical regions are in general smaller than changes in central regions. Overall developmental patterns revealed in our study confirm the general rules of white matter maturation. This work shows a promising framework to study and analyze white matter maturation in a tract-based fashion. Compared to most previous studies that are ROI-based, our approach has the potential to discover localized development patterns associated with fiber tracts of interest. PMID:22510254

  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

  5. 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

  6. Method for combining information from white matter fiber tracking and gray matter parcellation.

    PubMed

    Park, Hae-Jeong; Kubicki, Marek; Westin, Carl-Fredrik; Talos, Ion-Florin; Brun, Anders; Peiper, Steve; Kikinis, Ron; Jolesz, Ference A; McCarley, Robert W; Shenton, Martha E

    2004-09-01

    We introduce a method for combining fiber tracking from diffusion-tensor (DT) imaging with cortical gray matter parcellation from structural high-spatial-resolution 3D spoiled gradient-recalled acquisition in the steady state images. We applied this method to a tumor case to determine the impact of the tumor on white matter architecture. We conclude that this new method for combining structural and DT imaging data is useful for understanding cortical connectivity and the localization of fiber tracts and their relationship with cortical anatomy and brain abnormalities.

  7. 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

  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 < 0.05). Immunohistochemistry showed that LCN2 receptor 24p3R was expressed in oligodendrocytes, astrocytes, endothelial cells, and pericytes in the 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.

  9. Ionotropic glutamate receptor expression in human white matter.

    PubMed

    Christensen, Pia Crone; Samadi-Bahrami, Zahra; Pavlov, Vlady; Stys, Peter K; Moore, G R Wayne

    2016-09-01

    Glutamate is the key excitatory neurotransmitter of the central nervous system (CNS). Its role in human grey matter transmission is well understood, but this is less clear in white matter (WM). Ionotropic glutamate receptors (iGluR) are found on both neuronal cell bodies and glia as well as on myelinated axons in rodents, and rodent WM tissue is capable of glutamate release. Thus, rodent WM expresses many of the components of the traditional grey matter neuron-to-neuron synapse, but to date this has not been shown for human WM. We demonstrate the presence of iGluRs in human WM by immunofluorescence employing high-resolution spectral confocal imaging. We found that the obligatory N-methyl-d-aspartic acid (NMDA) receptor subunit GluN1 and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluA4 co-localized with myelin, oligodendroglial cell bodies and processes. Additionally, GluA4 colocalized with axons, often in distinct clusters. These findings may explain why human WM is vulnerable to excitotoxic events following acute insults such as stroke and traumatic brain injury and in more chronic inflammatory conditions such as multiple sclerosis (MS). Further exploration of human WM glutamate signalling could pave the way for developing future therapies modulating the glutamate-mediated damage in these and other CNS disorders. PMID:27443784

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

    PubMed

    Rosenzweig, Shira; Carmichael, S Thomas

    2015-10-14

    Approximately one quarter of all strokes in humans occur in white matter, and the progressive nature of white matter lesions often results in severe physical and mental disability. Unlike cortical grey matter stroke, the pathology of white matter stroke revolves around disrupted connectivity and injured axons and glial cells, rather than neuronal cell bodies. Consequently, the mechanisms behind ischemic damage to white matter elements, the regenerative responses of glial cells and their signaling pathways, all differ significantly from those in grey matter. Development of effective therapies for white matter stroke would require an enhanced understanding of the complex cellular and molecular interactions within the white matter, leading to the identification of new therapeutic targets. This review will address the unique properties of the axon-glia unit during white matter stroke, describe the challenging process of promoting effective white matter repair, and discuss recently-identified signaling pathways which may hold potential targets for repair in this disease. This article is part of a Special Issue entitled SI: Cell Interactions In Stroke.

  11. Discriminating the Difference between Remote and Close Association with Relation to White-Matter Structural Connectivity

    PubMed Central

    Wu, Chinglin; Zhong, Suyu; Chen, Hsuehchih

    2016-01-01

    Remote association is a core ability that influences creative output. In contrast to close association, remote association is commonly agreed to be connected with more original and unique concepts. However, although existing studies have discovered that creativity is closely related to the white-matter structure of the brain, there are no studies that examine the relevance between the connectivity efficiencies and creativity of the brain regions from the perspective of networks. Consequently, this study constructed a brain white matter network structure that consisted of cerebral tissues and nerve fibers and used graph theory to analyze the connection efficiencies among the network nodes, further illuminating the differences between remote and close association in relation to the connectivity of the brain network. Researchers analyzed correlations between the scores of 35 healthy adults with regard to remote and close associations and the connectivity efficiencies of the white-matter network of the brain. Controlling for gender, age, and verbal intelligence, the remote association positively correlated with the global efficiency and negatively correlated with the levels of small-world. A close association negatively correlated with the global efficiency. Notably, the node efficiency in the middle temporal gyrus (MTG) positively correlated with remote association and negatively correlated with close association. To summarize, remote and close associations work differently as patterns in the brain network. Remote association requires efficient and convenient mutual connections between different brain regions, while close association emphasizes the limited connections that exist in a local region. These results are consistent with previous results, which indicate that creativity is based on the efficient integration and connection between different regions of the brain and that temporal lobes are the key regions for discriminating remote and close associations. PMID

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

    PubMed

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

    2015-08-01

    Most studies examining associations between hypertension and brain white matter microstructure have focused on older adults or on cohorts with a large age range. Because hypertension effects on the brain may vary with age, it is important to focus on middle age, when hypertension becomes more prevalent. We used linear mixed-effect models to examine differences in white matter diffusion metrics as a function of hypertension in a well-characterized cohort of middle-aged men (n=316; mean, 61.8 years; range, 56.7-65.6). Diffusion metrics were examined in 9 tracts reported to be sensitive to hypertension in older adults. Relative to normotensive individuals, individuals with long-standing hypertension (>5.6 years) showed reduced fractional anisotropy or increased diffusivity in most tracts. Effects were stronger among carriers than among noncarriers of the apolipoprotein E ε4 allele for 2 tracts connecting frontal regions with other brain areas. Significant differences were observed even after adjustment for potentially related lifestyle and cardiovascular risk factors. Shorter duration of hypertension or better blood pressure control among hypertensive individuals did not lessen the adverse effects. These findings suggest that microstructural white matter alterations appear early in the course of hypertension and may persist despite adequate treatment. Although longitudinal studies are needed to confirm these findings, the results suggest that prevention-rather than management-of hypertension may be vital to preserving brain health in aging.

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

    PubMed Central

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

    2015-01-01

    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

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

    PubMed Central

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

    2015-01-01

    Most studies examining associations between hypertension and brain white matter microstructure have focused on older adults or on cohorts with a large age range. Since hypertension effects on the brain may vary with age it is important to focus on middle age, when hypertension becomes more prevalent. We used linear mixed effect models to examine differences in white matter diffusion metrics as a function of hypertension in a well-characterized cohort of middle-aged men (N=316, mean 61.8 years; range 56.7–65.6). Diffusion metrics were examined in nine tracts reported to be sensitive to hypertension in older adults. Relative to normotensive individuals, individuals with longstanding hypertension (> 5.6 years) showed reduced fractional anisotropy or increased diffusivity in most tracts. Effects were stronger among carriers than non-carriers of the apolipoprotein E ε4 allele for two tracts connecting frontal regions with other brain areas. Significant differences were observed even after adjustment for potentially-related lifestyle and cardiovascular risk factors. Shorter duration of hypertension or better blood pressure control among hypertensive individuals did not lessen the adverse effects. These findings suggest that microstructural white matter alterations appear early in the course of hypertension and may persist despite adequate treatment. Although longitudinal studies are needed to confirm these findings, the results suggest that prevention—rather than management—of hypertension may be vital to preserving brain health in aging. PMID:26056337

  15. Disruption of White Matter Integrity by Chronic Cerebral Hypoperfusion in Alzheimer's Disease Mouse Model.

    PubMed

    Zhai, Yun; Yamashita, Toru; Nakano, Yumiko; Sun, Zhuoran; Morihara, Ryuta; Fukui, Yusuke; Ohta, Yasuyuki; Hishikawa, Nozomi; Abe, Koji

    2016-04-12

    A rapidly progressing aging society has raised attention to white matter lesions in Alzheimer's disease. In the present study, we applied an AD plus cerebral hypoperfusion (HP) mouse model and investigated the alternation of key protein molecules in the nodal, paranodal, and intermodal sites in the white matter as well as the efficacy of galantamine. Cerebral HP was induced in APP23 mice by bilateral common carotid arteries stenosis with ameroid constrictors. Compared with the wild type and simple APP23 mice, APP23 + HP mice showed a progressive loss of MAG and NF186 from 6 to 12 months, broken misdistribution of MBP, and extended relocation of Nav1.6 and AnkG beyond the primary nodal region in the corpus callosum. Such abnormal neuropathological processes were retrieved with galantamine treatment. The present study demonstrated that cerebral HP strongly disrupted white matter integrity (WMI) at intermodal, paranodal, and Ranvier's nodal sites which may be associated with cognitive decline. Galantamine treatment significantly protected such WMI probably by allosterically potentiating ligand action. PMID:27079724

  16. Connectivity-driven white matter scaling and folding in primate cerebral cortex

    PubMed Central

    Herculano-Houzel, Suzana; Mota, Bruno; Kaas, Jon H.

    2010-01-01

    Larger brains have an increasingly folded cerebral cortex whose white matter scales up faster than the gray matter. Here we analyze the cellular composition of the subcortical white matter in 11 primate species, including humans, and one Scandentia, and show that the mass of the white matter scales linearly across species with its number of nonneuronal cells, which is expected to be proportional to the total length of myelinated axons in the white matter. This result implies that the average axonal cross-section area in the white matter, a, does not scale significantly with the number of neurons in the gray matter, N. The surface area of the white matter increases with N0.87, not N1.0. Because this surface can be defined as the product of N, a, and the fraction n of cortical neurons connected through the white matter, we deduce that connectivity decreases in larger cerebral cortices as a slowly diminishing fraction of neurons, which varies with N−0.16, sends myelinated axons into the white matter. Decreased connectivity is compatible with previous suggestions that neurons in the cerebral cortex are connected as a small-world network and should slow down the increase in global conduction delay in cortices with larger numbers of neurons. Further, a simple model shows that connectivity and cortical folding are directly related across species. We offer a white matter-based mechanism to account for increased cortical folding across species, which we propose to be driven by connectivity-related tension in the white matter, pulling down on the gray matter. PMID:20956290

  17. 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.

  18. Motor skill learning is associated with diffusion characteristics of white matter in individuals with chronic stroke

    PubMed Central

    Borich, Michael R.; Brown, Katlyn E.; Boyd, Lara A.

    2013-01-01

    Background and Purpose Imaging advances allow investigation of white matter following stroke; a growing body of literature has shown links between diffusion-based measures of white matter microstructure and motor function. However, the relationship between these measures and motor skill learning has not been considered in individuals with stroke. The aim of this study was to investigate the relationships between post-training white matter microstructural status, as indexed by diffusion tensor imaging (DTI) within the ipsilesional posterior limb of the internal capsule (PLIC) and learning of a novel motor task in individuals with chronic stroke. Methods Thirteen participants with chronic stroke and nine healthy controls practiced a visuomotor pursuit task across five sessions. Change in motor behavior associated with learning was indexed by comparing baseline performance with a delayed retention test. Fractional anisotropy (FA) indexed at the retention test was the primary DTI-derived outcome measure. Results In individuals with chronic stroke, we discovered an association between post-training ipsilesional PLIC FA and the magnitude of change associated with motor learning; hierarchical multiple linear regression analyses revealed that the combination of age, time post stroke and ipsilesional PLIC FA post-training was associated with motor learning related change (R2=0.649, p=0.02). Baseline motor performance was not related to post-training ipsilesional PLIC FA. Discussion and Conclusions Diffusion characteristics of post-training ipsilesional PLIC were linked to magnitude of change in skilled motor behavior. These results imply that the microstructural properties of regional white matter indexed by diffusion behavior may be an important factor to consider when determining potential response to rehabilitation in persons with stroke. Video Abstract available (See Video, Supplemental Digital Content 1.) for more insights from the authors. PMID:23934017

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

    PubMed

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

    2013-02-01

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

  20. Development of superficial white matter and its structural interplay with cortical gray matter in children and adolescents.

    PubMed

    Wu, Minjie; Lu, Lisa H; Lowes, Allison; Yang, Shaolin; Passarotti, Alessandra M; Zhou, Xiaohong J; Pavuluri, Mani N

    2014-06-01

    Healthy human brain undergoes significant changes during development. The developmental trajectory of superficial white matter (SWM) is less understood relative to cortical gray matter (GM) and deep white matter. In this study, a multimodal imaging strategy was applied to vertexwise map SWM microstructure and cortical thickness to characterize their developmental pattern and elucidate SWM-GM associations in children and adolescents. Microscopic changes in SWM were evaluated with water diffusion parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in 133 healthy subjects aged 10-18 years. Results demonstrated distinct maturational patterns in SWM and GM. SWM showed increasing FA and decreasing MD and RD underneath bilateral motor sensory cortices and superior temporal auditory cortex, suggesting increasing myelination. A second developmental pattern in SWM was increasing FA and AD in bilateral orbitofrontal regions and insula, suggesting improved axonal coherence. These SWM patterns diverge from the more widespread GM maturation, suggesting that cortical thickness changes in adolescence are not explained by the encroachment of SWM myelin into the GM-WM boundary. Interestingly, age-independent intrinsic association between SWM and cortical GM seems to follow functional organization of polymodal and unimodal brain regions. Unimodal sensory areas showed positive correlation between GM thickness and FA whereas polymodal regions showed negative correlation. Axonal coherence and differences in interstitial neuron composition between unimodal and polymodal regions may account for these SWM-GM association patterns. Intrinsic SWM-GM relationships unveiled by neuroimaging in vivo can be useful for examining psychiatric disorders with known WM/GM disturbances.

  1. Inelastic Behavior in Repeated Shearing of Bovine White Matter

    PubMed Central

    Cohen, Taylor S.; Smith, Andrew; Massouros, Panagiotis G.; Bayly, Philip V.; Shen, Amy Q.; Genin, Guy M.

    2008-01-01

    Understanding the brain's response to multiple loadings requires knowledge of how straining changes the mechanical response of brain tissue. We studied the inelastic behavior of bovine white matter and found that when this tissue is stretched beyond a critical strain threshold its reloading stiffness drops. An upper bound for this strain threshold was characterized, and was found to be strain-rate dependent at low strain rates, and strain-rate independent at higher strain rates. Results suggest that permanent changes to tissue mechanics can occur at strains below those believed to cause physiological disruption or rupture of axons. Such behavior is characteristic of disentanglement in fibrous networked solids, in which strain-induced mechanical changes may result from fiber realignment rather than fiber breakage. PMID:18601466

  2. Multi-scale characterization of white matter tract geometry.

    PubMed

    Savadjiev, Peter; Rathi, Yogesh; Bouix, Sylvain; Verma, Ragini; Westin, Carl-Fredrik

    2012-01-01

    The geometry of white matter tracts is of increased interest for a variety of neuroscientific investigations, as it is a feature reflective of normal neurodevelopment and disease factors that may affect it. In this paper, we introduce a novel method for computing multi-scale fibre tract shape and geometry based on the differential geometry of curve sets. By measuring the variation of a curve's tangent vector at a given point in all directions orthogonal to the curve, we obtain a 2D "dispersion distribution function" at that point. That is, we compute a function on the unit circle which describes fibre dispersion, or fanning, along each direction on the circle. Our formulation is then easily incorporated into a continuous scale-space framework. We illustrate our method on different fibre tracts and apply it to a population study on hemispheric lateralization in healthy controls. We conclude with directions for future work.

  3. 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., 20–50%) as those with Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). We hypothesized a gradient between cognition and white matter integrity, such that strongest brain-behavior relationships would emerge in NPSLE, intermediate in non-NPSLE, and minimal in controls. We studied thirty-one patients (16 non-NPSLE; 15 NPSLE), ranging in age from 18 to 59 years old (100% female), and eighteen age and gender matched healthy controls. DTI examinations were performed on a 1.5T scanner. A broad neuropsychological battery was administered, tapping attention, memory, processing speed, and executive functioning. The Total z-score consisted of the combined sum of all neuropsychological measures. In control subjects, we found no significant FA-Total z-score correlations. NPSLE, non-NPSLE, and control subjects differed significantly in terms of Total z-score (NPSLE = −2.25+/−1.77, non-NPSLE = −1.22+/−1.03, Controls = −0.10+/−.57; F = 13.2, p<.001). In non-NPSLE subjects, FA within the right external capsule was significantly correlated with Total z-score. In NPSLE subjects, the largest FA-Total z-score clusters were observed within the left anterior thalamic radiation and right superior longitudinal fasciculus. In subsequent analyses the largest number of significant voxels linked FA with the Processing Speed z-score in NPSLE. The current results reflect objective white matter correlates of neuropsychological dysfunction in both NPSLE and (to a lesser degree) in non-NPSLE. non-NPSLE and NPSLE subjects did not differ significantly in terms of depression, as measured by the GDI; thus, previous hypotheses suggesting moderating effects of depression upon neuropsychological performance do not impact the current FA results. PMID:22291880

  4. 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

  5. Histone Deacetylase Expression in White Matter Oligodendrocytes after Stroke

    PubMed Central

    Kassis, Haifa; Chopp, Michael; Liu, Xian Shuang; Shehadah, Amjad; Roberts, Cynthia; Zhang, Zheng Gang

    2015-01-01

    Histone deacetylases (HDACs) constitute a super-family of enzymes grouped into four major classes (Class I–IV) that deacetylate histone tails leading to chromatin condensation and gene repression. Whether stroke-induced oligodendrogenesis is related to the expression of individual HDACs in the oligodendrocyte lineage has not been investigated. We found that 2 days after stroke, oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes (OLGs) were substantially reduced in the peri-infarct corpus callosum, whereas at 7 days after stroke, a robust increase in OPCs and OLGs was observed. Ischemic brains isolated from rats sacrificed 7 days after stroke were used to test levels of individual members of Class I (1 and 2) and Class II (4 and 5) HDACs in white matter oligodendrocytes during stroke-induced oligodendrogenesis. Double immunohistochemistry analysis revealed that stroke substantially increased the number of NG2+ OPCs with nuclear HDAC1 and HDAC2 immunoreactivity and cytoplasmic HDAC4 which were associated with augmentation of proliferating OPCs, as determined by BrdU and Ki67 double reactive cells after stroke. A decrease in HDAC1 and an increase in HDAC2 immunoreactivity were detected in mature adenomatous polyposis coli (APC) positive OLGs, which paralleled an increase in newly generated BrdU positive OLGs in the peri-infarct corpus callosum. Concurrently, stroke substantially decreased the acetylation levels of histones H3 and H4 in both OPCs and OLGs. Taken together, these findings demonstrate that stroke induces distinct profiles of Class I and Class II HDACs in white matter OPCs and OLGs, suggesting that the individual members of Class I and II HDACs play divergent roles in the regulation of OPC proliferation and differentiation during brain repair after stroke. PMID:24657831

  6. Coevolution of white matter hyperintensities and cognition in the elderly

    PubMed Central

    Maillard, Pauline; Carmichael, Owen; Fletcher, Evan; Reed, Bruce; Mungas, Dan

    2012-01-01

    Objective: To investigate the effects of baseline white matter hyperintensity (WMH) and rates of WMH extension and emergence on rate of change in cognition (episodic memory and executive function). Methods: A total of 150 individuals including cognitively normal elderly individuals and those with Alzheimer disease and mild cognitive impairment completed serial episodic memory and executive function evaluations and serial MRI scans sufficient for longitudinal measurement of WMH (mean delay 4.0 years). Incident WMH voxels were categorized as extended (baseline WMH that grew larger) or emergent (newly formed WMH). We used a stepwise regression approach to investigate the effects of baseline WMH and rates of WMH extension and emergence on rate of change in cognition (episodic memory and executive function). Results: WMH burden significantly increased over time, and approximately 80% of incident WMH voxels represented extensions of existing lesions. Each 1 mL/y increase in WMH extension was associated with an additional 0.70 SD/y of subsequent episodic memory decrease (p = 0.0053) and an additional 0.55 SD/y of subsequent executive function decrease (p = 0.022). Emergent WMHs were not found to be associated with a change in cognitive measures. Conclusions: Aging-associated WMHs evolve significantly over a 4-year period. Most of this evolution represents worsening injury to the already compromised surround of existing lesions. Increasing WMH was also significantly associated with declining episodic memory and executive function. This finding supports the view that white matter disease is an insidious and continuously evolving process whose progression has clinically relevant cognitive consequences. PMID:22815562

  7. [Cerebral white matter bundle measurements by magnetic resonance imaging].

    PubMed

    Yoshii, F; Duara, R

    1989-04-01

    The width of the anterior whole white matter bundle (AWM), interhemispheric (AWM-TER), and intrahemispheric (AWM-TRA) components at the level of the foramen of Monro on horizontal inversion recovery (IR) magnetic resonance (MR) scans were measured in 32 healthy males. The mean age of subjects were 54.4 +/- 18.8, ranged 25 to 83 years old. MR scans were performed using a 0.5 Tesla superconductive magnet, with inversion time of 400 msec, repetition time of 2.1 sec and echo time of 35 msec. The slice thickness was 10mm. Horizontal maximum internal skull diameter (HISD) at the same level was also measured and normalized values of AWM, AWM-TER, AWM-TRA were calculated by dividing the width of AWM, AWM-TER, AWM-TRA by the width of HISD. When absolute values of each AWM width were compared between right and left sides, there were no differences in AWM and AWM-TER. However, AWM-TRA of the right side was significantly wider than that of the left side (t = 4.28, p less than 0.001). The width of AWM was not correlated with age, but the width of AWM-TER showed a significant decline in the left (r = -0.36, p = 0.04) and non-significant trend to decline in the right side (r = -0.33, p = 0.07). The width of AWM-TRA of the left side was tended to decrease with age. Normalized values of AWM, AWM-TER, AWM-TRA showed a similar results as that of the absolute values. The measurement of the white matter bundle width provide some insights into the connectivity of the brain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2612107

  8. 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…

  9. White matter integrity of cerebellar-cortical tracts in reading impaired children: A probabilistic tractography study

    PubMed Central

    Fernandez, Vindia G.; Juranek, Jenifer; Romanowska-Pawliczek, Anna; Stuebing, Karla; Williams, Victoria J.; Fletcher, Jack M.

    2016-01-01

    Little is known about the white matter integrity of cerebellar-cortical pathways in individuals with dyslexia. Building on previous findings of decreased volume in the anterior lobe of the cerebellum, we utilized novel cerebellar segmentation procedures and probabilistic tractography to examine tracts that connect the anterior lobe of the cerebellum and cortical regions typically associated with reading: the temporoparietal (TP), occipitotemporal (OT), and inferior frontal (IF) regions. The sample included 29 reading impaired children and 27 typical readers. We found greater fractional anisotropy (FA) for the poor readers in tracts connecting the cerebellum with TP and IF regions relative to typical readers. In the OT region, FA was greater for the older poor readers, but smaller for the younger ones. This study provides evidence for discrete, regionally-bound functions of the cerebellum and suggests that projections from the anterior cerebellum appear to have a regulatory effect on cortical pathways important for reading. PMID:26307492

  10. 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.

  11. 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.

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

    PubMed

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

    2015-09-01

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

  13. Fully automated grey and white matter spinal cord segmentation

    PubMed Central

    Prados, Ferran; Cardoso, M. Jorge; Yiannakas, Marios C.; Hoy, Luke R.; Tebaldi, Elisa; Kearney, Hugh; Liechti, Martina D.; Miller, David H.; Ciccarelli, Olga; Wheeler-Kingshott, Claudia A. M. Gandini; Ourselin, Sebastien

    2016-01-01

    Axonal loss in the spinal cord is one of the main contributing factors to irreversible clinical disability in multiple sclerosis (MS). In vivo axonal loss can be assessed indirectly by estimating a reduction in the cervical cross-sectional area (CSA) of the spinal cord over time, which is indicative of spinal cord atrophy, and such a measure may be obtained by means of image segmentation using magnetic resonance imaging (MRI). In this work, we propose a new fully automated spinal cord segmentation technique that incorporates two different multi-atlas segmentation propagation and fusion techniques: The Optimized PatchMatch Label fusion (OPAL) algorithm for localising and approximately segmenting the spinal cord, and the Similarity and Truth Estimation for Propagated Segmentations (STEPS) algorithm for segmenting white and grey matter simultaneously. In a retrospective analysis of MRI data, the proposed method facilitated CSA measurements with accuracy equivalent to the inter-rater variability, with a Dice score (DSC) of 0.967 at C2/C3 level. The segmentation performance for grey matter at C2/C3 level was close to inter-rater variability, reaching an accuracy (DSC) of 0.826 for healthy subjects and 0.835 people with clinically isolated syndrome MS. PMID:27786306

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

    PubMed

    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 R (2) = 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.

  15. 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…

  16. 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…

  17. 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…

  18. 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...

  19. 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…

  20. 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…

  1. 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…

  2. 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.

  3. White Matter Atrophy and Cognitive Dysfunctions in Neuromyelitis Optica

    PubMed Central

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

    2012-01-01

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

  4. 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.

  5. Understanding white matter integrity stability for bilinguals on language status and reading performance.

    PubMed

    Cummine, Jacqueline; Boliek, Carol A

    2013-03-01

    Recent studies using diffusion tensor imaging (DTI) have described overall white matter integrity in bilinguals but have not related structural neural pathways to language functions. The current study examined white matter integrity and its relationship to reading skill in monolingual English and bilingual Chinese-English speakers. Eleven monolingual speakers (mean age 28.5 years) and 13 bilingual speakers (mean age 24.2 years; English as a second language was acquired post 5 years of age) participated. Behavioural response times and accuracy rates to name regular and exception words were recorded. Participants were then scanned using a standardized DTI protocol. Fractional anisotropy (FA) and mean diffusivity values were derived from a voxelwise statistical analysis for comparisons between participant groups. Tests for relationships between response time and FA were also conducted. Our results show minimal regions of higher FA for monolinguals when compared to bilinguals and no regions of higher FA for bilinguals when compared to monolinguals, which indicates that white matter integrity may not stabilize in bilinguals until late adulthood. We do show several regions where an increase in FA is associated with faster response times. Interestingly, the FA-response time relationship varies between groups and between word types, which may reflect an increased processing demand for retrieval of difficult words (e.g., exception words). These results provide some support for the interference control and reduced frequency hypotheses outlined by Jones et al. (Cerebr Cortex 22:892-902, 2012). The current findings advance our understanding of the underlying cortical networks associated with language status and reading skill in monolingual and bilingual adults.

  6. DTI reveals structural differences in white matter tracts between bilingual and monolingual children.

    PubMed

    Mohades, Seyede Ghazal; Struys, Esli; Van Schuerbeek, Peter; Mondt, Katrien; Van De Craen, Piet; Luypaert, Robert

    2012-01-30

    The impact of bilingualism on the microstructure of the white matter pathways related to language processing is assessed in elementary school children by magnetic resonance diffusion tensor imaging (MR-DTI). Forty children, 8-11 years old, subdivided into 3 different groups (15 simultaneous bilinguals, 15 sequential bilinguals and 10 monolinguals), were scanned. The hypothesis was that the starting age and the manner of second language acquisition would affect the characteristics of language circuitry. In each subject the mean fractional anisotropy (FA) was obtained for four major white matter pathways: 1 - the left arcuate fasciculus/superior longitudinal fasciculus (lAF/lSLF) that connects Broca's area in the opercular and triangular regions of the left inferior frontal gyrus to the posterior language zone, 2 - the left inferior occipitofrontal fasciculus (lIFOF), connecting anterior regions in the frontal lobe with posterior regions in the temporal occipital lobes, 3 - the bundle arising from the anterior part of the corpus callosum projecting to the orbital lobe (AC-OL) and 4 - the fibers emerging from the anterior midbody (AMB) of the corpus callosum that associate with the premotor and supplementary motor cortices (AMB-PMC). The three groups did not show significant differences in mean FA over the lAF/lSLF or AMB-PMC tracts. In simultaneous bilingual subjects the lIFOF tracts had higher mean FA value compared to monolinguals and also sequential bilinguals, whereas the comparison for the AC-OL fibers yielded a significantly lower mean FA value in simultaneous bilingual subjects compared to monolinguals. In both cases the FA value for sequential bilinguals was intermediate to that of the other two groups. To our knowledge, this study provides the first evidence of bilingualism related adaptation of white matter microstructure in the human brain.

  7. In vivo evaluation of gray and white matter volume loss in the parkinsonian variant of multiple system atrophy using SPM8 plus DARTEL for VBM.

    PubMed

    Shigemoto, Yoko; Matsuda, Hiroshi; Kamiya, Kouhei; Maikusa, Norihide; Nakata, Yasuhiro; Ito, Kimiteru; Ota, Miho; Matsunaga, Naofumi; Sato, Noriko

    2013-01-01

    In multiple system atrophy with predominant parkinsonism (MSA-P), several voxel-based morphometry (VBM) studies have revealed gray matter loss; however, the white matter volume changes have been rarely reported. We investigated the volume changes of white matter as well as gray matter by VBM. A retrospective MRI study was performed in 20 patients with MSA-P and 30 age-matched healthy controls. We applied VBM with statistical parametric mapping (SPM8) plus diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) to explore the regional atrophy of gray and white matter in all of the MSA-P patients, 14 patients with left-side dominant and 6 patients with right-side dominant onset as compared to controls. In all of the MSA-P patients, VBM revealed a significant volume reduction of gray matter in the bilateral putamina, cerebellums and dorsal midbrain. White matter loss was located in bilateral globus pallidi, external capsules extending to the midbrain, right subcortical to precentral area through internal capsule, the pons, bilateral middle cerebellar peduncles and left cerebellum. In left-side dominant MSA-P patients, the gray and white matter volume loss was detected predominantly on the right side and vice versa in right-side dominant MSA-P patients. A correlation with disease duration and severity was not detected. VBM using SPM8 plus DARTEL detected significant volume loss not only in the gray but also in the white matter of the area affected by MSA-P.

  8. 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

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

    PubMed Central

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

    2012-01-01

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

  10. Longitudinal changes in grey and white matter during adolescence.

    PubMed

    Giorgio, A; Watkins, K E; Chadwick, M; James, S; Winmill, L; Douaud, G; De Stefano, N; Matthews, P M; Smith, S M; Johansen-Berg, H; James, A C

    2010-01-01

    Brain development continues actively during adolescence. Previous MRI studies have shown complex patterns of apparent loss of grey matter (GM) volume and increases in white matter (WM) volume and fractional anisotropy (FA), an index of WM microstructure. In this longitudinal study (mean follow-up=2.5+/-0.5 years) of 24 adolescents, we used a voxel-based morphometry (VBM)-style analysis with conventional T1-weighted images to test for age-related changes in GM and WM volumes. We also performed tract-based spatial statistics (TBSS) analysis of diffusion tensor imaging (DTI) data to test for age-related WM changes across the whole brain. Probabilistic tractography was used to carry out quantitative comparisons across subjects in measures of WM microstructure in two fiber tracts important for supporting speech and motor functions (arcuate fasciculus [AF] and corticospinal tract [CST]). The whole-brain analyses identified age-related increases in WM volume and FA bilaterally in many fiber tracts, including AF and many parts of the CST. FA changes were mainly driven by increases in parallel diffusivity, probably reflecting increases in the diameter of the axons forming the fiber tracts. FA values of both left and right AF (but not of the CST) were significantly higher at the end of the follow-up than at baseline. Over the same period, widespread reductions in the cortical GM volume were found. These findings provide imaging-based anatomical data suggesting that brain maturation in adolescence is associated with structural changes enhancing long-distance connectivities in different WM tracts, specifically in the AF and CST, at the same time that cortical GM exhibits synaptic "pruning". PMID:19679191

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

    PubMed Central

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

    2013-01-01

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

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. Social reward dependence and brain white matter microstructure.

    PubMed

    Bjørnebekk, Astrid; Westlye, Lars T; Fjell, Anders M; Grydeland, Håkon; 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.

  17. Preserved white matter in unmedicated pediatric bipolar disorder.

    PubMed

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

    2014-09-01

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

  18. 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

  19. 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.

  20. 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

  1. 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

  2. Depressive symptoms in adolescents: associations with white matter volume and marijuana use

    PubMed Central

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

    2008-01-01

    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 among adolescent marijuana users and controls. Methods Data were collected from marijuana users (n = 16) and demographically similar controls (n = 16) aged 16–18. Extensive exclusionary criteria included psychiatric and neurologic disorders, including major depression. Substance use, mood, and anatomical measures were collected after 28 days of monitored abstinence. Results Marijuana (MJ) users demonstrated more depressive symptoms than controls (p < .05). MJ use (β = .42, p < .005) and smaller white matter volume (β = −.34, p < .03) each predicted higher levels of depressive symptoms on the Hamilton Depression Rating Scale. MJ use interacted with white matter volume (β = −.55, p < .03) in predicting depression scores on the Beck Depression Inventory: among MJ users, but not controls, white matter volume was negatively associated with depressive symptoms. Conclusions Marijuana use and white matter volume were additive and interactive in predicting depressive symptoms among adolescents. Subtle neurodevelopmental white matter abnormalities may disrupt the connections between areas involved in mood regulation. PMID:17537075

  3. 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

  4. 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.

  5. 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 100μl 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.

  6. 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.

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

    PubMed Central

    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.

    2014-01-01

    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

  8. 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

  9. Infection and White Matter Injury in Infants with Congenital Heart Disease

    PubMed Central

    Glass, Hannah C.; Bowman, Chelsea; Chau, Vann; Moosa, Alisha; Hersh, Adam L.; Campbell, Andrew; Poskitt, Kenneth; Azakie, Anthony; Barkovich, A. James; Miller, Steven P; McQuillen, Patrick S

    2011-01-01

    More than 60 percent of newborns with severe congenital heart disease develop perioperative brain injuries. Known risk factors include: preoperative hypoxemia, cardiopulmonary bypass characteristics, and postoperative hypotension. Infection is an established risk factor for white matter injury in premature newborns. In this study, we examined term infants with congenital heart disease requiring surgical repair to determine whether infection is associated with white matter injury. Acquired infection was specified by site (bloodstream, pneumonia, or surgical site infection) according to strict definitions. Infection was present in 23/127. Pre and post-operative imaging was evaluated for acquired injury by a pediatric neuroradiologist. Overall, there was no difference in newly acquired postoperative white matter injury in infants with infection (30 percent), compared to those without (31 percent). When stratified by anatomy, infants with transposition of the great arteries and bloodstream infection had an estimated doubling of risk of white matter injury that was not significant, whereas those with single ventricle anatomy had no apparent added risk. When considering only infants without stroke, the estimated association was higher, and became significant after adjusting for duration of inotrope therapy. In this study, nosocomial infection was not associated with white matter injury. Nonetheless, when controlling for risk factors, there was an association between bloodstream infection and white matter injury in selected sub-populations. Infection prevention may have the potential to mitigate long-term neurologic impairment as a consequence of white matter injury, which underscores the importance of attention to infection control for these patients. PMID:21554828

  10. Baseline white matter microstructural integrity is not related to cognitive decline after 5 years: The RUN DMC study.

    PubMed

    van Uden, I W M; van der Holst, H M; Schaapsmeerders, P; Tuladhar, A M; van Norden, A G W; de Laat, K F; Norris, D G; Claassen, J A H R; van Dijk, E J; Richard, E; Kessels, R P C; de Leeuw, F-E

    2015-12-01

    •DTI can provide information on microstructural white matter integrity.•White matter microstructural integrity is not related to cognitive decline in SVD.•These results are in contrast with cross-sectional findings.•Other factors than white matter microstructural damage underlie this cognitive decline.

  11. The superficial white matter in temporal lobe epilepsy: a key link between structural and functional network disruptions.

    PubMed

    Liu, Min; Bernhardt, Boris C; Hong, Seok-Jun; Caldairou, Benoit; Bernasconi, Andrea; Bernasconi, Neda

    2016-09-01

    Drug-resistant temporal lobe epilepsy is increasingly recognized as a system-level disorder affecting the structure and function of large-scale grey matter networks. While diffusion magnetic resonance imaging studies have demonstrated deep fibre tract alterations, the superficial white matter immediately below the cortex has so far been neglected despite its proximity to neocortical regions and key role in maintaining cortico-cortical connectivity. Using multi-modal 3 T magnetic resonance imaging, we mapped the topography of superficial white matter diffusion alterations in 61 consecutive temporal lobe epilepsy patients relative to 38 healthy controls and studied the relationship to large-scale structural as well as functional networks. Our approach continuously sampled mean diffusivity and fractional anisotropy along surfaces running 2 mm below the cortex. Multivariate statistics mapped superficial white matter diffusion anomalies in patients relative to controls, while correlation and mediation analyses evaluated their relationship to structural (cortical thickness, mesiotemporal volumetry) and functional parameters (resting state functional magnetic resonance imaging amplitude) and clinical variables. Patients presented with overlapping anomalies in mean diffusivity and anisotropy, particularly in ipsilateral temporo-limbic regions. Diffusion anomalies did not relate to cortical thinning; conversely, they mediated large-scale functional amplitude decreases in patients relative to controls in default mode hub regions (i.e. anterior and posterior midline regions, lateral temporo-parietal cortices), and were themselves mediated by hippocampal atrophy. With respect to clinical variables, we observed more marked diffusion anomalies in patients with a history of febrile convulsions and those with longer disease duration. Similarly, more marked diffusion alterations were associated with seizure-free outcome. Bootstrap analyses indicated high reproducibility of our

  12. The superficial white matter in temporal lobe epilepsy: a key link between structural and functional network disruptions.

    PubMed

    Liu, Min; Bernhardt, Boris C; Hong, Seok-Jun; Caldairou, Benoit; Bernasconi, Andrea; Bernasconi, Neda

    2016-09-01

    Drug-resistant temporal lobe epilepsy is increasingly recognized as a system-level disorder affecting the structure and function of large-scale grey matter networks. While diffusion magnetic resonance imaging studies have demonstrated deep fibre tract alterations, the superficial white matter immediately below the cortex has so far been neglected despite its proximity to neocortical regions and key role in maintaining cortico-cortical connectivity. Using multi-modal 3 T magnetic resonance imaging, we mapped the topography of superficial white matter diffusion alterations in 61 consecutive temporal lobe epilepsy patients relative to 38 healthy controls and studied the relationship to large-scale structural as well as functional networks. Our approach continuously sampled mean diffusivity and fractional anisotropy along surfaces running 2 mm below the cortex. Multivariate statistics mapped superficial white matter diffusion anomalies in patients relative to controls, while correlation and mediation analyses evaluated their relationship to structural (cortical thickness, mesiotemporal volumetry) and functional parameters (resting state functional magnetic resonance imaging amplitude) and clinical variables. Patients presented with overlapping anomalies in mean diffusivity and anisotropy, particularly in ipsilateral temporo-limbic regions. Diffusion anomalies did not relate to cortical thinning; conversely, they mediated large-scale functional amplitude decreases in patients relative to controls in default mode hub regions (i.e. anterior and posterior midline regions, lateral temporo-parietal cortices), and were themselves mediated by hippocampal atrophy. With respect to clinical variables, we observed more marked diffusion anomalies in patients with a history of febrile convulsions and those with longer disease duration. Similarly, more marked diffusion alterations were associated with seizure-free outcome. Bootstrap analyses indicated high reproducibility of our

  13. 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

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

    PubMed Central

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

    2015-01-01

    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

  15. White matter impairment in the speech network of individuals with autism spectrum disorder.

    PubMed

    Peeva, M G; Tourville, J A; Agam, Y; Holland, B; Manoach, D S; Guenther, F H

    2013-01-01

    Impairments in language and communication are core features of Autism Spectrum Disorder (ASD), and a substantial percentage of children with ASD do not develop speech. ASD is often characterized as a disorder of brain connectivity, and a number of studies have identified white matter impairments in affected individuals. The current study investigated white matter integrity in the speech network of high-functioning adults with ASD. Diffusion tensor imaging (DTI) scans were collected from 18 participants with ASD and 18 neurotypical participants. Probabilistic tractography was used to estimate the connection strength between ventral premotor cortex (vPMC), a cortical region responsible for speech motor planning, and five other cortical regions in the network of areas involved in speech production. We found a weaker connection between the left vPMC and the supplementary motor area in the ASD group. This pathway has been hypothesized to underlie the initiation of speech motor programs. Our results indicate that a key pathway in the speech production network is impaired in ASD, and that this impairment can occur even in the presence of normal language abilities. Therapies that result in normalization of this pathway may hold particular promise for improving speech output in ASD.

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

    PubMed

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

    1978-04-01

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

  17. Altered white matter in early visual pathways of humans with amblyopia.

    PubMed

    Allen, Brian; Spiegel, Daniel P; Thompson, Benjamin; Pestilli, Franco; Rokers, Bas

    2015-09-01

    Amblyopia is a visual disorder caused by poorly coordinated binocular input during development. Little is known about the impact of amblyopia on the white matter within the visual system. We studied the properties of six major visual white-matter pathways in a group of adults with amblyopia (n=10) and matched controls (n=10) using diffusion weighted imaging (DWI) and fiber tractography. While we did not find significant differences in diffusion properties in cortico-cortical pathways, patients with amblyopia exhibited increased mean diffusivity in thalamo-cortical visual pathways. These findings suggest that amblyopia may systematically alter the white matter properties of early visual pathways.

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

    PubMed

    Minnerop, Martina; Weber, Bernd; Schoene-Bake, Jan-Christoph; Roeske, Sandra; Mirbach, Sandra; Anspach, Christian; Schneider-Gold, Christiane; Betz, Regina C; Helmstaedter, Christoph; Tittgemeyer, Marc; Klockgether, Thomas; Kornblum, Cornelia

    2011-12-01

    Myotonic dystrophy types 1 and 2 are progressive multisystemic disorders with potential brain involvement. We compared 22 myotonic dystrophy type 1 and 22 myotonic dystrophy type 2 clinically and neuropsychologically well-characterized patients and a corresponding healthy control group using structural brain magnetic resonance imaging at 3 T (T(1)/T(2)/diffusion-weighted). Voxel-based morphometry and diffusion tensor imaging with tract-based spatial statistics were applied for voxel-wise analysis of cerebral grey and white matter affection (P(corrected) < 0.05). We further examined the association of structural brain changes with clinical and neuropsychological data. White matter lesions rated visually were more prevalent and severe in myotonic dystrophy type 1 compared with controls, with frontal white matter most prominently affected in both disorders, and temporal lesions restricted to myotonic dystrophy type 1. Voxel-based morphometry analyses demonstrated extensive white matter involvement in all cerebral lobes, brainstem and corpus callosum in myotonic dystrophy types 1 and 2, while grey matter decrease (cortical areas, thalamus, putamen) was restricted to myotonic dystrophy type 1. Accordingly, we found more prominent white matter affection in myotonic dystrophy type 1 than myotonic dystrophy type 2 by diffusion tensor imaging. Association fibres throughout the whole brain, limbic system fibre tracts, the callosal body and projection fibres (e.g. internal/external capsules) were affected in myotonic dystrophy types 1 and 2. Central motor pathways were exclusively impaired in myotonic dystrophy type 1. We found mild executive and attentional deficits in our patients when neuropsychological tests were corrected for manual motor dysfunctioning. Regression analyses revealed associations of white matter affection with several clinical parameters in both disease entities, but not with neuropsychological performance. We showed that depressed mood and fatigue were

  19. Accelerated changes in white matter microstructure during aging: a longitudinal diffusion tensor imaging study.

    PubMed

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

    2014-11-12

    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.

  20. 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.

  1. 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

  2. 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

  3. 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

  4. The Association of Aging with White Matter Integrity and Functional Connectivity Hubs

    PubMed Central

    Yang, Albert C.; Tsai, Shih-Jen; Liu, Mu-En; Huang, Chu-Chung; Lin, Ching-Po

    2016-01-01

    Normal aging is associated with reduced cerebral structural integrity and altered functional brain activity, yet the association of aging with the relationship between structural and functional brain changes remains unclear. Using combined diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) modalities, we hypothesized that aging-related changes in white matter integrity (i.e., fractional anisotropy) was associated with the short- or long-range functional connectivity density (FCD) in hub regions. We tested this hypothesis by using a healthy aging cohort comprised of 140 younger adults aged 20–39 years and 109 older adults aged 60–79 years. Compared with the younger group, older adults exhibited widespread reductions in white matter integrity with selective preservation in brain stem tracts and the cingulum connected to the hippocampus and cingulate cortex, whereas FCD mapping in older adults showed a reduced FCD in the visual, somatosensory, and motor functional networks and an increased FCD in the default mode network. The older adults exhibited significantly increased short- or long-range FCD in functional hubs of the precuneus, posterior, and middle cingulate, and thalamus, hippocampus, fusiform, and inferior temporal cortex. Furthermore, DTI-fMRI relationship were predominantly identified in older adults in whom short- and long-range FCD in the left precuneus was negatively correlated to structural integrity of adjacent and nonadjacent white matter tracts, respectively. We also found that long-range FCD in the left precuneus was positively correlated to cognitive function. These results support the compensatory hypothesis of neurocognitive aging theory and reveal the DTI-fMRI relationship associated with normal aging. PMID:27378915

  5. Relationship Between Cortical Gyrification, White Matter Connectivity, and Autism Spectrum Disorder.

    PubMed

    Ecker, C; Andrews, D; Dell'Acqua, F; Daly, E; Murphy, C; Catani, M; Thiebaut de Schotten, M; Baron-Cohen, S; Lai, M C; Lombardo, M V; Bullmore, E T; Suckling, J; Williams, S; Jones, D K; Chiocchetti, A; Murphy, D G M

    2016-07-01

    Autism spectrum disorder (ASD) is a complex neurodevelopmental condition, which is accompanied by differences in gray matter neuroanatomy and white matter connectivity. However, it is unknown whether these differences are linked or reflect independent aetiologies. Using a multimodal neuroimaging approach, we therefore examined 51 male adults with ASD and 48 neurotypical controls to investigate the relationship between gray matter local gyrification (lGI) and white matter diffusivity in associated fiber tracts. First, ASD individuals had a significant increase in gyrification around the left pre- and post-central gyrus. Second, white matter fiber tracts originating and/or terminating in the cluster of increased lGI had a significant increase in axial diffusivity. This increase in diffusivity was predominantly observed in tracts in close proximity to the cortical sheet. Last, we demonstrate that the increase in lGI was significantly correlated with increased diffusivity of short tracts. This relationship was not significantly modulated by a main effect of group (i.e., ASD), which was more closely associated with gray matter gyrification than white matter diffusivity. Our findings suggest that differences in gray matter neuroanatomy and white matter connectivity are closely linked, and may reflect common rather than distinct aetiological pathways.

  6. Relationship Between Cortical Gyrification, White Matter Connectivity, and Autism Spectrum Disorder

    PubMed Central

    Ecker, C.; Andrews, D.; Dell'Acqua, F.; Daly, E.; Murphy, C.; Catani, M.; Thiebaut de Schotten, M.; Baron-Cohen, S.; Lai, M.C.; Lombardo, M.V.; Bullmore, E.T.; Suckling, J.; Williams, S.; Jones, D.K.; Chiocchetti, A.; Murphy, D.G.M.

    2016-01-01

    Autism spectrum disorder (ASD) is a complex neurodevelopmental condition, which is accompanied by differences in gray matter neuroanatomy and white matter connectivity. However, it is unknown whether these differences are linked or reflect independent aetiologies. Using a multimodal neuroimaging approach, we therefore examined 51 male adults with ASD and 48 neurotypical controls to investigate the relationship between gray matter local gyrification (lGI) and white matter diffusivity in associated fiber tracts. First, ASD individuals had a significant increase in gyrification around the left pre- and post-central gyrus. Second, white matter fiber tracts originating and/or terminating in the cluster of increased lGI had a significant increase in axial diffusivity. This increase in diffusivity was predominantly observed in tracts in close proximity to the cortical sheet. Last, we demonstrate that the increase in lGI was significantly correlated with increased diffusivity of short tracts. This relationship was not significantly modulated by a main effect of group (i.e., ASD), which was more closely associated with gray matter gyrification than white matter diffusivity. Our findings suggest that differences in gray matter neuroanatomy and white matter connectivity are closely linked, and may reflect common rather than distinct aetiological pathways. PMID:27130663

  7. Unsupervised white matter fiber clustering and tract probability map generation: applications of a Gaussian process framework for white matter fibers.

    PubMed

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

    2010-05-15

    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 article presents such a novel mathematical framework that facilitates mathematical operations between tracts using an inner product between fibres. Such inner product operation, based on Gaussian processes, spans 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 parameterization 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

  8. 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.

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

    PubMed

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

    2015-06-01

    Children with prenatal alcohol exposure (PAE) may have cognitive, behavioral and brain abnormalities. Here, we compare rates of white matter and subcortical gray matter volume change in PAE and control children, and examine relationships between annual volume change and arithmetic ability, behavior, and executive function. Participants (n = 75 PAE/64 control; age: 7.1-15.9 years) each received two structural magnetic resonance scans, ~2 years apart. Assessments included Wechsler Intelligence Scale for Children (WISC-IV), the Child Behavior Checklist and the Behavior Rating Inventory of Executive Function. Subcortical white and gray volumes were extracted for each hemisphere. Group volume differences were tested using false discovery rate (q < 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

  10. 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

  11. White matter microstructural properties correlate with sensorimotor synchronization abilities.

    PubMed

    Blecher, Tal; Tal, Idan; Ben-Shachar, Michal

    2016-09-01

    Sensorimotor synchronization (SMS) to an external auditory rhythm is a developed ability in humans, particularly evident in dancing and singing. This ability is typically measured in the lab via a simple task of finger tapping to an auditory beat. While simplistic, there is some evidence that poor performance on this task could be related to impaired phonological and reading abilities in children. Auditory-motor synchronization is hypothesized to rely on a tight coupling between auditory and motor neural systems, but the specific pathways that mediate this coupling have not been identified yet. In this study, we test this hypothesis and examine the contribution of fronto-temporal and callosal connections to specific measures of rhythmic synchronization. Twenty participants went through SMS and diffusion magnetic resonance imaging (dMRI) measurements. We quantified the mean asynchrony between an auditory beat and participants' finger taps, as well as the time to resynchronize (TTR) with an altered meter, and examined the correlations between these behavioral measures and diffusivity in a small set of predefined pathways. We found significant correlations between asynchrony and fractional anisotropy (FA) in the left (but not right) arcuate fasciculus and in the temporal segment of the corpus callosum. On the other hand, TTR correlated with FA in the precentral segment of the callosum. To our knowledge, this is the first demonstration that relates these particular white matter tracts with performance on an auditory-motor rhythmic synchronization task. We propose that left fronto-temporal and temporal-callosal fibers are involved in prediction and constant comparison between auditory inputs and motor commands, while inter-hemispheric connections between the motor/premotor cortices contribute to successful resynchronization of motor responses with a new external rhythm, perhaps via inhibition of tapping to the previous rhythm. Our results indicate that auditory

  12. 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

  13. 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.

    2016-06-01

    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 Hubble Space Telescope/Advanced Camera for Surveys observations of stars in the centre 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.

  14. Neurons in the White Matter of the Adult Human Neocortex

    PubMed Central

    Suárez-Solá, M. Luisa; González-Delgado, Francisco J.; Pueyo-Morlans, Mercedes; Medina-Bolívar, O. Carolina; Hernández-Acosta, N. Carolina; González-Gómez, Miriam; Meyer, Gundela

    2009-01-01

    The white matter (WM) of the adult human neocortex contains the so-called “interstitial neurons”. They are most numerous in the superficial WM underlying the cortical gyri, and decrease in density toward the deep WM. They are morphologically heterogeneous. A subgroup of interstitial neurons display pyramidal-cell like morphologies, characterized by a polarized dendritic tree with a dominant apical dendrite, and covered with a variable number of dendritic spines. In addition, a large contingent of interstitial neurons can be classified as interneurons based on their neurochemical profile as well as on morphological criteria. WM- interneurons have multipolar or bipolar shapes and express GABA and a variety of other neuronal markers, such as calbindin and calretinin, the extracellular matrix protein reelin, or neuropeptide Y, somatostatin, and nitric oxide synthase. The heterogeneity of interstitial neurons may be relevant for the pathogenesis of Alzheimer disease and schizophrenia. Interstitial neurons are most prominent in human brain, and only rudimentary in the brain of non-primate mammals. These evolutionary differences have precluded adequate experimental work on this cell population, which is usually considered as a relict of the subplate, a transient compartment proper of development and without a known function in the adult brain. The primate-specific prominence of the subplate in late fetal stages points to an important role in the establishment of interstitial neurons. Neurons in the adult WM may be actively involved in coordinating inter-areal connectivity and regulation of blood flow. Further studies in primates will be needed to elucidate the developmental history, adult components and activities of this large neuronal system. PMID:19543540

  15. White Matter Integrity and Reaction Time Intraindividual Variability in Healthy Aging and Early-Stage Alzheimer Disease

    PubMed Central

    Jackson, Jonathan D.; Balota, David A.; Duchek, Janet M.; Head, Denise

    2011-01-01

    Aging and early-stage Alzheimer disease (AD) have been shown to be associated with increased RT intraindividual variability (IIV, as reflected by the coefficient of variation) and an exaggeration of the slow tail of the RT distribution in attentional control tasks, based on ex-Gaussian analyses. The current study examined associations between white matter volume, IIV, and ex-Gaussian RT distribution parameters in cognitively normal aging and early-stage AD. Three RT attention tasks (Stroop, Simon, and a consonant-vowel odd-even switching task) in conjunction with MRI-based measures of cerebral and regional white matter volume were obtained in 133 cognitively normal and 33 early-stage AD individuals. Larger volumes were associated with less IIV and less slowing in the tail of the RT distribution, and larger cerebral and inferior parietal white matter volumes were associated with faster modal reaction time. Collectively, these results support a role of white matter integrity in IIV and distributional skewing, and are consistent with the hypothesis that IIV and RT distributional skewing are sensitive to breakdowns in executive control processes in normal and pathological aging. PMID:22172547

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

    PubMed Central

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

    2015-01-01

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

  17. Children with New Onset Epilepsy Exhibit Diffusion Abnormalities in Cerebral White Matter in the Absence of Volumetric Differences

    PubMed Central

    Hutchinson, Elizabeth; Pulsipher, Dalin; Dabbs, Kevin; Myers y Gutierrez, Adan; Sheth, Raj; Jones, Jana; Seidenberg, Michael; Meyerand, Elizabeth; Hermann, Bruce

    2010-01-01

    SUMMARY The purpose of this investigation was to examine the diffusion properties of cerebral white matter in children with recent onset epilepsy (n=19) compared to healthy controls (n=11). Subjects underwent DTI with quantification of mean diffusion (MD), fractional anisotropy (FA), axial diffusivity (Dax) and radial diffusivity (Drad) for regions of interest including anterior and posterior corpus callosum, fornix, cingulum, and internal and external capsules. Quantitative volumetrics were also performed for the corpus callosum and its subregions (anterior, midbody and posterior) and total lobar white and gray matter for the frontal, parietal, temporal and occipital lobes. The results demonstrated no group differences in total lobar gray or white matter volumes or volume of the corpus callosum and its subregions, but did show reduced FA and increased Drad in the posterior corpus callosum and cingulum. These results provide the earliest indication of microstructural abnormality in cerebral white matter among children with idiopathic epilepsies. This abnormality occurs in the context of normal volumetrics and suggests disruption in myelination processes. PMID:20044239

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

    PubMed

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

    2016-11-01

    The purpose of this study was to explore white matter microstructural alterations in the patients with generalized anxiety disorder (GAD) using diffusion tensor imaging (DTI) technique, and to assess neural associations with the symptom severity. Twenty-eight first-episode, treatment-naive GAD patients without co-morbidities and 28 matched healthy controls underwent DTI acquisition and clinical symptom assessments. Tract-based spati