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Sample records for white matter region

  1. Regional Grey and White Matter Changes in Heavy Male Smokers

    PubMed Central

    Yu, Rongjun; Zhao, Liyan; Lu, Lin

    2011-01-01

    Cigarette smoking is highly prevalent in the general population but the effects of chronic smoking on brain structures are still unclear. Previous studies have found mixed results regarding regional grey matter abnormalities in smokers. To characterize both grey and white matter changes in heavy male smokers, we investigated 16 heavy smokers and 16 matched healthy controls, using both univariate voxel-based morphometry (VBM) and multivariate pattern classification analysis. Compared with controls, heavy smokers exhibited smaller grey matter volume in cerebellum, as well as larger white matter volume in putamen, anterior and middle cingulate cortex. Further, the spatial patterns of grey matter or white matter both discriminated smokers from controls in these regions as well as in other brain regions. Our findings demonstrated volume abnormalities not only in the grey matter but also in the white matter in heavy male smokers. The multivariate analysis suggests that chronic smoking may be associated with volume alternations in broader brain regions than those identified in VBM analysis. These results may better our understanding of the neurobiological consequence of smoking and inform smoking treatment. PMID:22076160

  2. 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

  3. 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…

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. Regional White Matter Development in Very Preterm Infants: Perinatal Predictors and Early Developmental Outcomes

    PubMed Central

    Rogers, Cynthia E.; Smyser, Tara; Smyser, Christopher D.; Shimony, Joshua; Inder, Terrie E.; Neil, Jeffrey J.

    2015-01-01

    Background Preterm infants are at risk for white matter injury and adverse neurodevelopmental outcomes. Methods Serial diffusion tensor MRI data were obtained from very preterm infants (N=78) born <30 weeks gestation imaged up to four times from 26-42 weeks postmenstrual age. Slopes were calculated for fractional anisotropy (FA) and mean diffusivity (MD) within regions of interest for infants with ≥2 scans (N=50). Sixty-five children underwent neurodevelopmental testing at age two years. Results FA slope for the posterior limb of the internal capsule was greater than other regions. The anterior limb of the internal capsule (ALIC), corpus callosum and optic radiations demonstrated greater FA slope with increasing gestational age. Infants with PDA had lower FA slope in the ALIC. MD slope was lower with prolonged ventilation or lack of antenatal steroids. At age 2 years, lower motor scores were associated with lower FA in the left but higher FA in the right inferior temporal lobe at term-equivalent. Better social-emotional competence was related to lower FA in the left cingulum bundle. Conclusion This study demonstrates regional variability in the susceptibility/sensitivity of white matter maturation to perinatal factors and relationships between altered diffusion measures and developmental outcomes in preterm neonates. PMID:26372513

  10. 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

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

    PubMed

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

    2012-12-01

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

  12. REGIONAL WHITE MATTER VOLUME DIFFERENCES IN NONDEMENTED AGING AND ALZHEIMER’S DISEASE

    PubMed Central

    Salat, David H.; Greve, Douglas N.; Pacheco, Jennifer L.; Quinn, Brian T.; Helmer, Karl G.; Buckner, Randy L.; Fischl, Bruce

    2009-01-01

    Accumulating evidence suggests that altered cerebral white matter (WM) influences normal aging, and further that WM degeneration may modulate the clinical expression of Alzheimer’s disease (AD). Here we conducted a study of differences in WM volume across the adult age span and in AD employing a newly developed, automated method for regional parcellation of the subcortical WM that uses curvature landmarks and gray matter (GM)/WM surface boundary information. This procedure measures the volume of gyral WM, utilizing a distance constraint to limit the measurements from extending into the centrum semiovale. Regional estimates were first established to be reliable across two scan sessions in 20 young healthy individuals. Next, the method was applied to a large clinically-characterized sample of 299 individuals including 73 normal older adults and 91 age-matched participants with very mild to mild AD. The majority of measured regions showed a decline in volume with increasing age, with strong effects found in bilateral fusiform, lateral orbitofrontal, superior frontal, medial orbital frontal, inferior temporal, and middle temporal WM. The association between WM volume and age was quadratic in many regions suggesting that WM volume loss accelerates in advanced aging. A number of WM regions were further reduced in AD with parahippocampal, entorhinal, inferior parietal and rostral middle frontal WM showing the strongest AD-associated reductions. There were minimal sex effects after correction for intracranial volume, and there were associations between ventricular volume and regional WM volumes in the older adults and AD that were not apparent in the younger adults. Certain results, such as the loss of WM in the fusiform region with aging, were unexpected and provide novel insight into patterns of age associated neural and cognitive decline. Overall, these results demonstrate the utility of automated regional WM measures in revealing the distinct patterns of age and AD

  13. 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

  14. White matter dementia in CADASIL.

    PubMed

    Filley, C M; Thompson, L L; Sze, C I; Simon, J A; Paskavitz, J F; Kleinschmidt-DeMasters, B K

    1999-03-01

    Cerebral white matter disorders may be associated with profound neurobehavioral dysfunction. We report a 62-year-old man who had a slowly progressive 25-year history of personality change, psychosis, mood disorder, and dementia. Neurologic examination disclosed abulia, impaired memory retrieval, and preserved language, with only minimal motor impairment. Neuropsychological testing found a sustained attention deficit, cognitive slowing, impaired learning with intact recognition, and perseveration. Magnetic resonance imaging of the brain revealed extensive leukoencephalopathy. Right frontal brain biopsy showed ill-defined white matter pallor with hyaline narrowing of white matter arterioles. Granular osmiophilic material adjacent to vascular smooth muscle cells on electron microscopy of a skin biopsy, and an arginine for cysteine replacement at position 169 in the 4 EGF motif of the notch 3 region on chromosome 19q12 established the diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This case illustrates that CADASIL can manifest as an isolated neurobehavioral disorder over an extended time period. The dementia associated with CADASIL closely resembles that which may occur with other white matter disorders, and represents an example of white matter dementia. PMID:10371078

  15. Gray and white matter structures in the midcingulate cortex region contribute to body mass index in Chinese young adults.

    PubMed

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

    2015-01-01

    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). Voxel-based morphometry results showed significant negative correlations between BMI and gray-matter volumes in the midcingulate cortex (MCC), left orbital frontal cortex, and left ventromedial prefrontal cortex. There was also a significant negative correlation between BMI and white matter integrity as indexed by fractional anisotropy 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

  16. 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

  17. INTERINDIVIDUAL VARIATION IN SERUM CHOLESTEROL IS ASSOCIATED WITH REGIONAL WHITE MATTER TISSUE INTEGRITY IN OLDER ADULTS

    PubMed Central

    Williams, Victoria J.; Leritz, Elizabeth C.; Shepel, Juli; McGlinchey, Regina E.; Milberg, William P.; Rudolph, James L.; Lipsitz, Lewis A.; Salat, David H.

    2013-01-01

    Prior research has demonstrated links among vascular health and the occurrence of stroke, mild cognitive decline, and dementia in older adults. However, little is known about whether normal variation in vascular indicators may be related to changes in neural tissue integrity. Even less is known about how the brain is affected by cholesterol levels in the normal to moderate risk range, leading up to overt disease pathology. This study examined associations between serum lipid levels and DTI indicators of white matter (WM) structural integrity in a sample of 125 generally healthy older adults aged 43–87 years. Whole-brain voxelwise analysis, controlling for age and gender, revealed low density lipoprotein levels (LDL) as the most robust correlate of regional WM structural integrity of the measured lipids. Higher LDL was associated with decreased WM integrity in right frontal and temporal regions, the superior longitudinal fasciculus and internal/external capsules. Increasing LDL was associated with increased radial and axial diffusivity; however, more widespread statistical effects were found for radial diffusivity. These findings suggest that normal inter-individual variation in lipid levels is associated with compromised regional WM integrity, even in individuals below clinical thresholds for hyperlipidemia. Given the prevalence of cholesterol-associated sequelae in older adults, and mounting evidence suggesting a vascular role in the etiology of dementia, the current data suggest that understanding the relationship between cholesterol and brain tissue microstructure may have important clinical implications for early detection of vascular-related cognitive disorders and optimal regulation of serum lipids to maintain neural health in older adults. PMID:22438182

  18. 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…

  19. 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 ...

  20. 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

  1. 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

  2. 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

  3. White matter microstructure alterations in bipolar disorder

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2015-11-01

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

  5. 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.

  6. Regionally-specific alterations in myelin proteins in nonhuman primate white matter following prolonged cocaine self-administration

    PubMed Central

    Smith, Hilary R.; Beveridge, Thomas J.R.; Nader, Michael A.; Porrino, Linda J.

    2014-01-01

    Background Neuroimaging studies of cocaine users have demonstrated white matter abnormalities associated with behavioral measures of impulsivity and decision-making deficits. The underlying bases for this dysregulation in white matter structure and function have yet to be determined. The aim of the present studies was to investigate the influence of prolonged cocaine self-administration on the levels of myelin-associated proteins and mRNAs in nonhuman primate white matter. Methods Rhesus monkeys (n=4) self-administered cocaine (0.3 mg/kg/inj, 30 reinforcers per session) for 300 sessions. Control animals (n=4) responded for food. Following the final session monkeys were euthanized and white matter tissue at three brain levels was processed for immunoblotting analysis of proteolipid protein (PLP) and myelin basic protein (MBP), as well as for in situ hybridization histochemical analysis of PLP and MBP mRNAs. Results Both MBP and PLP immunoreactivities in white matter at the level of the precommissural striatum were significantly lower in tissue from monkeys self-administering cocaine as compared to controls. No significant differences were seen for either protein at the levels of the prefrontal cortex or postcommissural striatum. In addition, no differences were observed in expression of mRNA for either protein. Conclusions These preliminary findings, in a nonhuman model of prolonged cocaine self-administration, provide further evidence that compromised myelin may underlie the deficits in white matter integrity described in studies of human cocaine users. PMID:24529965

  7. 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

  8. 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

  9. 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.

  10. 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.

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

    PubMed Central

    Selip, D. B.; Jantzie, L. L.; Chang, M.; Jackson, M. C.; Fitzgerald, E. C.; Boll, G.; Murphy, A.; Jensen, F. E.

    2012-01-01

    Models of premature brain injury have largely focused on the white matter injury thought to underlie periventricular leukomalacia (PVL). However, with increased survival of very low birth weight infants, injury patterns involving grey matter are now recognized. We aimed to determine how grey matter lesions relate to hypoxic-ischemic- (HI) mediated white matter injury by modifying our rat model of PVL. Following HI, microglial infiltration, astrocytosis, and neuronal and axonal degeneration increased in a region-specific manner dependent on the severity of myelin loss in pericallosal white matter. The spectrum of injury ranged from mild, where diffuse white matter abnormalities were dominant and were associated with mild axonal injury and local microglial activation, to severe HI injury characterized by focal MBP loss, widespread neuronal degeneration, axonal damage, and gliosis throughout the neocortex, caudate putamen, and thalamus. In sum, selective regional white matter loss occurs in the preterm rat concomitantly with a clinically relevant spectrum of grey matter injury. These data demonstrate an interspecies similarity of brain injury patterns and further substantiates the reliable use of this model for the study of preterm brain injury. PMID:22530125

  12. 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

  13. 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. PMID:27123826

  14. 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.…

  15. White matter 'potholes' in early-onset schizophrenia: a new approach to evaluate white matter microstructure using diffusion tensor imaging.

    PubMed

    White, Tonya; Schmidt, Marcus; Karatekin, Canan

    2009-11-30

    There is considerable evidence implicating white matter abnormalities in the pathophysiology of schizophrenia. Many of the recent studies examining white matter have utilized diffusion tensor imaging (DTI) using either region of interest (ROI) or voxel-based approaches. Both voxel-based and ROI approaches are based on the assumption that the abnormalities in white matter overlap spatially. However, this is an assumption that has not been tested, and it is possible that aberrations in white matter occur in non-overlapping regions. In order to test for the presence of non-overlapping regions of aberrant white matter, we developed a novel image processing technique that evaluates for white matter 'potholes,' referring to within-subject clusters of white matter voxels that show a significant reduction in fractional anisotropy. We applied this algorithm to a group of children and adolescents with schizophrenia compared to controls and found an increased number of 'potholes' in the patient group. These results suggest that voxel-based and ROI approaches may be missing some white matter differences that do not overlap spatially. This algorithm may be also be well suited to detect white matter abnormalities in disorders such as substance abuse, head trauma, or specific neurological conditions affecting white matter. PMID:19853414

  16. Differential short-term regional effects of early high dose erythropoietin on white matter in preterm lambs after mechanical ventilation.

    PubMed

    Barton, Samantha K; McDougall, Annie R A; Melville, Jacqueline M; Moss, Timothy J M; Zahra, Valerie A; Lim, Tammy; Crossley, Kelly J; Polglase, Graeme R; Tolcos, Mary

    2016-03-01

    Inadvertently injurious ventilation of preterm neonates in the delivery room can cause cerebral white matter (WM) inflammation and injury. We investigated the impact of an early high dose of recombinant human erythropoietin (EPO) on ventilation-induced WM changes in preterm lambs. Injurious ventilation, targeting a V(T) of 15 ml kg(-1) with no positive end-expiratory pressure, was initiated for 15 min in preterm lambs (0.85 gestation). Conventional ventilation was continued for a further 105 min. Lambs received either 5000 IU kg(-1) of EPO (EPREX®; Vent+EPO; n = 6) or vehicle (Vent; n = 8) via an umbilical vein at 4 ± 2 min. Markers of WM injury and inflammation were assessed using quantitative real-time PCR (qPCR) and immunohistochemistry and compared to a group of unventilated controls (UVC; n = 4). In Vent+EPO lambs compared to Vent lambs: (i) interleukin (IL)-1β and IL-6 mRNA levels in the periventricular WM and IL-8 mRNA levels in the subcortical WM were higher (P < 0.05 for all); (ii) the density of microglia within the aggregations was not different in the periventricular WM and was lower in the subcortical WM (P = 0.001); (iii) the density of astrocytes was lower in the subcortical WM (P = 0.002); (iv) occludin and claudin-1 mRNA levels were higher in the periventricular WM (P < 0.02 for all) and (vi) the number of blood vessels with protein extravasation was lower (P < 0.05). Recombinant human EPO had variable regional effects within the WM when administered during injurious ventilation. The adverse short-term outcomes discourage the use of early high dose EPO administration in preterm ventilated babies. PMID:26332509

  17. 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

  18. 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

  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. PMID:18039544

  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. Microvasculature of the human cerebral white matter: arteries of the deep white matter.

    PubMed

    Nonaka, Hiroko; Akima, Michio; Hatori, Tsutomu; Nagayama, Tadashi; Zhang, Zean; Ihara, Fumie

    2003-06-01

    The vascular architecture of the human cerebral deep white matter was studied using soft X-ray and diaphanized specimens, achieved by intra-arterial injection of barium and vascular stain respectively, and also by electron microscopic examination of the corrosion cast of arteries in normal adult brains. The deep white matter arteries passed through the cerebral cortex with a few branches to the cortex and ran straight through the white matter. The arteries concentrated ventriculopetally to the white matter around the lateral ventricle. Anastomoses were noted around the ventricular wall at the terminals of the deep white matter arteries. No centrifugal branches irrigating the periventricular white matter from the lenticulo-striate arteries were observed in the present study. The presence of anastomoses among the terminal branches of deep white matter arteries protects against ischemic change or infarction in this area from an occlusion of a single deep white matter artery. This may lead to development of terminal zone infarction from ischemia or vascular diseases, affecting multiple deep white matter arteries. The subcortical and deep white matter arteries had thick adventitial sheaths and large adventitial spaces in the white matter but not in the cortex. The presence or absence of the adventitial space is regarded as another characteristic difference between the arteries in the white matter and cortex. This difference may influence pathological changes in vascular lesions in these respective areas. PMID:12777099

  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. 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.

  4. 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

  5. Heterozygous deletion of a 2-Mb region including the dystroglycan gene in a patient with mild myopathy, facial hypotonia, oral-motor dyspraxia and white matter abnormalities.

    PubMed

    Frost, Amy R; Böhm, Sabrina V; Sewduth, Raj N; Josifova, Dragana; Ogilvie, Caroline Mackie; Izatt, Louise; Roberts, Roland G

    2010-07-01

    Dystroglycan is a protein which binds directly to two proteins defective in muscular dystrophies (dystrophin and laminin alpha2) and whose own aberrant post-translational modification is the common aetiological route of neuromuscular diseases associated with mutations in genes encoding at least six other proteins (POMT1, POMT2, POMGnT1, LARGE, FKTN and FKRP). It is surprising, therefore, that to our knowledge no mutations of the human dystroglycan gene itself have yet been reported. In this study, we describe a patient with a heterozygous de novo deletion of a approximately 2-Mb region of chromosome 3, which includes the dystroglycan gene (DAG1). The patient is a 16-year-old female with learning difficulties, white matter abnormalities, elevated serum creatine kinase, oral-motor dyspraxia and facial hypotonia but minimal clinically significant involvement of other muscles. As these symptoms are a subset of those observed in disorders of dystroglycan glycosylation (muscle-eye-brain disease and Warker-Warburg syndrome), we assess the likely contribution to her phenotype of her heterogosity for a null mutation of DAG1. We also show that the transcriptional compensation observed in the Dag1(+/-) mouse is not observed in the patient. Although we cannot show that haploinsufficiency of DAG1 is the sole cause of this patient's myopathy and white matter changes, this case serves to constrain our ideas of the severity of the phenotypic consequences of heterozygosity for null DAG1 mutations. PMID:20234391

  6. Heterozygous deletion of a 2-Mb region including the dystroglycan gene in a patient with mild myopathy, facial hypotonia, oral-motor dyspraxia and white matter abnormalities

    PubMed Central

    Frost, Amy R; Böhm, Sabrina V; Sewduth, Raj N; Josifova, Dragana; Ogilvie, Caroline Mackie; Izatt, Louise; Roberts, Roland G

    2010-01-01

    Dystroglycan is a protein which binds directly to two proteins defective in muscular dystrophies (dystrophin and laminin α2) and whose own aberrant post-translational modification is the common aetiological route of neuromuscular diseases associated with mutations in genes encoding at least six other proteins (POMT1, POMT2, POMGnT1, LARGE, FKTN and FKRP). It is surprising, therefore, that to our knowledge no mutations of the human dystroglycan gene itself have yet been reported. In this study, we describe a patient with a heterozygous de novo deletion of a ∼2-Mb region of chromosome 3, which includes the dystroglycan gene (DAG1). The patient is a 16-year-old female with learning difficulties, white matter abnormalities, elevated serum creatine kinase, oral-motor dyspraxia and facial hypotonia but minimal clinically significant involvement of other muscles. As these symptoms are a subset of those observed in disorders of dystroglycan glycosylation (muscle–eye–brain disease and Warker–Warburg syndrome), we assess the likely contribution to her phenotype of her heterogosity for a null mutation of DAG1. We also show that the transcriptional compensation observed in the Dag1+/− mouse is not observed in the patient. Although we cannot show that haploinsufficiency of DAG1 is the sole cause of this patient's myopathy and white matter changes, this case serves to constrain our ideas of the severity of the phenotypic consequences of heterozygosity for null DAG1 mutations. PMID:20234391

  7. 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.

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

    PubMed Central

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

    2014-01-01

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

  9. 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.

  10. White matter ‘potholes’ in early-onset schizophrenia: a new approach to evaluate white matter microstructure using diffusion tensor imaging

    PubMed Central

    White, Tonya; Schmidt, Marcus; Karatekin, Canan

    2009-01-01

    There is considerable evidence implicating white matter abnormalities in the pathophysiology of schizophrenia. Many of the recent studies examining white matter have utilized diffusion tensor imaging (DTI) using either region of interest (ROI) or voxel based approaches. Both voxel-based and ROI approaches are based on the assumption that the abnormalities in white matter overlap spatially. However, this is an assumption that has not been tested and it is possible that aberrations in white matter occur in non-overlapping regions. In order to test for the presence of non-overlapping regions of aberrant white matter, we developed a novel image processing technique that evaluates for white matter ‘potholes,’ referring to within-subject clusters of white matter voxels that show a significant reduction in fractional anisotropy. We applied this algorithm to a group of children and adolescents with schizophrenia compared to controls and found an increased number of ‘potholes’ in the patient group. These results suggest that voxel-based and ROI approaches may be missing some white matter differences that do not overlap spatially. This algorithm may be also be well suited to detect white matter abnormalities in disorders such as substance abuse, head trauma, or specifc neurological conditions affecting white matter. PMID:19853414

  11. White matter of the brain

    MedlinePlus

    ... improves the speed and transmission of electrical nerve signals. By comparison, gray matter is tissue found on the surface of the brain (cortical). It contains the cell bodies of neurons, which give gray matter its color.

  12. 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

  13. Aerobic Fitness is Associated with Gray Matter Volume and White Matter Integrity in Multiple Sclerosis

    PubMed Central

    Prakash, Ruchika Shaurya; Snook, Erin M.; Motl, Robert W.; Kramer, Arthur F.

    2009-01-01

    Alterations in gray and white matter have been well documented in individuals with multiple sclerosis. Severity and extent of such brain tissue damage have been associated with cognitive impairment, disease duration and neurological disability, making quantitative indices of tissue damage important markers of disease progression. In this study, we investigated the association between cardiorespiratory fitness and measures of gray matter atrophy and white matter integrity. Employing a voxel-based approach to analyses of gray matter and white matter, we specifically examined whether higher levels of fitness in multiple sclerosis participants were associated with preserved gray matter volume and integrity of white matter. We found a positive association between cardiorespiratory fitness and regional gray matter volumes and higher focal fractional anisotropy values. Statistical mapping revealed that higher levels of fitness were associated with greater gray matter volume in the midline cortical structures including the medial frontal gyrus, anterior cingulate cortex and the precuneus. Further, we also found increasing levels of fitness were associated with higher fractional anisotropy in the left thalamic radiation and right anterior corona radiata. Both preserved gray matter volume and white-matter tract integrity were associated with better performance on measures of processing speed. Taken together, these results suggest that fitness exerts a prophylactic influence on the cerebral atrophy observed early on preserving neuronal integrity in multiple sclerosis, thereby reducing long-term disability. PMID:19560443

  14. Aerobic fitness is associated with gray matter volume and white matter integrity in multiple sclerosis.

    PubMed

    Prakash, Ruchika Shaurya; Snook, Erin M; Motl, Robert W; Kramer, Arthur F

    2010-06-23

    Alterations in gray and white matter have been well documented in individuals with multiple sclerosis. Severity and extent of such brain tissue damage have been associated with cognitive impairment, disease duration and neurological disability, making quantitative indices of tissue damage important markers of disease progression. In this study, we investigated the association between cardiorespiratory fitness and measures of gray matter atrophy and white matter integrity. Employing voxel-based approaches to analysis of gray matter and white matter, we specifically examined whether higher levels of fitness in multiple sclerosis participants were associated with preserved gray matter volume and integrity of white matter. We found a positive association between cardiorespiratory fitness and regional gray matter volumes and higher focal fractional anisotropy values. Statistical mapping revealed that higher levels of fitness were associated with greater gray matter volume in the midline cortical structures including the medial frontal gyrus, anterior cingulate cortex and the precuneus. Further, we also found that increasing levels of fitness were associated with higher fractional anisotropy in the left thalamic radiation and right anterior corona radiata. Both preserved gray matter volume and white matter tract integrity were associated with better performance on measures of processing speed. Taken together, these results suggest that fitness exerts a prophylactic influence on the structural decline observed early on, preserving neuronal integrity in multiple sclerosis, thereby reducing long-term disability. PMID:19560443

  15. White Matter Microstructure in Idiopathic Craniocervical Dystonia

    PubMed Central

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

    2015-01-01

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

  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. Alterations in White Matter Microstructure in Neurofibromatosis-1

    PubMed Central

    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

  18. 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. PMID:24099786

  19. 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

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

    SciTech Connect

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

    1994-02-01

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

  1. 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

  2. Specific white matter tissue microstructure changes associated with obesity

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-15

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

  4. 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

  5. Structural neuroimaging in Altheimer's disease: do white matter hyperintensities matter?

    PubMed

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

    2009-01-01

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

  6. 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

  7. White matter involvement in chronic musculoskeletal pain

    PubMed Central

    Lieberman, Gregory; Shpaner, Marina; Watts, Richard; Andrews, Trevor; Filippi, Christopher G.; Davis, Marcia; Naylor, Magdalena R.

    2014-01-01

    There is emerging evidence that chronic musculoskeletal pain is associated with anatomical and functional abnormalities in gray matter. However, little research has investigated the relationship between chronic musculoskeletal pain and white matter (WM). In this study, we used whole-brain tract-based spatial statistics, and region-of-interest analyses of diffusion tensor imaging (DTI) data to demonstrate that patients with chronic musculoskeletal pain exhibit several abnormal WM integrity as compared to healthy controls. Chronic musculoskeletal pain was associated with lower fractional anisotropy (FA) in the splenium of corpus callosum, and left cingulum adjacent to the hippocampus. Patients also had higher radial diffusivity (RD) in the splenium, right anterior and posterior limbs of internal capsule, external capsule, superior longitudinal fasciculus, and cerebral peduncle. Patterns of axial diffusivity (AD) varied: patients exhibited lower AD in the left cingulum adjacent to the hippocampus and higher AD bilaterally in the anterior limbs of internal capsule, and in the right cerebral peduncle. Several correlations between diffusion metrics and clinical variables were also significant at a p<0.01 level: FA in the left uncinate fasciculus correlated positively with Total Pain Experience and typical levels of pain severity. AD in the left anterior limb of internal capsule and left uncinate fasciculus were correlated with Total Pain Experience and typical pain level. Positive correlations were also found between AD in the right uncinate and both Total Pain Experience and Pain Catastrophizing. These results demonstrate that WM abnormalities play a role in chronic musculoskeletal pain; either as a cause, predisposing factor, consequence, or compensatory adaptation. PMID:25135468

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

    PubMed

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

    2014-06-01

    Recent functional neuroimaging studies have shown differences in brain activation between mathematically gifted adolescents and controls. The aim of this study was to investigate the relationship between mathematical giftedness, intelligent quotient (IQ), and the microstructure of white matter tracts in a sample composed of math-gifted adolescents and aged-matched controls. Math-gifted subjects were selected through a national program based on detecting enhanced visuospatial abilities and creative thinking. We used diffusion tensor imaging to assess white matter microstructure in neuroanatomical connectivity. The processing included voxel-wise and region of interest-based analyses of the fractional anisotropy (FA), a parameter which is purportedly related to white matter microstructure. In a whole-sample analysis, IQ showed a significant positive correlation with FA, mainly in the corpus callosum, supporting the idea that efficient information transfer between hemispheres is crucial for higher intellectual capabilities. In addition, math-gifted adolescents showed increased FA (adjusted for IQ) in white matter tracts connecting frontal lobes with basal ganglia and parietal regions. The enhanced anatomical connectivity observed in the forceps minor and splenium may underlie the greater fluid reasoning, visuospatial working memory, and creative capabilities of these children. PMID:24038774

  9. Diffusion imaging, white matter, and psychopathology.

    PubMed

    Thomason, Moriah E; Thompson, Paul M

    2011-01-01

    The functional significance of the brain's white matter was not fully appreciated until new imaging methods were developed to visualize fiber pathways and connections in the living brain. Rapid advances in diffusion tensor imaging (DTI) have led to substantial insights into human brain development and disease processes and have thrust white matter into the focus of researchers and clinicians alike. The full clinical potential of this relatively new technique remains to be determined, but early indicators suggest that DTI will be a significant new technology in mapping mechanisms of human health and disease. Here we review brain changes that have been studied with DTI over the human lifespan and findings in a variety of neuropsychiatric disorders. We also suggest future areas where DTI is likely to have significant impact. PMID:21219189

  10. 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

  11. White Matter Integrity and Executive Abilities in Individuals with Phenylketonuria

    PubMed Central

    Antenor-Dorsey, Jo Ann V.; Hershey, Tamara; Rutlin, Jerrel; Shimony, Joshua S.; McKinstry, Robert C.; Grange, Dorothy K.; Christ, Shawn E.; White, Desirée A.

    2013-01-01

    Previous studies have revealed white matter abnormalities in the brains of individuals with phenylketonuria (PKU), but the microstructural nature of these abnormalities and their relationship to phenylalanine (Phe) levels and cognitive outcomes is poorly understood. In the current study, the microstructural integrity of white matter in 29 individuals with early-treated PKU and 12 healthy controls was examined using two complementary diffusion tensor imaging (DTI) approaches: region-of-interest (ROI) based analysis and voxel-wise tract based spatial statistics (TBSS) analysis. Relationships among DTI, executive abilities, and Phe level findings were explored. DTI revealed widespread lowering of mean diffusivity (MD) in the white matter of the PKU group in comparison with the control group. Executive abilities were also poorer for individuals with PKU than controls. Within the PKU group, lower MD was associated with higher Phe level and poorer executive abilities. These findings are the first to demonstrate the interplay among microstructural white matter integrity, executive abilities, and Phe control in individuals with PKU. PMID:23608077

  12. 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

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

    PubMed Central

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

    2014-01-01

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

  14. 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…

  15. Age exacerbates HIV-associated white matter abnormalities.

    PubMed

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

    2016-04-01

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

  16. 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

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

    PubMed

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

    2015-02-01

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

  18. 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

  19. Imaging white matter in human brainstem.

    PubMed

    Ford, Anastasia A; Colon-Perez, Luis; Triplett, William T; Gullett, Joseph M; Mareci, Thomas H; Fitzgerald, David B

    2013-01-01

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

  20. 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

  1. Microglia of Prefrontal White Matter in Suicide

    PubMed Central

    Schnieder, Tatiana P.; Trencevska, Iskra; Rosoklija, Gorazd; Stankov, Aleksandr; Mann, J. John; Smiley, John; Dwork, Andrew J.

    2014-01-01

    Immune functions in the brain are associated with psychiatric illness and with temporary alteration of mental state. Microglia, the principal brain immunological cells, respond to changes in the internal brain milieu through a sequence of activated states, each with characteristic function and morphology. To assess a possible association of frontal white matter pathology with suicide, autopsy brain tissue samples from 11 suicide and 25 non-suicide subjects were stained for ionized calcium-binding adapter molecule 1 (Iba-1), CD68, and myelin. Groups were matched by age, sex, and psychiatric diagnosis. We classified Iba-1-immunoreactive cells on the basis of shape, immunoreactivity for CD68, and association with blood vessels to obtain stereologic estimates of densities of resting microglia, activated phagocytes, and perivascular cells. We found no effect of psychiatric diagnosis but 2 statistically significant effects of suicide: 1) the dorsal-ventral difference in activated microglial density was reversed such that with suicide, the density was greater in ventral than in dorsal prefrontal white matter, whereas in the absence of suicide, the opposite was true; and 2) with suicide there was a greater density of Iba-1-immunoreactive cells within or in contact with blood vessel walls in dorsal prefrontal white matter. These observations could reflect a mechanism for the stress/diathesis (state/trait) model of suicide whereby an acute stress activates a reactive process in the brain, either directly or by compromising the blood-brain barrier, and creates a suicidal state in an individual at risk. They also indicate the theoretical potential of imaging studies in live, vulnerable individuals for the assessment of suicide risk. Further studies are needed to investigate specific phenotypes of perivascular cells and blood-brain barrier changes associated with suicide. PMID:25101704

  2. Imaging White Matter in Human Brainstem

    PubMed Central

    Ford, Anastasia A.; Colon-Perez, Luis; Triplett, William T.; Gullett, Joseph M.; Mareci, Thomas H.; FitzGerald, David B.

    2013-01-01

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

  3. Age-Related White Matter Changes

    PubMed Central

    Xiong, Yun Yun; Mok, Vincent

    2011-01-01

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

  4. 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

  5. Cerebral white matter integrity during primary HIV infection

    PubMed Central

    Wright, Patrick W.; Vaida, Florin F.; Fernández, Ricardo J.; Rutlin, Jerrel; Price, Richard W.; Lee, Evelyn; Peterson, Julia; Fuchs, Dietmar; Shimony, Joshua S.; Robertson, Kevin R.; Walter, Rudolph; Meyerhoff, Dieter J.; Spudich, Serena; Ances, Beau M.

    2016-01-01

    Objective Inflammation and infection within the central nervous system is initiated during primary HIV infection (PHI), but the association of these processes with the integrity of brain white matter during PHI is unknown. Design We used diffusion tensor imaging (DTI) in this prospective cross-sectional neuroimaging study to determine the extent of white matter involvement in early HIV infection. Methods Antiretroviral-naive PHI (defined as <1 year after infection, n = 62), chronic HIV infection (CHI, n = 16), and HIV-uninfected (n = 19) participants had DTI, laboratory, and neuropsychometric performance assessments. DTI metrics were examined using region of interest and whole brain voxelwise analyses. Linear mixed-effects models assessed correlations between DTI measures and laboratory and neuropsychometric performance values. Results PHI participants were assessed at a median 4.1 months after estimated infection, and had median CD4+ cell count of 573 cells/µl, and HIV-1 RNA viral load of 4.5 log10 copies/ml in plasma and 2.6 log10 copies/ml in cerebrospinal fluid (CSF). DTI metrics in PHI individuals were similar to HIV— participants and correlated with disruptions in the blood-brain barrier (indicated by CSF/plasma albumin ratio and CSF protein). CHI participants had significant loss of white matter integrity that correlated with biomarkers of infection and inflammation (blood viral load, CD4+ T-cell count, and neopterin, and CSF white blood cell). Within the PHI group, DTI metrics inversely correlated with increasing days since infection. Conclusion In individuals assessed during PHI, group DTI measures suggested relative preservation of white matter microstructural integrity, but were associated with disruption of the blood-brain barrier and estimated duration of infection. PMID:25513818

  6. 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

  7. 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

  8. Modeling the Relationship among Gray Matter Atrophy, Abnormalities in Connecting White Matter, and Cognitive Performance in Early Multiple Sclerosis

    PubMed Central

    Kuceyeski, A.F.; Vargas, W.; Dayan, M.; Monohan, E.; Blackwell, C.; Raj, A.; Fujimoto, K.; Gauthier, S.A.

    2016-01-01

    Background and Purpose Quantitative assessment of clinical and pathologic consequences of white matter abnormalities in multiple sclerosis is critical in understanding the pathways of disease. This study aimed to test whether gray matter atrophy was related to abnormalities in connecting white matter and to identify patterns of imaging biomarker abnormalities that were related to patient processing speed. Materials and Methods Image data and Symbol Digit Modalities Test scores were collected from a cohort of patients with early multiple sclerosis. The Network Modification Tool was used to estimate connectivity irregularities by projecting white matter abnormalities onto connecting gray matter regions. Partial least-squares regression quantified the relationship between imaging biomarkers and processing speed as measured by the Symbol Digit Modalities Test. Results Atrophy in deep gray matter structures of the thalami and putamen had moderate and significant correlations with abnormalities in connecting white matter (r = 0.39–0.41, P < .05 corrected). The 2 models of processing speed, 1 for each of the WM imaging biomarkers, had goodness-of-fit (R2) values of 0.42 and 0.30. A measure of the impact of white matter lesions on the connectivity of occipital and parietal areas had significant nonzero regression coefficients. Conclusions We concluded that deep gray matter regions may be susceptible to inflammation and/or demyelination in white matter, possibly having a higher sensitivity to remote degeneration, and that lesions affecting visual processing pathways were related to processing speed. The Network Modification Tool may be used to quantify the impact of early white matter abnormalities on both connecting gray matter structures and processing speed. PMID:25414004

  9. 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

  10. Contemplating Alzheimer's disease and the contribution of white matter hyperintensities.

    PubMed

    Brickman, Adam M

    2013-12-01

    As the older adult segment of the population increases, Alzheimer's disease (AD) has emerged as a significant public health epidemic. Over the past 3 decades, advances in the understanding of the biology of AD have led to a somewhat unified hypothesis of disease pathogenesis that emphasizes the precipitating role of beta amyloid protein. However, several lines of evidence suggest that multiple pathologies are necessary for clinical manifestation of the disease. Our focus over the past several years has been on the contribution of small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMH) on magnetic resonance imaging, to AD. White matter hyperintensity volume, particularly in parietal regions, is elevated among individuals with and at risk for AD, predicts future diagnosis of AD, predicts the rate of progression of cognitive symptoms among individuals with AD, and increases over time among individuals destined to develop AD. White matter hyperintensities may represent an independent source of impairment and/or may interact more fundamentally with "primary" AD pathology. Future work should focus on more inclusive models of that better define "normal" vs "pathological" aging. PMID:24190781

  11. 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

  12. White Matter Abnormalities in Major Depression: A Tract-Based Spatial Statistics and Rumination Study

    PubMed Central

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

    2012-01-01

    Increasing evidence indicates that major depressive disorder (MDD) is usually accompanied by altered white matter in the prefrontal cortex, the parietal lobe and the limbic system. As a behavioral abnormity of MDD, rumination has been believed to be a substantial indicator of the mental state of the depressive state. So far, however, no report that we are aware of has evaluated the relationship between white matter alterations and the ruminative state. In this study, we first explored the altered white matter using a tract-based spatial statistics (TBSS) method based on diffusion tensor imaging of 19 healthy and 16 depressive subjects. We then investigated correlations between the altered white matter microstructure in the identified altered regions and the severity of ruminations measured by the ruminative response scale. Our results demonstrated altered white matter microstructure in circuits connecting the prefrontal lobe, the parietal lobe and the limbic system (p<0.005, uncorrected), findings which support previous research. More importantly, the result also indicated that a greater alteration in the white matter is associated with a more ruminative state (p<0.05, Bonferroni corrected). The detected abnormalities in the white matter should be interpreted cautiously because of the small sample size in this study. This finding supports the psychometric significance of white matter deficits in MDD. PMID:22666366

  13. 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

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

    PubMed

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

    2016-02-01

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

  15. 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

  16. 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. PMID

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

    PubMed

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

    2015-02-01

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

  18. Exploring connectivity of the brain's white matter with dynamic queries.

    PubMed

    Sherbondy, Anthony; Akers, David; Mackenzie, Rachel; Dougherty, Robert; Wandell, Brian

    2005-01-01

    Diffusion Tensor Imaging (DTI) is a magnetic resonance imaging method that can be used to measure local information about the structure of white matter within the human brain. Combining DTI data with the computational methods of MR tractography, neuroscientists can estimate the locations and sizes of nerve bundles (white matter pathways) that course through the human brain. Neuroscientists have used visualization techniques to better understand tractography data, but they often struggle with the abundance and complexity of the pathways. In this paper, we describe a novel set of interaction techniques that make it easier to explore and interpret such pathways. Specifically, our application allows neuroscientists to place and interactively manipulate box or ellipsoid-shaped regions to selectively display pathways that pass through specific anatomical areas. These regions can be used in coordination with a simple and flexible query language which allows for arbitrary combinations of these queries using Boolean logic operators. A representation of the cortical surface is provided for specifying queries of pathways that may be relevant to gray matter structures and for displaying activation information obtained from functional magnetic resonance imaging. By precomputing the pathways and their statistical properties, we obtain the speed necessary for interactive question-and-answer sessions with brain researchers. We survey some questions that researchers have been asking about tractography data and show how our system can be used to answer these questions efficiently. PMID:16138552

  19. 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…

  20. 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…

  1. 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. PMID:27021440

  2. White matter lesions and intra-arterial thrombolysis.

    PubMed

    Jung, Simon; Mono, Marie Luise; Findling, Oliver; Fischer, Urs; Galimanis, Aekaterini; Weck, Anja; De Marchis, Gian Marco; Ballinari, Pietro; Gralla, Jan; Brekenfeld, Caspar; Schroth, Gerhard; Arnold, Marcel; Mattle, Heinrich P; El-Koussy, Marwan

    2012-07-01

    The aim of the study was to assess the influence of white matter lesions in patients with acute ischemic stroke treated with intra-arterial thrombolysis (IAT). From September 2003 to January 2010, we treated 400 patients with IAT at our institution. Of these patients, 292 were evaluated with MRI scans and included in this observational study. Clinical data were collected prospectively. Outcome after 3 months was measured with the modified Rankin Scale (mRS); mRS 0-1 was considered as favorable outcome. White matter lesions were scored visually by two observers using the semiquantitative Scheltens and Fazekas scores. Logistic regression analysis was used to identify the association of white matter lesions and clinical outcome, recanalization, and cerebral hemorrhage. The severity of white matter lesions was inversely correlated with favorable outcome, survival and successful recanalization. White matter lesions were an independent predictor of outcome (OR 0.569, p = 0.007) and survival (OR 0.550, p = 0.018) and a weak but independent predictor for recanalization (OR 0.949, p = 0.038). Asymptomatic intracerebral bleeding after IAT was associated with white matter lesions in the basal ganglia in the univariate analysis (p = 0.036), but not after multivariable analysis. The severity of white matter lesions independently predicts clinical outcome and survival in patients treated with IAT. White matter lesions are also a weak but independent predictor for recanalization. Symptomatic intracranial bleeding after IAT are not associated with white matter lesions. Therefore, white matter lesions should not be considered as a contraindication against IAT. PMID:22249288

  3. 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. PMID:25605966

  4. 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. PMID:27114916

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

    PubMed Central

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

    2016-01-01

    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. PMID:27114916

  6. Non-Gaussian water diffusion in aging white matter.

    PubMed

    Coutu, Jean-Philippe; Chen, J Jean; Rosas, H Diana; Salat, David H

    2014-06-01

    Age-associated white matter degeneration has been well documented and is likely an important mechanism contributing to cognitive decline in older adults. Recent work has explored a range of noninvasive neuroimaging procedures to differentially highlight alterations in the tissue microenvironment. Diffusional kurtosis imaging (DKI) is an extension of diffusion tensor imaging (DTI) that accounts for non-Gaussian water diffusion and can reflect alterations in the distribution and diffusion properties of tissue compartments. We used DKI to produce whole-brain voxel-based maps of mean, axial, and radial diffusional kurtoses, quantitative indices of the tissue microstructure's diffusional heterogeneity, in 111 participants ranging from the age of 33 to 91 years. As suggested from prior DTI studies, greater age was associated with alterations in white-matter tissue microstructure, which was reflected by a reduction in all 3 DKI metrics. Prominent effects were found in prefrontal and association white matter compared with relatively preserved primary motor and visual areas. Although DKI metrics co-varied with DTI metrics on a global level, DKI provided unique regional sensitivity to the effects of age not available with DTI. DKI metrics were additionally useful in combination with DTI metrics for the classification of regions according to their multivariate "diffusion footprint", or pattern of relative age effect sizes. It is possible that the specific multivariate patterns of age-associated changes measured are representative of different types of microstructural pathology. These results suggest that DKI provides important complementary indices of brain microstructure for the study of brain aging and neurologic disease. PMID:24378085

  7. 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

  8. White matter integrity in older females is altered by increased body fat

    PubMed Central

    Ryan, Lee; Walther, Katrin

    2015-01-01

    Objective To assess whether the pattern of diffusion changes among a cohort of individuals showing BMI-related increases in white matter volume reflects healthy expansion of myelin or damaged white matter. Design and Methods Diffusion MRI measures (axial, radial, and fractional anisotropy) were obtained from 94 females, ages 52–92. Relationships between BMI and diffusion measures were assessed controlling for age, hypertension, and diabetes status using general linear modelling. Associations between diffusion measures and cognitive status (memory, executive functions, and visuomotor speed) were assessed using multiple regressions, controlling for age, education, hypertension, and diabetes status. Results Higher levels of BMI were associated with lower axial diffusion in frontal, temporal, parietal, internal capsule, and cerebellar white matter. Lower fractional anisotropy was observed in bilateral temporal white matter and the right corticospinal tract, with high radial diffusion in temporal and temporoparietal white matter. Importantly, diffusion measures predicted reductions in executive functioning, memory, and visuomotor speed. Conclusions The pattern of diffusion changes in regions of white matter showing BMI-related volume increases are not due to expansion of normal myelin, but instead suggest damage to white matter that has important consequences for cognitive functioning. PMID:24957741

  9. Disconnected aging: cerebral white matter integrity and age-related differences in cognition.

    PubMed

    Bennett, I J; Madden, D J

    2014-09-12

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

  10. 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

  11. White Matter Hyperintensities and Hypobaric Exposure

    PubMed Central

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

    2014-01-01

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

  12. 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. PMID:27143602

  13. 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

  14. Decreased White Matter Integrity in Neuropsychologically-Defined Mild Cognitive Impairment is Independent of Cortical Thinning

    PubMed Central

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

    2014-01-01

    Improved understanding of the pattern of white matter changes in early and prodromal Alzheimer's disease (AD) states such as Mild Cognitive Impairment (MCI) is necessary to support earlier preclinical detection of AD, and debate remains whether white matter changes in MCI are secondary to gray matter changes. We applied neuropsychologically-based MCI criteria to a sample of normally aging older adults; 32 participants met criteria for MCI and 81 participants were classified as normal control (NC) subjects. Whole-head high resolution T1 and DTI scans were completed. Tract-Based Spatial Statistics was applied and a priori selected ROIs were extracted. Hippocampal volume and cortical thickness averaged across regions with known vulnerability to AD were derived. Controlling for cortical thickness, the MCI group showed decreased average FA and decreased FA in parietal white matter and in white matter underlying the entorhinal and posterior cingulate cortices relative to the NC group. Statistically controlling for cortical thickness, medial temporal FA was related to memory and parietal FA was related to executive functioning. These results provide further support for the potential role of white matter integrity as an early biomarker for individuals at risk for AD and highlight that changes in white matter may be independent of gray matter changes. PMID:23809097

  15. 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

  16. 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

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

    PubMed

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

    2013-01-01

    Many brain imaging studies have demonstrated reductions in gray and white matter volumes in alcoholism, with fewer investigators using diffusion tensor imaging (DTI) to examine the integrity of white matter pathways. Among various medical conditions, alcoholism and post-traumatic stress disorder (PTSD) are two comorbid diseases that have similar degenerative effects on the white matter integrity. Therefore, understanding and differentiating these effects would be very important in characterizing alcoholism and PTSD. Alcoholics are known to have neurocognitive deficits in decision-making, particularly in decisions related to emotionally-motivated behavior, while individuals with PTSD have deficits in emotional regulation and enhanced fear response. It is widely believed that these types of abnormalities in both alcoholism and PTSD are related to fronto-limbic dysfunction. In addition, previous studies have shown cortico-limbic fiber degradation through fiber tracking in alcoholism. DTI was used to measure white matter fractional anisotropy (FA), which provides information about tissue microstructure, possibly indicating white matter integrity. We quantitatively investigated the microstructure of white matter through whole brain DTI analysis in healthy volunteers (HV) and alcohol dependent subjects without PTSD (ALC) and with PTSD (ALC+PTSD). These data show significant differences in FA between alcoholics and non-alcoholic HVs, with no significant differences in FA between ALC and ALC+PTSD in any white matter structure. We performed a post-hoc region of interest analysis that allowed us to incorporate multiple covariates into the analysis and found similar results. HV had higher FA in several areas implicated in the reward circuit, emotion, and executive functioning, suggesting that there may be microstructural abnormalities in white matter pathways that contribute to neurocognitive and executive functioning deficits observed in alcoholics. Furthermore, our data do

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  3. 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

  4. Diminished performance on neuropsychological testing in late life depression is correlated with microstructural white matter abnormalities

    PubMed Central

    Mettenburg, Joseph M; Benzinger, Tammie L.S.; Shimony, Joshua S; Snyder, Abraham Z.; Sheline, Yvette I

    2012-01-01

    Background Traditional T2 weighted MR imaging results are non-specific for the extent of underlying white matter structural abnormalities present in late life depression (LLD). Diffusion tensor imaging provides a unique opportunity to investigate the extent and nature of structural injury, but has been limited by examining only a subset of regions of interest (ROI) and by confounds common to the study of an elderly population, including comorbid vascular pathology. Furthermore, comprehensive correlation of diffusion tensor imaging (DTI) measurements, including axial and radial diffusivity measurements, has not been demonstrated in the late life depression population. Methods 51 depressed and 16 non-depressed, age- and cerebrovascular risk factor- matched elderly subjects underwent traditional anatomic T1 and T2 weight imaging, as well as DTI. The DTI data were skeletonized using tract based spatial statistics (TBSS), and both regional and global analyses were performed. Results Widespread structural abnormalities within white matter were detected in the LLD group, accounting for age, gender and education and matched for cerebrovascular risk factors and global T2 white matter hyperintensities (T2WMH). Regional differences were most prominent in uncinate and cingulate white matter and were generally characterized by an increase in radial diffusivity. Age-related changes particularly in the cingulate bundle were more advanced in individuals with LLD relative to controls. Regression analysis demonstrated significant correlations of regional fractional anisotropy and radial diffusivity with five different neuropsychological factor scores. TBSS analysis demonstrated a greater extent of white matter abnormalities in LLD not responsive to treatment, as compared to controls. Conclusions White matter integrity is compromised in late life depression, largely manifested by increased radial diffusivity in specific regions, suggesting underlying myelin injury. A possible

  5. 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

  6. 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. PMID:26158080

  7. 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

  8. 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. PMID:23108272

  9. Structure-Specific Statistical Mapping of White Matter Tracts

    PubMed Central

    Yushkevich, Paul A.; Zhang, Hui; Simon, Tony; Gee, James C.

    2008-01-01

    We present a new model-based framework for the statistical analysis of diffusion imaging data associated with specific white matter tracts. The framework takes advantage of the fact that several of the major white matter tracts are thin sheet-like structures that can be effectively modeled by medial representations. The approach involves segmenting major tracts and fitting them with deformable geometric medial models. The medial representation makes it possible to average and combine tensor-based features along directions locally perpendicular to the tracts, thus reducing data dimensionality and accounting for errors in normalization. The framework enables the analysis of individual white matter structures, and provides a range of possibilities for computing statistics and visualizing differences between cohorts. The framework is demonstrated in a study of white matter differences in pediatric chromosome 22q11.2 deletion syndrome. PMID:18407524

  10. Structure-specific statistical mapping of white matter tracts.

    PubMed

    Yushkevich, Paul A; Zhang, Hui; Simon, Tony J; Gee, James C

    2008-06-01

    We present a new model-based framework for the statistical analysis of diffusion imaging data associated with specific white matter tracts. The framework takes advantage of the fact that several of the major white matter tracts are thin sheet-like structures that can be effectively modeled by medial representations. The approach involves segmenting major tracts and fitting them with deformable geometric medial models. The medial representation makes it possible to average and combine tensor-based features along directions locally perpendicular to the tracts, thus reducing data dimensionality and accounting for errors in normalization. The framework enables the analysis of individual white matter structures, and provides a range of possibilities for computing statistics and visualizing differences between cohorts. The framework is demonstrated in a study of white matter differences in pediatric chromosome 22q11.2 deletion syndrome. PMID:18407524

  11. Neuropsychiatry and white matter microstructure in Huntington’s disease

    PubMed Central

    Gregory, Sarah; Scahill, Rachael I; Seunarine, Kiran K; Stopford, Cheryl; Zhang, Hui; Zhang, Jiaying; Orth, Michael; Durr, Alexandra; Roos, Raymund A. C.; Langbehn, Douglas R.; Long, Jeffrey D.; Johnson, Hans; Rees, Geraint; Tabrizi, Sarah J.; Craufurd, David

    2015-01-01

    BACKGROUND Neuropsychiatric symptoms in Huntington’s disease (HD) are often evident prior to clinical diagnosis. Apathy is highly correlated with disease progression, while depression and irritability occur at different stages of the disease, both before and after clinical onset. Little is understood about the neural bases of these neuropsychiatric symptoms and to what extent those neural bases are analogous to neuropsychiatric disorders in the general population. OBJECTIVE We used Diffusion Tensor Imaging (DTI) to investigate structural connectivity between brain regions and any putative microstructural changes associated with depression, apathy and irritability in HD. METHODS DTI data were collected from 39 premanifest and 45 early-HD participants in the TrackHD study and analysed using whole-brain Tract-Based Spatial Statistics. We used regression analyses to identify white matter tracts whose structural integrity (as measured by fractional anisotropy, FA) was correlated with HADS-depression, PBA-apathy or PBA-irritability scores in gene-carriers and related to cumulative probability to onset (CPO). RESULTS For those with the highest CPO, we found significant correlations between depression scores and reduced FA in the splenium of the corpus callosum. In contrast, those with lowest CPO demonstrated significant correlations between irritability scores and widespread FA reductions. There was no significant relationship between apathy and FA throughout the whole brain. CONCLUSIONS We demonstrate that white matter changes associated with both depression and irritability in HD occur at different stages of disease progression concomitant with their clinical presentation. PMID:26443926

  12. 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. PMID:26239997

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

    PubMed

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

    2015-01-01

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

  14. 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

  15. 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

  16. 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

  17. 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

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

    PubMed Central

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

    2015-01-01

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

  19. 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

  20. 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

  1. DIFFUSE MICROSTRUCTURAL ABNORMALITIES OF NORMAL APPEARING WHITE MATTER IN LATE LIFE DEPRESSION: A DIFFUSION TENSOR IMAGING STUDY

    PubMed Central

    Shimony, Joshua S.; Sheline, Yvette I.; D’Angelo, Gina; Epstein, Adrian A.; Benzinger, Tammie L.S.; Mintun, Mark A.; McKinstry, Robert C.; Snyder, Abraham Z.

    2009-01-01

    Many recent studies have identified white matter abnormalities in late life depression (LLD). These abnormalities include an increased volume of discrete white matter lesions (hyperintensities on T2-weighted imaging) and changes in the diffusion tensor properties of water. However, no study of LLD to date has examined the integrity of white matter outside of discrete lesions, i.e., in normal appearing white matter. We performed T1- and T2-weighted imaging as well as diffusion tensor imaging (DTI) in depressed elderly subjects (n=73) and non-depressed control subjects (n=23) matched for age and cerebrovascular risk factors. The structural images were segmented into white matter, gray matter, cerebrospinal fluid and discrete white matter lesions. DTI parameters were calculated in white matter regions of interest after excluding the white matter lesions. Widespread LLD vs. control group differences were found, particularly in prefrontal regions, where the DTI abnormalities correlated with cognitive processing speed. These results suggest that further investigation is warranted to determine the basic pathophysiology and potential reversibility of LLD. PMID:19375071

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

    PubMed

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

    2015-12-16

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

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

    PubMed

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

    2014-10-22

    Three genes, DYX1C1, DCDC2, and KIAA0319, have been previously associated with dyslexia, neuronal migration, and ciliary function. Three polymorphisms within these genes, rs3743204 (DYX1C1), rs793842 (DCDC2), and rs6935076 (KIAA0319) have also been linked to normal variability of left temporoparietal white matter volume connecting the middle temporal cortex to the angular and supramarginal gyri. Here, we assessed whether these polymorphisms are also related to the cortical thickness of the associated regions during childhood development using a longitudinal dataset of 76 randomly selected children and young adults who were scanned up to three times each, 2 years apart. rs793842 in DCDC2 was significantly associated with the thickness of left angular and supramarginal gyri as well as the left lateral occipital cortex. The cortex was significantly thicker for T-allele carriers, who also had lower white matter volume and lower reading comprehension scores. There was a negative correlation between white matter volume and cortical thickness, but only white matter volume predicted reading comprehension 2 years after scanning. These results show how normal variability in reading comprehension is related to gene, white matter volume, and cortical thickness in the inferior parietal lobe. Possibly, the variability of gray and white matter structures could both be related to the role of DCDC2 in ciliary function, which affects both neuronal migration and axonal outgrowth. PMID:25339756

  4. 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

  5. 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

    2016-01-01

    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 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. PMID:27283395

  6. 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. PMID:26815786

  7. White matter abnormalities and structural hippocampal disconnections in amnestic mild cognitive impairment and Alzheimer's disease.

    PubMed

    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

    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

  8. 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

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

    PubMed Central

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

    2014-01-01

    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 [7]. PMID:25066750

  10. 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

  11. A Voxel-Based Diffusion Tensor Imaging Study of White Matter in Bipolar Disorder

    PubMed Central

    Mahon, Katie; Wu, Jinghui; Malhotra, Anil K.; Burdick, Katherine E.; DeRosse, Pamela; Ardekani, Babak A.; Szeszko, Philip R.

    2008-01-01

    There is evidence from post-mortem and magnetic resonance imaging studies that hyperintensities, oligodendrioglial abnormalities and gross white matter volumetric alterations play a role in the pathophysiology of bipolar disorder. There is also functional imaging evidence for a defect in frontal cortico-subcortical pathways in bipolar disorder, but the white matter comprising these pathways has not been well-investigated. Few studies have investigated white matter integrity in patients with bipolar disorder compared to healthy volunteers and the majority of studies have used manual region-of-interest approaches. In this study, we compared fractional anisotropy (FA) values between 30 patients with bipolar disorder and 38 healthy volunteers in the brain white matter using a voxelwise analysis following inter-subject registration to Talairach space. Compared to healthy volunteers, patients demonstrated significantly (p < .001; cluster size ≥ 50) higher FA within the right and left frontal white matter and lower FA within the left cerebellar white matter. Examination of individual eigenvalues indicated that group differences in both axial and radial diffusivity contributed to abnormal FA within these regions. Tractography was performed in template space on averaged diffusion tensor imaging data from all individuals. Extraction of bundles passing through the clusters that differed significantly between groups suggested that white matter abnormalities along the pontine crossing tract, corticospinal/corticopontine tracts and thalamic radiation fibers may play a role in the pathogenesis of bipolar disorder. Our findings are consistent with models of bipolar disorder that implicate dysregulation of cortico-subcortical and cerebellar regions in the disorder and may have relevance for phenomenology. PMID:19145224

  12. 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...

  13. 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

  14. 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

  15. 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

  16. White matter correlates of apathy in HIV-positive subjects: a diffusion tensor imaging study.

    PubMed

    Hoare, Jacqueline; Fouche, Jean-Paul; Spottiswoode, Bruce; Joska, John A; Schoeman, Renata; Stein, Dan J; Carey, Paul D

    2010-01-01

    Apathy is commonly reported by patients infected with HIV. No previous work has assessed the relationship between white matter and apathy in HIV. The authors aimed to determine whether apathy in HIV reflects a direct effect of the virus on subcortical brain regions or a secondary neuropsychiatric symptom. Thirteen HIV+ participants with apathy, 13 HIV+ participants with no apathy, and 10 healthy comparison subjects were examined using diffusion tensor imaging in the region of the anterior cingulate and corpus callosum. Results of the study confirmed the hypothesis which anticipated changes associated with apathy in white matter tracts that relay through the medial prefrontal cortex. PMID:20686138

  17. 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

  18. 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

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

    PubMed Central

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

    2015-01-01

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

  20. Surface based laminar analysis of diffusion abnormalities in cortical and white matter layers in neocortical epilepsy

    PubMed Central

    Govindan, Rajkumar Munian; Asano, Eishi; Juhasz, Csaba; Jeong, Jeong-won; Chugani, Harry T.

    2013-01-01

    Summary Purpose Microstructural alterations seen in the epileptic cortex have been implicated as a cause and also result of multiple seizure activity. In the present study, we evaluated water diffusion changes at different cortical thickness fractions and in the underlying white matter of the epileptic cortex and compared them with electrographically normal cortex and also with corresponding cortical regions of healthy controls. Methods We selected 18 children with normal MRI who underwent two-stage epilepsy surgery to control seizures of neocortical origin, and compared their MR images with those of 18 age-matched healthy controls. First, delineation of the grey-white and grey-pial intersection surfaces was performed on high-resolution volumetric T1 MR images. Using the delineated surfaces as reference, diffusion values were measured at different cortical thickness fractions and in the underlying white matter at various depths, using diffusion tensor imaging (DTI). Cortical regions representing seizure onset and electrographically normal cortex were differentiated by electrocorticography in the epilepsy patients. Key findings We observed different patterns of diffusion abnormalities in both the seizure onset and electrographically normal cortical regions when compared to healthy controls. In the seizure onset regions, a marked increase in diffusivity was noted in the cortical grey matter and this increase was most pronounced in the outer fraction of the grey matter. Similarly, increased diffusivity was noted in the white matter underlying the epileptic cortex. The electrographically normal cortex, in contrast, showed decreased diffusivity in inner and middle cortical fractions compared to the controls. The white matter underlying the electrographically normal cortex did not show any difference in diffusivity between the epileptic children and controls. Finally, both the cortical grey matter and the underlying white matter regions showed decreased anisotropy in

  1. Evidence for White Dwarfs with Strange-Matter Cores

    NASA Astrophysics Data System (ADS)

    Mathews, Grant J.; Suh, Insaeng; Lan, Nguyen Q.; Otsuki, Kaori; Weber, Fridolin

    2008-09-01

    We summarize masses and radii for a number of white dwarfs as deduced from a combination of proper motion studies, Hipparcos parallax distances, effective temperatures, and binary or spectroscopic masses. A puzzling feature of these data, however, is that some stars appear to have radii which are significantly smaller than that expected for a standard electron-degenerate white-dwarf equations of state. We construct a projection of white-dwarf radii for fixed effective mass and conclude that there is at least marginal evidence for bimodality in the radius distribution for white dwarfs. We argue that if such compact white dwarfs exist it is unlikely that they contain an iron core. We propose an alternative of strange-quark matter within the white-dwarf core. We also discuss the impact of the so-called color-flavor locked (CFL) state in strange-matter core associated with color superconductivity. We show that the data exhibit several features consistent with the expected mass-radius relation of strange dwarfs. We identify eight nearby white dwarfs which are possible candidates for strange matter cores and suggest observational tests of this hypothesis.

  2. Evidence for White Dwarfs with Strange-Matter Cores

    NASA Astrophysics Data System (ADS)

    Mathews, Grant; Suh, Insaeng; Lan, Nguyen; Zech, William; Otsuki, Kaori; Weber, Friedolin

    2006-10-01

    We summarize masses and radii for a number of white dwarfs as deduced from a combination of proper motion studies, Hipparcos parallax distances, effective temperatures, and binary or spectroscopic masses. A puzzling feature of these data, however, is that some stars appear to have radii which are significantly smaller than that expected for a standard electron-degenerate white-dwarf equations of state. We construct a projection of white-dwarf radii for fixed effective mass and conclude that there is at least marginal evidence for bimodality in the radius distribution for white dwarfs. We argue that if such compact white dwarfs exist it is unlikely that they contain an iron core. We propose an alternative of strange-quark matter within the white-dwarf core. We also discuss the impact of the so-called color-flavor locked (CFL) state in strange-matter core associated with color superconductivity. We show that the data exhibit several features consistent with the expected mass-radius relation of strange dwarfs. We identify eight nearby white dwarfs which are possible candidates for strange matter cores and suggest observational tests of this hypothesis.

  3. Analysis of white dwarfs with strange-matter cores

    NASA Astrophysics Data System (ADS)

    Mathews, G. J.; Suh, I.-S.; O'Gorman, B.; Lan, N. Q.; Zech, W.; Otsuki, K.; Weber, F.

    2006-06-01

    We summarize masses and radii for a number of white dwarfs as deduced from a combination of proper motion studies, Hipparcos parallax distances, effective temperatures and binary or spectroscopic masses. A puzzling feature of these data, however, is that some stars appear to have radii which are significantly smaller than that expected for a standard electron-degenerate white-dwarf equations of state. We construct a projection of white-dwarf radii for fixed effective mass and conclude that there is at least marginal evidence for bimodality in the radius distribution for white dwarfs. We argue that if such compact white dwarfs exist it is unlikely that they contain an iron core. We propose an alternative of strange-quark matter within the white-dwarf core. We also discuss the impact of the so-called color-flavour-locked (CFL) state in strange-matter core associated with color superconductivity. We show that the data exhibit several features consistent with the expected mass-radius relation of strange dwarfs. We identify eight nearby white dwarfs which are possible candidates for strange-matter cores and suggest observational tests of this hypothesis.

  4. Defective Glial Maturation in Vanishing White Matter Disease

    PubMed Central

    Bugiani, Marianna; Boor, Ilja; van Kollenburg, Barbara; Postma, Nienke; Polder, Emiel; van Berkel, Carola; van Kesteren, Ronald E.; Windrem, Martha S.; Hol, Elly M.; Scheper, Gert C.; Goldman, Steven A.; van der Knaap, Marjo S.

    2014-01-01

    Vanishing white matter disease (VWM) is a genetic leukoencephalopathy linked to mutations in the eukaryotic translation initiation factor 2B (eIF2B). It is a disease of infants, children and adults, who experience a slowly progressive neurological deterioration with episodes of rapid clinical worsening triggered by stress and eventually leading to death. Characteristic neuropathological findings include cystic degeneration of the white matter with scarce reactive gliosis, dysmorphic astrocytes, and paucity of myelin despite an increase in oligodendrocytic density. To assess whether a defective maturation of macroglia may be responsible for the feeble gliosis and lack of myelin, we investigated the maturation status of astrocytes and oligodendrocytes in the brains of 8 VWM patients, 4 patients with other white matter disorders and 6 age-matched controls with a combination of immunocytochemistry, histochemistry, scratch-wound assays, Western blot and quantitative PCR. We observed increased proliferation and a defect in the maturation of VWM astrocytes. They show an anomalous composition of their intermediate filament network with predominance of the δ-isoform of the glial fibrillary acidic protein and an increase in the heat shock protein αB-crystallin, supporting the possibility that a deficiency in astrocyte function may contribute to the loss of white matter in VWM. We also demonstrated a significant increase in numbers of pre-myelinating oligodendrocyte progenitors in VWM, which may explain the co-existence of oligodendrocytosis and myelin paucity in the patients’ white matter. PMID:21157376

  5. Characterization of T2* Heterogeneity in Human Brain White Matter

    PubMed Central

    Li, Tie-Qiang; Yao, Bing; van Gelderen, Peter; Merkle, Hellmut; Dodd, Stephen; Talagala, Lalith; Koretsky, Alan P.; Duyn, Jeff

    2012-01-01

    Recent in vivo MRI studies at 7.0 T have demonstrated extensive heterogeneity of T2* relaxation in white matter of the human brain. In order to study the origin of this heterogeneity, we performed T2* measurements at 1.5, 3.0, and 7.0 T in normal volunteers. Formalin-fixed brain tissue specimens were also studied using T2*-weighted MRI, histological staining, chemical analysis, and electron microscopy. We found that T2* relaxation rate (R2*=1/ T2*) in white matter in living human brain is linearly dependent on the main magnetic field strength and the T2* heterogeneity in white matter observed at 7.0 T can also be detected, albeit weaker, at 1.5 and 3.0 T. The T2* heterogeneity exists also in white matter of the formalin fixed brain tissue specimens, with prominent differences between the major fiber bundles such as the cingulum and the superior corona radiada. The white matter specimen with substantial difference in T2*have no significant difference in the total iron content as determined by chemical analysis. On the other hand, evidence from histological staining and electron microscopy demonstrate these tissue specimen have apparent difference in myelin content and microstructure. PMID:19859939

  6. 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

  7. 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

  8. 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

  9. 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

  10. Brain white matter microstructure alterations in adolescent rhesus monkeys exposed to early life stress: associations with high cortisol during infancy

    PubMed Central

    2013-01-01

    Background Early adverse experiences, especially those involving disruption of the mother-infant relationship, are detrimental for proper socioemotional development in primates. Humans with histories of childhood maltreatment are at high risk for developing psychopathologies including depression, anxiety, substance abuse, and behavioral disorders. However, the underlying neurodevelopmental alterations are not well understood. Here we used a nonhuman primate animal model of infant maltreatment to study the long-term effects of this early life stress on brain white matter integrity during adolescence, its behavioral correlates, and the relationship with early levels of stress hormones. Methods Diffusion tensor imaging and tract based spatial statistics were used to investigate white matter integrity in 9 maltreated and 10 control animals during adolescence. Basal plasma cortisol levels collected at one month of age (when abuse rates were highest) were correlated with white matter integrity in regions with group differences. Total aggression was also measured and correlated with white matter integrity. Results We found significant reductions in white matter structural integrity (measured as fractional anisotropy) in the corpus callosum, occipital white matter, external medullary lamina, as well as in the brainstem of adolescent rhesus monkeys that experienced maternal infant maltreatment. In most regions showing fractional anisotropy reductions, opposite effects were detected in radial diffusivity, without changes in axial diffusivity, suggesting that the alterations in tract integrity likely involve reduced myelin. Moreover, in most regions showing reduced white matter integrity, this was associated with elevated plasma cortisol levels early in life, which was significantly higher in maltreated than in control infants. Reduced fractional anisotropy in occipital white matter was also associated with increased social aggression. Conclusions These findings highlight the

  11. Spatial characteristics of white matter abnormalities in schizophrenia.

    PubMed

    White, Tonya; Ehrlich, Stefan; Ho, Beng-Choon; Manoach, Dara S; Caprihan, Arvind; Schulz, S Charles; Andreasen, Nancy C; Gollub, Randy L; Calhoun, Vince D; Magnotta, Vincent A

    2013-09-01

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

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

    PubMed Central

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

    2014-01-01

    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 tesla 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. PMID:24144509

  13. 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

  14. 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

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

    PubMed

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

    2010-11-01

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

  16. Snake-based brain white matter fiber reconstruction.

    PubMed

    Lu, Meng; Di, Jia

    2014-01-01

    Diffusion tensor imaging (DTI) is a tractography algorithm that provides the only means of mapping white matter fibers. Furthermore, because of its wealth of applications, diffusion MRI tractography is gaining importance in clinical and neuroscience research. This paper presents a novel brain white matter fiber reconstruction method based on the snake model by minimizing the energy function, which is composed of both external energy and internal energy. Internal energy represents the assembly of the interaction potential between connected segments, whereas external energy represents the differences between predicted DTI signals and measured DTI signals. Through comparing the proposed method with other tractography algorithms in the Fiber Cup test, the present method was shown to perform superiorly to the majority of the other methods. In fact, the proposed test performed the third best out of the ten available methods, which demonstrates that present method can accurately formulate the brain white matter fiber reconstruction. PMID:25227001

  17. Sexually Dimorphic White Matter Geometry Abnormalities in Adolescent Onset Schizophrenia

    PubMed Central

    Savadjiev, P.; Whitford, T.J.; Hough, M.E.; Clemm von Hohenberg, C.; Bouix, S.; Westin, C.-F.; Shenton, M.E.; Crow, T.J.; James, A.C.; Kubicki, M.

    2014-01-01

    The normal human brain is characterized by a pattern of gross anatomical asymmetry. This pattern, known as the “torque”, is associated with a sexual dimorphism: The male brain tends to be more asymmetric than that of the female. This fact, along with well-known sex differences in brain development (faster in females) and onset of psychosis (earlier with worse outcome in males), has led to the theory that schizophrenia is a disorder in which sex-dependent abnormalities in the development of brain torque, the correlate of the capacity for language, cause alterations in interhemispheric connectivity, which are causally related to psychosis (Crow TJ, Paez P, Chance SE. 2007. Callosal misconnectivity and the sex difference in psychosis. Int Rev Psychiatry. 19(4):449–457.). To provide evidence toward this theory, we analyze the geometry of interhemispheric white matter connections in adolescent-onset schizophrenia, with a particular focus on sex, using a recently introduced framework for white matter geometry computation in diffusion tensor imaging data (Savadjiev P, Kindlmann GL, Bouix S, Shenton ME, Westin CF. 2010. Local white geometry from diffusion tensor gradients. Neuroimage. 49(4):3175–3186.). Our results reveal a pattern of sex-dependent white matter geometry abnormalities that conform to the predictions of Crow's torque theory and correlate with the severity of patients' symptoms. To the best of our knowledge, this is the first study to associate geometrical differences in white matter connectivity with torque in schizophrenia. PMID:23307635

  18. 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. PMID:25604464

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

    PubMed

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

    2016-01-01

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

  20. Mechanisms of white matter change induced by meditation training

    PubMed Central

    Posner, Michael I.; Tang, Yi-Yuan; Lynch, Gary

    2014-01-01

    Training can induce changes in specific brain networks and changes in brain state. In both cases it has been found that the efficiency of white matter as measured by diffusion tensor imaging is increased, often after only a few hours of training. In this paper we consider a plausible molecular mechanism for how state change produced by meditation might lead to white matter change. According to this hypothesis frontal theta induced by meditation produces a molecular cascade that increases myelin and improves connectivity. PMID:25386155

  1. Scalable brain network construction on white matter fibers

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

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

  2. 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. PMID:27159321

  3. [What matters more in the white matter: thinking inside of the brain].

    PubMed

    Uchihara, Toshiki; Shishido-Hara, Yukiko

    2015-04-01

    The proportion of white matter in the brain has increased during evolution, and white matter comprises approximately half of the human brain. Its macroscopic as well as microscopic structures change during development, aging, and disease progression as well as following physical or mental training. Knowledge about the structural plasticity of the white matter may alter our cortex-oriented view of brain functions and expand our strategies for diagnosis and treatment, including rehabilitation, since the gray and white matter are complementary. Although the presence of white matter lesions is easy to detect with magnetic resonance imaging of the brain, their qualitative differentiation requires vast knowledge about the underlying processes. Examples from multiple ischemic lesions caused by different disease processes affecting the cerebral arteries are presented for comparison. It is worth considering "what matters more in the white matter" by taking into account the basic structures of the brain as well as their plasticity. Such "thinking inside of the brain" may further expand our understanding of the brain to improve our clinical interpretations and treatments. PMID:25846587

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

    PubMed Central

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

    2016-01-01

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

  5. 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

  6. 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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2015-03-01

    White matter abnormalities have been observed in patients with classic galactosemia, an inborn error of galactose metabolism. However, magnetic resonance imaging (MRI) data collected in the past were generally qualitative in nature. Our objective was to investigate white matter microstructure pathology and examine correlations with outcome and behaviour in this disease, by using multi-shell diffusion weighted imaging. In addition to standard diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI) was used to estimate density and orientation dispersion of neurites in a group of eight patients (aged 16-21 years) and eight healthy controls (aged 15-20 years). Extensive white matter abnormalities were found: neurite density index (NDI) was lower in the patient group in bilateral anterior areas, and orientation dispersion index (ODI) was increased mainly in the left hemisphere. These specific regional profiles are in agreement with the cognitive profile observed in galactosemia, showing higher order cognitive impairments, and language and motor impairments, respectively. Less favourable white matter properties correlated positively with age and age at onset of diet, and negatively with behavioural outcome (e.g. visual working memory). To conclude, this study provides evidence of white matter pathology regarding density and dispersion of neurites in these patients. The results are discussed in light of suggested pathophysiological mechanisms. PMID:25344151

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2010-01-01

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

  15. 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,…

  16. 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…

  17. 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…

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

    PubMed Central

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

    2014-01-01

    White matter hyperintensities (WMH) in elderly individuals with vascular diseases are presumed to be due to ischemic small vessel diseases; however, their etiology is unknown. We examined the cross-sectional relationship between cerebrovascular hemodynamics and white matter structural integrity in elderly individuals with vascular risk factors. White matter hyperintensity volumes, fractional anisotropy (FA), and mean diffusivity (MD) were obtained from MRI in 48 subjects (75±7years). Pulsatility index (PI) and dynamic cerebral autoregulation (dCA) was assessed using transcranial Doppler ultrasound of the middle cerebral artery. Dynamic cerebral autoregulation was calculated from transfer function analysis (phase and gain) of spontaneous blood pressure and flow velocity oscillations in the low (LF, 0.03 to 0.15 Hz) and high (HF, 0.16 to 0.5 Hz) frequency ranges. Higher PI was associated with greater WMH (P<0.005). Higher phase across all frequency ranges was associated with greater FA and lower MD (P<0.005). Lower gain was associated with higher FA in the LF range (P=0.001). These relationships between phase and FA were significant in the territories limited to the middle cerebral artery as well as across the entire brain. Our results show a strong relationship between impaired cerebrovascular hemodynamics (PI and dCA) and loss of cerebral white matter structural integrity (WMH and DTI metrics) in elderly individuals. PMID:24129749

  19. 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

  20. 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

  1. 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

  2. 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 ...

  3. Bilirubin and its oxidation products damage brain white matter.

    PubMed

    Lakovic, Katarina; Ai, Jinglu; D'Abbondanza, Josephine; Tariq, Asma; Sabri, Mohammed; Alarfaj, Abdullah K; Vasdev, Punarjot; Macdonald, Robert Loch

    2014-11-01

    Brain injury after intracerebral hemorrhage (ICH) occurs in cortex and white matter and may be mediated by blood breakdown products, including hemoglobin and heme. Effects of blood breakdown products, bilirubin and bilirubin oxidation products, have not been widely investigated in adult brain. Here, we first determined the effect of bilirubin and its oxidation products on the structure and function of white matter in vitro using brain slices. Subsequently, we determined whether these compounds have an effect on the structure and function of white matter in vivo. In all, 0.5 mmol/L bilirubin treatment significantly damaged both the function and the structure of myelinated axons but not the unmyelinated axons in brain slices. Toxicity of bilirubin in vitro was prevented by dimethyl sulfoxide. Bilirubin oxidation products (BOXes) may be responsible for the toxicity of bilirubin. In in vivo experiments, unmyelinated axons were found more susceptible to damage from bilirubin injection. These results suggest that unmyelinated axons may have a major role in white-matter damage in vivo. Since bilirubin and BOXes appear in a delayed manner after ICH, preventing their toxic effects may be worth investigating therapeutically. Dimethyl sulfoxide or its structurally related derivatives may have a potential therapeutic value at antagonizing axonal damage after hemorrhagic stroke. PMID:25160671

  4. Bilirubin and its oxidation products damage brain white matter

    PubMed Central

    Lakovic, Katarina; Ai, Jinglu; D'Abbondanza, Josephine; Tariq, Asma; Sabri, Mohammed; Alarfaj, Abdullah K; Vasdev, Punarjot; Macdonald, Robert Loch

    2014-01-01

    Brain injury after intracerebral hemorrhage (ICH) occurs in cortex and white matter and may be mediated by blood breakdown products, including hemoglobin and heme. Effects of blood breakdown products, bilirubin and bilirubin oxidation products, have not been widely investigated in adult brain. Here, we first determined the effect of bilirubin and its oxidation products on the structure and function of white matter in vitro using brain slices. Subsequently, we determined whether these compounds have an effect on the structure and function of white matter in vivo. In all, 0.5 mmol/L bilirubin treatment significantly damaged both the function and the structure of myelinated axons but not the unmyelinated axons in brain slices. Toxicity of bilirubin in vitro was prevented by dimethyl sulfoxide. Bilirubin oxidation products (BOXes) may be responsible for the toxicity of bilirubin. In in vivo experiments, unmyelinated axons were found more susceptible to damage from bilirubin injection. These results suggest that unmyelinated axons may have a major role in white-matter damage in vivo. Since bilirubin and BOXes appear in a delayed manner after ICH, preventing their toxic effects may be worth investigating therapeutically. Dimethyl sulfoxide or its structurally related derivatives may have a potential therapeutic value at antagonizing axonal damage after hemorrhagic stroke. PMID:25160671

  5. 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...

  6. 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. PMID:27001498

  7. 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

  8. Body Mass and White Matter Integrity: The Influence of Vascular and Inflammatory Markers

    PubMed Central

    Bettcher, Brianne Magouirk; Walsh, Christine M.; Watson, Christa; Miller, Joshua W.; Green, Ralph; Patel, Nihar; Miller, Bruce L.; Neuhaus, John; Yaffe, Kristine; Kramer, Joel H.

    2013-01-01

    High adiposity is deleteriously associated with brain health, and may disproportionately affect white matter integrity; however, limited information exists regarding the mechanisms underlying the association between body mass (BMI) and white matter integrity. The present study evaluated whether vascular and inflammatory markers influence the relationship between BMI and white matter in healthy aging. We conducted a cross-sectional evaluation of white matter integrity, BMI, and vascular/inflammatory factors in a cohort of 138 healthy older adults (mean age: 71.3 years). Participants underwent diffusion tensor imaging, provided blood samples, and participated in a health evaluation. Vascular risk factors and vascular/inflammatory blood markers were assessed. The primary outcome measure was fractional anisotropy (FA) of the genu, body, and splenium (corpus callosum); exploratory measures included additional white matter regions, based on significant associations with BMI. Regression analyses indicated that higher BMI was associated with lower FA in the corpus callosum, cingulate, and fornix (p<.001). Vascular and inflammatory factors influenced the association between BMI and FA. Specifically, BMI was independently associated with the genu [β=-.21; B=-.0024; 95% CI, -.0048 to -.0000; p=.05] and cingulate fibers [β=-.39; B=-.0035; 95% CI,-.0056 to -.0015; p<.001], even after controlling for vascular/inflammatory risk factors and blood markers. In contrast, BMI was no longer significantly associated with the fornix and middle/posterior regions of the corpus callosum after controlling for these markers. Results partially support a vascular/inflammatory hypothesis, but also suggest a more complex relationship between BMI and white matter characterized by potentially different neuroanatomic vulnerability. PMID:24147070

  9. 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

  10. White Matter Abnormalities in Schizophrenia and Schizotypal Personality Disorder

    PubMed Central

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

    2015-01-01

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

  11. 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

  12. 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

  13. 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

  14. 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

  15. Cognitive associations of subcortical white matter lesions in older people.

    PubMed

    O'Brien, John T; Wiseman, Rebecca; Burton, Emma J; Barber, Bob; Wesnes, Keith; Saxby, Brian; Ford, Gary A

    2002-11-01

    Hyperintense lesions (HL), as visualized on T2-weighted or FLAIR MRI, are a common finding in older people, but their clinical significance and influence on cognitive function remain to be clarified. We investigated the relationship between HL in deep white and gray matter structures and cognition in older subjects. We recruited 154 nondemented (Mini-Mental State Examination > 24) subjects (79 males) over the age of 70 from primary care (103 subjects with mild hypertension and 51 normotensive subjects). All subjects underwent FLAIR and proton density and T2-weighted axial 1.5-tesla MRI scans (slice thickness: 5 mm). The scans were rated for the presence and distribution of HL in the subcortical gray matter (caudate, putamen, globus pallidus, thalamus) and associated white matter tracts (internal/external capsule). Subjects (n = 149) underwent a comprehensive cognitive assessment involving tests of attention, processing speed, episodic memory, working memory, and executive function. Partial correlations (correcting for age, systolic blood pressure, and New Adult Reading Test [NART] score) were performed to investigate the relationship between cognition and white matter change. HL were found in 49% of subjects. HL in both the gray (thalamus and caudate) and white matter were significantly associated with impaired cognitive function in tasks involving processing speed and/or executive function, but showed no associations with episodic or working memory. HL in both subcortical gray matter structures and associated fiber tracts correlate with impairments in attention, executive function and processing, and memory retrieval speed in nondemented older community-dwelling subjects. Such lesions may be an important cause of age-related attentional and executive dysfunction in the elderly, as well as temporal lobe and hippocampal changes that have previously been reported to be associated with impairments to the ability to actually store and retrieve information from memory

  16. 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. PMID:27315771

  17. 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.

  18. 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

  19. 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.…

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

    PubMed Central

    Ben-Shachar, Michal; Feldman, Heidi M.

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  2. 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

  3. 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

  4. 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.

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

    PubMed

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

    2015-01-01

    Lonely individuals may exhibit dysfunction, particularly with respect to social empathy and self-efficacy. White matter (WM) structures related to loneliness have not yet been identified. We investigated the association between regional WM density (rWMD) using the UCLA Loneliness Scale in 776 healthy young students aged 18-27 years old. Loneliness scores were negatively correlated with rWMD in eight clusters: the bilateral inferior parietal lobule (IPL), right anterior insula (AI), posterior temporoparietal junction (pTPJ), left posterior superior temporal sulcus (pSTS), dorsomedial prefrontal cortex (dmPFC), and rostrolateral prefrontal cortex (RLPFC). The bilateral IPL, right AI, left pSTS, pTPJ, and RLPFC were strongly associated with Empathy Quotient (EQ), whereas the bilateral IPL, right AI, left pTPJ, and dmPFC were associated with General Self-Efficacy Scale (GSES) score. The neural correlates of loneliness comprise widespread reduction in WMD in areas related to self- and social cognition as well as areas associated with empathy and self-efficacy. PMID:26585372

  6. Altered white matter architecture in BDNF met carriers.

    PubMed

    Ziegler, Erik; Foret, Ariane; Mascetti, Laura; Muto, Vincenzo; Le Bourdiec-Shaffii, Anahita; Stender, Johan; Balteau, Evelyne; Dideberg, Vinciane; Bours, Vincent; Maquet, Pierre; Phillips, Christophe

    2013-01-01

    Brain-derived neurotrophic factor (BDNF) modulates the pruning of synaptically silent axonal arbors. The Met allele of the BDNF gene is associated with a reduction in the neurotrophin's activity-dependent release. We used diffusion-weighted imaging to construct structural brain networks for 36 healthy subjects with known BDNF genotypes. Through permutation testing we discovered clear differences in connection strength between subjects carrying the Met allele and those homozygotic for the Val allele. We trained a Gaussian process classifier capable of identifying the subjects' allelic group with 86% accuracy and high predictive value. In Met carriers structural connectivity was greatly increased throughout the forebrain, particularly in connections corresponding to the anterior and superior corona radiata as well as corticothalamic and corticospinal projections from the sensorimotor, premotor, and prefrontal portions of the internal capsule. Interhemispheric connectivity was also increased via the corpus callosum and anterior commissure, and extremely high connectivity values were found between inferior medial frontal polar regions via the anterior forceps. We propose that the decreased availability of BDNF leads to deficits in axonal maintenance in carriers of the Met allele, and that this produces mesoscale changes in white matter architecture. PMID:23935975

  7. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-10-01

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

  11. Effects of aging and calorie restriction on white matter in rhesus macaques

    PubMed Central

    Bendlin, B.B.; Canu, E.; Willette, A.A.; Kastman, E.K.; McLaren, D.G.; Kosmatka, K.J.; Xu, G.; Field, A.S.; Colman, R.J.; Coe, C.L.; Weindruch, R.H.; Alexander, A.L.; Johnson, S.C.

    2010-01-01

    Rhesus macaques on a calorie restricted diet (CR) develop less age-related disease, have virtually no indication of diabetes, are protected against sarcopenia, and potentially live longer. Beneficial effects of CR likely include reductions in age-related inflammation and oxidative damage. Oligodendrocytes are particularly susceptible to inflammation and oxidative stress, therefore, we hypothesized that CR would have a beneficial effect on brain white matter and would attenuate age-related decline in this tissue. CR monkeys and controls underwent diffusion tensor imaging (DTI). A beneficial effect of CR indexed by DTI was observed in superior longitudinal fasciculus, fronto-occipital fasciculus, external capsule, and brainstem. Aging effects were observed in several regions, although CR appeared to attenuate age-related alterations in superior longitudinal fasciculus, frontal white matter, external capsule, right parahippocampal white matter and dorsal occipital bundle. The results, however, were regionally specific and also suggested that CR is not salutary across all white matter. Further evaluation of this unique cohort of elderly primates to mortality will shed light on the ultimate benefits of an adult-onset, moderate CR diet for deferring brain aging. PMID:20541839

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

    PubMed

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

    2015-08-01

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

  13. A case of Jacobsen syndrome with multifocal white matter lesions.

    PubMed

    Yu, Fang; Carter, John E; Bazan, Carlos

    2016-01-01

    Jacobsen syndrome is a rare disorder caused by partial deletions of the long arm of chromosome 11. The phenotype is variable with involvement of multiple organ systems, resulting in congenital heart defects, blood dyscrasias, and impaired growth. We describe a case of a 30-year-old man with multiple ophthalmic manifestations and brain magnetic resonance imaging (MRI) that was remarkable for multiple T2-hyperintense subcortical white matter lesions. It is important to be aware that patients with Jacobsen syndrome may have nonspecific white changes seen on MRI. PMID:27317214

  14. 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

  15. 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…

  16. Association between white matter microstructure, executive functions, and processing speed in older adults: the impact of vascular health.

    PubMed

    Jacobs, Heidi I L; Leritz, Elizabeth C; Williams, Victoria J; Van Boxtel, Martin P J; van der Elst, Wim; Jolles, Jelle; Verhey, Frans R J; McGlinchey, Regina E; Milberg, William P; Salat, David H

    2013-01-01

    Cerebral white matter damage is not only a commonly reported consequence of healthy aging, but is also associated with cognitive decline and dementia. The aetiology of this damage is unclear; however, individuals with hypertension have a greater burden of white matter signal abnormalities (WMSA) on MR imaging than those without hypertension. It is therefore possible that elevated blood pressure (BP) impacts white matter tissue structure which in turn has a negative impact on cognition. However, little information exists about whether vascular health indexed by BP mediates the relationship between cognition and white matter tissue structure. We used diffusion tensor imaging to examine the impact of vascular health on regional associations between white matter integrity and cognition in healthy older adults spanning the normotensive to moderate-severe hypertensive BP range (43-87 years; N = 128). We examined how white matter structure was associated with performance on tests of two cognitive domains, executive functioning (EF) and processing speed (PS), and how patterns of regional associations were modified by BP and WMSA. Multiple linear regression and structural equation models demonstrated associations between tissue structure, EF and PS in frontal, temporal, parietal, and occipital white matter regions. Radial diffusivity was more prominently associated with performance than axial diffusivity. BP only minimally influenced the relationship between white matter integrity, EF and PS. However, WMSA volume had a major impact on neurocognitive associations. This suggests that, although BP and WMSA are causally related, these differential metrics of vascular health may act via independent pathways to influence brain structure, EF and PS. PMID:21954054

  17. ASSOCIATION BETWEEN WHITE MATTER MICROSTRUCTURE, EXECUTIVE FUNCTIONS AND PROCESSING SPEED IN OLDER ADULTS: THE IMPACT OF VASCULAR HEALTH

    PubMed Central

    Jacobs, Heidi I.L.; Leritz, Elizabeth C.; Williams, Victoria J.; Van Boxtel, Martin P.J.; van der Elst, Wim; Jolles, Jelle; Verhey, Frans R. J.; McGlinchey, Regina E.; Milberg, William P.; Salat, David H.

    2013-01-01

    Cerebral white matter damage is a commonly reported consequence of healthy aging, but is also associated with cognitive decline and dementia. The aetiology of this damage is unclear, however, individuals with hypertension have a greater burden of white matter signal abnormalities (WMSA) on MR imaging than those without hypertension. It is therefore possible that elevated blood pressure (BP) impacts white matter tissue structure which in turn has a negative impact on cognition. However, little information exists about whether vascular health indexed by BP mediates the relationship between cognition and white matter tissue structure. We used diffusion tensor imaging to examine the impact of vascular health on regional associations between white matter integrity and cognition in healthy older adults spanning the normotensive to moderate-severe hypertensive BP range (43–87 years; N=128). We examined how white matter structure was associated with performance on tests of two cognitive domains, executive functioning (EF) and processing speed (PS), and how patterns of regional associations were modified by BP and WMSA. Multiple linear regression and structural equation models demonstrated associations between tissue structure, EF and PS in frontal, temporal, parietal and occipital white matter regions. Radial diffusivity was more prominently associated with performance than axial diffusivity. BP only minimally influenced the relationship between white matter integrity, EF and PS. However, WMSA volume had a major impact on neurocognitive associations. This suggests that, although BP and WMSA are causally related, these differential metrics of vascular health may act via independent pathways to influence brain structure, EF and PS. PMID:21954054

  18. 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

  19. Minocycline treatment reduces white matter damage after excitotoxic striatal injury.

    PubMed

    Guimarães, Joanilson S; Freire, Marco Aurelio M; Lima, Rafael R; Picanço-Diniz, Cristovam W; Pereira, Antonio; Gomes-Leal, Walace

    2010-05-01

    We investigated the protective effects of minocycline following white matter damage (WMD) in the rat striatum. Excitotoxic lesions were induced by N-Methyl-d-Aspartate (NMDA) microinjections and caused striatal damage, concomitant with microglial/macrophage activation. The excitotoxic lesion both damaged oligodendrocytes (Tau-1(+) cells) and caused a decrease in tissue reactivity for myelin basic protein (MBP) after post-lesional day 3 (PLD). Treatment with the semi-synthetic tetracycline antibiotic minocycline, however, led to oligodendrocyte preservation and decreased myelin impairment. Taken together, these results suggest that white matter damage (WMD) is an important component of the physiopathology of acute striatal damage and that microglial/macrophage activation contributes to this pathological phenomenon. PMID:20226770

  20. White matter stimulation for the treatment of epilepsy.

    PubMed

    Girgis, Fady; Miller, Jonathan P

    2016-04-01

    Electrical stimulation in the treatment of epilepsy has been tried in numerous forms and with a variety of targets. Some of these, such as anterior thalamic stimulation, responsive cortical stimulation, and vagal nerve stimulation, have shown promise. A relatively novel concept, that of white matter stimulation, offers a different mechanism in that a small population of stimulated axons can transmit current to a large population of epileptogenic neurons. In theory, this allows for the modulation of seizure circuits and neural networks using lower stimulation volumes. Although clinical data is currently sparse, we review the relevant studies pertaining to white matter stimulation in epilepsy thus far, and offer explanations as to its effects, potential advantages, and utility. PMID:26926734

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

    PubMed Central

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

    2007-01-01

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

  2. 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

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

    PubMed

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

    2016-03-15

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

  4. Patterns of gray and white matter changes in individuals at risk for Alzheimer's disease.

    PubMed

    Jacobs, Heidi I L; van Boxtel, Martin P J; Gronenschild, Ed H B M; Williams, Victoria J; Burgmans, Saartje; Uylings, Harry B M; Jolles, Jelle; Verhey, Frans R J

    2012-11-01

    Structural brain changes precede cognitive and clinical symptoms in Alzheimer's disease (AD). We aimed to examine the gray and white matter tissue changes in individuals with memory decline over a 12-year period, who might be at risk for AD. The participants were selected from the longitudinal Maastricht Aging Study based on their scores on the verbal word learning task. A group with profound memory decline over a 12-year period (n = 20) was identified and matched with a group that did not meet this criterion (n = 20). All of the participants underwent MRI scanning. Diffusion tensor imaging and cortical thickness analyses were performed to investigate the white and gray matter differences respectively. We found decreased white matter integrity in the memory decline group compared to the control group in frontal and parietal brain regions and in several cortico-cortical and cortico-subcortical tracts. Cortical thinning in the memory decline group was found in frontal, parietal, medial temporal and occipital areas. These results showed similarities with the structural brain changes observed in early AD. Thus, not only may cognitive changes be detected years before the clinical diagnosis, but typical gray and white matter changes appear to be present in older people with memory decline as well. This suggests that a combination of cognitive decline and structural brain changes might be an ideal biomarker for AD pathogenesis. PMID:22920268

  5. Alterations of White Matter Integrity Related to the Season of Birth in Schizophrenia: A DTI Study

    PubMed Central

    Giezendanner, Stéphanie; Walther, Sebastian; Razavi, Nadja; Van Swam, Claudia; Fisler, Melanie Sarah; Soravia, Leila Maria; Andreotti, Jennifer; Schwab, Simon; Jann, Kay; Wiest, Roland; Horn, Helge; Müller, Thomas Jörg; Dierks, Thomas; Federspiel, Andrea

    2013-01-01

    In schizophrenia there is a consistent epidemiological finding of a birth excess in winter and spring. Season of birth is thought to act as a proxy indicator for harmful environmental factors during foetal maturation. There is evidence that prenatal exposure to harmful environmental factors may trigger pathologic processes in the neurodevelopment, which subsequently increase the risk of schizophrenia. Since brain white matter alterations have repeatedly been found in schizophrenia, the objective of this study was to investigate whether white matter integrity was related to the season of birth in patients with schizophrenia. Thirty-four patients with schizophrenia and 33 healthy controls underwent diffusion tensor imaging. Differences in the fractional anisotropy maps of schizophrenia patients and healthy controls born in different seasons were analysed with tract-based spatial statistics. A significant main effect of season of birth and an interaction of group and season of birth showed that patients born in summer had significantly lower fractional anisotropy in widespread white matter regions than those born in the remainder of the year. Additionally, later age of schizophrenia onset was found in patients born in winter months. The current findings indicate a relationship of season of birth and white matter alterations in schizophrenia and consequently support the neurodevelopmental hypothesis of early pathological mechanisms in schizophrenia. PMID:24086548

  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. PMID:26275384

  7. Common genetic variants and gene expression associated with white matter microstructure in the human brain

    PubMed Central

    Sprooten, Emma; Knowles, Emma E; McKay, D Reese; Göring, Harald HH; Curran, Joanne E; Kent, Jack W; Carless, Melanie A; Dyer, Thomas D; Drigalenko, Eugene I; Olvera, Rene L; Fox, Peter T; Almasy, Laura; Duggirala, Ravi; Kochunov, Peter; Blangero, John; Glahn, David C

    2014-01-01

    Identifying genes that contribute to white matter microstructure should provide insights into the neurobiological processes that regulate white matter development, plasticity and pathology. We detected five significant SNPs using genome-wide association analysis on a global measure of fractional anisotropy in 776 individuals from large extended pedigrees. Genetic correlations and genome-wide association results indicated that the genetic signal was largely homogeneous across white matter regions. Using RNA transcripts derived from lymphocytes in the same individuals, we identified two genes (GNA13 and CCDC91) that are likely to be cis-regulated by top SNPs, and whose expression levels were also genetically correlated with fractional anisotropy. A transcript of HTR7 was phenotypically associated with FA, and was associated with an intronic genome-wide significant SNP. These results encourage further research in the mechanisms by which GNA13, HTR7 and CCDC91 influence brain structure, and emphasize a role for g-protein signaling in the development and maintenance of white matter microstructure in health and disease. PMID:24736177

  8. Common genetic variants and gene expression associated with white matter microstructure in the human brain.

    PubMed

    Sprooten, Emma; Knowles, Emma E; McKay, D Reese; Göring, Harald H; Curran, Joanne E; Kent, Jack W; Carless, Melanie A; Dyer, Thomas D; Drigalenko, Eugene I; Olvera, Rene L; Fox, Peter T; Almasy, Laura; Duggirala, Ravi; Kochunov, Peter; Blangero, John; Glahn, David C

    2014-08-15

    Identifying genes that contribute to white matter microstructure should provide insights into the neurobiological processes that regulate white matter development, plasticity and pathology. We detected five significant SNPs using genome-wide association analysis on a global measure of fractional anisotropy in 776 individuals from large extended pedigrees. Genetic correlations and genome-wide association results indicated that the genetic signal was largely homogeneous across white matter regions. Using RNA transcripts derived from lymphocytes in the same individuals, we identified two genes (GNA13 and CCDC91) that are likely to be cis-regulated by top SNPs, and whose expression levels were also genetically correlated with fractional anisotropy. A transcript of HTR7 was phenotypically associated with FA, and was associated with an intronic genome-wide significant SNP. These results encourage further research in the mechanisms by which GNA13, HTR7 and CCDC91 influence brain structure, and emphasize a role for g-protein signaling in the development and maintenance of white matter microstructure in health and disease. PMID:24736177

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

    PubMed Central

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

    2014-01-01

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

  10. 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