Sample records for abnormal white matter

  1. Axonal abnormalities in vanishing white matter.

    PubMed

    Klok, Melanie D; Bugiani, Marianna; de Vries, Sharon I; Gerritsen, Wouter; Breur, Marjolein; van der Sluis, Sophie; Heine, Vivi M; Kole, Maarten H P; Baron, Wia; van der Knaap, Marjo S

    2018-04-01

    We aimed to study the occurrence and development of axonal pathology and the influence of astrocytes in vanishing white matter. Axons and myelin were analyzed using electron microscopy and immunohistochemistry on Eif2b4 and Eif2b5 single- and double-mutant mice and patient brain tissue. In addition, astrocyte-forebrain co-culture studies were performed. In the corpus callosum of Eif2b5- mutant mice, myelin sheath thickness, axonal diameter, and G-ratio developed normally up to 4 months. At 7 months, however, axons had become thinner, while in control mice axonal diameters had increased further. Myelin sheath thickness remained close to normal, resulting in an abnormally low G-ratio in Eif2b5- mutant mice. In more severely affected Eif2b4-Eif2b5 double-mutants, similar abnormalities were already present at 4 months, while in milder affected Eif2b4 mutants, few abnormalities were observed at 7 months. Additionally, from 2 months onward an increased percentage of thin, unmyelinated axons and increased axonal density were present in Eif2b5 -mutant mice. Co-cultures showed that Eif2b5 mutant astrocytes induced increased axonal density, also in control forebrain tissue, and that control astrocytes induced normal axonal density, also in mutant forebrain tissue. In vanishing white matter patient brains, axons and myelin sheaths were thinner than normal in moderately and severely affected white matter. In mutant mice and patients, signs of axonal transport defects and cytoskeletal abnormalities were minimal. In vanishing white matter, axons are initially normal and atrophy later. Astrocytes are central in this process. If therapy becomes available, axonal pathology may be prevented with early intervention.

  2. 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

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    2013-01-01

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

  5. 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

  6. 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.

  7. White matter abnormalities are associated with overall cognitive status in blast-related mTBI.

    PubMed

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

    2017-08-01

    Blast-related mild traumatic brain injury (mTBI) is a common injury of the Iraq and Afghanistan Wars. Research has suggested that blast-related mTBI is associated with chronic white matter abnormalities, which in turn are associated with impairment in neurocognitive function. However, findings are inconsistent as to which domains of cognition are affected by TBI-related white matter disruption. Recent evidence that white matter abnormalities associated with blast-related mTBI are spatially variable raises the possibility that the associated cognitive impairment is also heterogeneous. Thus, the goals of this study were to examine (1) whether mTBI-related white matter abnormalities are associated with overall cognitive status and (2) whether white matter abnormalities provide a mechanism by which mTBI influences cognition. Ninety-six Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OEF) veterans were assigned to one of three groups: no-TBI, mTBI without loss of consciousness (LOC) (mTBI-LOC), and mTBI with LOC (mTBI + LOC). Participants were given a battery of neuropsychological tests that were selected for their sensitivity to mTBI. Results showed that number of white matter abnormalities was associated with the odds of having clinically significant cognitive impairment. A mediation analysis revealed that mTBI + LOC was indirectly associated with cognitive impairment through its effect on white matter integrity. These results suggest that cognitive difficulties in blast-related mTBI can be linked to injury-induced neural changes when taking into account the variability of injury as well as the heterogeneity in cognitive deficits across individuals.

  8. New daily persistent headache: A lack of an association with white matter abnormalities on neuroimaging.

    PubMed

    Rozen, Todd D

    2016-09-01

    To provide results from the largest study of new daily persistent headache patients to date and specifically evaluate if patients with primary new daily persistent headache develop white matter abnormalities or infarct-like lesions on neuroimaging. Retrospective analysis of patient medical records utilizing an electronic medical record system. All patients were seen at a headache specialty clinic by a single headache neurologist and diagnosed with primary new daily persistent headache during the time period of January 2009 to January 2013. Altogether, 97 patients were diagnosed with primary new daily persistent headache (65 women and 32 men). The mean average age of onset was slightly younger in women than men: 32.4 years vs. 35.8 years. In total, 84 of the 97 new daily persistent headache patients had no white matter abnormalities or infarct-like lesions on magnetic resonance imaging with a gender distribution of 56 women and 28 men. The mean age of onset of this white matter negative subgroup was 31.1 years. Of these individuals, 36% had cardiovascular/cerebrovascular risk factors and 44% had a history of migraine. Only 13 new daily persistent headache patients (nine women, four men) demonstrated white matter abnormalities on magnetic resonance imaging. None had infarct-like lesions. The mean age of onset of this white matter positive subgroup was 54.2 years, significantly older than the white matter negative population (p < .05). All new daily persistent headache patients in the white matter positive subgroup had cardiovascular/cerebrovascular risk factors and dual risk factors were noted in seven of 13 patients. Only 23% had a migraine history. Almost 40% of the patients in the white matter negative group were imaged 3 years after headache onset and at least six patients were imaged at least 9 years or more after onset of new daily persistent headache. Triggering events in both white matter lesion positive and negative populations were typical of the new

  9. Deficits in Neurite Density Underlie White Matter Structure Abnormalities in First-Episode Psychosis.

    PubMed

    Rae, Charlotte L; Davies, Geoff; Garfinkel, Sarah N; Gabel, Matt C; Dowell, Nicholas G; Cercignani, Mara; Seth, Anil K; Greenwood, Kathryn E; Medford, Nick; Critchley, Hugo D

    2017-11-15

    Structural abnormalities across multiple white matter tracts are recognized in people with early psychosis, consistent with dysconnectivity as a neuropathological account of symptom expression. We applied advanced neuroimaging techniques to characterize microstructural white matter abnormalities for a deeper understanding of the developmental etiology of psychosis. Thirty-five first-episode psychosis patients, and 19 healthy controls, participated in a quantitative neuroimaging study using neurite orientation dispersion and density imaging, a multishell diffusion-weighted magnetic resonance imaging technique that distinguishes white matter fiber arrangement and geometry from changes in neurite density. Fractional anisotropy (FA) and mean diffusivity images were also derived. Tract-based spatial statistics compared white matter structure between patients and control subjects and tested associations with age, symptom severity, and medication. Patients with first-episode psychosis had lower regional FA in multiple commissural, corticospinal, and association tracts. These abnormalities predominantly colocalized with regions of reduced neurite density, rather than aberrant fiber bundle arrangement (orientation dispersion index). There was no direct relationship with active symptoms. FA decreased and orientation dispersion index increased with age in patients, but not control subjects, suggesting accelerated effects of white matter geometry change. Deficits in neurite density appear fundamental to abnormalities in white matter integrity in early psychosis. In the first application of neurite orientation dispersion and density imaging in psychosis, we found that processes compromising axonal fiber number, density, and myelination, rather than processes leading to spatial disruption of fiber organization, are implicated in the etiology of psychosis. This accords with a neurodevelopmental origin of aberrant brain-wide structural connectivity predisposing individuals to

  10. Sexually dimorphic white matter geometry abnormalities in adolescent onset schizophrenia.

    PubMed

    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

    2014-05-01

    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.

  11. Impaired language abilities and white matter abnormalities in children born very preterm and/or very low birth weight

    PubMed Central

    Reidy, Natalie; Morgan, Angela; Thompson, Deanne K; Inder, Terrie E.; Doyle, Lex W; Anderson, Peter J

    2012-01-01

    Objectives To investigate language abilities in children born very preterm (VPT; <32 weeks’ gestational age (GA)) or very low birth weight (VLBW; <1500 g) at 7 years of age and compare their performances with children born at term, and to determine whether group differences could be explained by cerebral white matter abnormality on neonatal MRI. Study design A cohort of 198 children born <30 weeks’ GA and/or <1250 g, and 70 term controls were examined. White matter abnormalities were rated quantitatively on brain MRI at term-equivalent age. Language was assessed at age 7 years using standardized language tests. Differences between groups were tested in the five language sub-domains of phonological awareness, semantics, grammar, discourse, and pragmatics. A mediation effect was tested between birth group, white matter abnormality, and language sub-domains. Results The VPT/VLBW group performed significantly worse than controls on all language sub-domains (all p <.001). White matter abnormality mediated the effect of group differences on phonological awareness, and partly mediated this effect for semantics, grammar and discourse. White matter abnormality was not significantly associated with pragmatics (p = .13). Conclusions Language is an important area of concern in children born VPT/VLBW. Neonatal white matter abnormality is an important predictor of outcome; however, different language abilities are differentially associated with neonatal white matter abnormality. PMID:23158026

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

    PubMed

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

    2013-08-01

    Online game addiction (OGA) has attracted greater attention as a serious public mental health issue. However, there are only a few brain magnetic resonance imaging studies on brain structure about OGA. In the current study, we used voxel-based morphometry (VBM) analysis and tract-based spatial statistics (TBSS) to investigate the microstructural changes in OGA and assessed the relationship between these morphology changes and the Young's Internet Addiction Scale (YIAS) scores within the OGA group. Compared with healthy subjects, OGA individuals showed significant gray matter atrophy in the right orbitofrontal cortex, bilateral insula, and right supplementary motor area. According to TBSS analysis, OGA subjects had significantly reduced FA in the right genu of corpus callosum, bilateral frontal lobe white matter, and right external capsule. Gray matter volumes (GMV) of the right orbitofrontal cortex, bilateral insula and FA values of the right external capsule were significantly positively correlated with the YIAS scores in the OGA subjects. Our findings suggested that microstructure abnormalities of gray and white matter were present in OGA subjects. This finding may provide more insights into the understanding of the underlying neural mechanisms of OGA. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. White matter structural network abnormalities underlie executive dysfunction in amyotrophic lateral sclerosis.

    PubMed

    Dimond, Dennis; Ishaque, Abdullah; Chenji, Sneha; Mah, Dennell; Chen, Zhang; Seres, Peter; Beaulieu, Christian; Kalra, Sanjay

    2017-03-01

    Research in amyotrophic lateral sclerosis (ALS) suggests that executive dysfunction, a prevalent cognitive feature of the disease, is associated with abnormal structural connectivity and white matter integrity. In this exploratory study, we investigated the white matter constructs of executive dysfunction, and attempted to detect structural abnormalities specific to cognitively impaired ALS patients. Eighteen ALS patients and 22 age and education matched healthy controls underwent magnetic resonance imaging on a 4.7 Tesla scanner and completed neuropsychometric testing. ALS patients were categorized into ALS cognitively impaired (ALSci, n = 9) and ALS cognitively competent (ALScc, n = 5) groups. Tract-based spatial statistics and connectomics were used to compare white matter integrity and structural connectivity of ALSci and ALScc patients. Executive function performance was correlated with white matter FA and network metrics within the ALS group. Executive function performance in the ALS group correlated with global and local network properties, as well as FA, in regions throughout the brain, with a high predilection for the frontal lobe. ALSci patients displayed altered local connectivity and structural integrity in these same frontal regions that correlated with executive dysfunction. Our results suggest that executive dysfunction in ALS is related to frontal network disconnectivity, which potentially mediates domain-specific, or generalized cognitive impairment, depending on the degree of global network disruption. Furthermore, reported co-localization of decreased network connectivity and diminished white matter integrity suggests white matter pathology underlies this topological disruption. We conclude that executive dysfunction in ALSci is associated with frontal and global network disconnectivity, underlined by diminished white matter integrity. Hum Brain Mapp 38:1249-1268, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Assessment of white matter abnormalities in paranoid schizophrenia and bipolar mania patients.

    PubMed

    Cui, Liqian; Chen, Zhuangfei; Deng, Wei; Huang, Xiaoqi; Li, Mingli; Ma, Xiaohong; Huang, Chaohua; Jiang, Lijun; Wang, Yingcheng; Wang, Qiang; Collier, David A; Gong, Qiyong; Li, Tao

    2011-12-30

    White matter abnormalities have been repeatedly reported in both schizophrenia and bipolar disorder (BD) in diffusion tensor imaging (DTI) studies, but the empirical evidence about the diagnostic specificity of white matter abnormalities in these disorders is still limited. This study sought to investigate the alterations in fractional anisotropy (FA) in white matter throughout the entire brain of patients from Chengdu, China with paranoid schizophrenia and bipolar mania. For this purpose, DTI was used to assess white matter integrity in patients with paranoid schizophrenia (n=25) and psychotic bipolar mania (n=18) who had been treated with standard pharmacotherapy for fewer than 5 days at the time of study, as well as in normal controls (n=30). The differences in FA were measured by use of voxel-based analysis. The results show that reduced FA was found in the left posterior corona radiata (PCR) in patients with psychotic bipolar mania and paranoid schizophrenia compared to the controls. Patients with psychotic bipolar mania also showed a significant reduction in FA in right posterior corona radiata and in right anterior thalamic radiation (ATR). A direct comparison between the two patient groups found no significant differences in any regions, and none of the findings were associated with illness duration. Correlation analysis indicated that FA values showed a significant negative correlation with positive symptom scores on the Positive and Negative Syndrome Scale in the left frontal-parietal lobe in the paranoid schizophrenia. It was concluded that common abnormalities in the left PCR might imply an overlap in white matter pathology in the two disorders and might be related to shared risk factors for the two disorders. 2011 Elsevier Ireland Ltd. All rights reserved.

  15. [The effection of white matter abnormality to auditory and speech rehabilitation after cochlear implantation in prelingual deafness children].

    PubMed

    Zhang, X Y; Liang, M J; Liu, J H; Li, X H; Zhen, Y Q; Weng, Y L

    2017-04-20

    Objective: To investigatethe effection of white matter abnormality to auditory and speech rehabilitation after cochlear implantation in prelingual deafness children. Method: Thirty-five children with white matter abnormality were included in this study. The degree of leukoaraiosis was evaluated by Scheltens scale based on MRI.The hearing and speechrecovery level was rated by auditory behavior grading standards(CAP) and speech intelligibility grading standards(SIR) at 6 months, 12 months, and 24 months post operation. Result: The CAP scores and SIR scores of the children with white matter abnormality were lower than those of the control group at 6 months after operation ( P <0.05).The SIR scores of the children with white matter abnormality at 12 months and 24 months post operation were significantly lower than those of the control group.There was no statistically significant difference between the CAP scores of the two groups at 12 and 24 months after operation( P >0.05).Schelten classification had a greater impact on SIR scores than on CAP scores. Conclusion: The effect of white matter abnormality on auditory and speech rehabilitation after cochlear implantation was related to the degree of leukoencephalopathy. When the lesion of white matter abnormality was larger, the level of hearing and verbal rehabilitation was lower, and the speech rehabilitation was more significantly impacted by white matter lesions degree. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

  16. Abnormal cholesterol is associated with prefrontal white matter abnormalities among obese adults, a diffusion tensor imaging study

    PubMed Central

    Cohen, Jessica I.; Cazettes, Fanny; Convit, Antonio

    2011-01-01

    The brain is the most cholesterol-rich organ in the body. Although most of the cholesterol in the brain is produced endogenously, some studies suggest that systemic cholesterol may be able to enter the brain. We investigated whether abnormal cholesterol profiles correlated with diffusion-tensor-imaging-based estimates of white matter microstructural integrity of lean and overweight/obese (o/o) adults. Twenty-two lean and 39 obese adults underwent magnetic resonance imaging, kept a 3-day food diary, and had a standardized assessment of fasting blood lipids. The lean group ate less cholesterol rich food than o/o although both groups ate equivalent servings of food per day. Voxelwise correlational analyses controlling for age, diabetes, and white matter hyperintensities, resulted in two significant clusters of negative associations between abnormal cholesterol profile and fractional anisotropy, located in the left and right prefrontal lobes. When the groups were split, the lean subjects showed no associations, whereas the o/o group expanded the association to three significant clusters, still in the frontal lobes. These findings suggest that cholesterol profile abnormalities may explain some of the reductions in white matter microstructural integrity that are reported in obesity. PMID:22163070

  17. Distinct white matter abnormalities in different idiopathic generalized epilepsy syndromes.

    PubMed

    Liu, Min; Concha, Luis; Beaulieu, Christian; Gross, Donald W

    2011-12-01

    By definition idiopathic generalized epilepsy (IGE) is not associated with structural abnormalities on conventional magnetic resonance imaging (MRI). However, recent quantitative studies suggest white and gray matter alterations in IGE. The purpose of this study was to investigate whether there are white and/or gray matter structural differences between controls and two subsets of IGE, namely juvenile myoclonic epilepsy (JME) and IGE with generalized tonic-clonic seizures only (IGE-GTC). We assessed white matter integrity and gray matter volume using diffusion tensor tractography-based analysis of fractional anisotropy and voxel-based morphometry, respectively, in 25 patients with IGE, all of whom had experienced generalized tonic-clonic convulsions. Specifically, 15 patients with JME and 10 patients with IGE-GTC were compared to two groups of similarly matched controls separately. Correlations between total lifetime generalized tonic-clonic seizures and fractional anisotropy were investigated for both groups. Tractography revealed lower fractional anisotropy in specific tracts including the crus of the fornix, body of corpus callosum, uncinate fasciculi, superior longitudinal fasciculi, anterior limb of internal capsule, and corticospinal tracts in JME with respect to controls, whereas there were no fractional anisotropy differences in IGE-GTC. No correlation was found between fractional anisotropy and total lifetime generalized tonic-clonic seizures for either JME or IGE-GTC. Although false discovery rate-corrected voxel-based morphometry (VBM) showed no gray matter volume differences between patient and control groups, spatial extent cluster-corrected VBM analysis suggested a trend of gray matter volume reduction in frontal and central regions in both patient groups, more lateral in JME and more medial in IGE-GTC. The findings support the idea that the clinical syndromes of JME and IGE-GTC have unique anatomic substrates. The fact that the primary clinical

  18. The relationship between white matter abnormalities and cognitive functions in new-onset juvenile myoclonic epilepsy.

    PubMed

    Ekmekci, Burcu; Bulut, Hacı Taner; Gümüştaş, Funda; Yıldırım, Adem; Kuştepe, Ali

    2016-09-01

    Diffusion tensor imaging (DTI) has revealed evidence of subcortical white matter abnormalities in the frontal area in juvenile myoclonic epilepsy (JME). Decreased fractional anisotropy (FA) and increased mean diffusivity (MD) in the corticothalamic pathway have been detected in adult patients with JME. It has been demonstrated that, in adult patients with JME, frontal dysfunction is related to subcortical white matter damage and decreased volume in frontal cortical gray matter and the thalamus. Many studies have focused on adult patients. Twenty-four patients and 28 controls were evaluated. The group with JME had significantly worse results for the word fluency, trail-B, and Stroop tests that assessed executive functions. A significant decrease in FA values in the dorsolateral prefrontal cortex (DLPFC), the supplementary motor area (SMA), the right thalamus, the posterior cingulate, the corpus callosum anterior, the corona radiata, and the middle frontal white matter (MFWM) and an increase in ADC values in patients with JME were detected. The correlation between FA values in DLPFC and the letter fluency test results was positive, and the correlation with the Stroop and trail-B test results was negative. We found a negative correlation between SMA, anterior thalamus, and MFWM FA values and the trail-B test results and a positive correlation between the SMA, anterior thalamus, and MFWM FA values and the letter fluency test results. We detected white matter and gray matter abnormalities in patients with new-onset JME using DTI. In addition, we determined the relationship between cognitive deficit and microstructural abnormalities by evaluating the correlation between the neuropsychological test battery results and DTI parameters. We evaluated newly diagnosed patients with JME in our study. That leads us to believe that microstructural abnormalities exist from the very beginning of the disease and that they result from the genetic basis of the disease. Copyright

  19. Longitudinal assessment of white matter abnormalities following sports-related concussion.

    PubMed

    Meier, Timothy B; Bergamino, Maurizio; Bellgowan, Patrick S F; Teague, T K; Ling, Josef M; Jeromin, Andreas; Mayer, Andrew R

    2016-02-01

    There is great interest in developing physiological-based biomarkers such as diffusion tensor imaging to aid in the management of concussion, which is currently entirely dependent on clinical judgment. However, the time course for recovery of white matter abnormalities following sports-related concussion (SRC) is unknown. We collected diffusion tensor imaging and behavioral data in forty concussed collegiate athletes on average 1.64 days (T1; n = 33), 8.33 days (T2; n = 30), and 32.15 days post-concussion (T3; n = 26), with healthy collegiate contact-sport athletes (HA) serving as controls (n = 46). We hypothesized that fractional anisotropy (FA) would be increased acutely and partially recovered by one month post-concussion. Mood symptoms were assessed using structured interviews. FA differences were assessed using both traditional and subject-specific analyses. An exploratory analysis of tau plasma levels was conducted in a subset of participants. Results indicated that mood symptoms improved over time post-concussion, but remained elevated at T3 relative to HA. Across both group and subject-specific analyses, concussed athletes exhibited increased FA in several white matter tracts at each visit post-concussion with no longitudinal evidence of recovery. Increased FA at T1 and T3 was significantly associated with an independent, real-world outcome measure for return-to-play. Finally, we observed a nonsignificant trend for reduced tau in plasma of concussed athletes at T1 relative to HA, with tau significantly increasing by T2. These results suggest white matter abnormalities following SRC may persist beyond one month and have potential as an objective biomarker for concussion outcome. Hum Brain Mapp 37:833-845, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  20. Diffusion tensor imaging with tract-based spatial statistics reveals local white matter abnormalities in preterm infants.

    PubMed

    Anjari, Mustafa; Srinivasan, Latha; Allsop, Joanna M; Hajnal, Joseph V; Rutherford, Mary A; Edwards, A David; Counsell, Serena J

    2007-04-15

    Infants born preterm have a high incidence of neurodevelopmental impairment in later childhood, often associated with poorly defined cerebral white matter abnormalities. Diffusion tensor imaging quantifies the diffusion of water within tissues and can assess microstructural abnormalities in the developing preterm brain. Tract-based spatial statistics (TBSS) is an automated observer-independent method of aligning fractional anisotropy (FA) images from multiple subjects to allow groupwise comparisons of diffusion tensor imaging data. We applied TBSS to test the hypothesis that preterm infants have reduced fractional anisotropy in specific regions of white matter compared to term-born controls. We studied 26 preterm infants with no evidence of focal lesions on conventional magnetic resonance imaging (MRI) at term equivalent age and 6 healthy term-born control infants. We found that the centrum semiovale, frontal white matter and the genu of the corpus callosum showed significantly lower FA in the preterm group. Infants born at less than or equal to 28 weeks gestational age (n=11) displayed additional reductions in FA in the external capsule, the posterior aspect of the posterior limb of the internal capsule and the isthmus and middle portion of the body of the corpus callosum. This study demonstrates that TBSS provides an observer-independent method of identifying white matter abnormalities in the preterm brain at term equivalent age in the absence of focal lesions.

  1. Periventricular heterotopia and white matter abnormalities in a girl with mosaic ring chromosome 6.

    PubMed

    Nishigaki, Satsuki; Hamazaki, Takashi; Saito, Mika; Yamamoto, Toshiyuki; Seto, Toshiyuki; Shintaku, Haruo

    2015-01-01

    Ring chromosome 6 is a rare chromosome abnormality that arises typically de novo. The phenotypes can be highly variable, ranging from almost normal to severe malformations and neurological defects. We report a case of a 3-year-old girl with mosaic ring chromosome 6 who presented with being small for gestational age and intellectual disability, and whose brain MRI later revealed periventricular heterotopia and white matter abnormalities. Mosaicism was identified in peripheral blood cells examined by standard G-bands, mos 46,XX,r(6)(p25q27)[67]/45,XX,-6[25]/46,XX,dic r(6:6)(p25q27:p25q27)[6]/47,XX,r(6)(p25q27) × 2[2]. Using array-comparative genomic hybridization, we identified terminal deletion of 6q27 (1.5 Mb) and no deletion on 6p. To our knowledge, this is the first report of periventricular heterotopia and white matter abnormalities manifested in a patient with ring chromosome 6. These central nervous system malformations are further discussed in relation to molecular genetics.

  2. Affective traits of psychopathy are linked to white-matter abnormalities in impulsive male offenders.

    PubMed

    Vermeij, Anouk; Kempes, Maaike M; Cima, Maaike J; Mars, Rogier B; Brazil, Inti A

    2018-04-26

    Psychopathy is a personality disorder typified by lack of empathy and impulsive antisocial behavior. Psychopathic traits may partly relate to disrupted connections between brain regions. The aim of the present study was to link abnormalities in microstructural integrity of white-matter tracts to the severity of different psychopathic traits in 15 male offenders with impulse control problems and 10 without impulse control problems. Psychopathic traits were assessed using the Psychopathy Checklist-revised (PCL-R). Diffusion-weighted MRI was used to examine white-matter tracts. Fractional anisotropy (FA), an index of white-matter integrity, was calculated for each voxel. Clusters of voxels showing a significant relationship with psychopathy severity were submitted to probabilistic tractography. No significant correlations between psychopathy severity and FA were present in the whole group of impulsive and nonimpulsive offenders. In impulsive offenders, interpersonal-affective traits (PCL-R Factor 1) were negatively correlated with FA in the anterior and posterior temporal lobe and orbitofrontal area. Further analyses indicated that elevated affective traits (PCL-R Facet 2) were specifically related to reduced FA in the right temporal lobe. Our findings suggest that white-matter abnormalities in temporal and frontotemporal tracts may be linked to the interpersonal-affective deficits of psychopathy in offenders with relatively severe impulse control problems. Our study offers novel insights into the relationships between the four facets of psychopathy and disrupted structural connectivity, and may provide new leads for further characterization of different subtypes of antisocial populations. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  3. Early White-Matter Abnormalities of the Ventral Frontostriatal Pathway in Fragile X Syndrome

    ERIC Educational Resources Information Center

    Haas, Brian W.; Barnea-Goraly, Naama; Lightbody, Amy A.; Patnaik, Swetapadma S.; Hoeft, Fumiko; Hazlett, Heather; Piven, Joseph; Reiss, Allan L.

    2009-01-01

    Aim: Fragile X syndrome is associated with cognitive deficits in inhibitory control and with abnormal neuronal morphology and development. Method: In this study, we used a diffusion tensor imaging (DTI) tractography approach to reconstruct white-matter fibers in the ventral frontostriatal pathway in young males with fragile X syndrome (n = 17;…

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

    USDA-ARS?s Scientific Manuscript database

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

  5. Microstructural abnormalities of the brain white matter in attention-deficit/hyperactivity disorder

    PubMed Central

    Chen, Lizhou; Huang, Xiaoqi; Lei, Du; He, Ning; Hu, Xinyu; Chen, Ying; Li, Yuanyuan; Zhou, Jinbo; Guo, Lanting; Kemp, Graham J.; Gong, Qiyong

    2015-01-01

    Background Attention-deficit/hyperactivity disorder (ADHD) is an early-onset neurodevelopmental disorder with multiple behavioural problems and executive dysfunctions for which neuroimaging studies have reported a variety of abnormalities, with inconsistencies partly owing to confounding by medication and concurrent psychiatric disease. We aimed to investigate the microstructural abnormalities of white matter in unmedicated children and adolescents with pure ADHD and to explore the association between these abnormalities and behavioural symptoms and executive functions. Methods We assessed children and adolescents with ADHD and healthy controls using psychiatric interviews. Behavioural problems were rated using the revised Conners’ Parent Rating Scale, and executive functions were measured using the Stroop Colour-Word Test and the Wisconsin Card Sorting test. We acquired diffusion tensor imaging data using a 3 T MRI system, and we compared diffusion parameters, including fractional anisotropy (FA) and mean, axial and radial diffusivities, between the 2 groups. Results Thirty-three children and adolescents with ADHD and 35 healthy controls were included in our study. In patients compared with controls, FA was increased in the left posterior cingulum bundle as a result of both increased axial diffusivity and decreased radial diffusivity. In addition, the averaged FA of the cluster in this region correlated with behavioural measures as well as executive function in patients with ADHD. Limitations This study was limited by its cross-sectional design and small sample size. The cluster size of the significant result was small. Conclusion Our findings suggest that white matter abnormalities within the limbic network could be part of the neural underpinning of behavioural problems and executive dysfunction in patients with ADHD. PMID:25853285

  6. Exploratory analysis of diffusion tensor imaging in children with attention deficit hyperactivity disorder: evidence of abnormal white matter structure.

    PubMed

    Pastura, Giuseppe; Doering, Thomas; Gasparetto, Emerson Leandro; Mattos, Paulo; Araújo, Alexandra Prüfer

    2016-06-01

    Abnormalities in the white matter microstructure of the attentional system have been implicated in the aetiology of attention deficit hyperactivity disorder (ADHD). Diffusion tensor imaging (DTI) is a promising magnetic resonance imaging (MRI) technology that has increasingly been used in studies of white matter microstructure in the brain. The main objective of this work was to perform an exploratory analysis of white matter tracts in a sample of children with ADHD versus typically developing children (TDC). For this purpose, 13 drug-naive children with ADHD of both genders underwent MRI using DTI acquisition methodology and tract-based spatial statistics. The results were compared to those of a sample of 14 age- and gender-matched TDC. Lower fractional anisotropy was observed in the splenium of the corpus callosum, right superior longitudinal fasciculus, bilateral retrolenticular part of the internal capsule, bilateral inferior fronto-occipital fasciculus, left external capsule and posterior thalamic radiation (including right optic radiation). We conclude that white matter tracts in attentional and motor control systems exhibited signs of abnormal microstructure in this sample of drug-naive children with ADHD.

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

    PubMed

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

    2016-01-01

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

  8. Tryptophan Metabolism and White Matter Integrity in Schizophrenia

    PubMed Central

    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

    2016-01-01

    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 1H 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

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

    PubMed Central

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

    2015-01-01

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

  10. Regional white matter abnormalities in drug-naive, first-episode schizophrenia patients and their healthy unaffected siblings.

    PubMed

    Lyu, Hailong; Hu, Maorong; Eyler, Lisa T; Jin, Hua; Wang, Juan; Ou, Jianjun; Guo, Xiaofeng; He, Zhong; Liu, Fang; Zhao, Jingping; Guo, Wenbin

    2015-03-01

    Shared neuropathological features between schizophrenia patients and their siblings may represent intermediate phenotypes of schizophrenia and can be used to investigate genetic susceptibility to the illness. This study aimed to discover regional white matter abnormalities in first-episode schizophrenia (FES) patients and their unaffected siblings compared to healthy subjects in the Chinese Han population using optimized Voxel-Based Morphometry (VBM). A total of 51 drug-naive, FES patients, 45 of their unaffected siblings and 59 healthy comparisons were studied with magnetic resonance imaging (MRI). FES patients exhibited significant regional white matter deficits in the left inferior frontal gyrus and left joint of external capsule and internal capsule compared with healthy subjects (corrected FDR, p<0.005). The sibling group also showed significant white matter deficits in these two regions compared with the healthy comparison group (uncorrected, p<0.001). White matter deficits with a less stringent threshold for significance in the left cerebellum anterior lobe, left middle frontal gyrus, left hippocampus, right anterior cingulate and right internal capsule were observed in patients compared to their siblings. Our findings extend those from previous VBM analyses showing that FES patients and their unaffected siblings may share white matter deficits in the left inferior frontal gyrus and the left joint of external capsule and internal capsule. These regional white matter deficits may be related to genetic factors related to schizophrenia susceptibility. © The Royal Australian and New Zealand College of Psychiatrists 2014.

  11. Adult-onset glutaric aciduria type I presenting with white matter abnormalities and subependymal nodules.

    PubMed

    Pierson, T M; Nezhad, Mani; Tremblay, Matthew A; Lewis, Richard; Wong, Derek; Salamon, Noriko; Sicotte, Nancy

    2015-10-01

    A 55-year-old female presented with a 6-year history of paresthesias, incontinence, spasticity, and gait abnormalities. Neuroimaging revealed white matter abnormalities associated with subependymal nodules. Biochemical evaluation noted increased serum C5-DC glutarylcarnitines and urine glutaric and 3-hydroxyglutaric acids. Evaluation of the glutaryl-CoA dehydrogenase (GCDH) gene revealed compound heterozygosity consisting of a novel variant (c.1219C>G; p.Leu407Val) and pathogenic mutation (c.848delT; p.L283fs). Together, these results were consistent with a diagnosis of adult-onset type I glutaric aciduria.

  12. [Research on brain white matter network in cerebral palsy infant].

    PubMed

    Li, Jun; Yang, Cheng; Wang, Yuanjun; Nie, Shengdong

    2017-10-01

    Present study used diffusion tensor image and tractography to construct brain white matter networks of 15 cerebral palsy infants and 30 healthy infants that matched for age and gender. After white matter network analysis, we found that both cerebral palsy and healthy infants had a small-world topology in white matter network, but cerebral palsy infants exhibited abnormal topological organization: increased shortest path length but decreased normalize clustering coefficient, global efficiency and local efficiency. Furthermore, we also found that white matter network hub regions were located in the left cuneus, precuneus, and left posterior cingulate gyrus. However, some abnormal nodes existed in the frontal, temporal, occipital and parietal lobes of cerebral palsy infants. These results indicated that the white matter networks for cerebral palsy infants were disrupted, which was consistent with previous studies about the abnormal brain white matter areas. This work could help us further study the pathogenesis of cerebral palsy infants.

  13. Shades of white: diffusion properties of T1- and FLAIR-defined white matter signal abnormalities differ in stages from cognitively normal to dementia.

    PubMed

    Riphagen, Joost M; Gronenschild, Ed H B M; Salat, David H; Freeze, Whitney M; Ivanov, Dimo; Clerx, Lies; Verhey, Frans R J; Aalten, Pauline; Jacobs, Heidi I L

    2018-08-01

    The underlying pathology of white matter signal abnormalities (WMSAs) is heterogeneous and may vary dependent on the magnetic resonance imaging contrast used to define them. We investigated differences in white matter diffusivity as an indicator for white matter integrity underlying WMSA based on T1-weighted and fluid-attenuated inversion recovery (FLAIR) imaging contrast. In addition, we investigated which white matter region of interest (ROI) could predict clinical diagnosis best using diffusion metrics. One hundred three older individuals with varying cognitive impairment levels were included and underwent neuroimaging. Diffusion metrics were extracted from WMSA areas based on T1 and FLAIR contrast and from their overlapping areas, the border surrounding the WMSA and the normal-appearing white matter (NAWM). Regional diffusivity differences were calculated with linear mixed effects models. Multinomial logistic regression determined which ROI diffusion values classified individuals best into clinically defined diagnostic groups. T1-based WMSA showed lower white matter integrity compared to FLAIR WMSA-defined regions. Diffusion values of NAWM predicted diagnostic group best compared to other ROI's. To conclude, T1- or FLAIR-defined WMSA provides distinct information on the underlying white matter integrity associated with cognitive decline. Importantly, not the "diseased" but the NAWM is a potentially sensitive indicator for cognitive brain health status. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  14. 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.

  15. Microstructural abnormalities in white and gray matter in obese adolescents with and without type 2 diabetes.

    PubMed

    Nouwen, Arie; Chambers, Alison; Chechlacz, Magdalena; Higgs, Suzanne; Blissett, Jacqueline; Barrett, Timothy G; Allen, Harriet A

    2017-01-01

    In adults, type 2 diabetes and obesity have been associated with structural brain changes, even in the absence of dementia. Some evidence suggested similar changes in adolescents with type 2 diabetes but comparisons with a non-obese control group have been lacking. The aim of the current study was to examine differences in microstructure of gray and white matter between adolescents with type 2 diabetes, obese adolescents and healthy weight adolescents. Magnetic resonance imaging data were collected from 15 adolescents with type 2 diabetes, 21 obese adolescents and 22 healthy weight controls. Volumetric differences in the gray matter between the three groups were examined using voxel based morphology, while tract based spatial statistics was used to examine differences in the microstructure of the white matter. Adolescents with type 2 diabetes and obese adolescents had reduced gray matter volume in the right hippocampus, left putamen and caudate, bilateral amygdala and left thalamus compared to healthy weight controls. Type 2 diabetes was also associated with significant regional changes in fractional anisotropy within the corpus callosum, fornix, left inferior fronto-occipital fasciculus, left uncinate, left internal and external capsule. Fractional anisotropy reductions within these tracts were explained by increased radial diffusivity, which may suggest demyelination of white matter tracts. Mean diffusivity and axial diffusivity did not differ between the groups. Our data shows that adolescent obesity alone results in reduced gray matter volume and that adolescent type 2 diabetes is associated with both white and gray matter abnormalities.

  16. Abnormalities in white matter microstructure associated with chronic ketamine use.

    PubMed

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

    2014-01-01

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

  17. Relationship of hypertension, blood pressure, and blood pressure control with white matter abnormalities in the Women's Health Initiative Memory Study (WHIMS)-MRI trial.

    PubMed

    Kuller, Lewis H; Margolis, Karen L; Gaussoin, Sarah A; Bryan, Nick R; Kerwin, Diana; Limacher, Marian; Wassertheil-Smoller, Sylvia; Williamson, Jeff; Robinson, Jennifer G

    2010-03-01

    This paper evaluates the relationship of blood pressure (BP) levels at Women's Health Initiative (WHI) baseline, treatment of hypertension, and white matter abnormalities among women in conjugated equine estrogen (CEE) and medroxyprogesterone acetate and CEE-alone arms. The WHI Memory Study-Magnetic Resonance Imaging (WHIMS-MRI) trial scanned 1424 participants. BP levels at baseline were significantly positively related to abnormal white matter lesion (WML) volumes. Participants treated for hypertension but who had BP > or = 140/90 mm Hg had the greatest amount of WML volumes. Women with untreated BP > or = 140/90 mm Hg had intermediate WML volumes. Abnormal WML volumes were related to hypertension in most areas of the brain and were greater in the frontal lobe than in the occipital, parietal, or temporal lobes. Level of BP at baseline was strongly related to amount of WML volumes. The results of the study reinforce the relationship of hypertension and BP control and white matter abnormalities in the brain. The evidence to date supports tight control of BP levels, especially beginning at younger and middle age as a possible and perhaps only way to prevent dementia.

  18. The role of white matter abnormalities in treatment-resistant depression: a systematic review.

    PubMed

    Serafini, Gianluca; Pompili, Maurizio; Borgwardt, Stefan; Giuffra, Enrico; Howes, Oliver; Girardi, Paolo; Amore, Mario

    2015-01-01

    Patients with treatment-resistant depression (TRD) commonly report significant disability together with an increased risk of functional impairment. Neuroimaging techniques have been used to investigate the neuropathology of this complex illness, but it is still quite unknown whether abnormalities in the integrity of white matter (WM) of specific brain areas may be considered as trait markers of TRD. Electronic databases were searched from 1980 to 2013. Nine studies - comprising a total of 228 subjects and 171 controls - fulfilled our inclusion criteria and were analyzed in the present overview. Several cross-sectional studies showed the association between WM abnormalities and TRD. According to the selected studies, sub-callosal cingulated cortex (SCC) WM abnormalities were largely implicated in the pathogenesis of both major depressive disorder and TRD. However, alterations in cortical-limbic or cortical-subcortical circuits, particularly the left middle frontal gyrus (which is thought to have a major role in emotional regulation) may also be involved in the pathophysiology of TRD. TRD may be related to the presence of specific microstructural WM abnormalities. WM abnormalities of specific brain regions such as SCC may have a major involvement in the pathogenesis of TRD.

  19. White matter changes in Alzheimer's disease: a focus on myelin and oligodendrocytes.

    PubMed

    Nasrabady, Sara E; Rizvi, Batool; Goldman, James E; Brickman, Adam M

    2018-03-02

    Alzheimer's disease (AD) is conceptualized as a progressive consequence of two hallmark pathological changes in grey matter: extracellular amyloid plaques and neurofibrillary tangles. However, over the past several years, neuroimaging studies have implicated micro- and macrostructural abnormalities in white matter in the risk and progression of AD, suggesting that in addition to the neuronal pathology characteristic of the disease, white matter degeneration and demyelination may be also important pathophysiological features. Here we review the evidence for white matter abnormalities in AD with a focus on myelin and oligodendrocytes, the only source of myelination in the central nervous system, and discuss the relationship between white matter changes and the hallmarks of Alzheimer's disease. We review several mechanisms such as ischemia, oxidative stress, excitotoxicity, iron overload, Aβ toxicity and tauopathy, which could affect oligodendrocytes. We conclude that white matter abnormalities, and in particular myelin and oligodendrocytes, could be mechanistically important in AD pathology and could be potential treatment targets.

  20. Frontotemporal white matter changes in amyotrophic lateral sclerosis.

    PubMed

    Abrahams, Sharon; Goldstein, Laura H; Suckling, John; Ng, Virginia; Simmons, Andy; Chitnis, Xavier; Atkins, Louise; Williams, Steve C R; Leigh, P N

    2005-03-01

    Cognitive dysfunction can occur in some patients with amyotrophic lateral sclerosis (ALS) who are not suffering from dementia. The most striking and consistent cognitive deficit has been found using tests of verbal fluency. ALS patients with verbal fluency deficits have shown functional imaging abnormalities predominantly in frontotemporal regions using positron emission tomography (PET). This study used automated volumetric voxel-based analysis of grey and white matter densities of structural magnetic resonance imaging (MRI) scans to explore the underlying pattern of structural cerebral change in nondemented ALS patients with verbal fluency deficits. Two groups of ALS patients, defined by the presence or absence of cognitive impairment on the basis of the Written Verbal Fluency Test (ALSi, cognitively impaired, n=11; ALSu, cognitively unimpaired n=12) were compared with healthy age matched controls (n=12). A comparison of the ALSi group with controls revealed significantly (p<0.002) reduced white matter volume in extensive motor and non-motor regions, including regions corresponding to frontotemporal association fibres. These patients demonstrated a corresponding cognitive profile of executive and memory dysfunction. Less extensive white matter reductions were revealed in the comparison of the ALSu and control groups in regions corresponding to frontal association fibres. White matter volumes were also found to correlate with performance on memory tests. There were no significant reductions in grey matter volume in the comparison of either patient group with controls. The structural white matter abnormalities in frontal and temporal regions revealed here may underlie the cognitive and functional imaging abnormalities previously reported in non-demented ALS patients. The results also suggest that extra-motor structural abnormalities may be present in ALS patients with no evidence of cognitive change. The findings support the hypothesis of a continuum of extra

  1. Characteristics of early MRI in children and adolescents with vanishing white matter.

    PubMed

    van der Lei, Hannemieke D; Steenweg, Marjan E; Barkhof, Frederik; de Grauw, Ton; d'Hooghe, Marc; Morton, Richard; Shah, Siddharth; Wolf, Nicole; van der Knaap, Marjo S

    2012-02-01

    MRI in vanishing white matter typically shows diffuse abnormality of the cerebral white matter, which becomes increasingly rarefied and cystic. We investigated the MRI characteristics preceding this stage. In a retrospective observational study, we evaluated all available MRIs in our database of DNA-confirmed VWM patients and selected MRIs without diffuse cerebral white matter abnormalities and without signs of rarefaction or cystic degeneration in patients below 20 years of age. A previously established scoring list was used to evaluate the MRIs. An MRI of seven patients fulfilled the criteria. All had confluent and symmetrical abnormalities in the periventricular and bordering deep white matter. In young patients, myelination was delayed. The inner rim of the corpus callosum was affected in all patients. In early stages of VWM, MRI does not necessarily display diffuse cerebral white matter involvement and rarefaction or cystic degeneration. If the MRI abnormalities do not meet the criteria for VWM, it helps to look at the corpus callosum. If the inner rim (the callosal-septal interface) is affected, VWM should be considered. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  2. Relationship of Hypertension, Blood Pressure, and Blood Pressure Control With White Matter Abnormalities in the Women’s Health Initiative Memory Study (WHIMS)—MRI Trial

    PubMed Central

    Kuller, Lewis H.; Margolis, Karen L.; Gaussoin, Sarah A.; Bryan, Nick R.; Kerwin, Diana; Limacher, Marian; Wassertheil-Smoller, Sylvia; Williamson, Jeff; Robinson, Jennifer G.

    2010-01-01

    This paper evaluates the relationship of blood pressure (BP) levels at Women’s Health Initiative (WHI) baseline, treatment of hypertension, and white matter abnormalities among women in conjugated equine estrogen (CEE) and medroxyprogesterone acetate and CEE-alone arms. The WHI Memory Study—Magnetic Resonance Imaging (WHIMS-MRI) trial scanned 1424 participants. BP levels at baseline were significantly positively related to abnormal white matter lesion (WML) volumes. Participants treated for hypertension but who had BP ≥140/90 mm Hg had the greatest amount of WML volumes. Women with untreated BP ≥140/90 mm Hg had intermediate WML volumes. Abnormal WML volumes were related to hypertension in most areas of the brain and were greater in the frontal lobe than in the occipital, parietal, or temporal lobes. Level of BP at baseline was strongly related to amount of WML volumes. The results of the study reinforce the relationship of hypertension and BP control and white matter abnormalities in the brain. The evidence to date supports tight control of BP levels, especially beginning at younger and middle age as a possible and perhaps only way to prevent dementia. PMID:20433539

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

    PubMed Central

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

    2013-01-01

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

  4. Cerebellar White Matter Abnormalities following Primary Blast Injury in US Military Personnel

    PubMed Central

    Mac Donald, Christine; Johnson, Ann; Cooper, Dana; Malone, Thomas; Sorrell, James; Shimony, Joshua; Parsons, Matthew; Snyder, Abraham; Raichle, Marcus; Fang, Raymond; Flaherty, Stephen; Russell, Michael; Brody, David L.

    2013-01-01

    Little is known about the effects of blast exposure on the human brain in the absence of head impact. Clinical reports, experimental animal studies, and computational modeling of blast exposure have suggested effects on the cerebellum and brainstem. In US military personnel with isolated, primary blast-related ‘mild’ traumatic brain injury and no other known insult, we found diffusion tensor MRI abnormalities consistent with cerebellar white matter injury in 3 of 4 subjects. No abnormalities in other brain regions were detected. These findings add to the evidence supporting the hypothesis that primary blast exposure contributes to brain injury in the absence of head impact and that the cerebellum may be particularly vulnerable. However, the clinical effects of these abnormalities cannot be determined with certainty; none of the subjects had ataxia or other detected evidence of cerebellar dysfunction. The details of the blast events themselves cannot be disclosed at this time, thus additional animal and computational modeling will be required to dissect the mechanisms underlying primary blast-related traumatic brain injury. Furthermore, the effects of possible subconcussive impacts and other military-related exposures cannot be determined from the data presented. Thus many aspects of topic will require further investigation. PMID:23409052

  5. Persistence of abnormalities in white matter in children with type 1 diabetes.

    PubMed

    Fox, Larry A; Hershey, Tamara; Mauras, Nelly; Arbeláez, Ana Maria; Tamborlane, William V; Buckingham, Bruce; Tsalikian, Eva; Englert, Kim; Raman, Mira; Jo, Booil; Shen, Hanyang; Reiss, Allan; Mazaika, Paul

    2018-07-01

    Prior studies suggest white matter growth is reduced and white matter microstructure is altered in the brains of young children with type 1 diabetes when compared with brains of non-diabetic children, due in part to adverse effects of hyperglycaemia. This longitudinal observational study examines whether dysglycaemia alters the developmental trajectory of white matter microstructure over time in young children with type 1 diabetes. One hundred and eighteen children, aged 4 to <10 years old with type 1 diabetes and 58 age-matched, non-diabetic children were studied at baseline and 18 months, at five Diabetes Research in Children Network clinical centres. We analysed longitudinal trajectories of white matter using diffusion tensor imaging. Continuous glucose monitoring profiles and HbA 1c levels were obtained every 3 months. Axial diffusivity was lower in children with diabetes at baseline (p = 0.022) and at 18 months (p = 0.015), indicating that differences in white matter microstructure persist over time in children with diabetes. Within the diabetes group, lower exposure to hyperglycaemia, averaged over the time since diagnosis, was associated with higher fractional anisotropy (p = 0.037). Fractional anisotropy was positively correlated with performance (p < 0.002) and full-scale IQ (p < 0.02). These results suggest that hyperglycaemia is associated with altered white matter development, which may contribute to the mild cognitive deficits in this population.

  6. Early white matter abnormalities, progressive brain pathology and motor deficits in a novel knock-in mouse model of Huntington's disease

    PubMed Central

    Jin, Jing; Peng, Qi; Hou, Zhipeng; Jiang, Mali; Wang, Xin; Langseth, Abraham J.; Tao, Michael; Barker, Peter B.; Mori, Susumu; Bergles, Dwight E.; Ross, Christopher A.; Detloff, Peter J.; Zhang, Jiangyang; Duan, Wenzhen

    2015-01-01

    White matter abnormalities have been reported in premanifest Huntington's disease (HD) subjects before overt striatal neuronal loss, but whether the white matter changes represent a necessary step towards further pathology and the underlying mechanism of these changes remains unknown. Here, we characterized a novel knock-in mouse model that expresses mouse HD gene homolog (Hdh) with extended CAG repeat- HdhQ250, which was derived from the selective breeding of HdhQ150 mice. HdhQ250 mice manifest an accelerated and robust phenotype compared with its parent line. HdhQ250 mice exhibit progressive motor deficits, reduction in striatal and cortical volume, accumulation of mutant huntingtin aggregation, decreased levels of DARPP32 and BDNF and altered striatal metabolites. The abnormalities detected in this mouse model are reminiscent of several aspects of human HD. In addition, disturbed myelination was evident in postnatal Day 14 HdhQ250 mouse brain, including reduced levels of myelin regulatory factor and myelin basic protein, and decreased numbers of myelinated axons in the corpus callosum. Thinner myelin sheaths, indicated by increased G-ratio of myelin, were also detected in the corpus callosum of adult HdhQ250 mice. Moreover, proliferation of oligodendrocyte precursor cells is altered by mutant huntingtin both in vitro and in vivo. Our data indicate that this model is suitable for understanding comprehensive pathogenesis of HD in white matter and gray matter as well as developing therapeutics for HD. PMID:25609071

  7. Abnormal fronto-parietal white matter organisation in the superior longitudinal fasciculus branches in autism spectrum disorders.

    PubMed

    Fitzgerald, Jacqueline; Leemans, Alexander; Kehoe, Elizabeth; O'Hanlon, Erik; Gallagher, Louise; McGrath, Jane

    2018-03-01

    Core features of autism spectrum disorder (ASD) may be underpinned by disrupted functional and structural neural connectivity. Abnormal fronto-parietal functional connectivity has been widely reported in the literature; this may be underpinned by disrupted microstructural organisation of white matter. The superior longitudinal fasciculus (SLF) is a major fronto-parietal white matter tract, the structure of which has been little studied in ASD. The fronto-parietal projections of this tract (SLF I, II and III) are thought to play an important role in a number of cognitive functions including attention and visuospatial processing. To date, the isolation of the fronto-parietal branches of the SLF has been hampered by limitations of traditional tractography approaches. Constrained spherical deconvolution (CSD)-based tractography is an advanced approach that allows valid isolation of the fronto-parietal branches of the SLF. Diffusion MRI data were acquired from 45 participants with ASD and 45 age- and IQ-matched controls. The SLF I, II and III branches were isolated using CSD-based tractography in ExploreDTI. Significantly greater fractional anisotropy (FA) was observed in the right SLF II relative to controls. The ASD group also showed greater linear diffusion coefficient in the left SLF I and the right SLF II. In the SLF II, the ASD group had significantly greater right lateralisation of FA in comparison with the control group. The clinical and functional implications of increased FA in white matter are poorly understood; however, it is possible that this increased white matter organisation in the SLF in ASD may contribute to relative processing advantages in the condition. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  9. White-matter functional networks changes in patients with schizophrenia.

    PubMed

    Jiang, Yuchao; Luo, Cheng; Li, Xuan; Li, Yingjia; Yang, Hang; Li, Jianfu; Chang, Xin; Li, Hechun; Yang, Huanghao; Wang, Jijun; Duan, Mingjun; Yao, Dezhong

    2018-04-13

    Resting-state functional MRI (rsfMRI) is a useful technique for investigating the functional organization of human gray-matter in neuroscience and neuropsychiatry. Nevertheless, most studies have demonstrated the functional connectivity and/or task-related functional activity in the gray-matter. White-matter functional networks have been investigated in healthy subjects. Schizophrenia has been hypothesized to be a brain disorder involving insufficient or ineffective communication associated with white-matter abnormalities. However, previous studies have mainly examined the structural architecture of white-matter using MRI or diffusion tensor imaging and failed to uncover any dysfunctional connectivity within the white-matter on rsfMRI. The current study used rsfMRI to evaluate white-matter functional connectivity in a large cohort of ninety-seven schizophrenia patients and 126 healthy controls. Ten large-scale white-matter networks were identified by a cluster analysis of voxel-based white-matter functional connectivity and classified into superficial, middle and deep layers of networks. Evaluation of the spontaneous oscillation of white-matter networks and the functional connectivity between them showed that patients with schizophrenia had decreased amplitudes of low-frequency oscillation and increased functional connectivity in the superficial perception-motor networks. Additionally, we examined the interactions between white-matter and gray-matter networks. The superficial perception-motor white-matter network had decreased functional connectivity with the cortical perception-motor gray-matter networks. In contrast, the middle and deep white-matter networks had increased functional connectivity with the superficial perception-motor white-matter network and the cortical perception-motor gray-matter network. Thus, we presumed that the disrupted association between the gray-matter and white-matter networks in the perception-motor system may be compensated for

  10. Age-related differences in autism: The case of white matter microstructure.

    PubMed

    Koolschijn, P Cédric M P; Caan, Matthan W A; Teeuw, Jalmar; Olabarriaga, Sílvia D; Geurts, Hilde M

    2017-01-01

    Autism spectrum disorder (ASD) is typified as a brain connectivity disorder in which white matter abnormalities are already present early on in life. However, it is unknown if and to which extent these abnormalities are hard-wired in (older) adults with ASD and how this interacts with age-related white matter changes as observed in typical aging. The aim of this first cross-sectional study in mid- and late-aged adults with ASD was to characterize white matter microstructure and its relationship with age. We utilized diffusion tensor imaging with head motion control in 48 adults with ASD and 48 age-matched controls (30-74 years), who also completed a Flanker task. Intra-individual variability of reaction times (IIVRT) measures based on performance on the Flanker interference task were used to assess IIVRT-white matter microstructure associations. We observed primarily higher mean and radial diffusivity in white matter microstructure in ASD, particularly in long-range fibers, which persisted after taking head motion into account. Importantly, group-by-age interactions revealed higher age-related mean and radial diffusivity in ASD, in projection and association fiber tracts. Subtle dissociations were observed in IIVRT-white matter microstructure relations between groups, with the IIVRT-white matter association pattern in ASD resembling observations in cognitive aging. The observed white matter microstructure differences are lending support to the structural underconnectivity hypothesis in ASD. These reductions seem to have behavioral percussions given the atypical relationship with IIVRT. Taken together, the current results may indicate different age-related patterns of white matter microstructure in adults with ASD. Hum Brain Mapp 38:82-96, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Frontal white matter hyperintensities, clasmatodendrosis and gliovascular abnormalities in ageing and post-stroke dementia

    PubMed Central

    Chen, Aiqing; Akinyemi, Rufus O.; Hase, Yoshiki; Firbank, Michael J.; Ndung’u, Michael N.; Foster, Vincent; Craggs, Lucy J. L.; Washida, Kazuo; Okamoto, Yoko; Thomas, Alan J.; Polvikoski, Tuomo M.; Allan, Louise M.; Oakley, Arthur E.; O’Brien, John T.; Horsburgh, Karen; Ihara, Masafumi

    2016-01-01

    Abstract White matter hyperintensities as seen on brain T 2 -weighted magnetic resonance imaging are associated with varying degrees of cognitive dysfunction in stroke, cerebral small vessel disease and dementia. The pathophysiological mechanisms within the white matter accounting for cognitive dysfunction remain unclear. With the hypothesis that gliovascular interactions are impaired in subjects with high burdens of white matter hyperintensities, we performed clinicopathological studies in post-stroke survivors, who had exhibited greater frontal white matter hyperintensities volumes that predicted shorter time to dementia onset. Histopathological methods were used to identify substrates in the white matter that would distinguish post-stroke demented from post-stroke non-demented subjects. We focused on the reactive cell marker glial fibrillary acidic protein (GFAP) to study the incidence and location of clasmatodendrosis, a morphological attribute of irreversibly injured astrocytes. In contrast to normal appearing GFAP+ astrocytes, clasmatodendrocytes were swollen and had vacuolated cell bodies. Other markers such as aldehyde dehydrogenase 1 family, member L1 (ALDH1L1) showed cytoplasmic disintegration of the astrocytes. Total GFAP+ cells in both the frontal and temporal white matter were not greater in post-stroke demented versus post-stroke non-demented subjects. However, the percentage of clasmatodendrocytes was increased by >2-fold in subjects with post-stroke demented compared to post-stroke non-demented subjects ( P = 0.026) and by 11-fold in older controls versus young controls ( P < 0.023) in the frontal white matter. High ratios of clasmotodendrocytes to total astrocytes in the frontal white matter were consistent with lower Mini-Mental State Examination and the revised Cambridge Cognition Examination scores in post-stroke demented subjects. Double immunofluorescent staining showed aberrant co-localization of aquaporin 4 (AQP4) in retracted GFAP

  12. Frontal white matter hyperintensities, clasmatodendrosis and gliovascular abnormalities in ageing and post-stroke dementia.

    PubMed

    Chen, Aiqing; Akinyemi, Rufus O; Hase, Yoshiki; Firbank, Michael J; Ndung'u, Michael N; Foster, Vincent; Craggs, Lucy J L; Washida, Kazuo; Okamoto, Yoko; Thomas, Alan J; Polvikoski, Tuomo M; Allan, Louise M; Oakley, Arthur E; O'Brien, John T; Horsburgh, Karen; Ihara, Masafumi; Kalaria, Raj N

    2016-01-01

    White matter hyperintensities as seen on brain T2-weighted magnetic resonance imaging are associated with varying degrees of cognitive dysfunction in stroke, cerebral small vessel disease and dementia. The pathophysiological mechanisms within the white matter accounting for cognitive dysfunction remain unclear. With the hypothesis that gliovascular interactions are impaired in subjects with high burdens of white matter hyperintensities, we performed clinicopathological studies in post-stroke survivors, who had exhibited greater frontal white matter hyperintensities volumes that predicted shorter time to dementia onset. Histopathological methods were used to identify substrates in the white matter that would distinguish post-stroke demented from post-stroke non-demented subjects. We focused on the reactive cell marker glial fibrillary acidic protein (GFAP) to study the incidence and location of clasmatodendrosis, a morphological attribute of irreversibly injured astrocytes. In contrast to normal appearing GFAP+ astrocytes, clasmatodendrocytes were swollen and had vacuolated cell bodies. Other markers such as aldehyde dehydrogenase 1 family, member L1 (ALDH1L1) showed cytoplasmic disintegration of the astrocytes. Total GFAP+ cells in both the frontal and temporal white matter were not greater in post-stroke demented versus post-stroke non-demented subjects. However, the percentage of clasmatodendrocytes was increased by >2-fold in subjects with post-stroke demented compared to post-stroke non-demented subjects (P = 0.026) and by 11-fold in older controls versus young controls (P < 0.023) in the frontal white matter. High ratios of clasmotodendrocytes to total astrocytes in the frontal white matter were consistent with lower Mini-Mental State Examination and the revised Cambridge Cognition Examination scores in post-stroke demented subjects. Double immunofluorescent staining showed aberrant co-localization of aquaporin 4 (AQP4) in retracted GFAP+ astrocytes with

  13. Disrupted white matter structural connectivity in heroin abusers.

    PubMed

    Sun, Yan; Wang, Gui-Bin; Lin, Qi-Xiang; Lu, Lin; Shu, Ni; Meng, Shi-Qiu; Wang, Jun; Han, Hong-Bin; He, Yong; Shi, Jie

    2017-01-01

    Neurocognitive impairment is one of the factors that put heroin abusers at greater risk for relapse, and deficits in related functional brain connections have been found. However, the alterations in structural brain connections that may underlie these functional and neurocognitive impairments remain largely unknown. In the present study, we investigated topological organization alterations in the structural network of white matter in heroin abusers and examined the relationships between the network changes and clinical measures. We acquired diffusion tensor imaging datasets from 76 heroin abusers and 78 healthy controls. Network-based statistic was applied to identify alterations in interregional white matter connectivity, and graph theory methods were used to analyze the properties of global networks. The participants also completed a battery of neurocognitive measures. One increased subnetwork characterizing widespread abnormalities in structural connectivity was present in heroin users, which mainly composed of default-mode, attentional and visual systems. The connection strength was positively correlated with increases in fractional anisotropy in heroin abusers. Intriguingly, the changes in within-frontal and within-temporal connections in heroin abusers were significantly correlated with daily heroin dosage and impulsivity scores, respectively. These findings suggest that heroin abusers have extensive abnormal white matter connectivity, which may mediate the relationship between heroin dependence and clinical measures. The increase in white matter connectivity may be attributable to the inefficient microstructure integrity of white matter. The present findings extend our understanding of cerebral structural disruptions that underlie neurocognitive and functional deficits in heroin addiction and provide circuit-level markers for this chronic disorder. © 2015 Society for the Study of Addiction.

  14. White matter disease in midlife is heritable, related to hypertension, and shares some genetic influence with systolic blood pressure.

    PubMed

    Fennema-Notestine, Christine; McEvoy, Linda K; Notestine, Randy; Panizzon, Matthew S; Yau, Wai-Ying Wendy; Franz, Carol E; Lyons, Michael J; Eyler, Lisa T; Neale, Michael C; Xian, Hong; McKenzie, Ruth E; Kremen, William S

    2016-01-01

    White matter disease in the brain increases with age and cardiovascular disease, emerging in midlife, and these associations may be influenced by both genetic and environmental factors. We examined the frequency, distribution, and heritability of abnormal white matter and its association with hypertension in 395 middle-aged male twins (61.9 ± 2.6 years) from the Vietnam Era Twin Study of Aging, 67% of whom were hypertensive. A multi-channel segmentation approach estimated abnormal regions within the white matter. Using multivariable regression models, we characterized the frequency distribution of abnormal white matter in midlife and investigated associations with hypertension and Apolipoprotein E- ε4 status and the impact of duration and control of hypertension. Then, using the classical twin design, we estimated abnormal white matter heritability and the extent of shared genetic overlap with blood pressure. Abnormal white matter was predominantly located in periventricular and deep parietal and frontal regions; associated with age ( t  = 1.9, p  = 0.05) and hypertension ( t  = 2.9, p  = 0.004), but not Apolipoprotein ε4 status; and was greater in those with uncontrolled hypertension relative to controlled ( t  = 3.0, p  = 0.003) and normotensive ( t  = 4.0, p  = 0.0001) groups, suggesting that abnormal white matter may reflect currently active cerebrovascular effects. Abnormal white matter was highly heritable (a 2  = 0.81) and shared some genetic influences with systolic blood pressure (r A  = 0.26), although there was evidence for distinct genetic contributions and unique environmental influences. Future longitudinal research will shed light on factors impacting white matter disease presentation, progression, and potential recovery.

  15. Distributed abnormalities of brain white matter architecture in patients with dominant optic atrophy and OPA1 mutations.

    PubMed

    Rocca, Maria A; Bianchi-Marzoli, Stefania; Messina, Roberta; Cascavilla, Maria Lucia; Zeviani, Massimo; Lamperti, Costanza; Milesi, Jacopo; Carta, Arturo; Cammarata, Gabriella; Leocani, Letizia; Lamantea, Eleonora; Bandello, Francesco; Comi, Giancarlo; Falini, Andrea; Filippi, Massimo

    2015-05-01

    Using advanced MRI techniques, we investigated the presence and topographical distribution of brain grey matter (GM) and white matter (WM) alterations in dominant optic atrophy (DOA) patients with genetically proven OPA1 mutation as well as their correlation with clinical and neuro-ophthalmologic findings. Nineteen DOA patients underwent neurological, neuro-ophthalmologic and brainstem auditory evoked potentials (BAEP) evaluations. Voxel-wise methods were applied to assess regional GM and WM abnormalities in patients compared to 20 healthy controls. Visual acuity was reduced in 16 patients. Six DOA patients (4 with missense mutations) had an abnormal I peripheral component (auditory nerve) at BAEP. Compared to controls, DOA patients had significant atrophy of the optic nerves (p < 0.0001). Voxel-based morphometry (VBM) analysis showed that, compared to controls, DOA patients had significant WM atrophy of the chiasm and optic tracts; whereas no areas of GM atrophy were found. Tract-based spatial statistics (TBSS) analysis showed that compared to controls, DOA patients had significantly lower mean diffusivity, axial and radial diffusivity in the WM of the cerebellum, brainstem, thalamus, fronto-occipital-temporal lobes, including the cingulum, corpus callosum, corticospinal tract and optic radiation bilaterally. No abnormalities of fractional anisotropy were detected. No correlations were found between volumetric and diffusivity abnormalities quantified with MRI and clinical and neuro-ophthalmologic measures of disease severity. Consistently with pathological studies, tissue loss in DOA patients is limited to anterior optic pathways reflecting retinal ganglion cell degeneration. Distributed abnormalities of diffusivity indexes might reflect abnormal intracellular mitochondrial morphology as well as alteration of protein levels due to OPA1 mutations.

  16. γδT cells but not αβT cells contribute to sepsis-induced white matter injury and motor abnormalities in mice.

    PubMed

    Zhang, Xiaoli; Rocha-Ferreira, Eridan; Li, Tao; Vontell, Regina; Jabin, Darakhshan; Hua, Sha; Zhou, Kai; Nazmi, Arshed; Albertsson, Anna-Maj; Sobotka, Kristina; Ek, Joakim; Thornton, Claire; Hagberg, Henrik; Mallard, Carina; Leavenworth, Jianmei W; Zhu, Changlian; Wang, Xiaoyang

    2017-12-20

    Infection and sepsis are associated with brain white matter injury in preterm infants and the subsequent development of cerebral palsy. In the present study, we used a neonatal mouse sepsis-induced white matter injury model to determine the contribution of different T cell subsets (αβT cells and γδT cells) to white matter injury and consequent behavioral changes. C57BL/6J wild-type (WT), T cell receptor (TCR) δ-deficient (Tcrd -/- , lacking γδT cells), and TCRα-deficient (Tcra -/- , lacking αβT cells) mice were administered with lipopolysaccharide (LPS) at postnatal day (PND) 2. Brain myelination was examined at PNDs 12, 26, and 60. Motor function and anxiety-like behavior were evaluated at PND 26 or 30 using DigiGait analysis and an elevated plus maze. White matter development was normal in Tcrd -/- and Tcrα -/- compared to WT mice. LPS exposure induced reductions in white matter tissue volume in WT and Tcrα -/- mice, but not in the Tcrd -/- mice, compared with the saline-treated groups. Neither LPS administration nor the T cell deficiency affected anxiety behavior in these mice as determined with the elevated plus maze. DigiGait analysis revealed motor function deficiency after LPS-induced sepsis in both WT and Tcrα -/- mice, but no such effect was observed in Tcrd -/- mice. Our results suggest that γδT cells but not αβT cells contribute to sepsis-induced white matter injury and subsequent motor function abnormalities in early life. Modulating the activity of γδT cells in the early stages of preterm white matter injury might represent a novel therapeutic strategy for the treatment of perinatal brain injury.

  17. Hyperhomocysteinemia and MTHFR polymorphisms as antenatal risk factors of white matter abnormalities in two cohorts of late preterm and full term newborns.

    PubMed

    Marseglia, Lucia M; Nicotera, Antonio; Salpietro, Vincenzo; Giaimo, Elisa; Cardile, Giovanna; Bonsignore, Maria; Alibrandi, Angela; Caccamo, Daniela; Manti, Sara; D'Angelo, Gabriella; Mamì, Carmelo; Di Rosa, Gabriella

    2015-01-01

    Higher total homocysteine (tHcy) levels, and C677T and A1298C methylenetetrahydrofolate (MTHFR) polymorphisms, have been reported in preterm or full term newborns with neonatal encephalopathy following perinatal hypoxic-ischemic insult. This study investigated the causal role of tHcy and MTHFR polymorphisms together with other acquired risk factors on the occurrence of brain white matter abnormalities (WMA) detected by cranial ultrasound scans (cUS) in a population of late preterm and full term infants. A total of 171 newborns (81 M, 47.4%), 45 (26.3%) born <37 wks, and 126 (73.7%) born ≥37 wks were recruited in the study. cUS detected predominant WMA pattern in 36/171 newborns (21.1%) mainly characterized by abnormal periventricular white matter signal and mild-to-moderate periventricular white matter volume loss with ventricular dilatation (6/36, 16.6%). WMA resulted in being depending on tHcy levels (P < 0.014), lower GA (P < 0.000), lower Apgar score at 1 minutes (P < 0.000) and 5 minutes (P < 0.000), and 1298AC and 677CT/1298AC genotypes (P < 0.000 and P < 0.000). In conclusion, both acquired and genetic predisposing antenatal factors were significantly associated with adverse neonatal outcome and WMA. The role of A1298C polymorphism may be taken into account for prenatal assessment and treatment counseling.

  18. White matter alterations in narcolepsy patients with cataplexy: tract-based spatial statistics.

    PubMed

    Park, Yun K; Kwon, Oh-Hun; Joo, Eun Yeon; Kim, Jae-Hun; Lee, Jong M; Kim, Sung T; Hong, Seung B

    2016-04-01

    Functional imaging studies and voxel-based morphometry analysis of brain magnetic resonance imaging showed abnormalities in the hypothalamus-thalamus-orbitofrontal pathway, demonstrating altered hypocretin pathway in narcolepsy. Those distinct morphometric changes account for problems in wake-sleep control, attention and memory. It also raised the necessity to evaluate white matter changes. To investigate brain white matter alterations in drug-naïve narcolepsy patients with cataplexy and to explore relationships between white matter changes and patient clinical characteristics, drug-naïve narcolepsy patients with cataplexy (n = 22) and healthy age- and gender-matched controls (n = 26) were studied. Fractional anisotropy and mean diffusivity images were obtained from whole-brain diffusion tensor imaging, and tract-based spatial statistics were used to localize white matter abnormalities. Compared with controls, patients showed significant decreases in fractional anisotropy of white matter of the bilateral anterior cingulate, fronto-orbital area, frontal lobe, anterior limb of the internal capsule and corpus callosum, as well as the left anterior and medial thalamus. Patients and controls showed no differences in mean diffusivity. Among patients, mean diffusivity values of white matter in the bilateral superior frontal gyri, bilateral fronto-orbital gyri and right superior parietal gyrus were positively correlated with depressive mood. This tract-based spatial statistics study demonstrated that drug-naïve patients with narcolepsy had reduced fractional anisotropy of white matter in multiple brain areas and significant relationship between increased mean diffusivity of white matter in frontal/cingulate and depression. It suggests the widespread disruption of white matter integrity and prevalent brain degeneration of frontal lobes according to a depressive symptom in narcolepsy. © 2015 European Sleep Research Society.

  19. White matter abnormalities and their impact on attentional performance in adult attention-deficit/hyperactivity disorder.

    PubMed

    Konrad, Andreas; Dielentheis, Thomas F; El Masri, Dschamil; Dellani, Paulo R; Stoeter, Peter; Vucurevic, Goran; Winterer, Georg

    2012-06-01

    Inattention is the most important behavioral feature of adult patients with attention-deficit/hyperactivity disorder (ADHD). Neuroimaging studies in ADHD have demonstrated abnormalities primarily in the frontostriatal circuitry and were mostly conducted in children. We investigated white matter (WM) integrity in adult ADHD patients and the correlation of WM microstructure and neuropsychological parameters in 37 (21 men) never-medicated adult ADHD patients and 34 age- and gender-matched healthy controls. All subjects underwent clinical interviews, rating scales, and neuropsychological tests of attentional performance. Diffusion tensor imaging (DTI) was acquired, and 12 WM regions-of-interest (ROIs) within the attentional network were chosen. Group differences of mean fractional anisotropy (FA) and mean diffusivity (MD) values were calculated for each ROI, and patients' DTI measures were then correlated with measures of attentional performance. FA values in ADHD patients were significantly reduced in the left inferior longitudinal fasciculus (ILF), while MD values were significantly increased in ADHD patients in the frontal portion of the left frontooccipital fasciculus (IFO). In ADHD patients, MD values were negatively correlated with attentional performance in the left ILF. Our findings provide further support for disturbed frontostriatal structural connectivity and also point to an involvement of the left temporal white matter with an impact on attentional performance.

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

    PubMed

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

    2015-05-01

    Obsessive-compulsive disorder (OCD) is a debilitating disorder. However, existing neuroimaging findings involving executive function and structural abnormalities in OCD have been mixed. Here we conducted meta-analyses to investigate differences in OCD samples and controls in: Study 1 - grey matter structure; Study 2 - executive function task-related activations during (i) response inhibition, (ii) interference, and (iii) switching tasks; and Study 3 - white matter diffusivity. Results showed grey matter differences in the frontal, striatal, thalamus, parietal and cerebellar regions; task domain-specific neural differences in similar regions; and abnormal diffusivity in major white matter regions in OCD samples compared to controls. Our results reported concurrence of abnormal white matter diffusivity with corresponding abnormalities in grey matter and task-related functional activations. Our findings suggested the involvement of other brain regions not included in the cortico-striato-thalamo-cortical network, such as the cerebellum and parietal cortex, and questioned the involvement of the orbitofrontal region in OCD pathophysiology. Future research is needed to clarify the roles of these brain regions in the disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Cortisol Reactivity to Stress and Its Association With White Matter Integrity in Adults With Schizophrenia.

    PubMed

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

    2015-09-01

    Although acute hypothalamic-pituitary-adrenal axis response to stress is often adaptive, prolonged responses may have detrimental effects. Many components of white matter structures are sensitive to prolonged cortisol exposure. We aimed to identify a behavioral laboratory assay for cortisol response related to brain pathophysiology in schizophrenia. We hypothesized that an abnormally prolonged cortisol response to stress may be linked to abnormal white matter integrity in patients with schizophrenia. Acute and prolonged salivary cortisol response was measured outside the scanner at pretest and then at 0, 20, and 40 minutes after a psychological stress task in patients with schizophrenia (n = 45) and controls (n = 53). Tract-averaged white matter was measured by 64-direction diffusion tensor imaging in a subset of patients (n = 30) and controls (n = 33). Patients who did not tolerate the psychological stress task and quit had greater acute (t = 2.52 [p = .016] and t = 3.51 [p = .001] at 0 and 20 minutes) and prolonged (t = 3.62 [p = .001] at 40 minutes) cortisol reactivity compared with patients who finished the task. Abnormally prolonged cortisol reactivity in patients was significantly associated with reduced white matter integrity (r = -0.468, p = .009). Regardless of task completion status, acute cortisol response was not related to the white matter measures in patients or controls. This paradigm was successful at identifying a subset of patients whose cortisol response was associated with brain pathophysiology. Abnormal cortisol response may adversely affect white matter integrity, partly explaining this pathology observed in schizophrenia. Prolonged stress responses may be targeted for intervention to test for protective effects against white matter damages.

  2. The association between white-matter tract abnormalities, and neuropsychiatric and cognitive symptoms in retired professional football players with multiple concussions.

    PubMed

    Multani, Namita; Goswami, Ruma; Khodadadi, Mozhgan; Ebraheem, Ahmed; Davis, Karen D; Tator, Charles H; Wennberg, Richard; Mikulis, David J; Ezerins, Leo; Tartaglia, Maria Carmela

    2016-07-01

    Retired professional athletes, who have suffered repetitive concussions, report symptoms of depression, anxiety, and memory impairment over time. Moreover, recent imaging data suggest chronic white-matter tract deterioration in sport-related concussion. The aim of this study is to evaluate the impact of repetitive concussions in retired professional football players on white-matter tracts, and relate these changes to neuropsychological function. All subjects (18 retired professional football players and 17 healthy controls) underwent imaging, neuropsychological assessment, and reported on concussion-related symptoms. Whole brain tract-based spatial statistics analysis revealed increased axial diffusivity in the right hemisphere of retired players in the (1) superior longitudinal fasciculus (SLF), (2) corticospinal tract, and (3) anterior thalamic radiations, suggesting chronic axonal degeneration in these tracts. Moreover, retired players report significantly higher neuropsychiatric and cognitive symptoms than healthy controls, and worsening of these symptoms since their last concussion. Loss of integrity in the right SLF significantly correlated with participants' visual learning ability. In sum, these results suggest that repetitive concussions in retired professional football players are associated with focal white-matter tract abnormalities that could explain some of the neuropsychiatric symptoms and cognitive deficits experienced by these retired athletes.

  3. Preliminary evidence of white matter abnormality in the uncinate fasciculus in generalized social anxiety disorder.

    PubMed

    Phan, K Luan; Orlichenko, Anton; Boyd, Erin; Angstadt, Mike; Coccaro, Emil F; Liberzon, Israel; Arfanakis, Konstantinos

    2009-10-01

    Individuals with generalized social anxiety disorder (GSAD) exhibit exaggerated amygdala reactivity to aversive social stimuli. These findings could be explained by microstructural abnormalities in white matter (WM) tracts that connect the amygdala and prefrontal cortex, which is known to modulate the amygdala's response to threat. The goal of this study was to investigate brain frontal WM abnormalities using diffusion tensor imaging (DTI) in patients with social anxiety disorder. A Turboprop DTI sequence was used to acquire diffusion tensor images in 30 patients with GSAD and 30 matched healthy control subjects. Fractional anisotropy, an index of axonal organization, within WM was quantified in individual subjects, and an automated voxel-based, whole-brain method was used to analyze group differences. Compared with healthy control subjects, patients had significantly lower fractional anisotropy localized to the right uncinate fasciculus WM near the orbitofrontal cortex. There were no areas of higher fractional anisotropy in patients than controls. These findings point to an abnormality in the uncinate fasciculus, the major WM tract connecting the frontal cortex to the amygdala and other limbic temporal regions, in GSAD, which could underlie the aberrant amygdala-prefrontal interactions resulting in dysfunctional social threat processing in this illness.

  4. Decreased frontal white-matter volume in chronic substance abuse.

    PubMed

    Schlaepfer, Thomas E; Lancaster, Eric; Heidbreder, Rebecca; Strain, Eric C; Kosel, Markus; Fisch, Hans-Ulrich; Pearlson, Godfrey D

    2006-04-01

    There is quite a body of work assessing functional brain changes in chronic substance abuse, much less is known about structural brain abnormalities in this patient population. In this study we used magnetic resonance imaging (MRI) to determine if structural brain differences exist in patients abusing illicit drugs compared to healthy controls. Sixteen substance abusers who abused heroin, cocaine and cannabis but not alcohol and 16 age-, sex- and race-matched controls were imaged on a MRI scanner. Contiguous, 5-mm-thick axial slices were acquired with simultaneous T2 and proton density sequences. Volumes were estimated for total grey and white matter, frontal grey and white matter, ventricles, and CSF using two different methods: a conventional segmentation and a stereological method based on the Cavalieri principle. Overall brain volume differences were corrected for by expressing the volumes of interest as a percentage of total brain volume. Volume measures obtained with the two methods were highly correlated (r=0.65, p<0.001). Substance abusers had significantly less frontal white-matter volume percentage than controls. There were no significant differences in any of the other brain volumes measured. This difference in frontal lobe white matter might be explained by a direct neurotoxic effect of drug use on white matter, a pre-existing abnormality in the development of the frontal lobe or a combination of both effects. This last explanation might be compelling based on the fact that newer concepts on shared aspects of some neuropsychiatric disorders focus on the promotion and inhibition of the process of myelination throughout brain development and subsequent degeneration.

  5. White matter involvement in sporadic Creutzfeldt-Jakob disease

    PubMed Central

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

    2014-01-01

    matter abnormality either on T2-weighted or diffusion-weighted images. Widespread reduction in white matter mean diffusivity, however, was apparent visibly on the quantitative attenuation coefficient maps compared to healthy control subjects. Neuropathological analysis showed diffuse astrocytic gliosis and activated microglia in the white matter, rare prion deposition and subtle subcortical microvacuolization, and patchy foci of demyelination with no evident white matter axonal degeneration. Decreased mean diffusivity on attenuation coefficient maps might be associated with astrocytic gliosis. We show for the first time significant global reduced mean diffusivity within the white matter in sporadic Creutzfeldt-Jakob disease, suggesting possible primary involvement of the white matter, rather than changes secondary to neuronal degeneration/loss. PMID:25367029

  6. Differential vulnerability of gray matter and white matter to intrauterine growth restriction in preterm infants at 12 months corrected age.

    PubMed

    Padilla, Nelly; Junqué, Carme; Figueras, Francesc; Sanz-Cortes, Magdalena; Bargalló, Núria; Arranz, Angela; Donaire, Antonio; Figueras, Josep; Gratacos, Eduard

    2014-01-30

    Intrauterine growth restriction (IUGR) is associated with a high risk of abnormal neurodevelopment. Underlying neuroanatomical substrates are partially documented. We hypothesized that at 12 months preterm infants would evidence specific white-matter microstructure alterations and gray-matter differences induced by severe IUGR. Twenty preterm infants with IUGR (26-34 weeks of gestation) were compared with 20 term-born infants and 20 appropriate for gestational age preterm infants of similar gestational age. Preterm groups showed no evidence of brain abnormalities. At 12 months, infants were scanned sleeping naturally. Gray-matter volumes were studied with voxel-based morphometry. White-matter microstructure was examined using tract-based spatial statistics. The relationship between diffusivity indices in white matter, gray matter volumes, and perinatal data was also investigated. Gray-matter decrements attributable to IUGR comprised amygdala, basal ganglia, thalamus and insula bilaterally, left occipital and parietal lobes, and right perirolandic area. Gray-matter volumes positively correlated with birth weight exclusively. Preterm infants had reduced FA in the corpus callosum, and increased FA in the anterior corona radiata. Additionally, IUGR infants had increased FA in the forceps minor, internal and external capsules, uncinate and fronto-occipital white matter tracts. Increased axial diffusivity was observed in several white matter tracts. Fractional anisotropy positively correlated with birth weight and gestational age at birth. These data suggest that IUGR differentially affects gray and white matter development preferentially affecting gray matter. At 12 months IUGR is associated with a specific set of structural gray-matter decrements. White matter follows an unusual developmental pattern, and is apparently affected by IUGR and prematurity combined. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Neuropathology of White Matter Lesions, Blood-Brain Barrier Dysfunction, and Dementia.

    PubMed

    Hainsworth, Atticus H; Minett, Thais; Andoh, Joycelyn; Forster, Gillian; Bhide, Ishaan; Barrick, Thomas R; Elderfield, Kay; Jeevahan, Jamuna; Markus, Hugh S; Bridges, Leslie R

    2017-10-01

    We tested whether blood-brain barrier dysfunction in subcortical white matter is associated with white matter abnormalities or risk of clinical dementia in older people (n=126; mean age 86.4, SD: 7.7 years) in the MRC CFAS (Medical Research Council Cognitive Function and Ageing Study). Using digital pathology, we quantified blood-brain barrier dysfunction (defined by immunohistochemical labeling for the plasma marker fibrinogen). This was assessed within subcortical white matter tissue samples harvested from postmortem T 2 magnetic resonance imaging (MRI)-detected white matter hyperintensities, from normal-appearing white matter (distant from coexistent MRI-defined hyperintensities), and from equivalent areas in MRI normal brains. Histopathologic lesions were defined using a marker for phagocytic microglia (CD68, clone PGM1). Extent of fibrinogen labeling was not significantly associated with white matter abnormalities defined either by MRI (odds ratio, 0.90; 95% confidence interval, 0.79-1.03; P =0.130) or by histopathology (odds ratio, 0.93; 95% confidence interval, 0.77-1.12; P =0.452). Among participants with normal MRI (no detectable white matter hyperintensities), increased fibrinogen was significantly related to decreased risk of clinical dementia (odds ratio, 0.74; 95% confidence interval, 0.58-0.94; P =0.013). Among participants with histological lesions, increased fibrinogen was related to increased risk of dementia (odds ratio, 2.26; 95% confidence interval, 1.25-4.08; P =0.007). Our data suggest that some degree of blood-brain barrier dysfunction is common in older people and that this may be related to clinical dementia risk, additional to standard MRI biomarkers. © 2017 American Heart Association, Inc.

  8. Multimodal voxel-based meta-analysis of white matter abnormalities in obsessive-compulsive disorder.

    PubMed

    Radua, Joaquim; Grau, Mar; van den Heuvel, Odile A; Thiebaut de Schotten, Michel; Stein, Dan J; Canales-Rodríguez, Erick J; Catani, Marco; Mataix-Cols, David

    2014-06-01

    White matter (WM) abnormalities have long been suspected in obsessive-compulsive disorder (OCD) but the available evidence has been inconsistent. We conducted the first multimodal meta-analysis of WM volume (WMV) and fractional anisotropy (FA) studies in OCD. All voxel-wise studies comparing WMV or FA between patients with OCD and healthy controls in the PubMed, ScienceDirect, Google Scholar, Web of Knowledge and Scopus databases were retrieved. Manual searches were also conducted and authors were contacted soliciting additional data. Thirty-four data sets were identified, of which 22 met inclusion criteria (five of them unpublished; comprising 537 adult and pediatric patients with OCD and 575 matched healthy controls). Whenever possible, raw statistical parametric maps were also obtained from the authors. Peak and raw WMV and FA data were combined using novel multimodal meta-analytic methods implemented in effect-size signed differential mapping. Patients with OCD showed widespread WM abnormalities, but findings were particularly robust in the anterior midline tracts (crossing between anterior parts of cingulum bundle and body of corpus callosum), which showed both increased WMV and decreased FA, possibly suggesting an increase of fiber crossing in these regions. This finding was also observed when the analysis was limited to adult participants, and especially pronounced in samples with a higher proportion of medicated patients. Therefore, patients with OCD may have widespread WM abnormalities, particularly evident in anterior midline tracts, although these changes might be, at least in part, attributable to the effects of therapeutic drugs.

  9. Abnormal brain white matter network in young smokers: a graph theory analysis study.

    PubMed

    Zhang, Yajuan; Li, Min; Wang, Ruonan; Bi, Yanzhi; Li, Yangding; Yi, Zhang; Liu, Jixin; Yu, Dahua; Yuan, Kai

    2018-04-01

    Previous diffusion tensor imaging (DTI) studies had investigated the white matter (WM) integrity abnormalities in some specific fiber bundles in smokers. However, little is known about the changes in topological organization of WM structural network in young smokers. In current study, we acquired DTI datasets from 58 male young smokers and 51 matched nonsmokers and constructed the WM networks by the deterministic fiber tracking approach. Graph theoretical analysis was used to compare the topological parameters of WM network (global and nodal) and the inter-regional fractional anisotropy (FA) weighted WM connections between groups. The results demonstrated that both young smokers and nonsmokers had small-world topology in WM network. Further analysis revealed that the young smokers exhibited the abnormal topological organization, i.e., increased network strength, global efficiency, and decreased shortest path length. In addition, the increased nodal efficiency predominately was located in frontal cortex, striatum and anterior cingulate gyrus (ACG) in smokers. Moreover, based on network-based statistic (NBS) approach, the significant increased FA-weighted WM connections were mainly found in the PFC, ACG and supplementary motor area (SMA) regions. Meanwhile, the network parameters were correlated with the nicotine dependence severity (FTND) scores, and the nodal efficiency of orbitofrontal cortex was positive correlation with the cigarette per day (CPD) in young smokers. We revealed the abnormal topological organization of WM network in young smokers, which may improve our understanding of the neural mechanism of young smokers form WM topological organization level.

  10. Relationship of grey and white matter abnormalities with distance from the surface of the brain in multiple sclerosis.

    PubMed

    Pardini, Matteo; Sudre, Carole H; Prados, Ferran; Yaldizli, Özgür; Sethi, Varun; Muhlert, Nils; Samson, Rebecca S; van de Pavert, Steven H; Cardoso, M Jorge; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A M; Miller, David H; Chard, Declan T

    2016-11-01

    To assess the association between proximity to the inner (ventricular and aqueductal) and outer (pial) surfaces of the brain and the distribution of normal appearing white matter (NAWM) and grey matter (GM) abnormalities, and white matter (WM) lesions, in multiple sclerosis (MS). 67 people with relapse-onset MS and 30 healthy controls were included in the study. Volumetric T1 images and high-resolution (1 mm 3 ) magnetisation transfer ratio (MTR) images were acquired and segmented into 12 bands between the inner and outer surfaces of the brain. The first and last bands were discarded to limit partial volume effects with cerebrospinal fluid. MTR values were computed for all bands in supratentorial NAWM, cerebellar NAWM and brainstem NA tissue, and deep and cortical GM. Band WM lesion volumes were also measured. Proximity to the ventricular surfaces was associated with progressively lower MTR values in the MS group but not in controls in supratentorial and cerebellar NAWM, brainstem NA and in deep and cortical GM. The density of WM lesions was associated with proximity to the ventricles only in the supratentorial compartment, and no link was found with distance from the pial surfaces. In MS, MTR abnormalities in NAWM and GM are related to distance from the inner and outer surfaces of the brain, and this suggests that there is a common factor underlying their spatial distribution. A similar pattern was not found for WM lesions, raising the possibility that different factors promote their formation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  11. Abnormal brain white matter microstructure is associated with both pre-hypertension and hypertension

    PubMed Central

    Gao, He; Bai, Wenjia; Evangelou, Evangelos; Glocker, Ben; O’Regan, Declan P.; Elliott, Paul; Matthews, Paul M.

    2017-01-01

    Objectives To characterize effects of chronically elevated blood pressure on the brain, we tested for brain white matter microstructural differences associated with normotension, pre-hypertension and hypertension in recently available brain magnetic resonance imaging data from 4659 participants without known neurological or psychiatric disease (62.3±7.4 yrs, 47.0% male) in UK Biobank. Methods For assessment of white matter microstructure, we used measures derived from neurite orientation dispersion and density imaging (NODDI) including the intracellular volume fraction (an estimate of neurite density) and isotropic volume fraction (an index of the relative extra-cellular water diffusion). To estimate differences associated specifically with blood pressure, we applied propensity score matching based on age, sex, educational level, body mass index, and history of smoking, diabetes mellitus and cardiovascular disease to perform separate contrasts of non-hypertensive (normotensive or pre-hypertensive, N = 2332) and hypertensive (N = 2337) individuals and of normotensive (N = 741) and pre-hypertensive (N = 1581) individuals (p<0.05 after Bonferroni correction). Results The brain white matter intracellular volume fraction was significantly lower, and isotropic volume fraction was higher in hypertensive relative to non-hypertensive individuals (N = 1559, each). The white matter isotropic volume fraction also was higher in pre-hypertensive than in normotensive individuals (N = 694, each) in the right superior longitudinal fasciculus and the right superior thalamic radiation, where the lower intracellular volume fraction was observed in the hypertensives relative to the non-hypertensive group. Significance Pathological processes associated with chronically elevated blood pressure are associated with imaging differences suggesting chronic alterations of white matter axonal structure that may affect cognitive functions even with pre-hypertension. PMID:29145428

  12. Sex differences in white matter abnormalities after mild traumatic brain injury: localization and correlation with outcome.

    PubMed

    Fakhran, Saeed; Yaeger, Karl; Collins, Michael; Alhilali, Lea

    2014-09-01

    To evaluate sex differences in diffusion-tensor imaging (DTI) white matter abnormalities after mild traumatic brain injury (mTBI) using tract-based spatial statistics (TBSS) and to compare associated clinical outcomes. The institutional review board approved this study, with waiver of informed consent. DTI in 69 patients with mTBI (47 male and 22 female patients) and 21 control subjects (10 male and 11 female subjects) with normal conventional magnetic resonance (MR) images were retrospectively reviewed. Fractional anisotropy (FA) maps were generated as a measure of white matter integrity. Patients with mTBI underwent serial neurocognitive testing with Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT). Correlation between sex, white matter FA values, ImPACT scores, and time to symptom resolution (TSR) were analyzed with multivariate analysis and TBSS. No significant difference in age was seen between males and females (control subjects, P = .3; patients with mTBI, P = .34). No significant difference was seen in initial ImPACT symptom scores (P = .33) between male and female patients with mTBI. Male patients with mTBI had significantly decreased FA values in the uncinate fasciculus (UF) bilaterally (mean FA, 0.425; 95% confidence interval: 0.375, 0.476) compared with female patients with mTBI and control subjects (P < .05), with a significantly longer TSR (P = .04). Multivariate analysis showed sex and UF FA values independently correlated with TSR longer than 3 months (adjusted odds ratios, 2.27 and 2.38; P = .04 and P < .001, respectively), but initial symptom severity did not (adjusted odds ratio, 1.15; P = .35). Relative sparing of the UF is seen in female compared with male patients after mTBI, with sex and UF FA values as stronger predictors of TSR than initial symptom severity.

  13. Preliminary Evidence of White Matter Abnormality in the Uncinate Fasciculus in Generalized Social Anxiety Disorder

    PubMed Central

    Phan, K. Luan; Orlichenko, Anton; Boyd, Erin; Angstadt, Mike; Coccaro, Emil F.; Liberzon, Israel; Arfanakis, Konstantinos

    2009-01-01

    Background Individuals with generalized social anxiety disorder (GSAD) exhibit exaggerated amygdala reactivity to aversive social stimuli. These findings could be explained by microstructural abnormalities in white matter (WM) tracts that connect the amygdala and prefrontal cortex, which is known to modulate the amygdala’s response to threat. The goal of this study was to investigate brain frontal WM abnormalities by using diffusion tensor imaging (DTI) in patients with social anxiety disorder. Method A Turboprop DTI sequence was used to acquire diffusion tensor images in thirty patients with GSAD and thirty matched healthy controls. Fractional anisotropy, an index of axonal organization, within WM was quantified in individual subjects and an automated voxel-based, whole-brain method was used to analyze group differences. Results Compared to healthy controls, patients had significantly lower fractional anisotropy localized to the right uncinate fasciculus WM near the orbitofrontal cortex. There were no areas of higher fractional anisotropy in patients than controls. Conclusions These findings point to an abnormality in the uncinate fasciculus, the major WM tract connecting the frontal cortex to the amygdala and other limbic temporal regions, in GSAD which could underlie the aberrant amygdala-prefrontal interactions resulting in dysfunctional social threat processing in this illness. PMID:19362707

  14. 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.

  15. Increased white matter metabolic rates in autism spectrum disorder and schizophrenia.

    PubMed

    Mitelman, Serge A; Buchsbaum, Monte S; Young, Derek S; Haznedar, M Mehmet; Hollander, Eric; Shihabuddin, Lina; Hazlett, Erin A; Bralet, Marie-Cecile

    2017-11-22

    Both autism spectrum disorder (ASD) and schizophrenia are often characterized as disorders of white matter integrity. Multimodal investigations have reported elevated metabolic rates, cerebral perfusion and basal activity in various white matter regions in schizophrenia, but none of these functions has previously been studied in ASD. We used 18 fluorodeoxyglucose positron emission tomography to compare white matter metabolic rates in subjects with ASD (n = 25) to those with schizophrenia (n = 41) and healthy controls (n = 55) across a wide range of stereotaxically placed regions-of-interest. Both subjects with ASD and schizophrenia showed increased metabolic rates across the white matter regions assessed, including internal capsule, corpus callosum, and white matter in the frontal and temporal lobes. These increases were more pronounced, more widespread and more asymmetrical in subjects with ASD than in those with schizophrenia. The highest metabolic increases in both disorders were seen in the prefrontal white matter and anterior limb of the internal capsule. Compared to normal controls, differences in gray matter metabolism were less prominent and differences in adjacent white matter metabolism were more prominent in subjects with ASD than in those with schizophrenia. Autism spectrum disorder and schizophrenia are associated with heightened metabolic activity throughout the white matter. Unlike in the gray matter, the vector of white matter metabolic abnormalities appears to be similar in ASD and schizophrenia, may reflect inefficient functional connectivity with compensatory hypermetabolism, and may be a common feature of neurodevelopmental disorders.

  16. Abnormal white matter integrity in chronic users of codeine-containing cough syrups: a tract-based spatial statistics study.

    PubMed

    Qiu, Y-W; Su, H-H; Lv, X-F; Jiang, G-H

    2015-01-01

    Codeine-containing cough syrups have become one of the most popular drugs of abuse in young people in the world. Chronic codeine-containing cough syrup abuse is related to impairments in a broad range of cognitive functions. However, the potential brain white matter impairment caused by chronic codeine-containing cough syrup abuse has not been reported previously. Our aim was to investigate abnormalities in the microstructure of brain white matter in chronic users of codeine-containing syrups and to determine whether these WM abnormalities are related to the duration of the use these syrups and clinical impulsivity. Thirty chronic codeine-containing syrup users and 30 matched controls were evaluated. Diffusion tensor imaging was performed by using a single-shot spin-echo-planar sequence. Whole-brain voxelwise analysis of fractional anisotropy was performed by using tract-based spatial statistics to localize abnormal WM regions. The Barratt Impulsiveness Scale 11 was surveyed to assess participants' impulsivity. Volume-of-interest analysis was used to detect changes of diffusivity indices in regions with fractional anisotropy abnormalities. Abnormal fractional anisotropy was extracted and correlated with clinical impulsivity and the duration of codeine-containing syrup use. Chronic codeine-containing syrup users had significantly lower fractional anisotropy in the inferior fronto-occipital fasciculus of the bilateral temporo-occipital regions, right frontal region, and the right corona radiata WM than controls. There were significant negative correlations among fractional anisotropy values of the right frontal region of the inferior fronto-occipital fasciculus and the right superior corona radiata WM and Barratt Impulsiveness Scale total scores, and between the right frontal region of the inferior fronto-occipital fasciculus and nonplan impulsivity scores in chronic codeine-containing syrup users. There was also a significant negative correlation between fractional

  17. Microglial activation in white matter lesions and nonlesional white matter of ageing brains.

    PubMed

    Simpson, J E; Ince, P G; Higham, C E; Gelsthorpe, C H; Fernando, M S; Matthews, F; Forster, G; O'Brien, J T; Barber, R; Kalaria, R N; Brayne, C; Shaw, P J; Stoeber, K; Williams, G H; Lewis, C E; Wharton, S B

    2007-12-01

    White matter lesions (WML), a common feature in brain ageing, are classified as periventricular (PVL) or deep subcortical (DSCL), depending on their anatomical location. Microglial activation is implicated in a number of neurodegenerative diseases, but the microglial response in WML is poorly characterized and its role in pathogenesis unknown. We have characterized the microglial response in WML and control white matter using immunohistochemistry to markers of microglial activation and of proliferation. WML of brains from an unbiased population-based autopsy cohort (Medical Research Council's Cognitive Function and Ageing Study) were identified by post mortem magnetic resonance imaging and sampled for histology. PVL contain significantly more activated microglia, expressing major histocompatibility complex (MHC) class II and the costimulatory molecules B7-2 and CD40, than either control white matter (WM) or DSCL. Furthermore, we show that significantly more microglia express the replication licensing protein minichromosome maintenance protein 2 within PVL, suggesting this is a more proliferation-permissive environment than DSCL. Although microglial activation occurs in both PVL and DSCL, our findings suggest a difference in pathogenesis between these lesion-types: the ramified, activated microglia associated with PVL may reflect immune activation resulting from disruption of the blood brain barrier, while the microglia within DSCL may reflect an innate, amoeboid phagocytic phenotype. We also show that microglia in control WM from lesional cases express significantly more MHC II than control WM from nonlesional ageing brain, suggesting that WML occur in a 'field-effect' of abnormal WM.

  18. Alterations in White Matter Integrity in Young Adults with Smartphone Dependence

    PubMed Central

    Hu, Yuanming; Long, Xiaojing; Lyu, Hanqing; Zhou, Yangyang; Chen, Jianxiang

    2017-01-01

    Smartphone dependence (SPD) is increasingly regarded as a psychological problem, however, the underlying neural substrates of SPD is still not clear. High resolution magnetic resonance imaging provides a useful tool to help understand and manage the disorder. In this study, a tract-based spatial statistics (TBSS) analysis on diffusion tensor imaging (DTI) was used to measure white matter integrity in young adults with SPD. A total of 49 subjects were recruited and categorized into SPD and control group based on their clinical behavioral tests. To localize regions with abnormal white matter integrity in SPD, the voxel-wise analysis of fractional anisotropy (FA) and mean diffusivity (MD) on the whole brain was performed by TBSS. The correlation between the quantitative variables of brain structures and the behavior measures were performed. Our result demonstrated that SPD had significantly lower white matter integrity than controls in superior longitudinal fasciculus (SLF), superior corona radiata (SCR), internal capsule, external capsule, sagittal stratum, fornix/stria terminalis and midbrain structures. Correlation analysis showed that the observed abnormalities in internal capsule and stria terminalis were correlated with the severity of dependence and behavioral assessments. Our finding facilitated a primary understanding of white matter characteristics in SPD and indicated that the structural deficits might link to behavioral impairments. PMID:29163108

  19. Adolescent Toluene Inhalation in Rats Affects White Matter Maturation with the Potential for Recovery Following Abstinence

    PubMed Central

    Egan, Gary; Kolbe, Scott; Gavrilescu, Maria; Wright, David; Lubman, Dan Ian; Lawrence, Andrew John

    2012-01-01

    Inhalant misuse is common during adolescence, with ongoing chronic misuse associated with neurobiological and cognitive abnormalities. While human imaging studies consistently report white matter abnormalities among long-term inhalant users, longitudinal studies have been lacking with limited data available regarding the progressive nature of such abnormalities, including the potential for recovery following periods of sustained abstinence. We exposed adolescent male Wistar rats (postnatal day 27) to chronic intermittent inhaled toluene (3,000 ppm) for 1 hour/day, 3 times/week for 8 weeks to model abuse patterns observed in adolescent and young adult human users. This dosing regimen resulted in a significant retardation in weight gain during the exposure period (p<0.05). In parallel, we performed longitudinal magnetic resonance imaging (T2-weighted) and diffusion tensor imaging prior to exposure, and after 4 and 8 weeks, to examine the integrity of white matter tracts, including the anterior commissure and corpus callosum. We also conducted imaging after 8 weeks of abstinence to assess for potential recovery. Chronic intermittent toluene exposure during adolescence and early adulthood resulted in white matter abnormalities, including a decrease in axial (p<0.05) and radial (p<0.05) diffusivity. These abnormalities appeared region-specific, occurring in the anterior commissure but not the corpus callosum and were not present until after at least 4 weeks of exposure. Toluene-induced effects on both body weight and white matter parameters recovered following abstinence. Behaviourally, we observed a progressive decrease in rearing activity following toluene exposure but no difference in motor function, suggesting cognitive function may be more sensitive to the effects of toluene. Furthermore, deficits in rearing were present by 4 weeks suggesting that toluene may affect behaviour prior to detectable white matter abnormalities. Consequently, exposure to inhalants that

  20. Adolescent toluene inhalation in rats affects white matter maturation with the potential for recovery following abstinence.

    PubMed

    Duncan, Jhodie Rubina; Dick, Alec Lindsay Ward; Egan, Gary; Kolbe, Scott; Gavrilescu, Maria; Wright, David; Lubman, Dan Ian; Lawrence, Andrew John

    2012-01-01

    Inhalant misuse is common during adolescence, with ongoing chronic misuse associated with neurobiological and cognitive abnormalities. While human imaging studies consistently report white matter abnormalities among long-term inhalant users, longitudinal studies have been lacking with limited data available regarding the progressive nature of such abnormalities, including the potential for recovery following periods of sustained abstinence. We exposed adolescent male Wistar rats (postnatal day 27) to chronic intermittent inhaled toluene (3,000 ppm) for 1 hour/day, 3 times/week for 8 weeks to model abuse patterns observed in adolescent and young adult human users. This dosing regimen resulted in a significant retardation in weight gain during the exposure period (p<0.05). In parallel, we performed longitudinal magnetic resonance imaging (T₂-weighted) and diffusion tensor imaging prior to exposure, and after 4 and 8 weeks, to examine the integrity of white matter tracts, including the anterior commissure and corpus callosum. We also conducted imaging after 8 weeks of abstinence to assess for potential recovery. Chronic intermittent toluene exposure during adolescence and early adulthood resulted in white matter abnormalities, including a decrease in axial (p<0.05) and radial (p<0.05) diffusivity. These abnormalities appeared region-specific, occurring in the anterior commissure but not the corpus callosum and were not present until after at least 4 weeks of exposure. Toluene-induced effects on both body weight and white matter parameters recovered following abstinence. Behaviourally, we observed a progressive decrease in rearing activity following toluene exposure but no difference in motor function, suggesting cognitive function may be more sensitive to the effects of toluene. Furthermore, deficits in rearing were present by 4 weeks suggesting that toluene may affect behaviour prior to detectable white matter abnormalities. Consequently, exposure to inhalants that

  1. Accelerated White Matter Aging in Schizophrenia: Role of White Matter Blood Perfusion

    PubMed Central

    Chiappelli, Joshua; McMahon, Robert; Muellerklein, Florian; Wijtenburg, S. Andrea; White, Michael G.; Rowland, Laura M.; Hong, L. Elliot

    2014-01-01

    Elevated rate of age-related decline in white matter integrity, indexed by fractional anisotropy (FA) from diffusion tensor imaging, was reported in patients with schizophrenia. Its etiology is unknown. We hypothesized that a decline of blood perfusion to the white matter may underlie the accelerated age-related reduction in FA in schizophrenia. Resting white matter perfusion and FA were collected using pseudo-continuous arterial spin labeling and high-angular-resolution diffusion tensor imaging, respectively, in 50 schizophrenia patients and 70 controls (age=18-63 years). Main outcome measures were the diagnosis-by-age interaction on whole-brain white matter perfusion, and FA. Significant age-related decline in brain white matter perfusion and FA were present in both groups. Age-by-diagnosis interaction was significant for FA (p<0.001) but not white matter perfusion. Age-by-diagnosis interaction for FA values remained significant even after accounting for age-related decline in perfusion. Therefore, we replicated the finding of an increased rate of age-related white matter FA decline in schizophrenia, and observed a significant age-related decline in white matter blood perfusion, although the latter did not contribute to the accelerated age-related decline in FA. The results suggest that factors other than reduced perfusion account for the accelerated age-related decline in white matter integrity in schizophrenia. PMID:24680326

  2. 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

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

    PubMed

    Bernier, Denise; Cookey, Jacob; McAllindon, David; Bartha, Robert; Hanstock, Christopher C; Newman, Aaron J; Stewart, Sherry H; Tibbo, Philip G

    2013-10-17

    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. 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. 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 consideration the important confounding

  4. White Matter Microstructural Abnormalities in Type 2 Diabetes Mellitus: A Diffusional Kurtosis Imaging Analysis.

    PubMed

    Xie, Y; Zhang, Y; Qin, W; Lu, S; Ni, C; Zhang, Q

    2017-03-01

    Increasing DTI studies have demonstrated that white matter microstructural abnormalities play an important role in type 2 diabetes mellitus-related cognitive impairment. In this study, the diffusional kurtosis imaging method was used to investigate WM microstructural alterations in patients with type 2 diabetes mellitus and to detect associations between diffusional kurtosis imaging metrics and clinical/cognitive measurements. Diffusional kurtosis imaging and cognitive assessments were performed on 58 patients with type 2 diabetes mellitus and 58 controls. Voxel-based intergroup comparisons of diffusional kurtosis imaging metrics were conducted, and ROI-based intergroup comparisons were further performed. Correlations between the diffusional kurtosis imaging metrics and cognitive/clinical measurements were assessed after controlling for age, sex, and education in both patients and controls. Altered diffusion metrics were observed in the corpus callosum, the bilateral frontal WM, the right superior temporal WM, the left external capsule, and the pons in patients with type 2 diabetes mellitus compared with controls. The splenium of the corpus callosum and the pons had abnormal kurtosis metrics in patients with type 2 diabetes mellitus. Additionally, altered diffusion metrics in the right prefrontal WM were significantly correlated with disease duration and attention task performance in patients with type 2 diabetes mellitus. With both conventional diffusion and additional kurtosis metrics, diffusional kurtosis imaging can provide additional information on WM microstructural abnormalities in patients with type 2 diabetes mellitus. Our results indicate that WM microstructural abnormalities occur before cognitive decline and may be used as neuroimaging markers for predicting the early cognitive impairment in patients with type 2 diabetes mellitus. © 2017 by American Journal of Neuroradiology.

  5. White matter microstructure and cognitive decline in metabolic syndrome: a review of diffusion tensor imaging.

    PubMed

    Alfaro, Freddy J; Gavrieli, Anna; Saade-Lemus, Patricia; Lioutas, Vasileios-Arsenios; Upadhyay, Jagriti; Novak, Vera

    2018-01-01

    Metabolic syndrome is a cluster of cardiovascular risk factors defined by the presence of abdominal obesity, glucose intolerance, hypertension and/or dyslipidemia. It is a major public health epidemic worldwide, and a known risk factor for the development of cognitive dysfunction and dementia. Several studies have demonstrated a positive association between the presence of metabolic syndrome and worse cognitive outcomes, however, evidence of brain structure pathology is limited. Diffusion tensor imaging has offered new opportunities to detect microstructural white matter changes in metabolic syndrome, and a possibility to detect associations between functional and structural abnormalities. This review analyzes the impact of metabolic syndrome on white matter microstructural integrity, brain structure abnormalities and their relationship to cognitive function. Each of the metabolic syndrome components exerts a specific signature of white matter microstructural abnormalities. Metabolic syndrome and its components exert both additive/synergistic, as well as, independent effects on brain microstructure thus accelerating brain aging and cognitive decline. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. White matter microstructural abnormalities in the frontal lobe of adults with antisocial personality disorder.

    PubMed

    Sundram, Frederick; Deeley, Quinton; Sarkar, Sagari; Daly, Eileen; Latham, Richard; Craig, Michael; Raczek, Malgorzata; Fahy, Tom; Picchioni, Marco; Barker, Gareth J; Murphy, Declan G M

    2012-02-01

    Antisocial personality disorder (ASPD) and psychopathy involve significant interpersonal and behavioural impairments. However, little is known about their underlying neurobiology and in particular, abnormalities in white matter (WM) microstructure. A preliminary diffusion tensor magnetic resonance imaging (DT-MRI) study of adult psychopaths employing tractography revealed abnormalities in the right uncinate fasciculus (UF) (Craig et al., 2009), indicating fronto-limbic disconnectivity. However, it is not clear whether WM abnormalities are restricted to this tract or are or more widespread, including other tracts which are involved in connectivity with the frontal lobe. We performed whole brain voxel-based analyses on WM fractional anisotropy (FA) and mean diffusivity (MD) maps acquired with DT-MRI to compare 15 adults with ASPD and healthy age, handedness and IQ-matched controls. Also, within ASPD subjects we related differences in FA and MD to measures of psychopathy. Significant WM FA reduction and MD increases were found respectively in ASPD subjects relative to controls. FA was bilaterally reduced in the genu of corpus callosum while in the right frontal lobe FA reduction was found in the UF, inferior fronto-occipital fasciculus (IFOF), anterior corona radiata and anterior limb and genu of the internal capsule. These differences negatively correlated with measures of psychopathy. Also in the right frontal lobe, increased MD was found in the IFOF and UF, and the corpus callosum and anterior corona radiata. There was a significant positive correlation between MD and psychopathy scores. The present study confirms a previous report of reduced FA in the UF. Additionally, we report for the first time, FA deficits in tracts involved in interhemispheric as well as frontal lobe connectivity in conjunction with MD increases in the frontal lobe. Hence, we provide evidence of significant WM microstructural abnormalities in frontal brain regions in ASPD and psychopathy

  7. White matter changes in an untreated, newly diagnosed case of classical homocystinuria.

    PubMed

    Brenton, J Nicholas; Matsumoto, Julie A; Rust, Robert S; Wilson, William G

    2014-01-01

    The authors report the case of a 4-year-old boy who developed progressive unilateral weakness and developmental delays prior to his diagnosis of classical homocystinuria. Magnetic resonance imaging (MRI) of the brain demonstrated diffuse white matter changes, raising the concern for a secondary diagnosis causing leukoencephalopathy, since classical homocystinuria is not typically associated with these changes. Other inborn errors of the transsulfuration pathway have been reported as causing these changes. Once begun on therapy for his homocystinuria, his neurologic deficits resolved and his delays rapidly improved. Repeat MRI performed one year after instating therapy showed resolution of his white matter abnormalities. This case illustrates the need to consider homocystinuria and other amino acidopathies in the differential diagnosis of childhood white matter diseases and lends weight to the hypothesis that hypermethioninemia may induce white matter changes.

  8. Utilizing Mutual Information Analysis to Explore the Relationship Between Gray and White Matter Structural Pathologies in Schizophrenia.

    PubMed

    Lyall, Amanda E; Savadjiev, Peter; Del Re, Elisabetta C; Seitz, Johanna; O'Donnell, Lauren J; Westin, Carl-Fredrik; Mesholam-Gately, Raquelle I; Petryshen, Tracey; Wojcik, Joanne D; Nestor, Paul; Niznikiewicz, Margaret; Goldstein, Jill; Seidman, Larry J; McCarley, Robert W; Shenton, Martha E; Kubicki, Marek

    2018-04-03

    Schizophrenia has been characterized as a neurodevelopmental disorder, with structural brain abnormalities reported at all stages. However, at present, it remains unclear whether gray and white matter abnormalities represent related or independent pathologies in schizophrenia. In this study, we present findings from an integrative analysis exploring the morphological relationship between gray and white matter in 45 schizophrenia participants and 49 healthy controls. We utilized mutual information (MI), a measure of how much information two variables share, to assess the morphological dependence between gray and white matter in three segments of the corpus callsoum, and the gray matter regions these segments connect: (1) the genu and the left and right rostral middle frontal gyrus (rMFG), (2) the isthmus and the left and right superior temporal gyrus (STG), (3) the splenium and the left and right lateral occipital gyrus (LOG). We report significantly reduced MI between white matter tract dispersion of the right hemispheric callosal connections to the STG and both cortical thickness and area in the right STG in schizophrenia patients, despite a lack of group differences in cortical thickness, surface area, or dispersion. We believe that this reduction in morphological dependence between gray and white matter may reflect a possible decoupling of the developmental processes that shape morphological features of white and gray matter early in life. The present study also demonstrates the importance of studying the relationship between gray and white matter measures, as opposed to restricting analyses to gray and white matter measures independently.

  9. Novel white matter tract integrity metrics sensitive to Alzheimer disease progression.

    PubMed

    Fieremans, E; Benitez, A; Jensen, J H; Falangola, M F; Tabesh, A; Deardorff, R L; Spampinato, M V S; Babb, J S; Novikov, D S; Ferris, S H; Helpern, J A

    2013-01-01

    Along with cortical abnormalities, white matter microstructural changes such as axonal loss and myelin breakdown are implicated in the pathogenesis of Alzheimer disease. Recently, a white matter model was introduced that relates non-Gaussian diffusional kurtosis imaging metrics to characteristics of white matter tract integrity, including the axonal water fraction, the intra-axonal diffusivity, and the extra-axonal axial and radial diffusivities. This study reports these white matter tract integrity metrics in subjects with amnestic mild cognitive impairment (n = 12), Alzheimer disease (n = 14), and age-matched healthy controls (n = 15) in an effort to investigate their sensitivity, diagnostic accuracy, and associations with white matter changes through the course of Alzheimer disease. With tract-based spatial statistics and region-of-interest analyses, increased diffusivity in the extra-axonal space (extra-axonal axial and radial diffusivities) in several white matter tracts sensitively and accurately discriminated healthy controls from those with amnestic mild cognitive impairment (area under the receiver operating characteristic curve = 0.82-0.95), while widespread decreased axonal water fraction discriminated amnestic mild cognitive impairment from Alzheimer disease (area under the receiver operating characteristic curve = 0.84). Additionally, these white matter tract integrity metrics in the body of the corpus callosum were strongly correlated with processing speed in amnestic mild cognitive impairment (r = |0.80-0.82|, P < .001). These findings have implications for the course and spatial progression of white matter degeneration in Alzheimer disease, suggest the mechanisms by which these changes occur, and demonstrate the viability of these white matter tract integrity metrics as potential neuroimaging biomarkers of the earliest stages of Alzheimer disease and disease progression.

  10. White matter microstructure damage in tremor-dominant Parkinson's disease patients.

    PubMed

    Luo, ChunYan; Song, Wei; Chen, Qin; Yang, Jing; Gong, QiYong; Shang, Hui-Fang

    2017-07-01

    Resting tremor is one of the cardinal motor features of Parkinson's disease (PD). Several lines of evidence suggest resting tremor may have different underlying pathophysiological processes from those of bradykinesia and rigidity. The current study aims to identify white matter microstructural abnormalities associated with resting tremor in PD. We recruited 60 patients with PD (30 with tremor-dominant PD and 30 with nontremor-dominant PD) and 26 normal controls. All participants underwent clinical assessment and diffusion tensor MRI. We used tract-based spatial statistics to investigate white matter integrity across the entire white matter tract skeleton. Compared with both healthy controls and the nontremor-dominant PD patients, the tremor-dominant PD patients were characterized by increased mean diffusivity (MD) and axial diffusivity (AD) along multiple white matter tracts, mainly involving the cerebello-thalamo-cortical (CTC) pathway. The mean AD value in clusters with significant difference was correlated with resting tremor score in the tremor-dominant PD patients. There was no significant difference between the nontremor-dominant PD patients and controls. Our results support the notion that resting tremor in PD is a distinct condition in which significant microstructural white matter changes exist and provide evidence for the involvement of the CTC in tremor genesis of PD.

  11. Differing patterns of brain structural abnormalities between black and white patients with their first episode of psychosis.

    PubMed

    Morgan, K D; Dazzan, P; Morgan, C; Lappin, J; Hutchinson, G; Chitnis, X; Suckling, J; Fearon, P; Jones, P B; Leff, J; Murray, R M

    2010-07-01

    African-Caribbean and black African people living in the UK are reported to have a higher incidence of diagnosed psychosis compared with white British people. It has been argued that this may be a consequence of misdiagnosis. If this is true they might be less likely to show the patterns of structural brain abnormalities reported in white British patients. The aim of this study therefore was to investigate whether there are differences in the prevalence of structural brain abnormalities in white and black first-episode psychosis patients. We obtained dual-echo (proton density/T2-weighted) images from a sample of 75 first-episode psychosis patients and 68 healthy controls. We used high resolution magnetic resonance imaging and voxel-based methods of image analysis. Two separate analyses were conducted: (1) 34 white British patients were compared with 33 white British controls; (2) 41 African-Caribbean and black African patients were compared with 35 African-Caribbean and black African controls. White British patients and African-Caribbean/black African patients had ventricular enlargement and increased lenticular nucleus volume compared with their respective ethnic controls. The African-Caribbean/black African patients also showed reduced global grey matter and increased lingual gyrus grey-matter volume. The white British patients had no regional or global grey-matter loss compared with their normal ethnic counterparts but showed increased grey matter in the left superior temporal lobe and right parahippocampal gyrus. We found no evidence in support of our hypothesis. Indeed, the finding of reduced global grey-matter volume in the African-Caribbean/black African patients but not in the white British patients was contrary to our prediction.

  12. Creutzfeldt-Jakob disease with severe involvement of cerebral white matter and cerebellum.

    PubMed

    Berciano, J; Berciano, M T; Polo, J M; Figols, J; Ciudad, J; Lafarga, M

    1990-01-01

    We describe a patient with Creutzfeldt-Jakob disease (CJD) of the ataxic and panencephalopathic type. Postmortem examination revealed the characteristic lesions of CJD in the grey matter and profound white matter involvement was seen with immunocytochemical techniques. Ultrastructural white matter lesions were identical to those described in experimentally transmitted CJD. There was marked loss of cerebellar granule cells with virtual disappearance of parallel fibres, but Purkinje cells were only slightly reduced. Electron microscopic studies revealed extensive degenerative changes including cytoplasmic vacuoles in both cell types. Silver methods disclosed massive impregnation of white matter and striking abnormalities of Purkinje cells consisting of hypertrophy and flattening of thick dendritic branches, reduction in the number of terminal branchlets, segmentary loss of spines and polymorphic spines. These findings show the extensive involvement of all three cerebellar cortical layers and the reactive plasticity of Purkinje cells to deafferentiation. They favour the hypothesis that demyelination represents a primary lesion of the white matter.

  13. Gray and white matter volume abnormalities in monozygotic and same-gender dizygotic twins discordant for schizophrenia.

    PubMed

    Hulshoff Pol, Hilleke E; Brans, Rachel G H; van Haren, Neeltje E M; Schnack, Hugo G; Langen, Marieke; Baaré, Wim F C; van Oel, Clarine J; Kahn, René S

    2004-01-15

    Whole brain tissue volume decreases in schizophrenia have been related to both genetic risk factors and disease-related (possibly nongenetic) factors; however, whether genetic and environmental risk factors in the brains of patients with schizophrenia are differentially reflected in gray or white matter volume change is not known. Magnetic resonance imaging (1.5 T) brain scans of 11 monozygotic and 11 same-gender dizygotic twin pairs discordant for schizophrenia were acquired and compared with 11 monozygotic and 11 same-gender dizygotic healthy control twin pairs. Repeated-measures volume analysis of covariance revealed decreased whole brain volume in the patients with schizophrenia as compared with their co-twins and with healthy twin pairs. Decreased white matter volume was found in discordant twin pairs compared with healthy twin pairs, particularly in the monozygotic twin pairs. A decrease in gray matter was found in the patients compared with their co-twins and compared with the healthy twins. The results suggest that the decreases in white matter volume reflect the increased genetic risk to develop schizophrenia, whereas the decreases in gray matter volume are related to environmental risk factors. Study of genes involved in the (maintenance) of white matter structures may be particularly fruitful in schizophrenia.

  14. Abnormal functional connectivity during visuospatial processing is associated with disrupted organisation of white matter in autism

    PubMed Central

    McGrath, Jane; Johnson, Katherine; O'Hanlon, Erik; Garavan, Hugh; Leemans, Alexander; Gallagher, Louise

    2013-01-01

    Disruption of structural and functional neural connectivity has been widely reported in Autism Spectrum Disorder (ASD) but there is a striking lack of research attempting to integrate analysis of functional and structural connectivity in the same study population, an approach that may provide key insights into the specific neurobiological underpinnings of altered functional connectivity in autism. The aims of this study were (1) to determine whether functional connectivity abnormalities were associated with structural abnormalities of white matter (WM) in ASD and (2) to examine the relationships between aberrant neural connectivity and behavior in ASD. Twenty-two individuals with ASD and 22 age, IQ-matched controls completed a high-angular-resolution diffusion MRI scan. Structural connectivity was analysed using constrained spherical deconvolution (CSD) based tractography. Regions for tractography were generated from the results of a previous study, in which 10 pairs of brain regions showed abnormal functional connectivity during visuospatial processing in ASD. WM tracts directly connected 5 of the 10 region pairs that showed abnormal functional connectivity; linking a region in the left occipital lobe (left BA19) and five paired regions: left caudate head, left caudate body, left uncus, left thalamus, and left cuneus. Measures of WM microstructural organization were extracted from these tracts. Fractional anisotropy (FA) reductions in the ASD group relative to controls were significant for WM connecting left BA19 to left caudate head and left BA19 to left thalamus. Using a multimodal imaging approach, this study has revealed aberrant WM microstructure in tracts that directly connect brain regions that are abnormally functionally connected in ASD. These results provide novel evidence to suggest that structural brain pathology may contribute (1) to abnormal functional connectivity and (2) to atypical visuospatial processing in ASD. PMID:24133425

  15. The white matter query language: a novel approach for describing human white matter anatomy

    PubMed Central

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

    2016-01-01

    We have developed a novel method to describe human white matter anatomy using an approach that is both intuitive and simple to use, and which automatically extracts white matter tracts from diffusion MRI volumes. Further, our method simplifies the quantification and statistical analysis of white matter tracts on large diffusion MRI databases. This work reflects the careful syntactical definition of major white matter fiber tracts in the human brain based on a neuroanatomist’s expert knowledge. The framework is based on a novel query language with a near-to-English textual syntax. This query language makes it possible to construct a dictionary of anatomical definitions that describe white matter tracts. The definitions include adjacent gray and white matter regions, and rules for spatial relations. This novel method makes it possible to automatically label white matter anatomy across subjects. After describing this method, we provide an example of its implementation where we encode anatomical knowledge in human white matter for ten association and 15 projection tracts per hemisphere, along with seven commissural tracts. Importantly, this novel method is comparable in accuracy to manual labeling. Finally, we present results applying this method to create a white matter atlas from 77 healthy subjects, and we use this atlas in a small proof-of-concept study to detect changes in association tracts that characterize schizophrenia. PMID:26754839

  16. The white matter query language: a novel approach for describing human white matter anatomy.

    PubMed

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

    2016-12-01

    We have developed a novel method to describe human white matter anatomy using an approach that is both intuitive and simple to use, and which automatically extracts white matter tracts from diffusion MRI volumes. Further, our method simplifies the quantification and statistical analysis of white matter tracts on large diffusion MRI databases. This work reflects the careful syntactical definition of major white matter fiber tracts in the human brain based on a neuroanatomist's expert knowledge. The framework is based on a novel query language with a near-to-English textual syntax. This query language makes it possible to construct a dictionary of anatomical definitions that describe white matter tracts. The definitions include adjacent gray and white matter regions, and rules for spatial relations. This novel method makes it possible to automatically label white matter anatomy across subjects. After describing this method, we provide an example of its implementation where we encode anatomical knowledge in human white matter for ten association and 15 projection tracts per hemisphere, along with seven commissural tracts. Importantly, this novel method is comparable in accuracy to manual labeling. Finally, we present results applying this method to create a white matter atlas from 77 healthy subjects, and we use this atlas in a small proof-of-concept study to detect changes in association tracts that characterize schizophrenia.

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

    PubMed Central

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

    2015-01-01

    Schizophrenia is a chronic and debilitating mental illness characterized by a broad range of abnormal behaviors, including delusions and hallucinations, impaired cognitive function, as well as mood disturbances and social withdrawal. Due to the heterogeneous nature of the disease, the causes of schizophrenia are very complex; its etiology is believed to involve multiple brain regions and the connections between them, and includes alterations in both gray and white matter regions. The onset of symptoms varies with age and severity, and there is some debate over a degenerative or developmental etiology. Longitudinal magnetic resonance imaging studies have detected progressive gray matter loss in the first years of disease, suggesting neurodegeneration; but there is also increasing recognition of a temporal association between clinical complications at birth and disease onset that supports a neurodevelopmental origin. Presently, neuronal abnormalities in schizophrenia are better understood than alterations in myelin-producing cells of the brain, the oligodendrocytes, which are the predominant constituents of white matter structures. Proper white matter development and its structural integrity critically impacts brain connectivity, which affects sensorimotor coordination and cognitive ability. Evidence of defective white matter growth and compromised white matter integrity has been found in individuals at high risk of psychosis, and decreased numbers of mature oligodendrocytes are detected in schizophrenia patients. Inflammatory markers, including proinflammatory cytokines and chemokines, are also associated with psychosis. A relationship between risk of psychosis, white matter defects and prenatal inflammation is being established. Animal models of perinatal brain injury are successful in producing white matter damage in the brain, typified by hypomyelination and/or dysmyelination, impaired motor coordination and prepulse inhibition of the acoustic startle reflex

  18. Structural white matter changes in adolescents and young adults with maple syrup urine disease.

    PubMed

    Klee, D; Thimm, E; Wittsack, H J; Schubert, D; Primke, R; Pentang, G; Schaper, J; Mödder, U; Antoch, A; Wendel, U; Cohnen, M

    2013-11-01

    To get insight into the nature of magnetic resonance (MR) white matter abnormalities of patients with classic maple syrup urine disease (MSUD) under diet control. Ten patients with classic MSUD and one with a severe MSUD variant (mean age 21.5 ± 5.1 years) on diet and 11 age and sex-matched healthy subjects were enrolled. Apart from standard MR sequences, diffusion weighted images (DWI), diffusion tensor images (DTI), and magnetization transfer images (MT) were obtained and comparatively analyzed for apparent diffusion coefficient (ADC), tensor fractional anisotropy (FA) and MT maps in 11 regions of interest (ROI) within the white matter. In MSUD patients DWI, DTI and FA showed distinct signal changes in the cerebral hemispheres, the dorsal limb of internal capsule, the brain stem and the central cerebellum. Signal intensity was increased in DWI with a reduced ADC and decreased values for FA. MT did not reveal differences between patients and control subjects. Signal abnormalities in the white matter of adolescents and young adults under diet control may be interpreted as consequence of structural alterations like dysmyelination. The reduced ADC and FA in the white matter with preserved MT indicate a reduction in fiber tracks.

  19. White matter integrity deficits in prefrontal-amygdala pathways in Williams syndrome.

    PubMed

    Avery, Suzanne N; Thornton-Wells, Tricia A; Anderson, Adam W; Blackford, Jennifer Urbano

    2012-01-16

    Williams syndrome is a neurodevelopmental disorder associated with significant non-social fears. Consistent with this elevated non-social fear, individuals with Williams syndrome have an abnormally elevated amygdala response when viewing threatening non-social stimuli. In typically-developing individuals, amygdala activity is inhibited through dense, reciprocal white matter connections with the prefrontal cortex. Neuroimaging studies suggest a functional uncoupling of normal prefrontal-amygdala inhibition in individuals with Williams syndrome, which might underlie both the extreme amygdala activity and non-social fears. This functional uncoupling might be caused by structural deficits in underlying white matter pathways; however, prefrontal-amygdala white matter deficits have yet to be explored in Williams syndrome. We used diffusion tensor imaging to investigate prefrontal-amygdala white matter integrity differences in individuals with Williams syndrome and typically-developing controls with high levels of non-social fear. White matter pathways between the amygdala and several prefrontal regions were isolated using probabilistic tractography. Within each pathway, we tested for between-group differences in three measures of white matter integrity: fractional anisotropy (FA), radial diffusivity (RD), and parallel diffusivity (λ(1)). Individuals with Williams syndrome had lower FA, compared to controls, in several of the prefrontal-amygdala pathways investigated, indicating a reduction in white matter integrity. Lower FA in Williams syndrome was explained by significantly higher RD, with no differences in λ(1), suggestive of lower fiber density or axon myelination in prefrontal-amygdala pathways. These results suggest that deficits in the structural integrity of prefrontal-amygdala white matter pathways might underlie the increased amygdala activity and extreme non-social fears observed in Williams syndrome. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Chronic Ketamine Exposure Causes White Matter Microstructural Abnormalities in Adolescent Cynomolgus Monkeys.

    PubMed

    Li, Qi; Shi, Lin; Lu, Gang; Yu, Hong-Luan; Yeung, Fu-Ki; Wong, Nai-Kei; Sun, Lin; Liu, Kai; Yew, David; Pan, Fang; Wang, De-Feng; Sham, Pak C

    2017-01-01

    Acute and repeated exposures to ketamine mimic aspects of positive, negative, and cognitive symptoms of schizophrenia in humans. Recent studies by our group and others have shown that chronicity of ketamine use may be a key element for establishing a more valid model of cognitive symptoms of schizophrenia. However, current understanding on the long-term consequences of ketamine exposure on brain circuits has remained incomplete, particularly with regard to microstructural changes of white matter tracts that underpin the neuropathology of schizophrenia. Thus, the present study aimed to expand on previous investigations by examining causal effects of repeated ketamine exposure on white matter integrity in a non-human primate model. Ketamine or saline (control) was administered intravenously for 3 months to male adolescent cynomolgus monkeys ( n = 5/group). Diffusion tensor imaging (DTI) experiments were performed and tract-based spatial statistics (TBSS) was used for data analysis. Fractional anisotropy (FA) was quantified across the whole brain. Profoundly reduced FA on the right side of sagittal striatum, posterior thalamic radiation (PTR), retrolenticular limb of the internal capsule (RLIC) and superior longitudinal fasciculus (SLF), and on the left side of PTR, middle temporal gyrus and inferior frontal gyrus were observed in the ketamine group compared to controls. Diminished white matter integrity found in either fronto-thalamo-temporal or striato-thalamic connections with tracts including the SLF, PTR, and RLIC lends support to similar findings from DTI studies on schizophrenia in humans. This study suggests that chronic ketamine exposure is a useful pharmacological paradigm that might provide translational insights into the pathophysiology and treatment of schizophrenia.

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

    PubMed Central

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

    2014-01-01

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

  2. Disrupted white matter integrity in heroin dependence: a controlled study utilizing diffusion tensor imaging.

    PubMed

    Liu, Haihong; Li, Lin; Hao, Yihui; Cao, Dong; Xu, Lin; Rohrbaugh, Robert; Xue, Zhimin; Hao, Wei; Shan, Baoci; Liu, Zhening

    2008-01-01

    Fractional anisotropy (FA) via diffusion tensor imaging (DTI) can quantify the white matter integrity. Exposure to addictive drugs, such as alcohol, cocaine, methamphetamine, marijuana, and nicotine has been shown to alter FA. White matter abnormalities have been shown, but it remains unclear whether the white matter FA is altered in heroin dependence. Utilizing DTI, we investigated the FA difference between heroin-dependent and control subjects by a voxel-based strategy. The FA values of the identified regions were calculated from the FA image of each subject and were correlated with clinical features including months of heroin use, age, education, and dose of methadone. Reduced FA among 16 heroin dependent subjects was located in the bilateral frontal sub-gyral regions, right precentral and left cingulate gyrus. FA in the right frontal sub-gyral was negatively correlated with duration of heroin use. The disrupted white matter integrity in right frontal white matter may occur in continuous heroin abuse.

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

    PubMed

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

    2012-11-30

    Numerous studies in first-episode schizophrenia suggest the involvement of white matter (WM) abnormalities in multiple regions underlying the pathogenesis of this condition. However, there has never been a neuroimaging study in patients with first-episode, drug-naive paranoid schizophrenia by using tract-based spatial statistics (TBSS) method. Here, we used diffusion tensor imaging (DTI) with TBSS method to investigate the brain WM integrity in patients with first-episode, drug-naive paranoid schizophrenia. Twenty patients with first-episode, drug-naive paranoid schizophrenia and 26 healthy subjects matched with age, gender, and education level were scanned with DTI. An automated TBSS approach was employed to analyze the data. Voxel-wise statistics revealed that patients with paranoid schizophrenia had decreased fractional anisotropy (FA) values in the right superior longitudinal fasciculus (SLF) II, the right fornix, the right internal capsule, and the right external capsule compared to healthy subjects. Patients did not have increased FA values in any brain regions compared to healthy subjects. There was no correlation between the FA values in any brain regions and patient demographics and the severity of illness. Our findings suggest right-sided alterations of WM integrity in the WM tracts of cortical and subcortical regions may play an important role in the pathogenesis of paranoid schizophrenia. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  4. An unusual neuroimaging finding and response to immunotherapy in a child with genetically confirmed vanishing white matter disease.

    PubMed

    Singh, Rahul Raman; Livingston, John; Lim, Ming; Berry, Ian R; Siddiqui, Ata

    2017-03-01

    We present an unusual neuroimaging finding in a young girl with genetically confirmed vanishing white matter disease and a possible response to immunotherapy. 2.5 yr old girl, presented with acute onset unsteadiness and encephalopathy following a viral illness. MRI showed global symmetric white matter abnormality, with symmetric enhancement of cranial nerves (III and V) and of cervical and lumbar roots. She received immunotherapy for her encephalopathic illness with white matter changes. Follow up neuroimaging showed resolution of white matter edema and resolution of the change in the brainstem. Genetic testing confirmed a diagnosis of vanishing white matter disease (VWMD). Craniospinal nerve enhancement and possible response to immunotherapy has not been described in vanishing white matter disease. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  5. Cocaine dependence does not contribute substantially to white matter abnormalities in HIV infection.

    PubMed

    Cordero, Daniella M; Towe, Sheri L; Chen, Nan-Kuei; Robertson, Kevin R; Madden, David J; Huettel, Scott A; Meade, Christina S

    2017-06-01

    This study investigated the association of HIV infection and cocaine dependence with cerebral white matter integrity using diffusion tensor imaging (DTI). One hundred thirty-five participants stratified by HIV and cocaine status (26 HIV+/COC+, 37 HIV+/COC-, 37 HIV-/COC+, and 35 HIV-/COC-) completed a comprehensive substance abuse assessment, neuropsychological testing, and MRI with DTI. Among HIV+ participants, all were receiving HIV care and 46% had an AIDS diagnosis. All COC+ participants were current users and met criteria for cocaine use disorder. We used tract-based spatial statistics (TBSS) to assess the relation of HIV and cocaine to fractional anisotropy (FA) and mean diffusivity (MD). In whole-brain analyses, HIV+ participants had significantly reduced FA and increased MD compared to HIV- participants. The relation of HIV and FA was widespread throughout the brain, whereas the HIV-related MD effects were restricted to the corpus callosum and thalamus. There were no significant cocaine or HIV-by-cocaine effects. These DTI metrics correlated significantly with duration of HIV disease, nadir CD4+ cell count, and AIDS diagnosis, as well as some measures of neuropsychological functioning. These results suggest that HIV is related to white matter integrity throughout the brain, and that HIV-related effects are more pronounced with increasing duration of infection and greater immune compromise. We found no evidence for independent effects of cocaine dependence on white matter integrity, and cocaine dependence did not appear to exacerbate the effects of HIV.

  6. White Matter Injury in Ischemic Stroke

    PubMed Central

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

    2017-01-01

    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

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

    PubMed

    Kassem, Hassan; Wafaie, Ahmed; Abdelfattah, Sherif; Farid, Tarek

    2014-01-01

    Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) is a recently identified autosomal recessive disorder with early onset of symptoms and slowly progressive pyramidal, cerebellar and dorsal column dysfunction. LBSL is characterized by distinct white matter abnormalities and selective involvement of brainstem and spinal cord tracts. The purpose of this study is to assess the imaging features of the involved white matter tracts in cases of LBSL by MRI. We retrospectively reviewed the imaging features of the selectively involved white matter tracts in sixteen genetically proven cases of leukoencephalopathy with brainstem and spinal cord involvement and elevated brain lactate (LBSL). All patients presented with slowly progressive cerebellar sensory ataxia with spasticity and dorsal column dysfunction. MRI of the brain and spine using 1.5 T machine and proton magnetic resonance spectroscopy (1H MRS) on the abnormal white matter were done to all patients. The MRI and MRS data sets were analyzed according to lesion location, extent, distribution and signal pattern as well as metabolite values and ratios in MRS. Laboratory examinations ruled out classic leukodystrophies. In all cases, MRI showed high signal intensity in T2-weighted and FLAIR images within the cerebral subcortical, periventricular and deep white matter, posterior limbs of internal capsules, centrum semiovale, medulla oblongata, intraparenchymal trajectory of trigeminal nerves and deep cerebellar white matter. In the spine, the signal intensity of the dorsal column and lateral cortico-spinal tracts were altered in all patients. The subcortical U fibers, globi pallidi, thalami, midbrain and transverse pontine fibers were spared in all cases. In 11 cases (68.8%), the signal changes were inhomogeneous and confluent whereas in 5 patients (31.2%), the signal abnormalities were spotty. MRI also showed variable signal abnormalities in the sensory and pyramidal tracts in

  8. Prenatal and Neonatal Brain Structure and White Matter Maturation in Children at High Risk for Schizophrenia

    PubMed Central

    Gilmore, John H.; Kang, Chaeryon; Evans, Dianne D.; Wolfe, Honor M.; Smith, J. Keith; Lieberman, Jeffrey A.; Lin, Weili; Hamer, Robert M.; Styner, Martin; Gerig, Guido

    2011-01-01

    Objective Schizophrenia is a neurodevelopmental disorder associated with abnormalities of brain structure and white matter, although little is known about when these abnormalities arise. This study was conducted to identify structural brain abnormalities in the prenatal and neonatal periods associated with genetic risk for schizophrenia. Method Prenatal ultrasound scans and neonatal structural magnetic resonance imaging (MRI) and diffusion tensor imaging were prospectively obtained in the offspring of mothers with schizophrenia or schizoaffective disorder (N=26) and matched comparison mothers without psychiatric illness (N=26). Comparisons were made for prenatal lateral ventricle width and head circumference, for neonatal intracranial, CSF, gray matter, white matter, and lateral ventricle volumes, and for neonatal diffusion properties of the genu and splenium of the corpus callosum and corticospinal tracts. Results Relative to the matched comparison subjects, the offspring of mothers with schizophrenia did not differ in prenatal lateral ventricle width or head circumference. Overall, the high-risk neonates had nonsignificantly larger intracranial, CSF, and lateral ventricle volumes. Subgroup analysis revealed that male high-risk infants had significantly larger intracranial, CSF, total gray matter, and lateral ventricle volumes; the female high-risk neonates were similar to the female comparison subjects. There were no group differences in white matter diffusion tensor properties. Conclusions Male neonates at genetic risk for schizophrenia had several larger than normal brain volumes, while females did not. To the authors' knowledge, this study provides the first evidence, in the context of its limitations, that early neonatal brain development may be abnormal in males at genetic risk for schizophrenia. PMID:20516153

  9. Diffusion-tensor imaging of white matter tracts in patients with cerebral neoplasm.

    PubMed

    Witwer, Brian P; Moftakhar, Roham; Hasan, Khader M; Deshmukh, Praveen; Haughton, Victor; Field, Aaron; Arfanakis, Konstantinos; Noyes, Jane; Moritz, Chad H; Meyerand, M Elizabeth; Rowley, Howard A; Alexander, Andrew L; Badie, Behnam

    2002-09-01

    Preserving vital cerebral function while maximizing tumor resection is a principal goal in surgical neurooncology. Although functional magnetic resonance imaging has been useful in the localization of eloquent cerebral cortex, this method does not provide information about the white matter tracts that may be involved in invasive, intrinsic brain tumors. Recently, diffusion-tensor (DT) imaging techniques have been used to map white matter tracts in the normal brain. The aim of this study was to demonstrate the role of DT imaging in preoperative mapping of white matter tracts in relation to cerebral neoplasms. Nine patients with brain malignancies (one pilocytic astrocytoma, five oligodendrogliomas, one low-grade oligoastrocytoma, one Grade 4 astrocytoma, and one metastatic adenocarcinoma) underwent DT imaging examinations prior to tumor excision. Anatomical information about white matter tract location, orientation, and projections was obtained in every patient. Depending on the tumor type and location, evidence of white matter tract edema (two patients), infiltration (two patients), displacement (five patients), and disruption (two patients) could be assessed with the aid of DT imaging in each case. Diffusion-tensor imaging allowed for visualization of white matter tracts and was found to be beneficial in the surgical planning for patients with intrinsic brain tumors. The authors' experience with DT imaging indicates that anatomically intact fibers may be present in abnormal-appearing areas of the brain. Whether resection of these involved fibers results in subtle postoperative neurological deficits requires further systematic study.

  10. in vivo quantification of white matter microstructure for use in aging: A focus on two emerging techniques

    PubMed Central

    Lamar, Melissa; Zhou, Xiaohong Joe; Charlton, Rebecca A.; Dean, Douglas; Little, Deborah; Deoni, Sean C

    2013-01-01

    Human brain imaging has seen many advances in the quantification of white matter in vivo. For example, these advances have revealed the association between white matter damage and vascular disease as well as their impact on risk for and development of dementia and depression in an aging population. Current neuroimaging methods to quantify white matter damage provide a foundation for understanding such age-related neuropathology; however, these methods are not as adept at determining the underlying microstructural abnormalities signaling at risk tissue or driving white matter damage in the aging brain. This review will begin with a brief overview of the use of diffusion tensor imaging (DTI) in understanding white matter alterations in aging before focusing in more detail on select advances in both diffusion-based methods and multi-component relaxometry techniques for imaging white matter microstructural integrity within myelin sheaths and the axons they encase. While DTI greatly extended the field of white matter interrogation, these more recent technological advances will add clarity to the underlying microstructural mechanisms that contribute to white matter damage. More specifically, the methods highlighted in this review may prove more sensitive (and specific) for determining the contribution of myelin versus axonal integrity to the aging of white matter in brain. PMID:24080382

  11. White Matter Injury and General Movements in High-Risk Preterm Infants.

    PubMed

    Peyton, C; Yang, E; Msall, M E; Adde, L; Støen, R; Fjørtoft, T; Bos, A F; Einspieler, C; Zhou, Y; Schreiber, M D; Marks, J D; Drobyshevsky, A

    2017-01-01

    Very preterm infants (birth weight, <1500 g) are at increased risk of cognitive and motor impairment, including cerebral palsy. These adverse neurodevelopmental outcomes are associated with white matter abnormalities on MR imaging at term-equivalent age. Cerebral palsy has been predicted by analysis of spontaneous movements in the infant termed "General Movement Assessment." The goal of this study was to determine the utility of General Movement Assessment in predicting adverse cognitive, language, and motor outcomes in very preterm infants and to identify brain imaging markers associated with both adverse outcomes and aberrant general movements. In this prospective study of 47 preterm infants of 24-30 weeks' gestation, brain MR imaging was performed at term-equivalent age. Infants underwent T1- and T2-weighted imaging for volumetric analysis and DTI. General movements were assessed at 10-15 weeks' postterm age, and neurodevelopmental outcomes were evaluated at 2 years by using the Bayley Scales of Infant and Toddler Development III. Nine infants had aberrant general movements and were more likely to have adverse neurodevelopmental outcomes, compared with infants with normal movements. In infants with aberrant movements, Tract-Based Spatial Statistics analysis identified significantly lower fractional anisotropy in widespread white matter tracts, including the corpus callosum, inferior longitudinal and fronto-occipital fasciculi, internal capsule, and optic radiation. The subset of infants having both aberrant movements and abnormal neurodevelopmental outcomes in cognitive, language, and motor skills had significantly lower fractional anisotropy in specific brain regions. Aberrant general movements at 10-15 weeks' postterm are associated with adverse neurodevelopmental outcomes and specific white matter microstructure abnormalities for cognitive, language, and motor delays. © 2017 by American Journal of Neuroradiology.

  12. Increased White Matter Gyral Depth in Dyslexia: Implications for Corticocortical Connectivity

    ERIC Educational Resources Information Center

    Casanova, Manuel F.; El-Baz, Ayman S.; Giedd, Jay; Rumsey, Judith M.; Switala, Andrew E.

    2010-01-01

    Recent studies provide credence to the minicolumnar origin of several developmental conditions, including dyslexia. Characteristics of minicolumnopathies include abnormalities in how the cortex expands and folds. This study examines the depth of the gyral white matter measured in an MRI series of 15 dyslexic adult men and eleven age-matched…

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

    PubMed

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

    2016-02-01

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

  14. Whole brain white matter connectivity analysis using machine learning: An application to autism.

    PubMed

    Zhang, Fan; Savadjiev, Peter; Cai, Weidong; Song, Yang; Rathi, Yogesh; Tunç, Birkan; Parker, Drew; Kapur, Tina; Schultz, Robert T; Makris, Nikos; Verma, Ragini; O'Donnell, Lauren J

    2018-05-15

    In this paper, we propose an automated white matter connectivity analysis method for machine learning classification and characterization of white matter abnormality via identification of discriminative fiber tracts. The proposed method uses diffusion MRI tractography and a data-driven approach to find fiber clusters corresponding to subdivisions of the white matter anatomy. Features extracted from each fiber cluster describe its diffusion properties and are used for machine learning. The method is demonstrated by application to a pediatric neuroimaging dataset from 149 individuals, including 70 children with autism spectrum disorder (ASD) and 79 typically developing controls (TDC). A classification accuracy of 78.33% is achieved in this cross-validation study. We investigate the discriminative diffusion features based on a two-tensor fiber tracking model. We observe that the mean fractional anisotropy from the second tensor (associated with crossing fibers) is most affected in ASD. We also find that local along-tract (central cores and endpoint regions) differences between ASD and TDC are helpful in differentiating the two groups. These altered diffusion properties in ASD are associated with multiple robustly discriminative fiber clusters, which belong to several major white matter tracts including the corpus callosum, arcuate fasciculus, uncinate fasciculus and aslant tract; and the white matter structures related to the cerebellum, brain stem, and ventral diencephalon. These discriminative fiber clusters, a small part of the whole brain tractography, represent the white matter connections that could be most affected in ASD. Our results indicate the potential of a machine learning pipeline based on white matter fiber clustering. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. White matter atrophy and myelinated fiber disruption in a rat model of depression.

    PubMed

    Gao, Yuan; Ma, Jing; Tang, Jing; Liang, Xin; Huang, Chun-Xia; Wang, San-Rong; Chen, Lin-Mu; Wang, Fei-Fei; Tan, Chuan-Xue; Chao, Feng-Lei; Zhang, Lei; Qiu, Xuan; Luo, Yan-Min; Xiao, Qian; Du, Lian; Xiao, Qian; Tang, Yong

    2017-06-01

    Brain imaging and postmortem studies have indicated that white matter abnormalities may contribute to the pathology and pathogenesis of depression. However, until now, no study has quantitatively investigated white matter changes in depression in rats. The current study used the chronic unpredictable stress (CUS) model of depression. Body weight and sucrose preference test (SPT) scores were assessed weekly. Upon successfully establishing the CUS animal model, all animals were tested using the SPT and the open field test (OFT). Then, transmission electron microscopy and unbiased stereological methods were used to investigate white matter changes in the rats. Compared with the control group, the body weight and sucrose preference of the CUS rats were significantly decreased (p < .001, p < .001, respectively). In the OFT, the total time spent and the total distance traveled in the inner area by the CUS rats were significantly lower than those of the control group (p = .002, p = .001, respectively). The stereological results revealed that white matter volume, the total volume, and the total length and mean diameter of myelinated fibers in the white matter of the CUS rats were significantly decreased compared to the control rats (p = .042, p = .038, p = .035, p = .019, respectively). The results of this study suggested that white matter atrophy and disruption of myelinated fibers in the white matter may contribute to the pathophysiology underlying depression, which might provide new targets for the development of novel therapeutic interventions for depression. © 2017 Wiley Periodicals, Inc.

  16. A COMPREHENSIVE EXAMINATION OF WHITE MATTER TRACTS AND CONNECTOMETRY IN MAJOR DEPRESSIVE DISORDER

    PubMed Central

    Delaparte, Lauren; Yeh, Fang‐Cheng; DeLorenzo, Christine; McGrath, Patrick J.; Weissman, Myrna M.; Adams, Phillip; Fava, Maurizio; Deckersbach, Thilo; McInnis, Melvin G.; Carmody, Thomas J.; Cooper, Crystal M.; Kurian, Benji T.; Lu, Hanzhang; Toups, Marisa S.; Trivedi, Madhukar H.; Parsey, Ramin V.

    2015-01-01

    Background Major depressive disorder (MDD) is a debilitating disorder characterized by widespread brain abnormalities. The literature is mixed as to whether or not white matter abnormalities are associated with MDD. This study sought to examine fractional anisotropy (FA) in white matter tracts in individuals with MDD using diffusion tensor imaging (DTI). Methods 139 participants with MDD and 39 healthy controls (HC) in a multisite study were included. DTI scans were acquired in 64 directions and FA was determined in the brain using four methods: region of interest (ROI), tract‐based spatial statistics (TBSS), and diffusion tractography. Diffusion connectometry was used to identify white matter pathways associated with MDD. Results There were no significant differences when comparing FA in MDD and HC groups using any method. In the MDD group, there was a significant relationship between depression severity and FA in the right medial orbitofrontal cortex, and between age of onset of MDD and FA in the right caudal anterior cingulate cortex using the ROI method. There was a significant relationship between age of onset and connectivity in the thalamocortical radiation, inferior longitudinal fasciculus, and cerebellar tracts using diffusion connectometry. Conclusions The lack of group differences in FA and connectometry analysis may result from the clinically heterogenous nature of MDD. However, the relationship between FA and depression severity may suggest a state biomarker of depression that should be investigated as a potential indicator of response. Age of onset may also be a significant clinical feature to pursue when studying white matter tracts. PMID:26477532

  17. In vivo quantification of white matter microstructure for use in aging: a focus on two emerging techniques.

    PubMed

    Lamar, Melissa; Zhou, Xiaohong Joe; Charlton, Rebecca A; Dean, Douglas; Little, Deborah; Deoni, Sean C

    2014-02-01

    Human brain imaging has seen many advances in the quantification of white matter in vivo. For example, these advances have revealed the association between white matter damage and vascular disease as well as their impact on risk for and development of dementia and depression in an aging population. Current neuroimaging methods to quantify white matter damage provide a foundation for understanding such age-related neuropathology; however, these methods are not as adept at determining the underlying microstructural abnormalities signaling at risk tissue or driving white matter damage in the aging brain. This review will begin with a brief overview of the use of diffusion tensor imaging (DTI) in understanding white matter alterations in aging before focusing in more detail on select advances in both diffusion-based methods and multi-component relaxometry techniques for imaging white matter microstructural integrity within myelin sheaths and the axons they encase. Although DTI greatly extended the field of white matter interrogation, these more recent technological advances will add clarity to the underlying microstructural mechanisms that contribute to white matter damage. More specifically, the methods highlighted in this review may prove more sensitive (and specific) for determining the contribution of myelin versus axonal integrity to the aging of white matter in brain. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  18. White Matter and Development in Children with an Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Mak-Fan, Kathleen M.; Morris, Drew; Vidal, Julie; Anagnostou, Evdokia; Roberts, Wendy; Taylor, Margot J.

    2013-01-01

    Recent research suggests that brain development follows an abnormal trajectory in children with autism spectrum disorders (ASD). The current study examined changes in diffusivity with age within defined white matter tracts in a group of typically developing children and a group of children with an ASD, aged 6 to 14 years. Age by group interactions…

  19. Functional connectivity and microstructural white matter changes in phenocopy frontotemporal dementia.

    PubMed

    Meijboom, R; Steketee, R M E; de Koning, I; Osse, R J; Jiskoot, L C; de Jong, F J; van der Lugt, A; van Swieten, J C; Smits, M

    2017-04-01

    Phenocopy frontotemporal dementia (phFTD) is a rare and poorly understood clinical syndrome. PhFTD shows core behavioural variant FTD (bvFTD) symptoms without associated cognitive deficits and brain abnormalities on conventional MRI and without progression. In contrast to phFTD, functional connectivity and white matter (WM) microstructural abnormalities have been observed in bvFTD. We hypothesise that phFTD belongs to the same disease spectrum as bvFTD and investigated whether functional connectivity and microstructural WM changes similar to bvFTD are present in phFTD. Seven phFTD patients without progression or alternative psychiatric diagnosis, 12 bvFTD patients and 17 controls underwent resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI). Default mode network (DMN) connectivity and WM measures were compared between groups. PhFTD showed subtly increased DMN connectivity and subtle microstructural changes in frontal WM tracts. BvFTD showed abnormalities in similar regions as phFTD, but had lower increased DMN connectivity and more extensive microstructural WM changes. Our findings can be interpreted as neuropathological changes in phFTD and are in support of the hypothesis that phFTD and bvFTD may belong to the same disease spectrum. Advanced MRI techniques, objectively identifying brain abnormalities, would therefore be potentially suited to improve the diagnosis of phFTD. • PhFTD shows brain abnormalities that are similar to bvFTD. • PhFTD shows increased functional connectivity in the parietal default mode network. • PhFTD shows microstructural white matter abnormalities in the frontal lobe. • We hypothesise phFTD and bvFTD may belong to the same disease spectrum.

  20. Vanishing white matter disease with a novel EIF2B5 mutation: A 10-year follow-up.

    PubMed

    Bektaş, Gonca; Yeşil, Gözde; Özkan, Melis Ulak; Yıldız, Edibe Pembegül; Uzunhan, Tuğçe Aksu; Çalışkan, Mine

    2018-06-19

    Vanishing white matter disease is a heterogeneous disorder caused by mutation in one of the five genes encoding subunits of the eukaryotic initiation factor eIF2B. It is a heterogeneous disorder due to phenotypic variation and a clear genotype-phenotype correlation could not be established so far. We describe a novel mutation in the EIF2B5 gene by analyzing the clinical phenotype and the progression of brain lesions for 10 years. A novel mutation in the EIF2B5 gene was detected in the heterozygous state; c.1688G > A (p. Arg563Gln) mutation in exon 12, accompanied by a previously detected c.806G > A (p. Arg269Gln) mutation in exon 6, leading to substitution of arginine for a glutamine. This compound heterozygous mutation was associated with disease onset at early childhood and relatively slow progression of neurological deterioration. In contrast to previous findings indicated the association of c.806G > A mutation and peripheral neuropathy in patients with vanishing white matter disease, electromyography of our case was normal. The corpus callosum inner rim was the affected area at early stages, which may be remarkable for early diagnosis of vanishing white matter disease. Serial follow-up magnetic resonance imaging revealed the white matter signal abnormality, subsequently cystic degeneration and decrease in white matter volume. The novel mutation c.1688G > A in compound heterozygous state leads to intermediate phenotype of the vanishing white matter disease. In the early stages of the disease the signal abnormality in the corpus callosum inner rim might be remarkable. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. White matter and cognition: making the connection

    PubMed Central

    Fields, R. Douglas

    2016-01-01

    Whereas the cerebral cortex has long been regarded by neuroscientists as the major locus of cognitive function, the white matter of the brain is increasingly recognized as equally critical for cognition. White matter comprises half of the brain, has expanded more than gray matter in evolution, and forms an indispensable component of distributed neural networks that subserve neurobehavioral operations. White matter tracts mediate the essential connectivity by which human behavior is organized, working in concert with gray matter to enable the extraordinary repertoire of human cognitive capacities. In this review, we present evidence from behavioral neurology that white matter lesions regularly disturb cognition, consider the role of white matter in the physiology of distributed neural networks, develop the hypothesis that white matter dysfunction is relevant to neurodegenerative disorders, including Alzheimer's disease and the newly described entity chronic traumatic encephalopathy, and discuss emerging concepts regarding the prevention and treatment of cognitive dysfunction associated with white matter disorders. Investigation of the role of white matter in cognition has yielded many valuable insights and promises to expand understanding of normal brain structure and function, improve the treatment of many neurobehavioral disorders, and disclose new opportunities for research on many challenging problems facing medicine and society. PMID:27512019

  2. White Matter Volume Predicts Language Development in Congenital Heart Disease

    PubMed Central

    Rollins, Caitlin K.; Asaro, Lisa A.; Akhondi-Asl, Alireza; Kussman, Barry D.; Rivkin, Michael J.; Bellinger, David C.; Warfield, Simon K.; Wypij, David; Newburger, Jane W.; Soul, Janet S.

    2016-01-01

    Objective To determine whether brain volume is reduced at one year and whether these volumes are associated with neurodevelopment in biventricular congenital heart disease (CHD) repaired in infancy. Study design Infants with biventricular CHD (n = 48) underwent brain magnetic resonance imaging (MRI) and neurodevelopmental testing with the Bayley Scales of Infant Development-II (BSID-II) and the MacArthur-Bates Communicative Development Inventories (CDI) at one year. A multi-template based probabilistic segmentation algorithm was applied to volumetric MRI data. We compared volumes with those of 13 healthy control infants of comparable ages. In the CHD group, we measured Spearman correlations between neurodevelopmental outcomes and the residuals from linear regression of the volumes on corrected chronological age at MRI and sex. Results Compared with controls, CHD infant had reductions of 54 mL in total brain (P = 0.009), 40 mL in cerebral white matter (P < 0.001), and 1.2 mL in brainstem (P = 0.003) volumes. Within the CHD group, brain volumes were not correlated with BSID-II scores but did correlate positively with CDI language development. Conclusion Infants with biventricular CHD show total brain volume reductions at one year of age, driven by differences in cerebral white matter. White matter volume correlates with language development, but not broader developmental indices. These findings suggest that abnormalities in white matter development detected months after corrective heart surgery may contribute to language impairment. Trial registration ClinicalTrials.gov: NCT00006183 PMID:27837950

  3. White Matter Disruptions in Schizophrenia Are Spatially Widespread and Topologically Converge on Brain Network Hubs

    PubMed Central

    Baker, Simon T.; Cropley, Vanessa L.; Bousman, Chad; Fornito, Alex; Cocchi, Luca; Fullerton, Janice M.; Rasser, Paul; Schall, Ulrich; Henskens, Frans; Michie, Patricia T.; Loughland, Carmel; Catts, Stanley V.; Mowry, Bryan; Weickert, Thomas W.; Shannon Weickert, Cynthia; Carr, Vaughan; Lenroot, Rhoshel; Pantelis, Christos; Zalesky, Andrew

    2017-01-01

    Abstract White matter abnormalities associated with schizophrenia have been widely reported, although the consistency of findings across studies is moderate. In this study, neuroimaging was used to investigate white matter pathology and its impact on whole-brain white matter connectivity in one of the largest samples of patients with schizophrenia. Fractional anisotropy (FA) and mean diffusivity (MD) were compared between patients with schizophrenia or schizoaffective disorder (n = 326) and age-matched healthy controls (n = 197). Between-group differences in FA and MD were assessed using voxel-based analysis and permutation testing. Automated whole-brain white matter fiber tracking and the network-based statistic were used to characterize the impact of white matter pathology on the connectome and its rich club. Significant reductions in FA associated with schizophrenia were widespread, encompassing more than 40% (234ml) of cerebral white matter by volume and involving all cerebral lobes. Significant increases in MD were also widespread and distributed similarly. The corpus callosum, cingulum, and thalamic radiations exhibited the most extensive pathology according to effect size. More than 50% of cortico-cortical and cortico-subcortical white matter fiber bundles comprising the connectome were disrupted in schizophrenia. Connections between hub regions comprising the rich club were disproportionately affected. Pathology did not differ between patients with schizophrenia and schizoaffective disorder and was not mediated by medication. In conclusion, although connectivity between cerebral hubs is most extensively disturbed in schizophrenia, white matter pathology is widespread, affecting all cerebral lobes and the cerebellum, leading to disruptions in the majority of the brain’s fiber bundles. PMID:27535082

  4. Impaired functional but preserved structural connectivity in limbic white matter tracts in youth with conduct disorder or oppositional defiant disorder plus psychopathic traits.

    PubMed

    Finger, Elizabeth Carrie; Marsh, Abigail; Blair, Karina Simone; Majestic, Catherine; Evangelou, Iordanis; Gupta, Karan; Schneider, Marguerite Reid; Sims, Courtney; Pope, Kayla; Fowler, Katherine; Sinclair, Stephen; Tovar-Moll, Fernanda; Pine, Daniel; Blair, Robert James

    2012-06-30

    Youths with conduct disorder or oppositional defiant disorder and psychopathic traits (CD/ODD+PT) are at high risk of adult antisocial behavior and psychopathy. Neuroimaging studies demonstrate functional abnormalities in orbitofrontal cortex and the amygdala in both youths and adults with psychopathic traits. Diffusion tensor imaging in psychopathic adults demonstrates disrupted structural connectivity between these regions (uncinate fasiculus). The current study examined whether functional neural abnormalities present in youths with CD/ODD+PT are associated with similar white matter abnormalities. Youths with CD/ODD+PT and comparison participants completed 3.0 T diffusion tensor scans and functional magnetic resonance imaging scans. Diffusion tensor imaging did not reveal disruption in structural connections within the uncinate fasiculus or other white matter tracts in youths with CD/ODD+PT, despite the demonstration of disrupted amygdala-prefrontal functional connectivity in these youths. These results suggest that disrupted amygdala-frontal white matter connectivity as measured by fractional anisotropy is less sensitive than imaging measurements of functional perturbations in youths with psychopathic traits. If white matter tracts are intact in youths with this disorder, childhood may provide a critical window for intervention and treatment, before significant structural brain abnormalities solidify. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  5. 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 ...

  6. Spatial coherence of oriented white matter microstructure: Applications to white matter regions associated with genetic similarity.

    PubMed

    Hallgrímsson, Haraldur T; Cieslak, Matthew; Foschini, Luca; Grafton, Scott T; Singh, Ambuj K

    2018-05-15

    We present a method to discover differences between populations with respect to the spatial coherence of their oriented white matter microstructure in arbitrarily shaped white matter regions. This method is applied to diffusion MRI scans of a subset of the Human Connectome Project dataset: 57 pairs of monozygotic and 52 pairs of dizygotic twins. After controlling for morphological similarity between twins, we identify 3.7% of all white matter as being associated with genetic similarity (35.1 k voxels, p<10 -4 , false discovery rate 1.5%), 75% of which spatially clusters into twenty-two contiguous white matter regions. Furthermore, we show that the orientation similarity within these regions generalizes to a subset of 47 pairs of non-twin siblings, and show that these siblings are on average as similar as dizygotic twins. The regions are located in deep white matter including the superior longitudinal fasciculus, the optic radiations, the middle cerebellar peduncle, the corticospinal tract, and within the anterior temporal lobe, as well as the cerebellum, brain stem, and amygdalae. These results extend previous work using undirected fractional anisotrophy for measuring putative heritable influences in white matter. Our multidirectional extension better accounts for crossing fiber connections within voxels. This bottom up approach has at its basis a novel measurement of coherence within neighboring voxel dyads between subjects, and avoids some of the fundamental ambiguities encountered with tractographic approaches to white matter analysis that estimate global connectivity. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Differential Hemispheric Predilection of Microstructural White Matter and Functional Connectivity Abnormalities between Respectively Semantic and Behavioral Variant Frontotemporal Dementia.

    PubMed

    Meijboom, Rozanna; Steketee, Rebecca M E; Ham, Leontine S; van der Lugt, Aad; van Swieten, John C; Smits, Marion

    2017-01-01

    Semantic dementia (SD) and behavioral variant frontotemporal dementia (bvFTD), subtypes of frontotemporal dementia, are characterized by distinct clinical symptoms and neuroimaging features, with predominant left temporal grey matter (GM) atrophy in SD and bilateral or right frontal GM atrophy in bvFTD. Such differential hemispheric predilection may also be reflected by other neuroimaging features, such as brain connectivity. This study investigated white matter (WM) microstructure and functional connectivity differences between SD and bvFTD, focusing on the hemispheric predilection of these differences. Eight SD and 12 bvFTD patients, and 17 controls underwent diffusion tensor imaging and resting state functional MRI at 3T. Whole-brain WM microstructure was assessed to determine distinct WM tracts affected in SD and bvFTD. For these tracts, diffusivity measures and lateralization indices were calculated. Functional connectivity was established for GM regions affected in early stage SD or bvFTD. Results of a direct comparison between SD and bvFTD are reported. Whole-brain WM microstructure abnormalities were more pronounced in the left hemisphere in SD and bilaterally- with a slight predilection for the right- in bvFTD. Lateralization of tract-specific abnormalities was seen in SD only, toward the left hemisphere. Functional connectivity of disease-specific regions was mainly decreased bilaterally in SD and in the right hemisphere in bvFTD. SD and bvFTD show WM microstructure and functional connectivity abnormalities in different regions, that are respectively more pronounced in the left hemisphere in SD and in the right hemisphere in bvFTD. This indicates differential hemispheric predilection of brain connectivity abnormalities between SD and bvFTD.

  8. Tissue signature characterisation of diffusion tensor abnormalities in cerebral gliomas.

    PubMed

    Price, Stephen J; Peña, Alonso; Burnet, Neil G; Jena, Raj; Green, Hadrian A L; Carpenter, T Adrian; Pickard, John D; Gillard, Jonathan H

    2004-10-01

    The inherent invasiveness of malignant cells is a major determinant of the poor prognosis of cerebral gliomas. Diffusion tensor MRI (DTI) can identify white matter abnormalities in gliomas that are not seen on conventional imaging. By breaking down DTI into its isotropic (p) and anisotropic (q) components, we can determine tissue diffusion "signatures". In this study we have characterised these abnormalities in peritumoural white matter tracts. Thirty-five patients with cerebral gliomas and seven normal volunteers were imaged with DTI and T2-weighted sequences at 3 T. Displaced, infiltrated and disrupted white matter tracts were identified using fractional anisotropy (FA) maps and directionally encoded colour maps and characterised using tissue signatures. The diffusion tissue signatures were normal in ROIs where the white matter was displaced. Infiltrated white matter was characterised by an increase in the isotropic component of the tensor (p) and a less marked reduction of the anisotropic component (q). In disrupted white matter tracts, there was a marked reduction in q and increase in p. The direction of water diffusion was grossly abnormal in these cases. Diffusion tissue signatures may be a useful method of assessing occult white matter infiltration. Copyright 2004 Springer-Verlag

  9. The role of white matter microstructure in inhibitory deficits in patients with schizophrenia.

    PubMed

    Du, Xiaoming; Kochunov, Peter; Summerfelt, Ann; Chiappelli, Joshua; Choa, Fow-Sen; Hong, L Elliot

    Inhibitory-excitatory (I-E) imbalance has increasingly been proposed as a fundamental mechanism giving rise to many schizophrenia-related pathophysiology. The integrity of I-E functions should require precise and rapid electrical signal transmission. We hypothesized that part of the I-E abnormality in schizophrenia may originate from their known abnormal white matter connectivity that may interfere the I-E functions. We test this using short-interval intracortical inhibition (SICI) vs. intracortical facilitation (ICF) which is a non-invasive measurement of I-E signaling. SICI-ICF from left motor cortex and white matter microstructure were assessed in schizophrenia patients and healthy controls. Schizophrenia patients showed significantly reduced SICI but not ICF. White matter microstructure as measured by fraction anisotropy (FA) in diffusion tensor imaging had a significant effect on SICI in patients, such that weaker SICI was associated with lower FA in several white matter tracts, most strongly with left corona radiata (r = -0.68, p = 0.0002) that contains the fibers connecting with left motor cortex. Left corticospinal tract, which carries the motor fibers to peripheral muscular output, also showed significant correlation with SICI (r = -0.54, p = 0.005). Mediation analysis revealed that much of the schizophrenia disease effect on SICI can be accounted for by mediation through left corona radiata. SICI was also significantly associated with the performance of processing speed in patients. This study demonstrated the importance of structural circuitry integrity in inhibitory signaling in schizophrenia, and encouraged modeling the I-E dysfunction in schizophrenia from a circuitry perspective. Published by Elsevier Inc.

  10. 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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Brain white matter changes associated with urological chronic pelvic pain syndrome: multisite neuroimaging from a MAPP case-control study.

    PubMed

    Huang, Lejian; Kutch, Jason J; Ellingson, Benjamin M; Martucci, Katherine T; Harris, Richard E; Clauw, Daniel J; Mackey, Sean; Mayer, Emeran A; Schaeffer, Anthony J; Apkarian, A Vania; Farmer, Melissa A

    2016-12-01

    Clinical phenotyping of urological chronic pelvic pain syndromes (UCPPSs) in men and women have focused on end organ abnormalities to identify putative clinical subtypes. Initial evidence of abnormal brain function and structure in male pelvic pain has necessitated large-scale, multisite investigations into potential UCPPS brain biomarkers. We present the first evidence of regional white matter (axonal) abnormalities in men and women with UCPPS, compared with positive (irritable bowel syndrome, IBS) and healthy controls. Epidemiological and neuroimaging data were collected from participants with UCPPS (n = 52), IBS (n = 39), and healthy sex- and age-matched controls (n = 61). White matter microstructure, measured as fractional anisotropy (FA), was examined by diffusion tensor imaging. Group differences in regional FA positively correlated with pain severity, including segments of the right corticospinal tract and right anterior thalamic radiation. Increased corticospinal FA was specific and sensitive to UCPPS, positively correlated with pain severity, and reflected sensory (not affective) features of pain. Reduced anterior thalamic radiation FA distinguished patients with IBS from those with UCPPS and controls, suggesting greater microstructural divergence from normal tract organization. Findings confirm that regional white matter abnormalities characterize UCPPS and can distinguish between visceral diagnoses, suggesting that regional axonal microstructure is either altered with ongoing pain or predisposes its development.

  12. Destruction of white matter integrity in patients with mild cognitive impairment and Alzheimer disease.

    PubMed

    Sun, Xiaoyan; Salat, David; Upchurch, Kristen; Deason, Rebecca; Kowall, Neil; Budson, Andrew

    2014-10-01

    Accumulating evidence shows that gradual loss of white matter integrity plays an important role in the development of Alzheimer disease (AD). The aim of this research was to study the microstructural integrity of white matter in AD in vivo. Global fractional anisotropy, global axial diffusivity (AxD), and global radial diffusivity (RD) were analyzed in subjects with normal controls (NC), mild cognitive impairment (MCI), and AD using Alzheimer's Disease Neuroimaging Initiative data (total N = 210). We further compared specific white matter tracts among the 3 groups. Compared with the NC group, the MCI group had significantly increased global AxD and global RD. Compared with the NC and MCI groups, the AD group had significantly decreased global fractional anisotropy, increased global AxD, and increased global RD. With regard to specific white matter tracts, in the MCI group, we found increased AxD and increased RD in the external capsule, part of the lateral cholinergic pathway, in addition to the tracts connecting the limbic regions, predominantly in the left hemisphere. In the AD group, white matter abnormalities were widespread, including in the external capsule (cholinergic pathway) and limbic region tracts as well as tracts connecting anterior to posterior regions bilaterally. The radiographic manifestation of damaged white matter microstructural integrity in the cholinergic pathway in MCI patients may provide a rational basis for the use of cholinesterase inhibitor drugs in the MCI stage of AD.

  13. Enhancement of multiple cranial and spinal nerves in vanishing white matter: expanding the differential diagnosis.

    PubMed

    Eluvathingal Muttikkal, Thomas Jose; Montealegre, Denia Ramirez; Matsumoto, Julie Ann

    2018-03-01

    Abnormal cranial or spinal nerve contrast enhancement on MRI in cases of suspected pediatric leukodystrophy is recognized as an important clue to the diagnosis of either metachromatic leukodystrophy or globoid cell leukodystrophy (Krabbe disease). We report a case of genetically confirmed childhood vanishing white matter with enhancement of multiple cranial and spinal nerves in addition to the more typical intracranial findings. This case expands the limited differential diagnosis of cranial nerve or spinal nerve enhancement in cases of suspected leukodystrophy and may aid in more efficient work-up and earlier diagnosis of vanishing white matter.

  14. Perilesional and contralateral white matter evolution and integrity in patients with periventricular nodular heterotopia and epilepsy: a longitudinal diffusion tensor imaging study.

    PubMed

    Liu, W; Yan, B; An, D; Niu, R; Tang, Y; Tong, X; Gong, Q; Zhou, D

    2017-12-01

    This study aimed to assess the evolution of perinodular and contralateral white matter abnormalities in patients with periventricular nodular heterotopia (PNH) and epilepsy. Diffusion tensor imaging (DTI) (64 directions) and 3 T structural magnetic resonance imaging were performed in 29 PNH patients (mean age 27.3 years), and 16 patients underwent a second scan (average time between the two scans 1.1 years). Fractional anisotropy and mean diffusivity were measured within the perilesional and contralateral white matter. Longitudinal analysis showed that white matter located 10 mm from the focal nodule displayed characteristics intermediate to tissue 5 mm away, and normal-appearing white matter (NAWM) also established evolution profiles of perinodular white matter in different cortical lobes. Compared to 29 age- and sex-matched healthy controls, significant decreased fractional anisotropy and elevated mean diffusivity values were observed in regions 5 and 10 mm from nodules (P < 0.01), whilst DTI metrics of the remaining NAWM did not differ significantly from controls. Additionally, normal DTI metrics were shown in the contralateral region in patients with unilateral PNH. Periventricular nodular heterotopia is associated with microstructural abnormalities within the perilesional white matter and the extent decreases with increasing distance from the nodule. In the homologous contralateral region, white matter diffusion metrics were unchanged in unilateral PNH. These findings have clinical implications with respect to the medical and surgical interventions of PNH-related epilepsy. © 2017 EAN.

  15. Widespread White Matter Differences in Children and Adolescents with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Vogan, V. M.; Morgan, B. R.; Leung, R. C.; Anagnostou, E.; Doyle-Thomas, K.; Taylor, M. J.

    2016-01-01

    Diffusion tensor imaging studies show white matter (WM) abnormalities in children with autism spectrum disorder (ASD). However, investigations are often limited by small samples, particularly problematic given the heterogeneity of ASD. We explored WM using DTI in a large sample of 130 children and adolescents (7-15 years) with and without ASD,…

  16. White Matter Volume Predicts Language Development in Congenital Heart Disease.

    PubMed

    Rollins, Caitlin K; Asaro, Lisa A; Akhondi-Asl, Alireza; Kussman, Barry D; Rivkin, Michael J; Bellinger, David C; Warfield, Simon K; Wypij, David; Newburger, Jane W; Soul, Janet S

    2017-02-01

    To determine whether brain volume is reduced at 1 year of age and whether these volumes are associated with neurodevelopment in biventricular congenital heart disease (CHD) repaired in infancy. Infants with biventricular CHD (n = 48) underwent brain magnetic resonance imaging (MRI) and neurodevelopmental testing with the Bayley Scales of Infant Development-II and the MacArthur-Bates Communicative Development Inventories at 1 year of age. A multitemplate based probabilistic segmentation algorithm was applied to volumetric MRI data. We compared volumes with those of 13 healthy control infants of comparable ages. In the group with CHD, we measured Spearman correlations between neurodevelopmental outcomes and the residuals from linear regression of the volumes on corrected chronological age at MRI and sex. Compared with controls, infants with CHD had reductions of 54 mL in total brain (P = .009), 40 mL in cerebral white matter (P <.001), and 1.2 mL in brainstem (P = .003) volumes. Within the group with CHD, brain volumes were not correlated with Bayley Scales of Infant Development-II scores but did correlate positively with MacArthur-Bates Communicative Development Inventory language development. Infants with biventricular CHD show total brain volume reductions at 1 year of age, driven by differences in cerebral white matter. White matter volume correlates with language development, but not broader developmental indices. These findings suggest that abnormalities in white matter development detected months after corrective heart surgery may contribute to language impairment. ClinicalTrials.gov: NCT00006183. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2016-01-01

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

  18. Leukoencephalopathy with brain stem and spinal cord involvement and high lactate: a genetically proven case without elevated white matter lactate.

    PubMed

    Sharma, Suvasini; Sankhyan, Naveen; Kumar, Atin; Scheper, Gert C; van der Knaap, Marjo S; Gulati, Sheffali

    2011-06-01

    A 17-year-old Indian boy with gradually progressive ataxia with onset at 12 years of age is described. Magnetic resonance imaging (MRI) of the brain revealed extensive, inhomogeneous signal abnormalities in the cerebral white matter, with involvement of selected tracts in the brain stem and spinal cord. The imaging findings were characteristic of leukoencephalopathy with brain stem and spinal cord involvement and high lactate, a recently described leukodystrophy. Interestingly, magnetic resonance spectroscopy of the abnormal white matter did not reveal elevated lactate. The patient was compound heterozygous for 2 new mutations in DARS2, genetically confirming the diagnosis.

  19. Insight and white matter fractional anisotropy in first-episode schizophrenia.

    PubMed

    Asmal, Laila; du Plessis, Stefan; Vink, Matthijs; Fouche, Jean-Paul; Chiliza, Bonginkosi; Emsley, Robin

    2017-05-01

    Impaired insight is a hallmark feature of schizophrenia. Structural studies implicate predominantly prefrontal, cingulate, cuneus/precuneus, and inferior temporal brain regions. The cortical midline structures (CMS) are also implicated in functional studies primarily through self-reflective processing tasks. However, few studies have explored the relationship between white matter tracts and insight in schizophrenia, and none in first-episode schizophrenia (FES). Here, we examined for fractional anisotropy (FA) differences in 89 minimally treated FES patients and 98 matched controls, and identified those FA differences associated with impaired clinical insight in patients. We found widespread FA reduction in FES patients compared to controls. Poorer insight in patients was predicted by lower FA values in a number of white matter tracts with a predilection for tracts associated with cortical midline structures (fronto-occipital, cingulate, cingulate hippocampus, uncinate, anterior corona radiata), and more severe depressive symptoms. The association between FA abnormalities and insight was most robust for the awareness of symptoms and illness awareness domains. Our study implicates a network of tracts involved in impaired insight in schizophrenia with a predilection for the CMS. This study is a first step in delineating the white matter tracts involved in insight impairment in schizophrenia prior to chronicity. Copyright © 2016. Published by Elsevier B.V.

  20. 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.

  1. Brain white matter changes associated with urological chronic pelvic pain syndrome: Multi-site neuroimaging from a MAPP case-control study

    PubMed Central

    Huang, Lejian; Kutch, Jason J.; Ellingson, Benjamin M.; Martucci, Katherine T.; Harris, Richard E.; Clauw, Daniel J.; Mackey, Sean; Mayer, Emeran A.; Schaeffer, Anthony J.; Apkarian, A. Vania; Farmer, Melissa A.

    2016-01-01

    Clinical phenotyping of urological chronic pelvic pain syndromes (UCPPS) in men and women has focused on end-organ abnormalities to identify putative clinical subtypes. Initial evidence of abnormal brain function and structure in male pelvic pain has necessitated large-scale, multi-site investigations into potential UCPPS brain biomarkers. We present the first evidence of regional white matter (axonal) abnormalities in men and women with UCPPS, compared to positive (irritable bowel syndrome, IBS) and healthy controls. Epidemiological and neuroimaging data was collected from participants with UCPPS (n=52), IBS (n=39), and healthy, sex- and age-matched controls (n=61). White matter microstructure, measured as fractional anisotropy (FA), was examined with diffusion tensor imaging (DTI). Group differences in regional FA positively correlated with pain severity, including segments of the right corticospinal tract and right anterior thalamic radiation. Increased corticospinal FA was specific and sensitive to UCPPS, positively correlated with pain severity, and reflected sensory (not affective) features of pain. Reduced anterior thalamic radiation FA distinguished IBS from UCPPS patients and controls, suggesting greater microstructural divergence from normal tract organization. Findings confirm that regional white matter abnormalities characterize UCPPS and can distinguish between visceral diagnoses, suggesting that regional axonal microstructure is either altered with ongoing pain or predisposes its development. PMID:27842046

  2. White Matter Disruptions in Schizophrenia Are Spatially Widespread and Topologically Converge on Brain Network Hubs.

    PubMed

    Klauser, Paul; Baker, Simon T; Cropley, Vanessa L; Bousman, Chad; Fornito, Alex; Cocchi, Luca; Fullerton, Janice M; Rasser, Paul; Schall, Ulrich; Henskens, Frans; Michie, Patricia T; Loughland, Carmel; Catts, Stanley V; Mowry, Bryan; Weickert, Thomas W; Shannon Weickert, Cynthia; Carr, Vaughan; Lenroot, Rhoshel; Pantelis, Christos; Zalesky, Andrew

    2017-03-01

    White matter abnormalities associated with schizophrenia have been widely reported, although the consistency of findings across studies is moderate. In this study, neuroimaging was used to investigate white matter pathology and its impact on whole-brain white matter connectivity in one of the largest samples of patients with schizophrenia. Fractional anisotropy (FA) and mean diffusivity (MD) were compared between patients with schizophrenia or schizoaffective disorder (n = 326) and age-matched healthy controls (n = 197). Between-group differences in FA and MD were assessed using voxel-based analysis and permutation testing. Automated whole-brain white matter fiber tracking and the network-based statistic were used to characterize the impact of white matter pathology on the connectome and its rich club. Significant reductions in FA associated with schizophrenia were widespread, encompassing more than 40% (234ml) of cerebral white matter by volume and involving all cerebral lobes. Significant increases in MD were also widespread and distributed similarly. The corpus callosum, cingulum, and thalamic radiations exhibited the most extensive pathology according to effect size. More than 50% of cortico-cortical and cortico-subcortical white matter fiber bundles comprising the connectome were disrupted in schizophrenia. Connections between hub regions comprising the rich club were disproportionately affected. Pathology did not differ between patients with schizophrenia and schizoaffective disorder and was not mediated by medication. In conclusion, although connectivity between cerebral hubs is most extensively disturbed in schizophrenia, white matter pathology is widespread, affecting all cerebral lobes and the cerebellum, leading to disruptions in the majority of the brain's fiber bundles. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  3. White matter tracts in first-episode psychosis: A DTI tractography study of the uncinate fasciculus

    PubMed Central

    Price, Gary; Cercignani, Mara; Parker, Geoffrey J.M.; Altmann, Daniel R.; Barnes, Thomas R.E.; Barker, Gareth J.; Joyce, Eileen M.; Ron, Maria A.

    2008-01-01

    A model of disconnectivity involving abnormalities in the cortex and connecting white matter pathways may explain the symptoms and cognitive abnormalities of schizophrenia. Recently, diffusion imaging tractography has made it possible to study white matter pathways in detail, and we present here a study of patients with first-episode psychosis using this technique. We studied the uncinate fasciculus (UF), the largest white matter tract that connects the frontal and temporal lobes, two brain regions significantly implicated in schizophrenia. Nineteen patients with first-episode schizophrenia and 23 controls were studied using a probabilistic tractography algorithm (PICo). Fractional anisotropy (FA) and probability of connection were obtained for every voxel in the tract, and the group means and distributions of these variables were compared. The spread of the FA distribution in the upper tail, as measured by the squared coefficient of variance (SCV), was reduced in the left UF in the patient group, indicating that the number of voxels with high FA values was reduced in the core of the tract and suggesting the presence of changes in fibre alignment and tract coherence in the patient group. The SCV of FA was lower in females across both groups and there was no correlation between the SCV of FA and clinical ratings. PMID:17988894

  4. 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.

  5. Similar white matter but opposite grey matter changes in schizophrenia and high-functioning autism.

    PubMed

    Katz, J; d'Albis, M-A; Boisgontier, J; Poupon, C; Mangin, J-F; Guevara, P; Duclap, D; Hamdani, N; Petit, J; Monnet, D; Le Corvoisier, P; Leboyer, M; Delorme, R; Houenou, J

    2016-07-01

    High-functioning autism (HFA) and schizophrenia (SZ) are two of the main neurodevelopmental disorders, sharing several clinical dimensions and risk factors. Their exact relationship is poorly understood, and few studies have directly compared both disorders. Our aim was thus to directly compare neuroanatomy of HFA and SZ using a multimodal MRI design. We scanned 79 male adult subjects with 3T MRI (23 with HFA, 24 with SZ and 32 healthy controls, with similar non-verbal IQ). We compared them using both diffusion-based whole-brain tractography and T1 voxel-based morphometry. HFA and SZ groups exhibited similar white matter alterations in the left fronto-occipital inferior fasciculus with a decrease in generalized fractional anisotropy compared with controls. In grey matter, the HFA group demonstrated bilateral prefrontal and anterior cingulate increases in contrast with prefrontal and left temporal reductions in SZ. HFA and SZ may share common white matter deficits in long-range connections involved in social functions, but opposite grey matter abnormalities in frontal regions that subserve complex cognitive functions. Our results are consistent with the fronto-occipital underconnectivity theory of HFA and the altered connectivity hypothesis of SZ and suggest the existence of both associated and diametrical liabilities to these two conditions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. White matter structural alterations in pediatric obsessive-compulsive disorder: relation to symptom dimensions.

    PubMed

    Lázaro, L; Ortiz, A G; Calvo, A; Ortiz, A E; Moreno, E; Morer, A; Calvo, R; Bargallo, N

    2014-10-03

    The aims of this study were to identify gray matter (GM) and white matter (WM) volume abnormalities in pediatric obsessive-compulsive patients, to examine their relationship between these abnormalities and the severity of disorder, and to explore whether they could be explained by the different symptom dimensions. 62 child and adolescent OCD patients (11-18years old) and 46 healthy subjects of the same gender and similar age and estimated intellectual quotient were assessed by means of psychopathological scales and magnetic resonance imaging (MRI). Axial three-dimensional T1-weighted images were obtained in a 3T scanner and analyzed using optimized voxel-based morphometry (VBM). Compared with healthy controls, OCD patients showed lower white matter (WM) volume in the left dorsolateral and cingulate regions involving the superior and middle frontal gyri and anterior cingulate gyrus (t=4.35, p=0.049 FWE (family wise error)-corrected). There was no significant correlation between WM and the severity of obsessive-compulsive symptomatology. There were no regions with lower gray matter (GM) volume in OCD patients than in controls. Compared with healthy controls, only the "harm/checking" OCD dimension showed a cluster with a near significant decrease in WM volume in the right superior temporal gyrus extending into the insula (t=5.61, p=.056 FWE-corrected). The evidence suggests that abnormalities in the dorsolateral prefrontal cortex, anterior cingulate cortex, temporal and limbic regions play a central role in the pathophysiology of OCD. Moreover, regional brain volumes in OCD may vary depending on specific OCD symptom dimensions, indicating the clinical heterogeneity of the condition. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. White matter injury induced by diabetes in acute stroke is clinically relevant: A preliminary study.

    PubMed

    Yu, Xinfeng; Song, Ruirui; Jiaerken, Yerfan; Yuan, Lixia; Huang, Peiyu; Lou, Min; Jiang, Quan; Zhang, Minming

    2017-01-01

    The importance of white matter injury induced by diabetes in stroke severity and prognosis is largely unknown. We aimed to investigate the relationship between diabetes-related white matter injury beyond stroke lesions with acute neurological deficits and clinical outcome after stroke. In total, 36 stroke patients within 3-7 days after onset were enrolled. Neurological deficits on admission were assessed by National Institute of Health Stroke Score, and poor outcome at 3 months was defined as modified Rankin score >2. White matter tracts were compared between patients with diabetic and non-diabetic stroke using fractional anisotropy from diffusion tensor imaging. Regional white matter abnormality with decreased fractional anisotropy was observed in diabetic patients (n = 18) when compared to non-diabetic patients (n = 18). Decreased fractional anisotropy in ipsilesional distal corticospinal tract was independently associated with higher National Institute of Health Stroke Score motor component score (β = -0.444, p = 0.005), and decreased fractional anisotropy in contralesional superior longitudinal fasciculus I was independently related to poor outcome (odds ratio, 0.900; p = 0.033). Our findings suggested that only white matter injury induced by diabetes in specific tracts like corticospinal tract and superior longitudinal fasciculus beyond stroke lesions has clinically relevant, providing insight into the mechanism of stroke recovery under the diabetic condition. © The Author(s) 2016.

  8. Spaceflight Effect on White Matter Structural Integrity

    NASA Technical Reports Server (NTRS)

    Lee, Jessica K.; Kopplemans, Vincent; Paternack, Ofer; Bloomberg, Jacob J.; Mulavara, Ajitkumar P.; Seidler, Rachael D.

    2017-01-01

    Recent reports of elevated brain white matter hyperintensity (WMH) counts and volume in postflight astronaut MRIs suggest that further examination of spaceflight's impact on the microstructure of brain white matter is warranted. To this end, retrospective longitudinal diffusion-weighted MRI scans obtained from 15 astronauts were evaluated. In light of the recent reports of microgravity-induced cephalad fluid shift and gray matter atrophy seen in astronauts, we applied a technique to estimate diffusion tensor imaging (DTI) metrics corrected for free water contamination. This approach enabled the analysis of white matter tissue-specific alterations that are unrelated to fluid shifts, occurring from before spaceflight to after landing. After spaceflight, decreased fractional anisotropy (FA) values were detected in an area encompassing the superior and inferior longitudinal fasciculi and the inferior fronto-occipital fasciculus. Increased radial diffusivity (RD) and decreased axial diffusivity (AD) were also detected within overlapping regions. In addition, FA values in the corticospinal tract decreased and RD measures in the precentral gyrus white matter increased from before to after flight. The results show disrupted structural connectivity of white matter in tracts involved in visuospatial processing, vestibular function, and movement control as a result of spaceflight. The findings may help us understand the structural underpinnings of the extensive spaceflight-induced sensorimotor remodeling. Prospective longitudinal assessment of the white matter integrity in astronauts is needed to characterize the evolution of white matter microstructural changes associated with spaceflight, their behavioral consequences, and the time course of recovery. Supported by a grant from the National Space Biomedical Research Institute, NASA NCC 9-58.

  9. White Matter Injury and Recovery after Hypertensive Intracerebral Hemorrhage

    PubMed Central

    Zuo, Shilun; Pan, Pengyu; Li, Qiang

    2017-01-01

    Hypertensive intracerebral hemorrhage (ICH) could very probably trigger white matter injury in patients. Through the continuous study of white matter injury after hypertensive ICH, we achieve a more profound understanding of the pathophysiological mechanism of its occurrence and development. At the same time, we found a series of drugs and treatment methods for the white matter repair. In the current reality, the research paradigm of white matter injury after hypertensive ICH is relatively obsolete or incomplete, and there are still lots of deficiencies in the research. In the face of the profound changes of stroke research perspective, we believe that the combination of the lenticulostriate artery, nerve nuclei of the hypothalamus-thalamus-basal ganglia, and the white matter fibers located within the capsula interna will be beneficial to the research of white matter injury and repair. This paper has classified and analyzed the study of white matter injury and repair after hypertensive ICH and also rethought the shortcomings of the current research. We hope that it could help researchers further explore and study white matter injury and repair after hypertensive ICH. PMID:28680884

  10. Acute White-Matter Abnormalities in Sports-Related Concussion: A Diffusion Tensor Imaging Study from the NCAA-DoD CARE Consortium.

    PubMed

    Mustafi, Sourajit Mitra; Harezlak, Jaroslaw; Koch, Kevin M; Nencka, Andrew S; Meier, Timothy; West, John D; Giza, Christopher C; DiFiori, John; Guskiewicz, Kevin K; Mihalik, Jason; LaConte, Stephen M; Duma, Stefan M; Broglio, Steven P; Saykin, Andrew J; McCrea, Michael; McAllister, Thomas; Wu, Yu-Chien

    2017-10-25

    Sport-related concussion (SRC) is an important public health issue. While standardized assessment tools are useful in the clinical management of acute concussion, the underlying pathophysiology of SRC and the time course of physiological recovery after injury remain unclear. In this study, we used diffusion tensor imaging (DTI) to detect white-matter alterations in football players within 48 hours after SRC. As part of the NCAA-DoD CARE Consortium study of SRC, 30 American football players diagnosed with acute concussion, and 28 matched controls received clinical assessments and underwent advanced MRI scans. To avoid selection bias and partial voluming effects, whole-brain skeletonized white matter was examined via tract-based spatial statistics (TBSS) to investigate between group differences in DTI metrics and their associations with clinical outcome measures. Mean diffusivity was significantly higher in the brain white matter of the concussed athletes, particularly in frontal and sub-frontal long white-matter tracts. While no DTI metric was associated to any clinical measure in the contact-sport controls, in the concussed group, DTI exhibited correlations with clinical measures. Axial diffusivity demonstrated a significant positive correlation with the Brief Symptom Inventory (BSI) and a trend for a positive correlation with the symptom severity score of the Sports Concussion Assessment Tool (SCAT). In addition, concussed athletes with higher fractional anisotropy performed worse on the cognitive component of the Standardized Assessment of Concussion (SAC). Overall, the results of this study are consistent with the hypothesis that SRC is associated with changes in white-matter tracts shortly after injury, and these differences are correlated clinically with acute symptoms and functional impairments.

  11. A probabilistic atlas of the cerebellar white matter.

    PubMed

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

    2016-01-01

    Imaging of the cerebellar cortex, deep cerebellar nuclei and their connectivity are gaining attraction, due to the important role the cerebellum plays in cognition and motor control. Atlases of the cerebellar cortex and nuclei are used to locate regions of interest in clinical and neuroscience studies. However, the white matter that connects these relay stations is of at least similar functional importance. Damage to these cerebellar white matter tracts may lead to serious language, cognitive and emotional disturbances, although the pathophysiological mechanism behind it is still debated. Differences in white matter integrity between patients and controls might shed light on structure-function correlations. A probabilistic parcellation atlas of the cerebellar white matter would help these studies by facilitating automatic segmentation of the cerebellar peduncles, the localization of lesions and the comparison of white matter integrity between patients and controls. In this work a digital three-dimensional probabilistic atlas of the cerebellar white matter is presented, based on high quality 3T, 1.25mm resolution diffusion MRI data from 90 subjects participating in the Human Connectome Project. The white matter tracts were estimated using probabilistic tractography. Results over 90 subjects were symmetrical and trajectories of superior, middle and inferior cerebellar peduncles resembled the anatomy as known from anatomical studies. This atlas will contribute to a better understanding of cerebellar white matter architecture. It may eventually aid in defining structure-function correlations in patients with cerebellar disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2016-09-01

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

  13. White matter microstructural abnormalities in girls with chromosome 22q11.2 deletion syndrome, Fragile X or Turner syndrome as evidenced by diffusion tensor imaging

    PubMed Central

    Villalon, Julio; Jahanshad, Neda; Beaton, Elliott; Toga, Arthur W.; Thompson, Paul M.; Simon, Tony J.

    2014-01-01

    Children with chromosome 22q11.2 Deletion Syndrome (22q11.2DS), Fragile X Syndrome (FXS), or Turner Syndrome (TS) are considered to belong to distinct genetic groups, as each disorder is caused by separate genetic alterations. Even so, they have similar cognitive and behavioral dysfunctions, particularly in visuospatial and numerical abilities. To assess evidence for common underlying neural microstructural alterations, we set out to determine whether these groups have partially overlapping white matter abnormalities, relative to typically developing controls. We scanned 101 female children between 7 and 14 years old: 25 with 22q11.2DS, 18 with FXS, 17 with TS, and 41 aged-matched controls using diffusion tensor imaging (DTI). Anisotropy and diffusivity measures were calculated and all brain scans were nonlinearly aligned to population and site-specific templates. We performed voxel-based statistical comparisons of the DTI-derived metrics between each disease group and the controls, while adjusting for age. Girls with 22q11.2DS showed lower fractional anisotropy (FA) than controls in the association fibers of the superior and inferior longitudinal fasciculi, the splenium of the corpus callosum, and the corticospinal tract. FA was abnormally lower in girls with FXS in the posterior limbs of the internal capsule, posterior thalami, and precentral gyrus. Girls with TS had lower FA in the inferior longitudinal fasciculus, right internal capsule and left cerebellar peduncle. Partially overlapping neurodevelopmental anomalies were detected in all three neurogenetic disorders. Altered white matter integrity in the superior and inferior longitudinal fasciculi and thalamic to frontal tracts may contribute to the behavioral characteristics of all of these disorders. PMID:23602925

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

    PubMed Central

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

    2016-01-01

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

  15. White matter 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.

  16. White matter injuries induced by MK-801 in a mouse model of schizophrenia based on NMDA antagonism.

    PubMed

    Xiu, Yun; Kong, Xiang-Ru; Zhang, Lei; Qiu, Xuan; Chao, Feng-Lei; Peng, Chao; Gao, Yuan; Huang, Chun-Xia; Wang, San-Rong; Tang, Yong

    2014-08-01

    The etiology of schizophrenia (SZ) is complex and largely unknown. Neuroimaging and postmortem studies have suggested white matter disturbances in SZ. In the present study, we tested the white matter deficits hypothesis of SZ using a mouse model of SZ induced by NMDA receptor antagonist MK-801. We found that mice with repeated chronic MK-801 administration showed increased locomotor activity in the open field test, less exploration of a novel environment in the hole-board test, and increased anxiety in the elevated plus maze but no impairments were observed in coordination or motor function on accelerating rota-rod. The total white matter volume and corpus callosum volume in mice treated with MK-801 were significantly decreased compared to control mice treated with saline. Myelin basic protein and 2', 3'-cyclic nucleotide 3'-phosphodiesterase were also significantly decreased in the mouse model of SZ. Furthermore, we observed degenerative changes of myelin sheaths in the mouse model of SZ. These results provide further evidence of white matter deficits in SZ and indicate that the animal model of SZ induced by MK-801 is a useful model to investigate mechanisms underlying white matter abnormalities in SZ. Copyright © 2014 Wiley Periodicals, Inc.

  17. Corpus callosum vasculature predicts white matter microstructure abnormalities following pediatric mild traumatic brain injury.

    PubMed

    Wendel, Kara M; Lee, Jeong Bin; Affeldt, Bethann; Hamer, Mary; Harahap-Carrillo, Indira S; Pardo, Andrea C; Obenaus, Andre

    2018-05-09

    Emerging data suggest that pediatric traumatic brain injury (TBI) is associated with impaired developmental plasticity and poorer neuropsychological outcomes than adults with similar head injuries. Unlike adult mild TBI (mTBI), the effects of mTBI on white matter (WM) microstructure and vascular supply are not well-understood in the pediatric population. The cerebral vasculature plays an important role providing necessary nutrients and removing waste. To address this critical element, we examined the microstructure of the corpus callosum (CC) following pediatric mTBI using diffusion tensor imaging (DTI), and investigated myelin, oligodendrocytes, and vasculature of WM with immunohistochemistry. We hypothesized that pediatric mTBI leads to abnormal WM microstructure and impacts the vasculature within the CC, and that these alterations to WM vasculature contribute to the long-term altered microstructure. We induced a closed head injury mTBI at postnatal day 14, then at 4, 14, and 60 days post injury (DPI) mice were sacrificed for analysis. We observed persistent changes in apparent diffusion coefficient (ADC) within the ipsilateral CC following mTBI, indicating microstructural changes, but surprisingly changes in myelin and oligodendrocyte densities were minimal. However, vasculature features of the ipsilateral CC such as vessel density, length, and number of junctions were persistently altered following mTBI. Correlative analysis showed a strong inverse relationship between ADC and vessel density at 60 DPI, suggesting increased vessel density following mTBI may restrict WM diffusion characteristics. Our findings suggest that WM vasculature contributes to the long-term microstructural changes within the ipsilateral CC following mTBI.

  18. Characterization of white matter integrity deficits in cocaine-dependent individuals with substance-induced psychosis compared with non-psychotic cocaine users.

    PubMed

    Willi, Taylor S; Barr, Alasdair M; Gicas, Kristina; Lang, Donna J; Vila-Rodriguez, Fidel; Su, Wayne; Thornton, Allen E; Leonova, Olga; Giesbrecht, Chantelle J; Procyshyn, Ric M; Rauscher, Alexander; MacEwan, William G; Honer, William G; Panenka, William J

    2017-05-01

    With sufficient drug exposure, some individuals develop transient psychotic symptoms referred to as 'substance-induced psychosis' (SIP), which closely resemble the symptoms observed in schizophrenia spectrum disorders. The comparability in psychotic presentation between SIP and the schizophrenias suggests that similar underlying neural deficits may contribute to the emergence of psychosis across these disorders. Only a small number of studies have investigated structural alterations in SIP, and all have been limited to volumetric imaging methods, with none controlling for the effects of chronic drug exposure. To investigate white matter abnormalities associated with SIP, diffusion tensor imaging was employed in a group of individuals with cocaine-associated psychosis (CAP; n = 24) and a cocaine-dependent non-psychotic (CDN) group (n = 43). Tract-based spatial statistics was used to investigate group differences in white matter diffusion parameters. The CAP group showed significantly lower fractional anisotropy values than the CDN group (p < 0.05) in voxels within white matter tracts of fronto-temporal, fronto-thalamic and interhemispheric pathways. The greatest differences in white matter integrity were present in the corpus callosum, corona radiata, bilateral superior longitudinal fasciculi and bilateral inferior longitudinal fasciculi. Additionally, the CAP group had voxels of significantly higher radial diffusivity in a subset of the previously mentioned pathways. These results are the first description of white matter integrity abnormalities in a SIP sample and indicate that differences in these pathways may be a shared factor in the expression of different forms of psychosis. © 2016 Society for the Study of Addiction.

  19. 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…

  20. Evidence for Functional Networks within the Human Brain's White Matter.

    PubMed

    Peer, Michael; Nitzan, Mor; Bick, Atira S; Levin, Netta; Arzy, Shahar

    2017-07-05

    Investigation of the functional macro-scale organization of the human cortex is fundamental in modern neuroscience. Although numerous studies have identified networks of interacting functional modules in the gray-matter, limited research was directed to the functional organization of the white-matter. Recent studies have demonstrated that the white-matter exhibits blood oxygen level-dependent signal fluctuations similar to those of the gray-matter. Here we used these signal fluctuations to investigate whether the white-matter is organized as functional networks by applying a clustering analysis on resting-state functional MRI (RSfMRI) data from white-matter voxels, in 176 subjects (of both sexes). This analysis indicated the existence of 12 symmetrical white-matter functional networks, corresponding to combinations of white-matter tracts identified by diffusion tensor imaging. Six of the networks included interhemispheric commissural bridges traversing the corpus callosum. Signals in white-matter networks correlated with signals from functional gray-matter networks, providing missing knowledge on how these distributed networks communicate across large distances. These findings were replicated in an independent subject group and were corroborated by seed-based analysis in small groups and individual subjects. The identified white-matter functional atlases and analysis codes are available at http://mind.huji.ac.il/white-matter.aspx Our results demonstrate that the white-matter manifests an intrinsic functional organization as interacting networks of functional modules, similarly to the gray-matter, which can be investigated using RSfMRI. The discovery of functional networks within the white-matter may open new avenues of research in cognitive neuroscience and clinical neuropsychiatry. SIGNIFICANCE STATEMENT In recent years, functional MRI (fMRI) has revolutionized all fields of neuroscience, enabling identifications of functional modules and networks in the human

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

    PubMed

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

    2014-01-01

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

  2. Concurrent white matter bundles and grey matter networks using independent component analysis.

    PubMed

    O'Muircheartaigh, Jonathan; Jbabdi, Saad

    2018-04-15

    Developments in non-invasive diffusion MRI tractography techniques have permitted the investigation of both the anatomy of white matter pathways connecting grey matter regions and their structural integrity. In parallel, there has been an expansion in automated techniques aimed at parcellating grey matter into distinct regions based on functional imaging. Here we apply independent component analysis to whole-brain tractography data to automatically extract brain networks based on their associated white matter pathways. This method decomposes the tractography data into components that consist of paired grey matter 'nodes' and white matter 'edges', and automatically separates major white matter bundles, including known cortico-cortical and cortico-subcortical tracts. We show how this framework can be used to investigate individual variations in brain networks (in terms of both nodes and edges) as well as their associations with individual differences in behaviour and anatomy. Finally, we investigate correspondences between tractography-based brain components and several canonical resting-state networks derived from functional MRI. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Brain Perfusion Is Increased at Term in the White Matter of Very Preterm Newborns and Newborns with Congenital Heart Disease: Does this Reflect Activated Angiogenesis?

    PubMed

    Wintermark, Pia; Lechpammer, Mirna; Kosaras, Bela; Jensen, Frances E; Warfield, Simon K

    2015-10-01

    This study aims to evaluate brain perfusion at term in very preterm newborns and newborns with congenital heart disease before their corrective surgery, and to search for histopathological indicators of whether the brain perfusion abnormalities of these newborns may be related to an activated angiogenesis. Using magnetic resonance imaging and arterial spin labeling, regional cerebral blood flow was measured at a term-equivalent age for three very preterm newborns (born at < 32 weeks), one newborn with congenital heart disease before his corrective surgery and three healthy newborns. In addition, a histopathological analysis was performed on a newborn with congenital heart disease. The very preterm newborns and the newborn with congenital heart disease included in this study all displayed an increased signal in their white matter on T2-weighted imaging. The cerebral blood flow of these newborns was increased in their white matter, compared with the healthy term newborns. The vascular endothelial growth factor was overexpressed in the injured white matter of the newborn with congenital heart disease. Brain perfusion may be increased at term in the white matter, in very preterm newborns, and newborns with congenital heart disease, and it correlates with white matter abnormalities on conventional imaging. Georg Thieme Verlag KG Stuttgart · New York.

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

    PubMed

    Ruess, Lynne; Dent, Carly M; Tiarks, Hailey J; Yoshida, Michelle A; Rusin, Jerome A

    2014-11-01

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

  5. Defining the nature of the cerebral abnormalities in the premature infant: a qualitative magnetic resonance imaging study.

    PubMed

    Inder, Terrie E; Wells, Scott J; Mogridge, Nina B; Spencer, Carole; Volpe, Joseph J

    2003-08-01

    The aim of this study was to define qualitatively the nature and extent of white and gray matter abnormalities in a longitudinal population-based study of infants with very low birth weight. Perinatal factors were then related to the presence and severity of magnetic resonance imaging (MRI) abnormalities. From November 1998 to December 2000, 100 consecutive premature infants admitted to the neonatal intensive care unit at Christchurch Women's Hospital were recruited (98% eligible) after informed parental consent to undergo an MRI scan at term equivalent. The scans were analyzed by a single neuroradiologist experienced in pediatric MRI, with a second independent scoring of the MRI using a combination of criteria for white matter (cysts, signal abnormality, loss of volume, ventriculomegaly, corpus callosal thinning, myelination) and gray matter (gray matter signal abnormality, gyration, subarachnoid space). Results were analyzed against individual item scores as well as the presence of moderate-severe white matter score, total gray matter score, and total brain score. The mean gestational age was 27.9+/-2.4 weeks (range, 23-32 weeks), and mean birth weight was 1063+/-292 g. The greatest univariate predictors for moderate-severe white matter abnormality were lower gestational age (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.1-1.7; P<.01), maternal fever (OR, 2.2; 95% CI, 1.1-4.6; P<.04), proven sepsis in the infant at delivery (OR, 1.8; 95% CI, 1.1-3.6; P=0.03), inotropic support (OR, 2.7; 95% CI, 1.5-4.5; P<.001), patent ductus arteriosus (OR, 2.2; 95% CI, 1.2-3.8; P=.01), grade III/IV intraventricular hemorrhage (P=.015), and the occurrence of a pneumothorax (P=.05). There was a significant protective effect of intrauterine growth restriction (OR, 0.51; 95% CI, 0.23-0.99; P=.04). Gray matter abnormality was highly related to the presence and severity of white matter abnormality. A unique pattern of cerebral abnormality consisting of significant diffuse

  6. Correlation between white matter damage and gray matter lesions in multiple sclerosis patients.

    PubMed

    Han, Xue-Mei; Tian, Hong-Ji; Han, Zheng; Zhang, Ce; Liu, Ying; Gu, Jie-Bing; Bakshi, Rohit; Cao, Xia

    2017-05-01

    We observed the characteristics of white matter fibers and gray matter in multiple sclerosis patients, to identify changes in diffusion tensor imaging fractional anisotropy values following white matter fiber injury. We analyzed the correlation between fractional anisotropy values and changes in whole-brain gray matter volume. The participants included 20 patients with relapsing-remitting multiple sclerosis and 20 healthy volunteers as controls. All subjects underwent head magnetic resonance imaging and diffusion tensor imaging. Our results revealed that fractional anisotropy values decreased and gray matter volumes were reduced in the genu and splenium of corpus callosum, left anterior thalamic radiation, hippocampus, uncinate fasciculus, right corticospinal tract, bilateral cingulate gyri, and inferior longitudinal fasciculus in multiple sclerosis patients. Gray matter volumes were significantly different between the two groups in the right frontal lobe (superior frontal, middle frontal, precentral, and orbital gyri), right parietal lobe (postcentral and inferior parietal gyri), right temporal lobe (caudate nucleus), right occipital lobe (middle occipital gyrus), right insula, right parahippocampal gyrus, and left cingulate gyrus. The voxel sizes of atrophic gray matter positively correlated with fractional anisotropy values in white matter association fibers in the patient group. These findings suggest that white matter fiber bundles are extensively injured in multiple sclerosis patients. The main areas of gray matter atrophy in multiple sclerosis are the frontal lobe, parietal lobe, caudate nucleus, parahippocampal gyrus, and cingulate gyrus. Gray matter atrophy is strongly associated with white matter injury in multiple sclerosis patients, particularly with injury to association fibers.

  7. Visual White Matter Integrity in Schizophrenia

    PubMed Central

    Butler, Pamela D.; Hoptman, Matthew J.; Nierenberg, Jay; Foxe, John J.; Javitt, Daniel C.; Lim, Kelvin O.

    2007-01-01

    Objective Patients with schizophrenia have visual-processing deficits. This study examines visual white matter integrity as a potential mechanism for these deficits. Method Diffusion tensor imaging was used to examine white matter integrity at four levels of the visual system in 17 patients with schizophrenia and 21 comparison subjects. The levels examined were the optic radiations, the striate cortex, the inferior parietal lobule, and the fusiform gyrus. Results Schizophrenia patients showed a significant decrease in fractional anisotropy in the optic radiations but not in any other region. Conclusions This finding indicates that white matter integrity is more impaired at initial input, rather than at higher levels of the visual system, and supports the hypothesis that visual-processing deficits occur at the early stages of processing. PMID:17074957

  8. White Matter Damage Relates to Oxygen Saturation in Children With Sickle Cell Anemia Without Silent Cerebral Infarcts.

    PubMed

    Kawadler, Jamie M; Kirkham, Fenella J; Clayden, Jonathan D; Hollocks, Matthew J; Seymour, Emma L; Edey, Rosanna; Telfer, Paul; Robins, Andrew; Wilkey, Olu; Barker, Simon; Cox, Tim C S; Clark, Chris A

    2015-07-01

    Sickle cell anemia is associated with compromised oxygen-carrying capability of hemoglobin and a high incidence of overt and silent stroke. However, in children with no evidence of cerebral infarction, there are changes in brain morphometry relative to healthy controls, which may be related to chronic anemia and oxygen desaturation. A whole-brain tract-based spatial statistics analysis was carried out in 25 children with sickle cell anemia with no evidence of abnormality on T2-weighted magnetic resonance imaging (13 male, age range: 8-18 years) and 14 age- and race-matched controls (7 male, age range: 10-19 years) to determine the extent of white matter injury. The hypotheses that white matter damage is related to daytime peripheral oxygen saturation and steady-state hemoglobin were tested. Fractional anisotropy was found to be significantly lower in patients in the subcortical white matter (corticospinal tract and cerebellum), whereas mean diffusivity and radial diffusivity were higher in patients in widespread areas. There was a significant negative relationship between radial diffusivity and oxygen saturation (P<0.05) in the anterior corpus callosum and a trend-level negative relationship between radial diffusivity and hemoglobin (P<0.1) in the midbody of the corpus callosum. These data show widespread white matter abnormalities in a sample of asymptomatic children with sickle cell anemia, and provides for the first time direct evidence of a relationship between brain microstructure and markers of disease severity (eg, peripheral oxygen saturation and steady-state hemoglobin). This study suggests that diffusion tensor imaging metrics may serve as a biomarker for future trials of reducing hypoxic exposure. © 2015 American Heart Association, Inc.

  9. Superficial white matter damage in anti-NMDA receptor encephalitis.

    PubMed

    Phillips, Owen Robert; Joshi, Shantanu H; Narr, Katherine L; Shattuck, David W; Singh, Manpreet; Di Paola, Margherita; Ploner, Christoph J; Prüss, Harald; Paul, Friedemann; Finke, Carsten

    2018-05-01

    Clinical brain MRI is normal in the majority of patients with anti- N -methyl-D-aspartate receptor (NMDAR) encephalitis. However, extensive deep white matter damage wasrecently identifiedin these patients using diffusion weighted imaging. Here, our aim was to study a particularly vulnerable brain compartment, the late myelinating superficial white matter. Forty-six patients with anti-NMDAR encephalitis were included. Ten out of these were considered neurologically recovered (modified Rankin scale of zero), while 36 patients were non-recovered. In addition, 30 healthy controls were studied. MRI data were collected from all subjects and superficial white matter mean diffusivity derived from diffusion tensor imaging was compared between groups in whole brain, lobar and vertex-based analyses. Patients underwent comprehensive cognitive testing, and correlation analyses were performed between cognitive performance and superficial white matter integrity. Non-recovered patients showed widespread superficial white matter damage in comparison to recovered patients and healthy controls. Vertex-based analyses revealed that damage predominated in frontal and temporal lobes. In contrast, the superficial white matter was intact in recovered patients. Importantly, persistent cognitive impairments in working memory, verbal memory, visuospatial memory and attention significantly correlated with damage of the superficial white matter in patients. Anti-NMDAR encephalitis is associated with extensive superficial white matter damage in patients with incomplete recovery. The strong association with impairment in several cognitive domains highlights the clinical relevance of white matter damage in this disorder and warrants investigations of the underlying pathophysiological mechanisms. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. 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. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Long-term white matter tract reorganization following prolonged febrile seizures.

    PubMed

    Pujar, Suresh S; Seunarine, Kiran K; Martinos, Marina M; Neville, Brian G R; Scott, Rod C; Chin, Richard F M; Clark, Chris A

    2017-05-01

    Diffusion magnetic resonance imaging (MRI) studies have demonstrated acute white matter changes following prolonged febrile seizures (PFS), but their longer-term evolution is unknown. We investigated a population-based cohort to determine white matter diffusion properties 8 years after PFS. We used diffusion tensor imaging (DTI) and applied Tract-Based Spatial Statistics for voxel-wise comparison of white matter microstructure between 26 children with PFS and 27 age-matched healthy controls. Age, gender, handedness, and hippocampal volumes were entered as covariates for voxel-wise analysis. Mean duration between the episode of PFS and follow-up was 8.2 years (range 6.7-9.6). All children were neurologically normal, and had normal conventional neuroimaging. On voxel-wise analysis, compared to controls, the PFS group had (1) increased fractional anisotropy in early maturing central white matter tracts, (2) increased mean and axial diffusivity in several peripheral white matter tracts and late-maturing central white matter tracts, and (3) increased radial diffusivity in peripheral white matter tracts. None of the tracts had reduced fractional anisotropy or diffusivity indices in the PFS group. In this homogeneous, population-based sample, we found increased fractional anisotropy in early maturing central white matter tracts and increased mean and axial diffusivity with/without increased radial diffusivity in several late-maturing peripheral white matter tracts 8 years post-PFS. We propose disruption in white matter maturation secondary to seizure-induced axonal injury, with subsequent neuroplasticity and microstructural reorganization as a plausible explanation. © 2017 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

  12. Astrocyte pathology in the ventral prefrontal white matter in depression.

    PubMed

    Rajkowska, Grazyna; Legutko, Beata; Moulana, Mohadetheh; Syed, Maryam; Romero, Damian G; Stockmeier, Craig A; Miguel-Hidalgo, Jose Javier

    2018-04-07

    Astrocyte functions in white matter are less well understood than in gray matter. Our recent study of white matter in ventral prefrontal cortex (vPFC) revealed alterations in expression of myelin-related genes in major depressive disorder (MDD). Since white matter astrocytes maintain myelin, we hypothesized that morphometry of these cells will be altered in MDD in the same prefrontal white matter region in which myelin-related genes are altered. White matter adjacent to vPFC was examined in 25 MDD and 21 control subjects. Density and size of GFAP-immunoreactive (-ir) astrocyte cell bodies was measured. The area fraction of GFAP-ir astrocytes (cell bodies + processes) was also estimated. GFAP mRNA expression was determined using qRT-PCR. The density of GFAP-ir astrocytes was also measured in vPFC white matter of rats subjected to chronic unpredictable stress (CUS) and control animals. Fibrous and smooth GFAP-ir astrocytes were distinguished in human white matter. The density of both types of astrocytes was significantly decreased in MDD. Area fraction of GFAP immunoreactivity was significantly decreased in MDD, but mean soma size remained unchanged. Expression of GFAP mRNA was significantly decreased in MDD. In CUS rats there was a significant decrease in astrocyte density in prefrontal white matter. The decrease in density and area fraction of white matter astrocytes and GFAP mRNA in MDD may be linked to myelin pathology previously noted in these subjects. Astrocyte pathology may contribute to axon disturbances in axon integrity reported by neuroimaging studies in MDD and interfere with signal conduction in the white matter. Copyright © 2018. Published by Elsevier Ltd.

  13. Cortex Parcellation Associated Whole White Matter Parcellation in Individual Subjects.

    PubMed

    Schiffler, Patrick; Tenberge, Jan-Gerd; Wiendl, Heinz; Meuth, Sven G

    2017-01-01

    The investigation of specific white matter areas is a growing field in neurological research and is typically achieved through the use of atlases. However, the definition of anatomically based regions remains challenging for the white matter and thus hinders region-specific analysis in individual subjects. In this article, we focus on creating a whole white matter parcellation method for individual subjects where these areas can be associated to cortex regions. This is done by combining cortex parcellation and fiber tracking data. By tracking fibers out of each cortex region and labeling the fibers according to their origin, we populate a candidate image. We then derive the white matter parcellation by classifying each white matter voxel according to the distribution of labels in the corresponding voxel from the candidate image. The parcellation of the white matter with the presented method is highly reliable and is not as dependent on registration as with white matter atlases. This method allows for the parcellation of the whole white matter into individual cortex region associated areas and, therefore, associates white matter alterations to cortex regions. In addition, we compare the results from the presented method to existing atlases. The areas generated by the presented method are not as sharply defined as the areas in most existing atlases; however, they are computed directly in the DWI space of the subject and, therefore, do not suffer from distortion caused by registration. The presented approach might be a promising tool for clinical and basic research to investigate modalities or system specific micro structural alterations of white matter areas in a quantitative manner.

  14. Cortex Parcellation Associated Whole White Matter Parcellation in Individual Subjects

    PubMed Central

    Schiffler, Patrick; Tenberge, Jan-Gerd; Wiendl, Heinz; Meuth, Sven G.

    2017-01-01

    The investigation of specific white matter areas is a growing field in neurological research and is typically achieved through the use of atlases. However, the definition of anatomically based regions remains challenging for the white matter and thus hinders region-specific analysis in individual subjects. In this article, we focus on creating a whole white matter parcellation method for individual subjects where these areas can be associated to cortex regions. This is done by combining cortex parcellation and fiber tracking data. By tracking fibers out of each cortex region and labeling the fibers according to their origin, we populate a candidate image. We then derive the white matter parcellation by classifying each white matter voxel according to the distribution of labels in the corresponding voxel from the candidate image. The parcellation of the white matter with the presented method is highly reliable and is not as dependent on registration as with white matter atlases. This method allows for the parcellation of the whole white matter into individual cortex region associated areas and, therefore, associates white matter alterations to cortex regions. In addition, we compare the results from the presented method to existing atlases. The areas generated by the presented method are not as sharply defined as the areas in most existing atlases; however, they are computed directly in the DWI space of the subject and, therefore, do not suffer from distortion caused by registration. The presented approach might be a promising tool for clinical and basic research to investigate modalities or system specific micro structural alterations of white matter areas in a quantitative manner. PMID:28729829

  15. Profiles of White Matter Tract Pathology in Frontotemporal Dementia

    PubMed Central

    Mahoney, Colin J; Ridgway, Gerard R; Malone, Ian B; Downey, Laura E; Beck, Jonathan; Kinnunen, Kirsi M; Schmitz, Nicole; Golden, Hannah L; Rohrer, Jonathan D; Schott, Jonathan M; Rossor, Martin N; Ourselin, Sebastien; Mead, Simon; Fox, Nick C; Warren, Jason D

    2014-01-01

    Despite considerable interest in improving clinical and neurobiological characterisation of frontotemporal dementia and in defining the role of brain network disintegration in its pathogenesis, information about white matter pathway alterations in frontotemporal dementia remains limited. Here we investigated white matter tract damage using an unbiased, template-based diffusion tensor imaging (DTI) protocol in a cohort of 27 patients with the behavioral variant of frontotemporal dementia (bvFTD) representing both major genetic and sporadic forms, in relation both to healthy individuals and to patients with Alzheimer's disease. Widespread white matter tract pathology was identified in the bvFTD group compared with both healthy controls and Alzheimer's disease group, with prominent involvement of uncinate fasciculus, cingulum bundle and corpus callosum. Relatively discrete and distinctive white matter profiles were associated with genetic subgroups of bvFTD associated with MAPT and C9ORF72 mutations. Comparing diffusivity metrics, optimal overall separation of the bvFTD group from the healthy control group was signalled using radial diffusivity, whereas optimal overall separation of the bvFTD group from the Alzheimer's disease group was signalled using fractional anisotropy. Comparing white matter changes with regional grey matter atrophy (delineated using voxel based morphometry) in the bvFTD cohort revealed co-localisation between modalities particularly in the anterior temporal lobe, however white matter changes extended widely beyond the zones of grey matter atrophy. Our findings demonstrate a distributed signature of white matter alterations that is likely to be core to the pathophysiology of bvFTD and further suggest that this signature is modulated by underlying molecular pathologies. PMID:24510641

  16. Alcohol Use and Cerebral White Matter Compromise in Adolescence

    PubMed Central

    Elofson, Jonathan; Gongvatana, Win; Carey, Kate B.

    2013-01-01

    Alcohol use is typically initiated during adolescence, a period known to be critical in neurodevelopment. The adolescent brain may be particularly susceptible to the harmful effects of alcohol. While the cognitive deficits associated with alcohol use during adolescence have been well-documented, the neural substrates underlying these effects remain inadequately understood. Cerebral white matter has been suggested as a primary site of alcohol-related damage and diffusion tensor imaging (DTI) allows for the quantification of white matter integrity in vivo. This review summarizes results from both cross-sectional and longitudinal studies employing DTI that indicate that white matter tracts, particularly those thought to be involved in executive functioning, continue to develop throughout adolescence and into adulthood. Numerous DTI studies reveal a positive correlation between white matter integrity and neurocognitive performance and, in adults, the detrimental effects of prolonged alcohol-dependence on white matter integrity. We provide a comprehensive review of the DTI studies exploring the relationship between alcohol use and white matter integrity in adolescents. Results from most of these studies suggest that alcohol use is associated with reduced white matter integrity, particularly in the superior longitudinal fasciculus (SLF), and some evidence suggests that this relationship may be influenced by sex. We conclude by highlighting confounds and limitations of the available research and suggesting directions for future research. PMID:23583835

  17. Retinal microvasculature and white matter microstructure: The Rotterdam Study.

    PubMed

    Mutlu, Unal; Cremers, Lotte G M; de Groot, Marius; Hofman, Albert; Niessen, Wiro J; van der Lugt, Aad; Klaver, Caroline C W; Ikram, M Arfan; Vernooij, Meike W; Ikram, M Kamran

    2016-09-06

    To investigate whether retinal microvascular damage is related to normal-appearing white matter microstructure on diffusion tensor MRI. We included 2,436 participants (age ≥45 years) from the population-based Rotterdam Study (2005-2009) who had gradable retinal images and brain MRI scans. Retinal arteriolar and venular calibers were measured semiautomatically on fundus photographs. White matter microstructure was assessed using diffusion tensor MRI. We used linear regression models to investigate the associations of retinal vascular calibers with markers of normal-appearing white matter microstructure, adjusting for age, sex, the fellow vascular caliber, and additionally for structural MRI markers and cardiovascular risk factors. Narrower arterioles and wider venules were associated with poor white matter microstructure: adjusted difference in fractional anisotropy per SD decrease in arteriolar caliber -0.061 (95% confidence interval -0.106 to -0.016), increase in venular caliber -0.054 (-0.096 to -0.011), adjusted difference in mean diffusivity per SD decrease in arteriolar caliber 0.048 (0.007-0.088), and increase in venular caliber 0.047 (0.008-0.085). The associations for venules were more prominent in women. Retinal vascular calibers are related to normal-appearing white matter microstructure. This suggests that microvascular damage in the white matter is more widespread than visually detectable as white matter lesions. © 2016 American Academy of Neurology.

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

    PubMed

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

    2013-09-01

    It is well documented that neuroanatomical differences exist between adults who stutter and their fluently speaking peers. Specifically, adults who stutter have been found to have more grey matter volume (GMV) in speech relevant regions including inferior frontal gyrus, insula and superior temporal gyrus (Beal et al., 2007; Song et al., 2007). Despite stuttering having its onset in childhood only one study has investigated the neuroanatomical differences between children who do and do not stutter. Chang et al. (2008) reported children who stutter had less GMV in the bilateral inferior frontal gyri and middle temporal gyrus relative to fluently speaking children. Thus it appears that children who stutter present with unique neuroanatomical abnormalities as compared to those of adults who stutter. In order to better understand the neuroanatomical correlates of stuttering earlier in its development, near the time of onset, we used voxel-based morphometry to examine volumetric differences between 11 children who stutter and 11 fluent children. Children who stutter had less GMV in the bilateral inferior frontal gyri and left putamen but more GMV in right Rolandic operculum and superior temporal gyrus relative to fluent children. Children who stutter also had less white matter volume bilaterally in the forceps minor of the corpus callosum. We discuss our findings of widespread anatomic abnormalities throughout the cortical network for speech motor control within the context of the speech motor skill limitations identified in people who stutter (Namasivayam and van Lieshout, 2008; Smits-Bandstra et al., 2006). Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    PubMed Central

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

    2010-01-01

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

  20. The energetics of central nervous system white matter

    PubMed Central

    Harris, Julia J.; Attwell, David

    2012-01-01

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

  1. Severe retinopathy of prematurity predicts delayed white matter maturation and poorer neurodevelopment.

    PubMed

    Glass, Torin J A; Chau, Vann; Gardiner, Jane; Foong, Justin; Vinall, Jillian; Zwicker, Jill G; Grunau, Ruth E; Synnes, Anne; Poskitt, Kenneth J; Miller, Steven P

    2017-11-01

    To determine whether severe retinopathy of prematurity (ROP) is associated with (1) abnormal white matter maturation and (2) neurodevelopmental outcomes at 18 months' corrected age (CA) compared with neonates without severe ROP. We conducted a prospective longitudinal cohort of extremely preterm neonates born 24-28 weeks' gestational age recruited between 2006 and 2013 with brain MRIs obtained both early in life and at term-equivalent age. Severe ROP was defined as ROP treated with retinal laser photocoagulation. Using diffusion tensor imaging and tract-based spatial statistics (TBSS), white matter maturation was assessed by mean fractional anisotropy (FA) in seven predefined regions of interest. Neurodevelopmental outcomes were assessed with Bayley Scales of Infant and Toddler Development-III (Bayley-III) composite scores at 18 months' CA. Subjects were compared using Fisher's exact, Kruskal-Wallis and generalised estimating equations. Families were recruited from the neonatal intensive care unit at BC Women's Hospital. Of 98 extremely preterm neonates (median: 26.0 weeks) assessed locally for ROP, 19 (19%) had severe ROP and 83 (85%) were assessed at 18 months' CA. Severe ROP was associated with lower FA in the posterior white matter, and with decreased measures of brain maturation in the optic radiations, posterior limb of the internal capsule (PLIC) and external capsule on TBSS. Bayley-III cognitive and motor scores were lower in infants with severe ROP. Severe ROP is associated with maturational delay in the optic radiations, PLIC, external capsule and posterior white matter, housing the primary visual and motor pathways, and is associated with poorer cognitive and motor outcomes at 18 months' CA. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. White Matter Hyperintensities Improve Ischemic Stroke Recurrence Prediction.

    PubMed

    Andersen, Søren Due; Larsen, Torben Bjerregaard; Gorst-Rasmussen, Anders; Yavarian, Yousef; Lip, Gregory Y H; Bach, Flemming W

    2017-01-01

    Nearly one in 5 patients with ischemic stroke will invariably experience a second stroke within 5 years. Stroke risk stratification schemes based solely on clinical variables perform only modestly in non-atrial fibrillation (AF) patients and improvement of these schemes will enhance their clinical utility. Cerebral white matter hyperintensities are associated with an increased risk of incident ischemic stroke in the general population, whereas their association with the risk of ischemic stroke recurrence is more ambiguous. In a non-AF stroke cohort, we investigated the association between cerebral white matter hyperintensities and the risk of recurrent ischemic stroke, and we evaluated the predictive performance of the CHA2DS2VASc score and the Essen Stroke Risk Score (clinical scores) when augmented with information on white matter hyperintensities. In a registry-based, observational cohort study, we included 832 patients (mean age 59.6 (SD 13.9); 42.0% females) with incident ischemic stroke and no AF. We assessed the severity of white matter hyperintensities using MRI. Hazard ratios stratified by the white matter hyperintensities score and adjusted for the components of the CHA2DS2VASc score were calculated based on the Cox proportional hazards analysis. Recalibrated clinical scores were calculated by adding one point to the score for the presence of moderate to severe white matter hyperintensities. The discriminatory performance of the scores was assessed with the C-statistic. White matter hyperintensities were significantly associated with the risk of recurrent ischemic stroke after adjusting for clinical risk factors. The hazard ratios ranged from 1.65 (95% CI 0.70-3.86) for mild changes to 5.28 (95% CI 1.98-14.07) for the most severe changes. C-statistics for the prediction of recurrent ischemic stroke were 0.59 (95% CI 0.51-0.65) for the CHA2DS2VASc score and 0.60 (95% CI 0.53-0.68) for the Essen Stroke Risk Score. The recalibrated clinical scores showed

  3. White Matter Glia Pathology in Autism

    DTIC Science & Technology

    2013-09-01

    www.ncbi.nlm.nih.gov/pubmed/21078227 5 . Sundaram SK, Kumar A, Makki MI, Behen ME, Chugani HT , Chugani DC. Diffusion tensor imaging of frontal lobe in autism ...AD_________________ Award Number: W81XWH-12-1-0302 TITLE: White matter glia pathology in autism PRINCIPAL INVESTIGATOR...COVERED 01 September 2012 – 31 August 2013 4. TITLE AND SUBTITLE White matter glia pathology in autism 5a. CONTRACT NUMBER W81XWH-12-1-0302 5b

  4. 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

  5. Intranasal Insulin Prevents Cognitive Decline, Cerebral Atrophy and White Matter Changes in Murine Type I Diabetic Encephalopathy

    ERIC Educational Resources Information Center

    Francis, George J.; Martinez, Jose A.; Liu, Wei Q.; Xu, Kevin; Ayer, Amit; Fine, Jared; Tuor, Ursula I.; Glazner, Gordon; Hanson, Leah R.; Frey, William H., II; Toth, Cory

    2008-01-01

    Insulin deficiency in type I diabetes may lead to cognitive impairment, cerebral atrophy and white matter abnormalities. We studied the impact of a novel delivery system using intranasal insulin (I-I) in a mouse model of type I diabetes (streptozotocin-induced) for direct targeting of pathological and cognitive deficits while avoiding potential…

  6. Changes of migraine-related white matter hyperintensities after 3 years: a longitudinal MRI study.

    PubMed

    Erdélyi-Bótor, Szilvia; Aradi, Mihály; Kamson, David Olayinka; Kovács, Norbert; Perlaki, Gábor; Orsi, Gergely; Nagy, Szilvia Anett; Schwarcz, Attila; Dóczi, Tamás; Komoly, Sámuel; Deli, Gabriella; Trauninger, Anita; Pfund, Zoltán

    2015-01-01

    The aim of this longitudinal study was to investigate changes of migraine-related brain white matter hyperintensities 3 years after an initial study. Baseline quantitative magnetic resonance imaging (MRI) studies of migraine patients with hemispheric white matter hyperintensities performed in 2009 demonstrated signs of tissue damage within the hyperintensities. The hyperintensities appeared most frequently in the deep white matter of the frontal lobe with a similar average hyperintensity size in all hemispheric lobes. Since in this patient group the repeated migraine attacks were the only known risk factors for the development of white matter hyperintensities, the remeasurements of migraineurs after a 3-year long follow-up may show changes in the status of these structural abnormalities as the effects of the repeated headaches. The same patient group was reinvestigated in 2012 using the same MRI scanner and acquisition protocol. MR measurements were performed on a 3.0-Tesla clinical MRI scanner. Beyond the routine T1-, T2-weighted, and fluid-attenuated inversion recovery imaging, diffusion and perfusion-weighted imaging, proton magnetic resonance spectroscopy, and T1 and T2 relaxation time measurements were also performed. Findings of the baseline and follow-up studies were compared with each other. The follow-up proton magnetic resonance spectroscopy studies of white matter hyperintensities showed significantly decreased N-acetyl-aspartate (median values 8.133 vs 7.153 mmol/L, P=.009) and creatine/phosphocreatine (median values 4.970 vs 4.641 mmol/L, P=.015) concentrations compared to the baseline, indicating a more severe axonal loss and glial hypocellularity with decreased intracellular energy production. The diffusion values, the T1 and T2 relaxation times, and the cerebral blood flow and volume measurements presented only mild changes between the studies. The number (median values 21 vs 25, P<.001) and volume (median values 0.896 vs 1.140 mL, P<.001) of

  7. Gray and white matter changes and their relation to illness trajectory in first episode psychosis.

    PubMed

    Keymer-Gausset, Alejandro; Alonso-Solís, Anna; Corripio, Iluminada; Sauras-Quetcuti, Rosa B; Pomarol-Clotet, Edith; Canales-Rodriguez, Erick J; Grasa-Bello, Eva; Álvarez, Enric; Portella, Maria J

    2018-03-01

    Previous works have studied structural brain characteristics in first-episode psychosis (FEP), but few have focused on the relation between brain differences and illness trajectories. The aim of this study is to analyze gray and white matter changes in FEP patients and their relation with one-year clinical outcomes. A sample of 41 FEP patients and 41 healthy controls (HC), matched by age and educational level was scanned with a 3T MRI during the first month of illness onset. One year later, patients were assigned to two illness trajectories (schizophrenia and non-schizophrenia). Voxel-based morphometry (VBM) was used for gray matter and Tract-based spatial statistics (TBSS) was used for white matter data analysis. VBM revealed significant and widespread bilateral gray matter density differences between FEP and HC groups in areas that included the right insular Cortex, the inferior frontal gyrus and orbito-frontal cortices, and segments of the occipital cortex. TBSS showed a significant lower fractional anisotropy (FA) in 8 clusters that included segments of the anterior thalamic radiation, the left body and forceps minor of corpus callosum, the right anterior segment of the inferior fronto-occipital fasciculus and the anterior segments of the cingulum. The sub-groups comparison revealed significant lower FA in the schizophrenia sub-group in two clusters: the anterior thalamic radiation and the anterior segment of left cingulum. These findings are coherent with previous morphology studies. The results suggest that gray and white matter abnormalities are present at early stages of the disease, and white matter differences may distinguish different illness prognosis. Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.

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

    PubMed Central

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

    2014-01-01

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

  9. [Ultrastructural pathology of oligodendrocytes in the white matter in continuous paranoid schizophrenia: a role for microglia].

    PubMed

    Uranova, N A; Vikhreva, O V; Rakhmanova, V I; Orlovskaya, D D

    Previously the authors have reported the ultrastructural pathology and deficit of oligodendrocytes in gray and white matter of the prefrontal cortex in schizophrenia. The aim of the study was to determine of the effects of microglia on the ultrastructure of oligodendrocytes in the white matter underlying the prefrontal cortex in continuous schizophrenia. Postmortem morphometric electron microscopic study of oligodendrocytes in close apposition to microglia was performed in white matter underlying the prefrontal cortex (BA10). Eleven cases of chronic continuous schizophrenia and 11 normal controls were studied. Areas of oligodendrocytes, of their nuclei and cytoplasm, volume density (Vv) and the number of mitochondria, vacuoles of endoplasmic reticulum and lipofuscin granules were estimated. Group comparison was performed using ANCOVA. The schizophrenia group differed from the control group by paucity of ribosomes in the cytoplasm of oligodendrocytes, a significant decrease in Vv and the number of mitochondria and increase in the number of lipofuscin granules. Significant correlations between the parameters of lipofuscin granules, mitochondria and vacuoles were found only in the schizophrenia group. The number of lipofuscin granules were correlated positively with the illness duration. Dystrophic alterations of oligodendrocytes attached to microglial cells were found in the white matter of the prefrontal cortex in chronic paranoid schizophrenia as compared to controls. The data obtained suggest that microglia might contribute to abnormalities of energy, lipid and protein metabolism of oligodendrocytes in schizophrenia.

  10. Sleep Duration and White Matter Quality in Middle-Aged Adults

    PubMed Central

    Yaffe, Kristine; Nasrallah, Ilya; Hoang, Tina D.; Lauderdale, Diane S.; Knutson, Kristen L.; Carnethon, Mercedes R.; Launer, Lenore J.; Lewis, Cora E.; Sidney, Stephen

    2016-01-01

    Study Objectives: Sleep duration has been associated with risk of dementia and stroke, but few studies have investigated the relationship between sleep duration and brain MRI measures, particularly in middle age. Methods: In a prospective cohort of 613 black and white adults (mean age = 45.4 years) enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study, participants reported typical sleep duration, dichotomized into moderate sleep duration (> 6 to ≤ 8 h) and short sleep duration (≤ 6 h) at baseline (2005–2006). Five years later, we obtained brain MRI markers of white matter including fractional anisotropy, mean diffusivity, and white matter hyperintensities. Results: Compared to moderate sleepers, short sleepers had an elevated ratio of white matter hyperintensities to normal tissue in the parietal region (OR = 2.31, 95% CI: 1.47, 3.61) adjusted for age, race/sex, education, hypertension, stroke/TIA, depression, smoking status, and physical activity. White matter diffusivity was also higher, approximately a 0.2 standard deviation difference, in frontal, parietal, and temporal white matter regions, among those reporting shorter sleep duration in (P < 0.05 for all). Conclusions: Short sleep duration was associated with worse markers of white matter integrity in midlife. These mid-life differences in white matter may underlie the link between poor sleep and risk of dementia and stroke. Citation: Yaffe K, Nasrallah I, Hoang TD, Lauderdale DS, Knutson KL, Carnethon MR, Launer LJ, Lewis CE, Sidney S. Sleep duration and white matter quality in middle-aged adults. SLEEP 2016;39(9):1743–1747. PMID:27397561

  11. White matter integrity in individuals at ultra-high risk for psychosis: a systematic review and discussion of the role of polyunsaturated fatty acids.

    PubMed

    Vijayakumar, Nandita; Bartholomeusz, Cali; Whitford, Thomas; Hermens, Daniel F; Nelson, Barnaby; Rice, Simon; Whittle, Sarah; Pantelis, Christos; McGorry, Patrick; Schäfer, Miriam R; Amminger, G Paul

    2016-08-11

    Schizophrenia is thought to be a neurodevelopmental disorder with pathophysiological processes beginning in the brain prior to the emergence of clinical symptoms. Recent evidence from neuroimaging studies using techniques such as diffusion tensor imaging has identified white matter abnormalities that are suggestive of disrupted brain myelination and neuronal connectivity. Identifying whether such effects exist in individuals at high risk for developing psychosis may help with prevention and early intervention strategies. In addition, there is preliminary evidence for a role of lipid biology in the onset of psychosis, along with well-established evidence of its role in myelination of white matter tracts. As such, this article synthesises the literature on polyunsaturated fatty acids (PUFAs) in myelination and schizophrenia, hypothesizing that white matter abnormalities may potentially mediate the relationship between PUFAs and schizophrenia. Diffusion tensor imaging studies were identified through a systematic search of existing literature. Studies examined white matter integrity in ultra-high risk (UHR) samples, as assessed using structured diagnostic interviews. Data was extracted and summarised as a narrative review. Twelve studies met inclusion criteria, and findings identified reduced fractional anisotropy and higher diffusivity. Although the exact location of abnormalities remains uncertain, fronto-temporal and fronto-limbic connections, including the superior longitudinal and uncinate fasiculus, cingulum, and corpus callosum appear to be implicated. Because of preliminary evidence suggesting lipid biology may be relevant for the onset of psychosis, a discussion is provided of the role of polyunsaturated fatty acids (PUFAs) in myelination and risk for psychosis. While the function of PUFAs in myelination is well-established, there is growing evidence of reduced PUFA concentration in UHR samples, highlighting the need for research to examine the relationship

  12. Minocycline protects the immature white matter against hyperoxia.

    PubMed

    Schmitz, Thomas; Krabbe, Grietje; Weikert, Georg; Scheuer, Till; Matheus, Friederike; Wang, Yan; Mueller, Susanne; Kettenmann, Helmut; Matyash, Vitali; Bührer, Christoph; Endesfelder, Stefanie

    2014-04-01

    Poor neurological outcome in preterm infants is associated with periventricular white matter damage and hypomyelination, often caused by perinatal inflammation, hypoxia-ischemia, and hyperoxia. Minocycline has been demonstrated in animal models to protect the immature brain against inflammation and hypoxia-ischemia by microglial inhibition. Here we studied the effect of minocycline on white matter damage caused by hyperoxia. To mimic the 3- to 4-fold increase of oxygen tension caused by preterm birth, we have used the hyperoxia model in neonatal rats providing 24h exposure to 4-fold increased oxygen concentration (80% instead of 21% O2) from P6 to P7. We analyzed whether minocycline prevents activation of microglia and damage of oligodendroglial precursor cell development, and whether acute treatment of hyperoxia-exposed rats with minocycline improves long term white matter integrity. Minocycline administration during exposure to hyperoxia resulted in decreased apoptotic cell death and in improved proliferation and maturation of oligodendroglial precursor cells (OPC). Minocycline blocked changes in microglial morphology and IL-1β release induced by hyperoxia. In primary microglial cell cultures, minocycline inhibited cytokine release while in mono-cultures of OPCs, it improved survival and proliferation. Long term impairment of white matter diffusivity in MRI/DTI in P30 and P60 animals after neonatal hyperoxia was attenuated by minocycline. Minocycline protects white matter development against oxygen toxicity through direct protection of oligodendroglia and by microglial inhibition. This study moreover demonstrates long term benefits of minocycline on white matter integrity. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Epigenetic Age Acceleration Assessed with Human White-Matter Images.

    PubMed

    Hodgson, Karen; Carless, Melanie A; Kulkarni, Hemant; Curran, Joanne E; Sprooten, Emma; Knowles, Emma E; Mathias, Samuel; Göring, Harald H H; Yao, Nailin; Olvera, Rene L; Fox, Peter T; Almasy, Laura; Duggirala, Ravi; Blangero, John; Glahn, David C

    2017-05-03

    The accurate estimation of age using methylation data has proved a useful and heritable biomarker, with acceleration in epigenetic age predicting a number of age-related phenotypes. Measures of white matter integrity in the brain are also heritable and highly sensitive to both normal and pathological aging processes across adulthood. We consider the phenotypic and genetic interrelationships between epigenetic age acceleration and white matter integrity in humans. Our goal was to investigate processes that underlie interindividual variability in age-related changes in the brain. Using blood taken from a Mexican-American extended pedigree sample ( n = 628; age = 23.28-93.11 years), epigenetic age was estimated using the method developed by Horvath (2013). For n = 376 individuals, diffusion tensor imaging scans were also available. The interrelationship between epigenetic age acceleration and global white matter integrity was investigated with variance decomposition methods. To test for neuroanatomical specificity, 16 specific tracts were additionally considered. We observed negative phenotypic correlations between epigenetic age acceleration and global white matter tract integrity (ρ pheno = -0.119, p = 0.028), with evidence of shared genetic (ρ gene = -0.463, p = 0.013) but not environmental influences. Negative phenotypic and genetic correlations with age acceleration were also seen for a number of specific white matter tracts, along with additional negative phenotypic correlations between granulocyte abundance and white matter integrity. These findings (i.e., increased acceleration in epigenetic age in peripheral blood correlates with reduced white matter integrity in the brain and shares common genetic influences) provide a window into the neurobiology of aging processes within the brain and a potential biomarker of normal and pathological brain aging. SIGNIFICANCE STATEMENT Epigenetic measures can be used to predict age with a high degree of accuracy and so

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

    PubMed

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

    2014-02-01

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

  15. Widespread reductions of white matter integrity in patients with long-term remission of Cushing's disease.

    PubMed

    van der Werff, Steven J A; Andela, Cornelie D; Nienke Pannekoek, J; Meijer, Onno C; van Buchem, Mark A; Rombouts, Serge A R B; van der Mast, Roos C; Biermasz, Nienke R; Pereira, Alberto M; van der Wee, Nic J A

    2014-01-01

    Hypercortisolism leads to various physical, psychological and cognitive symptoms, which may partly persist after the treatment of Cushing's disease. The aim of the present study was to investigate abnormalities in white matter integrity in patients with long-term remission of Cushing's disease, and their relation with psychological symptoms, cognitive impairment and clinical characteristics. In patients with long-term remission of Cushing's disease (n = 22) and matched healthy controls (n = 22) we examined fractional anisotropy (FA) values of white matter in a region-of-interest (ROI; bilateral cingulate cingulum, bilateral hippocampal cingulum, bilateral uncinate fasciculus and corpus callosum) and the whole brain, using 3 T diffusion tensor imaging (DTI) and a tract-based spatial statistics (TBSS) approach. Psychological and cognitive functioning were assessed with validated questionnaires and clinical severity was assessed using the Cushing's syndrome Severity Index. The ROI analysis showed FA reductions in all of the hypothesized regions, with the exception of the bilateral hippocampal cingulum, in patients when compared to controls. The exploratory whole brain analysis showed multiple regions with lower FA values throughout the brain. Patients reported more apathy (p = .003) and more depressive symptoms (p < .001), whereas depression symptom severity in the patient group was negatively associated with FA in the left uncinate fasciculus (p < 0.05). Post-hoc analyses showed increased radial and mean diffusivity in the patient group. Patients with a history of endogenous hypercortisolism in present remission show widespread changes of white matter integrity in the brain, with abnormalities in the integrity of the uncinate fasciculus being related to the severity of depressive symptoms, suggesting persistent structural effects of hypercortisolism.

  16. Cerebral grey, white matter and csf in never-medicated, first-episode schizophrenia.

    PubMed

    Chua, Siew E; Cheung, Charlton; Cheung, Vinci; Tsang, Jack T K; Chen, Eric Y H; Wong, Jason C H; Cheung, Jason P Y; Yip, Lawrance; Tai, Kin-Shing; Suckling, John; McAlonan, Gráinne M

    2007-01-01

    We report the first voxel-based morphometric (VBM) study to examine cerebral grey and white matter and cerebrospinal fluid (CSF) using computational morphometry in never-medicated, first-episode psychosis (FEP). Region-of-interest (ROI) analysis was also performed blind to group membership. 26 never-medicated individuals with FEP (23 with DSM-IV schizophrenia) and 38 healthy controls had MRI brain scans. Groups were balanced for age, sex, handedness, ethnicity, paternal socio-economic status, and height. Healthy controls were recruited from the local community by advertisement. Grey matter, white matter, and CSF: global brain volume ratios were significantly smaller in patients. Patients had significantly less grey matter volume in L and R caudate nuclei, cingulate gyri, parahippocampal gyri, superior temporal gyri, cerebellum and R thalamus, prefrontal cortex. They also had significantly less white matter volume in the R anterior limb of the internal capsule fronto-occipital fasciculus and L and R fornices, and significantly greater CSF volume especially in the R lateral ventricle. Excluding the 3 subjects with brief psychotic disorder did not alter our results. Our data suggest that fronto-temporal and subcortical-limbic circuits are morphologically abnormal in never-medicated, schizophrenia. ROI analysis comparing the schizophrenia group (n=23) with the healthy controls (n=38) confirmed caudate volumes were significantly smaller bilaterally by 11%, and lateral ventricular volume was significantly larger on the right by 26% in the patients. Caudate nuclei and lateral ventricular volume measurements were uncorrelated (Pearson correlation coefficient 0.30, p=0.10), ruling out the possibility of segmentation artefact. Ratio of lateral ventricle to caudate volume was bilaterally significantly increased (p<0.005, 2-tailed), which could represent an early biomarker in first-episode, never-medicated schizophrenia.

  17. Altered temporal lobe white matter lipid ion profiles in an experimental model of sporadic Alzheimer's disease.

    PubMed

    Tong, Ming; Leão, Raiane; Vimbela, Gina V; Yalcin, Emine B; Kay, Jared; Krotow, Alexander; de la Monte, Suzanne M

    2017-07-01

    White matter is an early and important yet under-evaluated target of Alzheimer's disease (AD). Metabolic impairments due to insulin and insulin-like growth factor resistance contribute to white matter degeneration because corresponding signal transduction pathways maintain oligodendrocyte function and survival. This study utilized a model of sporadic AD in which adult Long Evans rats administered intracerebral streptozotocin (i.c. STZ) developed AD-type neurodegeneration. Temporal lobe white matter lipid ion profiles were characterized by matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS). Although the lipid ion species expressed in the i.c. STZ and control groups were virtually identical, i.c. STZ mainly altered the abundances of various lipid ions. Correspondingly, the i.c. STZ group was distinguished from control by principal component analysis and data bar plots. i.c. STZ mainly reduced expression of lipid ions with low m/z's (less than 810) as well as the upper range m/z lipids (m/z 964-986), and increased expression of lipid ions with m/z's between 888 and 937. Phospholipids were mainly included among the clusters inhibited by i.c. STZ, while both sulfatides and phospholipids were increased by i.c. STZ. However, Chi-Square analysis demonstrated significant i.c. STZ-induced trend reductions in phospholipids and increases in sulfatides (P<0.00001). The i.c. STZ model of sporadic AD is associated with broad and sustained abnormalities in temporal lobe white matter lipids. The findings suggest that the i.c. STZ model could be used for pre-clinical studies to assess therapeutic measures for their ability to restore white matter integrity in AD. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Cortical gray and subcortical white matter associations in Parkinson's disease.

    PubMed

    Sterling, Nicholas W; Du, Guangwei; Lewis, Mechelle M; Swavely, Steven; Kong, Lan; Styner, Martin; Huang, Xuemei

    2017-01-01

    Cortical atrophy has been documented in both Parkinson's disease (PD) and healthy aging, but its relationship to changes in subcortical white matter is unknown. This was investigated by obtaining T1- and diffusion-weighted images from 76 PD and 70 controls at baseline and 18 and 36 months, from which cortical volumes and underlying subcortical white matter axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) were determined. Twelve of 69 cortical subregions had significant group differences, and for these, underlying subcortical white matter was explored. At baseline, higher cortical volumes were significantly correlated with lower underlying subcortical white matter AD, RD, and higher FA (ps ≤ 0.017) in PD. Longitudinally, higher rates of cortical atrophy in PD were associated with increased rates of change in AD RD, and FA values (ps ≤ 0.0013) in 2 subregions explored. The significant gray-white matter associations were not found in controls. Thus, unlike healthy aging, cortical atrophy and subcortical white matter changes may not be independent events in PD. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Usefulness of the apparent diffusion coefficient for the evaluation of the white matter to differentiate between glioblastoma and brain metastases.

    PubMed

    Miquelini, L A; Pérez Akly, M S; Funes, J A; Besada, C H

    2016-01-01

    To determine whether there are significant differences in the apparent diffusion coefficient (ADC) between the apparently normal peritumor white matter surrounding glioblastomas and that surrounding brain metastases. We retrospectively reviewed 42 patients with histologically confirmed glioblastomas and 42 patients with a single cerebral metastasis. We measured the signal intensity in the apparently normal peritumor white matter and in the abnormal peritumor white matter on the ADC maps. We used mean ADC values in the contralateral occipital white matter as a reference from which to design normalized ADC indices. We compared mean values between the two tumor types. We calculated the area under the receiver operator characteristic curve and estimated the sensitivity and specificity of the measurements taken. Supratentorial lesions and compromise of the corpus callosum were more common in patients with glioblastoma than in patients with brain metastases. The maximum diameter of the enhanced area after injection of a contrast agent was greater in the glioblastomas (p<0.001). The minimum ADC value measured in the apparently normal peritumor white matter was higher for the glioblastomas than for the metastases (p=0.002). Significant differences in the ADC index were found only for the minimum ADC value in apparently normal peritumor white matter. The sensitivity and specificity were less than 70% for all variables analyzed. There are differences in the ADC values of apparently normal peritumor white matter between glioblastomas and cerebral metastases, but the magnitude of these differences is slight and the application of these differences in clinical practice is still limited. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

  20. White matter microstructure integrity in relation to reading proficiency☆.

    PubMed

    Nikki Arrington, C; Kulesz, Paulina A; Juranek, Jenifer; Cirino, Paul T; Fletcher, Jack M

    2017-11-01

    Components of reading proficiency such asaccuracy, fluency, and comprehension require the successful coordination of numerous, yet distinct, cortical regions. Underlying white matter tracts allow for communication among these regions. This study utilized unique residualized tract - based spatial statistics methodology to identify the relations of white matter microstructure integrity to three components of reading proficiency in 49 school - aged children with typically developing phonological decoding skills and 27 readers with poor decoders. Results indicated that measures of white matter integrity were differentially associated with components of reading proficiency. In both typical and poor decoders, reading comprehension correlated with measures of integrity of the right uncinate fasciculus; reading comprehension was also related to the left inferior longitudinal fasciculus in poor decoders. Also in poor decoders, word reading fluency was related to the right uncinate and left inferior fronto - occipital fasciculi. Word reading was unrelated to white matter integrity in either group. These findings expand our knowledge of the association between white matter integrity and different elements of reading proficiency. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Chronic Kidney Disease Is Associated With White Matter Hyperintensity Volume

    PubMed Central

    Khatri, Minesh; Wright, Clinton B.; Nickolas, Thomas L.; Yoshita, Mitsuhiro; Paik, Myunghee C.; Kranwinkel, Grace; Sacco, Ralph L.; DeCarli, Charles

    2010-01-01

    Background and Purpose White matter hyperintensities have been associated with increased risk of stroke, cognitive decline, and dementia. Chronic kidney disease is a risk factor for vascular disease and has been associated with inflammation and endothelial dysfunction, which have been implicated in the pathogenesis of white matter hyperintensities. Few studies have explored the relationship between chronic kidney disease and white matter hyperintensities. Methods The Northern Manhattan Study is a prospective, community-based cohort of which a subset of stroke-free participants underwent MRIs. MRIs were analyzed quantitatively for white matter hyperintensities volume, which was log-transformed to yield a normal distribution (log-white matter hyperintensity volume). Kidney function was modeled using serum creatinine, the Cockcroft-Gault formula for creatinine clearance, and the Modification of Diet in Renal Disease formula for estimated glomerular filtration rate. Creatinine clearance and estimated glomerular filtration rate were trichotomized to 15 to 60 mL/min, 60 to 90 mL/min, and >90 mL/min (reference). Linear regression was used to measure the association between kidney function and log-white matter hyperintensity volume adjusting for age, gender, race–ethnicity, education, cardiac disease, diabetes, homocysteine, and hypertension. Results Baseline data were available on 615 subjects (mean age 70 years, 60% women, 18% whites, 21% blacks, 62% Hispanics). In multivariate analysis, creatinine clearance 15 to 60 mL/min was associated with increased log-white matter hyperintensity volume (β 0.322; 95% CI, 0.095 to 0.550) as was estimated glomerular filtration rate 15 to 60 mL/min (β 0.322; 95% CI, 0.080 to 0.564). Serum creatinine, per 1-mg/dL increase, was also positively associated with log-white matter hyperintensity volume (β 1.479; 95% CI, 1.067 to 2.050). Conclusions The association between moderate–severe chronic kidney disease and white matter

  2. Framework for shape analysis of white matter fiber bundles.

    PubMed

    Glozman, Tanya; Bruckert, Lisa; Pestilli, Franco; Yecies, Derek W; Guibas, Leonidas J; Yeom, Kristen W

    2018-02-15

    Diffusion imaging coupled with tractography algorithms allows researchers to image human white matter fiber bundles in-vivo. These bundles are three-dimensional structures with shapes that change over time during the course of development as well as in pathologic states. While most studies on white matter variability focus on analysis of tissue properties estimated from the diffusion data, e.g. fractional anisotropy, the shape variability of white matter fiber bundle is much less explored. In this paper, we present a set of tools for shape analysis of white matter fiber bundles, namely: (1) a concise geometric model of bundle shapes; (2) a method for bundle registration between subjects; (3) a method for deformation estimation. Our framework is useful for analysis of shape variability in white matter fiber bundles. We demonstrate our framework by applying our methods on two datasets: one consisting of data for 6 normal adults and another consisting of data for 38 normal children of age 11 days to 8.5 years. We suggest a robust and reproducible method to measure changes in the shape of white matter fiber bundles. We demonstrate how this method can be used to create a model to assess age-dependent changes in the shape of specific fiber bundles. We derive such models for an ensemble of white matter fiber bundles on our pediatric dataset and show that our results agree with normative human head and brain growth data. Creating these models for a large pediatric longitudinal dataset may improve understanding of both normal development and pathologic states and propose novel parameters for the examination of the pediatric brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Medial frontal white and gray matter contributions to general intelligence.

    PubMed

    Ohtani, Toshiyuki; Nestor, Paul G; Bouix, Sylvain; Saito, Yukiko; Hosokawa, Taiga; 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.

  4. Lifespan Trajectories of White Matter Changes in Rhesus Monkeys.

    PubMed

    Kubicki, M; Baxi, M; Pasternak, O; Tang, Y; Karmacharya, S; Chunga, N; Lyall, A E; Rathi, Y; Eckbo, R; Bouix, S; Mortazavi, F; Papadimitriou, G; Shenton, M E; Westin, C F; Killiany, R; Makris, N; Rosene, D L

    2018-04-26

    Progress in neurodevelopmental brain research has been achieved through the use of animal models. Such models not only help understanding biological changes that govern brain development, maturation and aging, but are also essential for identifying possible mechanisms of neurodevelopmental and age-related chronic disorders, and to evaluate possible interventions with potential relevance to human disease. Genetic relationship of rhesus monkeys to humans makes those animals a great candidate for such models. With the typical lifespan of 25 years, they undergo cognitive maturation and aging that is similar to this observed in humans. Quantitative structural neuroimaging has been proposed as one of the candidate in vivo biomarkers for tracking white matter brain maturation and aging. While lifespan trajectories of white matter changes have been mapped in humans, such knowledge is not available for nonhuman primates. Here, we analyze and model lifespan trajectories of white matter microstructure using in vivo diffusion imaging in a sample of 44 rhesus monkeys. We report quantitative parameters (including slopes and peaks) of lifespan trajectories for 8 individual white matter tracts. We show different trajectories for cellular and extracellular microstructural imaging components that are associated with white matter maturation and aging, and discuss similarities and differences between those in humans and rhesus monkeys, the importance of our findings, and future directions for the field.Significance Statement: Quantitative structural neuroimaging has been proposed as one of the candidate in vivo biomarkers for tracking brain maturation and aging. While lifespan trajectories of structural white matter changes have been mapped in humans, such knowledge is not available for rhesus monkeys. We present here results of the analysis and modeling of the lifespan trajectories of white matter microstructure using in vivo diffusion imaging in a sample of 44 rhesus monkeys (age 4

  5. 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…

  6. White and gray matter damage in primary progressive MS

    PubMed Central

    Chard, Declan; Altmann, Daniel R.; Tozer, Daniel; Miller, David H.; Thompson, Alan J.; Wheeler-Kingshott, Claudia; Ciccarelli, Olga

    2016-01-01

    Objective: The temporal relationship between white matter (WM) and gray matter (GM) damage in vivo in early primary progressive multiple sclerosis (PPMS) was investigated testing 2 hypotheses: (1) WM tract abnormalities predict subsequent changes in the connected cortex (“primary WM damage model”); and (2) cortical abnormalities predict later changes in connected WM tracts (“primary GM damage model”). Methods: Forty-seven patients with early PPMS and 18 healthy controls had conventional and magnetization transfer imaging at baseline; a subgroup of 35 patients repeated the protocol after 2 years. Masks of the corticospinal tracts, genu of the corpus callosum and optic radiations, and of connected cortical regions, were used for extracting the mean magnetization transfer ratio (MTR). Multiple regressions within each of 5 tract-cortex pairs were performed, adjusting for the dependent variable's baseline MTR; tract lesion load and MTR, spinal cord area, age, and sex were examined for potential confounding. Results: The baseline MTR of most regions was lower in patients than in healthy controls. The tract-cortex pair relationships in the primary WM damage model were significant for the bilateral motor pair and right visual pair, while those in the primary GM damage model were only significant for the right motor pair. Lower lesion MTR at baseline was associated with lower MTR in the same tract normal-appearing WM at 2 years in 3 tracts. Conclusion: These results are consistent with the hypothesis that in early PPMS, cortical damage is for the most part a sequela of normal-appearing WM pathology, which, in turn, is predicted by abnormalities within WM lesions. PMID:26674332

  7. Association of Retinopathy and Retinal Microvascular Abnormalities With Stroke and Cerebrovascular Disease.

    PubMed

    Hughes, Alun D; Falaschetti, Emanuela; Witt, Nicholas; Wijetunge, Sumangali; Thom, Simon A McG; Tillin, Therese; Aldington, Steve J; Chaturvedi, Nish

    2016-11-01

    Abnormalities of the retinal circulation may be associated with cerebrovascular disease. We investigated associations between retinal microvascular abnormalities and (1) strokes and subclinical cerebral infarcts and (2) cerebral white matter lesions in a UK-based triethnic population-based cohort. A total of 1185 participants (age, 68.8±6.1 years; 77% men) underwent retinal imaging and cerebral magnetic resonance imaging. Cerebral infarcts and white matter hyperintensities were identified on magnetic resonance imaging, retinopathy was graded, and retinal vessels were measured. Higher retinopathy grade (odds ratio [OR], 1.40 [95% confidence interval (95% CI), 1.16-1.70]), narrower arteriolar diameter (OR, 0.98 [95% CI, 0.97-0.99]), fewer symmetrical arteriolar bifurcations (OR, 0.84 [95% CI, 0.75-0.95]), higher arteriolar optimality deviation (OR, 1.16 [95% CI, 1.00-1.34]), and more tortuous venules (OR, 1.20 [95% CI, 1.09-1.32]) were associated with strokes/infarcts and white matter hyperintensities. Associations with quantitative retinal microvascular measures were independent of retinopathy. Abnormalities of the retinal microvasculature are independently associated with stroke, cerebral infarcts, and white matter lesions. © 2016 American Heart Association, Inc.

  8. Neonatal Brain Abnormalities and Memory and Learning Outcomes at 7 Years in Children Born Very Preterm

    PubMed Central

    Omizzolo, Cristina; Scratch, Shannon E; Stargatt, Robyn; Kidokoro, Hiroyuki; Thompson, Deanne K; Lee, Katherine J; Cheong, Jeanie; Neil, Jeffrey; Inder, Terrie E; Doyle, Lex W; Anderson, Peter J

    2014-01-01

    Using prospective longitudinal data from 198 very preterm and 70 full term children, this study characterised the memory and learning abilities of very preterm children at 7 years of age in both verbal and visual domains. The relationship between the extent of brain abnormalities on neonatal magnetic resonance imaging (MRI) and memory and learning outcomes at 7 years of age in very preterm children was also investigated. Neonatal MRI scans were qualitatively assessed for global, white-matter, cortical grey-matter, deep grey-matter, and cerebellar abnormalities. Very preterm children performed less well on measures of immediate memory, working memory, long-term memory, and learning compared with term born controls. Neonatal brain abnormalities, and in particular deep grey matter abnormality, were associated with poorer memory and learning performance at 7 years in very preterm children, especially global, white-matter, grey-matter and cerebellar abnormalities. Findings support the importance of cerebral neonatal pathology for predicting later memory and learning function. PMID:23805915

  9. Normal gray and white matter volume after weight restoration in adolescents with anorexia nervosa.

    PubMed

    Lázaro, Luisa; Andrés, Susana; Calvo, Anna; Cullell, Clàudia; Moreno, Elena; Plana, M Teresa; Falcón, Carles; Bargalló, Núria; Castro-Fornieles, Josefina

    2013-12-01

    The aim of this study was to determine whether treated, weight-stabilized adolescents with anorexia nervosa (AN) present brain volume differences in comparison with healthy controls. Thirty-five adolescents with weight-recovered AN and 17 healthy controls were assessed by means of psychopathology scales and magnetic resonance imaging. Axial three-dimensional T1-weighted images were obtained in a 1.5 Tesla scanner and analyzed using optimized voxel-based morphometry (VBM). There were no significant differences between controls and weight-stabilized AN patients with regard to global volumes of either gray or white brain matter, or in the regional VBM study. Differences were not significant between patients with psychopharmacological treatment and without, between those with amenorrhea and without, as well as between patients with restrictive versus purgative AN. The present findings reveal no global or regional gray or white matter abnormalities in this sample of adolescents following weight restoration. Copyright © 2013 Wiley Periodicals, Inc.

  10. White matter disease and cognitive impairment in FMR1 premutation carriers.

    PubMed

    Filley, Christopher M; Brown, Mark S; Onderko, Karen; Ray, Megan; Bennett, Rachael E; Berry-Kravis, Elizabeth; Grigsby, Jim

    2015-05-26

    This cross-sectional, observational study examined the role of white matter involvement in the cognitive impairment of individuals with the fragile X mental retardation 1 (FMR1) premutation. Eight asymptomatic premutation carriers, 5 participants with fragile X tremor/ataxia syndrome (FXTAS), and 7 noncarrier controls were studied. The mean age of the asymptomatic premutation carriers, participants with FXTAS, and noncarrier controls was 60, 71, and 67 years, respectively. Magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) were used to examine the middle cerebellar peduncles (MCP) and the genu and splenium of the corpus callosum in relation to executive function and processing speed. MRS measures were N-acetyl aspartate/creatine (NAA/Cr) and choline/creatine, and fractional anisotropy (FA) was used for DTI. Executive function was assessed with the Behavioral Dyscontrol Scale and the Controlled Oral Word Association Test (COWAT), and processing speed with the Symbol Digit Modalities Test. Among all 13 FMR1 premutation carriers, significant correlations were found between N-acetyl aspartate/creatine and choline/creatine in the MCP and COWAT scores, and between FA in the genu and performance on the Behavioral Dyscontrol Scale, COWAT, and Symbol Digit Modalities Test; a correlation was also found between FA in the splenium and COWAT performance. In all regions studied, participants with FXTAS had the lowest mean FA. Microstructural white matter disease as determined by MRS and DTI correlated with executive dysfunction and slowed processing speed in these FMR1 premutation carriers. Neuroimaging abnormalities in the genu and MCP suggest that disruption of white matter within frontocerebellar networks has an important role in the cognitive impairment associated with the FMR1 premutation. © 2015 American Academy of Neurology.

  11. Characterization of White Matter Injury in a Rat Model of Chronic Cerebral Hypoperfusion.

    PubMed

    Choi, Bo-Ryoung; Kim, Dong-Hee; Back, Dong Bin; Kang, Chung Hwan; Moon, Won-Jin; Han, Jung-Soo; Choi, Dong-Hee; Kwon, Kyoung Ja; Shin, Chan Young; Kim, Bo-Ram; Lee, Jongmin; Han, Seol-Heui; Kim, Hahn Young

    2016-02-01

    Chronic cerebral hypoperfusion can lead to ischemic white matter injury resulting in vascular dementia. To characterize white matter injury in vascular dementia, we investigated disintegration of diverse white matter components using a rat model of chronic cerebral hypoperfusion. Chronic cerebral hypoperfusion was modeled in Wistar rats by permanent occlusion of the bilateral common carotid arteries. We performed cognitive behavioral tests, including the water maze task, odor discrimination task, and novel object test; histological investigation of neuroinflammation, oligodendrocytes, myelin basic protein, and nodal or paranodal proteins at the nodes of Ranvier; and serial diffusion tensor imaging. Cilostazol was administered to protect against white matter injury. Diverse cognitive impairments were induced by chronic cerebral hypoperfusion. Disintegration of white matter was characterized by neuroinflammation, loss of oligodendrocytes, attenuation of myelin density, structural derangement at the nodes of Ranvier, and disintegration of white matter tracts. Cilostazol protected against cognitive impairments and white matter disintegration. White matter injury induced by chronic cerebral hypoperfusion can be characterized by disintegration of diverse white matter components. Cilostazol might be a therapeutic strategy against white matter disintegration in patients with vascular dementia. © 2015 American Heart Association, Inc.

  12. Widespread reductions of white matter integrity in patients with long-term remission of Cushing's disease

    PubMed Central

    van der Werff, Steven J.A.; Andela, Cornelie D.; Nienke Pannekoek, J.; Meijer, Onno C.; van Buchem, Mark A.; Rombouts, Serge A.R.B.; van der Mast, Roos C.; Biermasz, Nienke R.; Pereira, Alberto M.; van der Wee, Nic J.A.

    2014-01-01

    Background Hypercortisolism leads to various physical, psychological and cognitive symptoms, which may partly persist after the treatment of Cushing's disease. The aim of the present study was to investigate abnormalities in white matter integrity in patients with long-term remission of Cushing's disease, and their relation with psychological symptoms, cognitive impairment and clinical characteristics. Methods In patients with long-term remission of Cushing's disease (n = 22) and matched healthy controls (n = 22) we examined fractional anisotropy (FA) values of white matter in a region-of-interest (ROI; bilateral cingulate cingulum, bilateral hippocampal cingulum, bilateral uncinate fasciculus and corpus callosum) and the whole brain, using 3 T diffusion tensor imaging (DTI) and a tract-based spatial statistics (TBSS) approach. Psychological and cognitive functioning were assessed with validated questionnaires and clinical severity was assessed using the Cushing's syndrome Severity Index. Results The ROI analysis showed FA reductions in all of the hypothesized regions, with the exception of the bilateral hippocampal cingulum, in patients when compared to controls. The exploratory whole brain analysis showed multiple regions with lower FA values throughout the brain. Patients reported more apathy (p = .003) and more depressive symptoms (p < .001), whereas depression symptom severity in the patient group was negatively associated with FA in the left uncinate fasciculus (p < 0.05). Post-hoc analyses showed increased radial and mean diffusivity in the patient group. Conclusion Patients with a history of endogenous hypercortisolism in present remission show widespread changes of white matter integrity in the brain, with abnormalities in the integrity of the uncinate fasciculus being related to the severity of depressive symptoms, suggesting persistent structural effects of hypercortisolism. PMID:24936417

  13. White Matter Microstructure Correlates of Narrative Production in Typically Developing Children and Children with High Functioning Autism

    PubMed Central

    Mills, Brian; Lai, Janie; Brown, Timothy T.; Erhart, Matthew; Halgren, Eric; Reilly, Judy; Dale, Anders; Appelbaum, Mark; Moses, Pamela

    2013-01-01

    This study investigated the relationship between white matter microstructure and the development of morphosyntax in a spoken narrative in typically developing children (TD) and in children with high functioning autism (HFA). Autism is characterized by language and communication impairments, yet the relationship between morphosyntactic development in spontaneous discourse contexts and neural development is not well understood in either this population or typical development. Diffusion tensor imaging (DTI) was used to assess multiple parameters of diffusivity as indicators of white matter tract integrity in language-related tracts in children between 6 and 13 years of age. Children were asked to spontaneously tell a story about at time when someone made them sad, mad, or angry. The story was evaluated for morphological accuracy and syntactic complexity. Analysis of the relationship between white matter microstructure and language performance in TD children showed that diffusivity correlated with morphosyntax production in the superior longitudinal fasciculus (SLF), a fiber tract traditionally associated with language. At the anatomical level, the HFA group showed abnormal diffusivity in the right inferior longitudinal fasciculus (ILF) relative to the TD group. Within the HFA group, children with greater white matter integrity in the right ILF displayed greater morphological accuracy during their spoken narrative. Overall, the current study shows an association between white matter structure in a traditional language pathway and narrative performance in TD children. In the autism group, associations were only found in the ILF, suggesting that during real world language use, children with HFA rely less on typical pathways and instead rely on alternative ventral pathways that possibly mediate visual elements of language. PMID:23810972

  14. 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…

  15. Brain-peripheral cell crosstalk in white matter damage and repair.

    PubMed

    Hayakawa, Kazuhide; Lo, Eng H

    2016-05-01

    White matter damage is an important part of cerebrovascular disease and may be a significant contributing factor in vascular mechanisms of cognitive dysfunction and dementia. It is well accepted that white matter homeostasis involves multifactorial interactions between all cells in the axon-glia-vascular unit. But more recently, it has been proposed that beyond cell-cell signaling within the brain per se, dynamic crosstalk between brain and systemic responses such as circulating immune cells and stem/progenitor cells may also be important. In this review, we explore the hypothesis that peripheral cells contribute to damage and repair after white matter damage. Depending on timing, phenotype and context, monocyte/macrophage can possess both detrimental and beneficial effects on oligodendrogenesis and white matter remodeling. Endothelial progenitor cells (EPCs) can be activated after CNS injury and the response may also influence white matter repair process. These emerging findings support the hypothesis that peripheral-derived cells can be both detrimental or beneficial in white matter pathology in cerebrovascular disease. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Mapping White Matter Microstructure in the One Month Human Brain.

    PubMed

    Dean, D C; Planalp, E M; Wooten, W; Adluru, N; Kecskemeti, S R; Frye, C; Schmidt, C K; Schmidt, N L; Styner, M A; Goldsmith, H H; Davidson, R J; Alexander, A L

    2017-08-29

    White matter microstructure, essential for efficient and coordinated transmission of neural communications, undergoes pronounced development during the first years of life, while deviations to this neurodevelopmental trajectory likely result in alterations of brain connectivity relevant to behavior. Hence, systematic evaluation of white matter microstructure in the normative brain is critical for a neuroscientific approach to both typical and atypical early behavioral development. However, few studies have examined the infant brain in detail, particularly in infants under 3 months of age. Here, we utilize quantitative techniques of diffusion tensor imaging and neurite orientation dispersion and density imaging to investigate neonatal white matter microstructure in 104 infants. An optimized multiple b-value diffusion protocol was developed to allow for successful acquisition during non-sedated sleep. Associations between white matter microstructure measures and gestation corrected age, regional asymmetries, infant sex, as well as newborn growth measures were assessed. Results highlight changes of white matter microstructure during the earliest periods of development and demonstrate differential timing of developing regions and regional asymmetries. Our results contribute to a growing body of research investigating the neurobiological changes associated with neurodevelopment and suggest that characteristics of white matter microstructure are already underway in the weeks immediately following birth.

  17. Genetic disorders affecting white matter in the pediatric age.

    PubMed

    Di Rocco, Maja; Biancheri, Roberta; Rossi, Andrea; Filocamo, Mirella; Tortori-Donati, Paolo

    2004-08-15

    Pediatric white matter disorders can be distinguished into well-defined leukoencephalopathies, and undefined leukoencephalopathies. The first category may be subdivided into: (a) hypomyelinating disorders; (b) dysmyelinating disorders; (c) leukodystrophies; (d) disorders related to cystic degeneration of myelin; and (e) disorders secondary to axonal damage. The second category, representing up to 50% of leukoencephalopathies in childhood, requires a multidisciplinar approach in order to define novel homogeneous subgroups of patients, possibly representing "new genetic disorders" (such as megalencephalic leukoencepahlopathy with subcortical cysts and vanishing white matter disease that have recently been identified). In the majority of cases, pediatric white matter disorders are inherited diseases. An integrated description of the clinical, neuroimaging and pathophysiological features is crucial for categorizing myelin disorders and better understanding their genetic basis. A review of the genetic disorders affecting white matter in the pediatric age, including some novel entities, is provided. Copyright 2004 Wiley-Liss, Inc.

  18. The association of mid-to late-life systemic inflammation with white matter structure in older adults: The Atherosclerosis Risk in Communities Study.

    PubMed

    Walker, Keenan A; Windham, B Gwen; Power, Melinda C; Hoogeveen, Ron C; Folsom, Aaron R; Ballantyne, Christie M; Knopman, David S; Selvin, Elizabeth; Jack, Clifford R; Gottesman, Rebecca F

    2018-08-01

    We examined whether the pattern of middle- to late-life systemic inflammation was associated with white matter (WM) structural abnormalities in older adults. A total of 1532 participants (age = 76.5; standard deviations = 5.4) underwent 3T brain magnetic resonance imaging to quantify white matter hyperintensity volume and whole-brain WM microstructural integrity (fractional anisotropy, mean diffusivity). High-sensitivity C-reactive protein (CRP), a marker of systemic inflammation, was measured at 3 visits (21 and 14 years before, and concurrent with, neuroimaging). Participants were categorized into 1 of 6 groups based on their 21-year pattern of low (<3 mg/L) versus elevated (≥3 mg/L) CRP. Compared to the group with low CRP at all 3 visits, the group that transitioned from low to elevated CRP during midlife demonstrated greatest white matter hyperintensity volume and poorest WM microstructural integrity, after adjusting for demographic variables and cardiovascular risk factors. Participants with high CRP at all visits also demonstrated greater WM structural abnormalities, but only after accounting for differential attrition. These results suggest that increasing and persistent inflammation in the decades spanning middle-to late-life may promote WM disease in older adults. Copyright © 2018 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2014-01-03

    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. © 2013.

  20. 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

  1. White matter microstructure in boys with persistent depressive disorder.

    PubMed

    Vilgis, Veronika; Vance, Alasdair; Cunnington, Ross; Silk, Timothy J

    2017-10-15

    Persistent depressive symptoms in children and adolescents are considered a risk factor for the development of major depressive disorder (MDD) later in life. Previous research has shown alterations in white matter microstructure in pediatric MDD but discrepancies exist as to the specific tracts affected. The current study aimed to improve upon previous methodology and address the question whether previous findings of lower fractional anisotropy (FA) replicate in a sample of children with persistent depressive disorder characterized by mild but more chronic symptoms of depression. White matter microstructure was examined in 25 boys with persistent depressive disorder and 25 typically developing children. Tract specific analysis implemented with the Diffusion Tensor Imaging - ToolKit (DTI-TK) was used to probe fractional anisotropy (FA) in eleven major white matter tracts. Clusters within the left uncinate, inferior fronto-occipital and cerebrospinal tracts showed lower FA in the clinical group. FA in the left uncinate showed a negative association with self-reported symptoms of depression. The results demonstrate lower FA in several white matter tracts in children with persistent depressive disorder. These findings support the contention that early onset depression is associated with altered white matter microstructure, which may contribute to the maintenance and recurrence of symptoms. Copyright © 2017. Published by Elsevier B.V.

  2. White matter hyperintensities and headache: A population-based imaging study (HUNT MRI).

    PubMed

    Honningsvåg, Lasse-Marius; Håberg, Asta Kristine; Hagen, Knut; Kvistad, Kjell Arne; Stovner, Lars Jacob; Linde, Mattias

    2018-01-01

    Objective To examine the relationship between white matter hyperintensities and headache. Methods White matter hyperintensities burden was assessed semi-quantitatively using Fazekas and Scheltens scales, and by manual and automated volumetry of MRI in a sub-study of the general population-based Nord-Trøndelag Health Study (HUNT MRI). Using validated questionnaires, participants were categorized into four cross-sectional headache groups: Headache-free (n = 551), tension-type headache (n = 94), migraine (n = 91), and unclassified headache (n = 126). Prospective questionnaire data was used to further categorize participants into groups according to the evolution of headache during the last 12 years: Stable headache-free, past headache, new onset headache, and persistent headache. White matter hyperintensities burden was compared across headache groups using adjusted multivariate regression models. Results Individuals with tension-type headache were more likely to have extensive white matter hyperintensities than headache-free subjects, with this being the case across all methods of white matter hyperintensities assessment (Scheltens scale: Odds ratio, 2.46; 95% CI, 1.44-4.20). Migraine or unclassified headache did not influence the odds of having extensive white matter hyperintensities. Those with new onset headache were more likely to have extensive white matter hyperintensities than those who were stable headache-free (Scheltens scale: Odds ratio, 2.24; 95% CI, 1.13-4.44). Conclusions Having tension-type headache or developing headache in middle age was linked to extensive white matter hyperintensities. These results were similar across all methods of assessing white matter hyperintensities. If white matter hyperintensities treatment strategies emerge in the future, this association should be taken into consideration.

  3. 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.

  4. White matter tractography using diffusion tensor deflection.

    PubMed

    Lazar, Mariana; Weinstein, David M; Tsuruda, Jay S; Hasan, Khader M; Arfanakis, Konstantinos; Meyerand, M Elizabeth; Badie, Benham; Rowley, Howard A; Haughton, Victor; Field, Aaron; Alexander, Andrew L

    2003-04-01

    Diffusion tensor MRI provides unique directional diffusion information that can be used to estimate the patterns of white matter connectivity in the human brain. In this study, the behavior of an algorithm for white matter tractography is examined. The algorithm, called TEND, uses the entire diffusion tensor to deflect the estimated fiber trajectory. Simulations and imaging experiments on in vivo human brains were performed to investigate the behavior of the tractography algorithm. The simulations show that the deflection term is less sensitive than the major eigenvector to image noise. In the human brain imaging experiments, estimated tracts were generated in corpus callosum, corticospinal tract, internal capsule, corona radiata, superior longitudinal fasciculus, inferior longitudinal fasciculus, fronto-occipital fasciculus, and uncinate fasciculus. This approach is promising for mapping the organizational patterns of white matter in the human brain as well as mapping the relationship between major fiber trajectories and the location and extent of brain lesions. Copyright 2003 Wiley-Liss, Inc.

  5. White matter correlates of psychopathic traits in a female community sample

    PubMed Central

    Budhiraja, Meenal; Westerman, Johan; Savic, Ivanka; Jokinen, Jussi; Tiihonen, Jari; Hodgins, Sheilagh

    2017-01-01

    Abstract Psychopathy comprises interpersonal, affective, lifestyle and antisocial facets that vary dimensionally in the population and are associated with criminal offending and adverse psychosocial outcomes. Evidence associating these facets with white matter microstructure of the uncinate fasciculus and the cingulum tracts is inconsistent and derives principally from studies of male offenders. In a sample of 99 young women presenting a range of scores on the Psychopathy Checklist: Screening Version, we used Diffusion Tensor Imaging, tractography and Tract-Based Spatial Statistics to investigate microstructure across the brain and of the uncinate fasciculus and cingulum. Right uncinate fasciculus microstructure was negatively associated with the interpersonal facet, while cingulum integrity was not associated with any facet of psychopathy. Whole-brain analyses revealed that both affective and lifestyle facets were negatively correlated with white matter microstructure adjacent to the fusiform gyrus, and the interpersonal facet correlated negatively with the integrity of the fornix. Findings survived adjustment for the other facet scores, and age, verbal and performance IQ. A similar negative association between the interpersonal facet and uncinate fasciculus integrity was previously observed in male offenders. Thus, previous evidence showing that psychopathic traits are associated with functional and structural abnormalities within limbic networks may also apply to females. PMID:28992269

  6. Structural abnormality of the corticospinal tract in major depressive disorder

    PubMed Central

    2014-01-01

    Background Scientists are beginning to document abnormalities in white matter connectivity in major depressive disorder (MDD). Recent developments in diffusion-weighted image analyses, including tractography clustering methods, may yield improved characterization of these white matter abnormalities in MDD. In this study, we acquired diffusion-weighted imaging data from MDD participants and matched healthy controls. We analyzed these data using two tractography clustering methods: automated fiber quantification (AFQ) and the maximum density path (MDP) procedure. We used AFQ to compare fractional anisotropy (FA; an index of water diffusion) in these two groups across major white matter tracts. Subsequently, we used the MDP procedure to compare FA differences in fiber paths related to the abnormalities in major fiber tracts that were identified using AFQ. Results FA was higher in the bilateral corticospinal tracts (CSTs) in MDD (p’s < 0.002). Secondary analyses using the MDP procedure detected primarily increases in FA in the CST-related fiber paths of the bilateral posterior limbs of the internal capsule, right superior corona radiata, and the left external capsule. Conclusions This is the first study to implicate the CST and several related fiber pathways in MDD. These findings suggest important new hypotheses regarding the role of CST abnormalities in MDD, including in relation to explicating CST-related abnormalities to depressive symptoms and RDoC domains and constructs. PMID:25295159

  7. Implications of white striping and wooden breast abnormalities on quality traits of raw and marinated chicken meat.

    PubMed

    Mudalal, S; Lorenzi, M; Soglia, F; Cavani, C; Petracci, M

    2015-04-01

    One of the consequences of intense genetic selection for growth of poultry is the recent appearance of abnormalities in chicken breast muscles, such as white striping (characterised by superficial white striations) and wooden breast (characterised by pale and bulged areas with substantial hardness). The aim of this study was to evaluate the quality traits of chicken fillets affected by white striping and wooden breast abnormalities. In two replications, 192 fillets were divided into the following four classes: normal (n=48; absence of any visual defects), white striping (n=48, presence of white striations), wooden breast (n=48; diffusely presence of hardened areas) and white striping/wooden breast (n=48; fillets affected by both abnormalities). Morphology, raw meat texture and technological properties were assessed in both unprocessed (pH, colour, drip loss, cooking loss and cooked meat shear force) and marinated meat (marinade uptake, purge loss, cooking loss and cooked meat shear force). Fillets affected by white striping, wooden breast or both abnormalities exhibited higher breast weights compared with normal fillets (305.5, 298.7, 318.3 and 244.7 g, respectively; P<0.001). Wooden breast, either alone or in combination with white striping, was associated with a significant (P<0.001) increase of fillet thickness in the caudal area and raw meat hardness compared with both normal and the white striping abnormality, for which there was no difference. Overall, the occurrence of the individual and combined white striping and wooden breast abnormalities resulted in substantial reduction in the quality of breast meat, although these abnormalities are associated with distinct characteristics. Wooden breast fillets showed lower marinade uptake and higher cooking losses than white-striped fillets for both unprocessed and marinated meats. On the other hand, white-striped fillets showed a moderate decline in marinade and cooking yield. Fillets affected by both abnormalities

  8. Sex-related difference in human white matter volumes studied: Inspection of the corpus callosum and other white matter by VBM

    NASA Astrophysics Data System (ADS)

    Shiino, Akihiko; Chen, Yen-Wei; Tanigaki, Kenji; Yamada, Atsushi; Vigers, Piers; Watanabe, Toshiyuki; Tooyama, Ikuo; Akiguchi, Ichiro

    2017-01-01

    It has been contended that any observed difference of the corpus callosum (CC) size between men and women is not sex-related but brain-size-related. A recent report, however, showed that the midsagittal CC area was significantly larger in women in 37 brain-size-matched pairs of normal young adults. Since this constituted strong evidence of sexual dimorphism and was obtained from publicly available data in OASIS, we examined volume differences within the CC and in other white matter using voxel-based morphometry (VBM). We created a three-dimensional region of interest of the CC and measured its volume. The VBM statistics were analyzed by permutation test and threshold-free cluster enhancement (TFCE) with the significance levels at FWER < 0.05. The CC volume was significantly larger in women in the same 37 brain-size-matched pairs. We found that the CC genu was the subregion showing the most significant sex-related difference. We also found that white matter in the bilateral anterior frontal regions and the left lateral white matter near to Broca’s area were larger in women, whereas there were no significant larger regions in men. Since we used brain-size-matched subjects, our results gave strong volumetric evidence of localized sexual dimorphism of white matter.

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

    PubMed

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

    2015-03-20

    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.

  10. White matter changes and word finding failures with increasing age.

    PubMed

    Stamatakis, Emmanuel A; Shafto, Meredith A; Williams, Guy; Tam, Phyllis; Tyler, Lorraine K

    2011-01-07

    Increasing life expectancy necessitates the better understanding of the neurophysiological underpinnings of age-related cognitive changes. The majority of research examining structural-cognitive relationships in aging focuses on the role of age-related changes to grey matter integrity. In the current study, we examined the relationship between age-related changes in white matter and language production. More specifically, we concentrated on word-finding failures, which increase with age. We used Diffusion tensor MRI (a technique used to image, in vivo, the diffusion of water molecules in brain tissue) to relate white matter integrity to measures of successful and unsuccessful picture naming. Diffusion tensor images were used to calculate Fractional Anisotropy (FA) images. FA is considered to be a measure of white matter organization/integrity. FA images were related to measures of successful picture naming and to word finding failures using voxel-based linear regression analyses. Successful naming rates correlated positively with white matter integrity across a broad range of regions implicated in language production. However, word finding failure rates correlated negatively with a more restricted region in the posterior aspect of superior longitudinal fasciculus. The use of DTI-MRI provides evidence for the relationship between age-related white matter changes in specific language regions and word finding failures in old age.

  11. Age Differentiation within Gray Matter, White Matter, and between Memory and White Matter in an Adult Life Span Cohort.

    PubMed

    de Mooij, Susanne M M; Henson, Richard N A; Waldorp, Lourens J; Kievit, Rogier A

    2018-06-20

    It is well established that brain structures and cognitive functions change across the life span. A long-standing hypothesis called "age differentiation" additionally posits that the relations between cognitive functions also change with age. To date, however, evidence for age-related differentiation is mixed, and no study has examined differentiation of the relationship between brain and cognition. Here we use multigroup structural equation models (SEMs) and SEM trees to study differences within and between brain and cognition across the adult life span (18-88 years) in a large ( N > 646, closely matched across sexes), population-derived sample of healthy human adults from the Cambridge Centre for Ageing and Neuroscience (www.cam-can.org). After factor analyses of gray matter volume (from T1- and T2-weighted MRI) and white matter organization (fractional anisotropy from diffusion-weighted MRI), we found evidence for the differentiation of gray and white matter, such that the covariance between brain factors decreased with age. However, we found no evidence for age differentiation among fluid intelligence, language, and memory, suggesting a relatively stable covariance pattern among cognitive factors. Finally, we observed a specific pattern of age differentiation between brain and cognitive factors, such that a white matter factor, which loaded most strongly on the hippocampal cingulum, became less correlated with memory performance in later life. These patterns are compatible with the reorganization of cognitive functions in the face of neural decline, and/or with the emergence of specific subpopulations in old age. SIGNIFICANCE STATEMENT The theory of age differentiation posits age-related changes in the relationships among cognitive domains, either weakening (differentiation) or strengthening (dedifferentiation), but evidence for this hypothesis is mixed. Using age-varying covariance models in a large cross-sectional adult life span sample, we found age

  12. Loss of Cation-Chloride Cotransporter Expression in Preterm Infants With White Matter Lesions: Implications for the Pathogenesis of Epilepsy

    PubMed Central

    Robinson, Shenandoah; Mikolaenko, Irina; Thompson, Ian; Cohen, Mark L.; Goyal, Monisha

    2011-01-01

    Epilepsy associated with preterm birth is often refractory to anticonvulsants. Children who are born preterm are also prone to cognitive delay and behavioral problems. Brains from these children often show diffuse abnormalities in cerebral circuitry that is likely caused by disrupted development during critical stages of cortical formation. To test the hypothesis that prenatal injury impairs the developmental switch of γ-amino butyric acid (GABA)ergic synapses from excitatory to inhibitory, thereby disrupting cortical circuit formation and predisposing to epilepsy, we used immunohistochemistry to compare the expression of cation-chloride transporters that developmentally regulate postsynaptic GABAergic discharges in postmortem cerebral samples from infants born preterm with known white matter injury (n = 11) with that of controls with minimal white matter gliosis (n = 7). Controls showed the expected developmental expression of cation-chloride transporters NKCC1 and KCC2 and of calretinin, a marker of a GABAergic neuronal subpopulation. Samples from infants with white matter damage showed a significant loss of expression of both NKCC1 and KCC2 in subplate and white matter. By contrast, there were no significant differences in total cell number or glutamate transporter VGLUT1 expression. Together, these novel findings suggest a molecular mechanism involved in the disruption of a critical stage of cerebral circuit development after brain injury from preterm birth that may predispose to epilepsy. PMID:20467335

  13. Financial Literacy is Associated with White Matter Integrity in Old Age

    PubMed Central

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

    2016-01-01

    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

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

    PubMed

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

    2016-06-01

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

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

    PubMed Central

    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.

    2016-01-01

    Abstract 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

  16. White Matter Integrity Reductions in Intermittent Explosive Disorder

    PubMed Central

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

    2016-01-01

    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. 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.

  18. Increased White Matter Inflammation in Aging- and Alzheimer's Disease Brain.

    PubMed

    Raj, Divya; Yin, Zhuoran; Breur, Marjolein; Doorduin, Janine; Holtman, Inge R; Olah, Marta; Mantingh-Otter, Ietje J; Van Dam, Debby; De Deyn, Peter P; den Dunnen, Wilfred; Eggen, Bart J L; Amor, Sandra; Boddeke, Erik

    2017-01-01

    Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer's disease (AD)-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis. Particularly in white matter microglia of 24-month-old mice, abundant expression of phagocytic markers including Mac-2, Axl, CD16/32, Dectin1, CD11c, and CD36 was detected. Interestingly, in white matter of human brain tissue the first signs of inflammatory activity were already detected during middle age. Thus quantification of microglial proteins, such as CD68 (commonly associated with phagocytosis) and HLA-DR (associated with antigen presentation), in postmortem human white matter brain tissue showed an age-dependent increase in immunoreactivity already in middle-aged people (53.2 ± 2.0 years). This early inflammation was also detectable by non-invasive positron emission tomography imaging using [ 11 C]-(R)-PK11195, a ligand that binds to activated microglia. Increased microglia activity was also prominently present in the white matter of human postmortem early-onset AD (EOAD) brain tissue. Interestingly, microglia activity in the white matter of late-onset AD (LOAD) CNS was similar to that of the aged clinically silent AD cases. These data indicate that microglia-induced neuroinflammation is predominant in the white matter of aging mice and humans as well as in EOAD brains. This white matter inflammation may contribute to the progression of neurodegeneration, and have prognostic value for detecting the onset and progression of aging and neurodegeneration.

  19. Effects of exercise on capillaries in the white matter of transgenic AD mice.

    PubMed

    Zhang, Yi; Chao, Feng-Lei; Zhou, Chun-Ni; Jiang, Lin; Zhang, Lei; Chen, Lin-Mu; Luo, Yan-Min; Xiao, Qian; Tang, Yong

    2017-09-12

    Previous studies have shown that exercise can prevent white matter atrophy in APP/PS1 transgenic Alzheimer's disease (AD) mice. However, the mechanism of this protective effect remains unknown. To further understand this issue, we investigated the effects of exercise on the blood supply of white matter in transgenic AD mice. Six-month-old male APP/PS1 mice were randomly divided into a control group and a running group, and age-matched non-transgenic littermates were used as a wild-type control group. Mice in the running group ran on a treadmill at low intensity for four months. Then, spatial learning and memory abilities, white matter and white matter capillaries were examined in all mice. The 10-month-old AD mice exhibited deficits in cognitive function, and 4 months of exercise improved these deficits. The white matter volume and the total length, total volume and total surface area of the white matter capillaries were decreased in the 10-month-old AD mice, and 4 months of exercise dramatically delayed the changes in these parameters in the AD mice. Our results demonstrate that even low-intensity running exercise can improve spatial learning and memory abilities, delay white matter atrophy and protect white matter capillaries in early-stage AD mice. Protecting capillaries might be an important structural basis for the exercise-induced protection of the structural integrity of white matter in AD.

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

    PubMed Central

    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

    2016-01-01

    Abstract 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

  1. White matter abnormalities in major depressive disorder with melancholic and atypical features: A diffusion tensor imaging study.

    PubMed

    Ota, Miho; Noda, Takamasa; Sato, Noriko; Hattori, Kotaro; Hori, Hiroaki; Sasayama, Daimei; Teraishi, Toshiya; Nagashima, Anna; Obu, Satoko; Higuchi, Teruhiko; Kunugi, Hiroshi

    2015-06-01

    The DSM-IV recognizes some subtypes of major depressive disorder (MDD). It is known that the effectiveness of antidepressants differs among the MDD subtypes, and thus the differentiation of the subtypes is important. However, little is known as to structural brain changes in MDD with atypical features (aMDD) in comparison with MDD with melancholic features (mMDD), which prompted us to examine possible differences in white matter integrity assessed with diffusion tensor imaging (DTI) between these two subtypes. Subjects were 21 patients with mMDD, 24 with aMDD, and 37 age- and sex-matched healthy volunteers whose DTI data were obtained by 1.5 tesla magnetic resonance imaging. We compared fractional anisotropy and mean diffusivity value derived from DTI data on a voxel-by-voxel basis among the two diagnostic groups and healthy subjects. There were significant decreases of fractional anisotropy and increases of mean diffusivity in patients with MDD compared with healthy subjects in the corpus callosum, inferior fronto-occipital fasciculus, and left superior longitudinal fasciculus. However, we detected no significant difference in any brain region between mMDD and aMDD. Our results suggest that patients with MDD had reduced white matter integrity in some regions; however, there was no major difference between aMDD and mMDD. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

  2. Altered white matter development in children born very preterm.

    PubMed

    Young, Julia M; Vandewouw, Marlee M; Morgan, Benjamin R; Smith, Mary Lou; Sled, John G; Taylor, Margot J

    2018-06-01

    Children born very preterm (VPT) at less than 32 weeks' gestational age (GA) are prone to disrupted white matter maturation and impaired cognitive development. The aims of the present study were to identify differences in white matter microstructure and connectivity of children born VPT compared to term-born children, as well as relations between white matter measures with cognitive outcomes and early brain injury. Diffusion images and T1-weighted anatomical MR images were acquired along with developmental assessments in 31 VPT children (mean GA: 28.76 weeks) and 28 term-born children at 4 years of age. FSL's tract-based spatial statistics was used to create a cohort-specific template and mean fractional anisotropy (FA) skeleton that was applied to each child's DTI data. Whole brain deterministic tractography was performed and graph theoretical measures of connectivity were calculated based on the number of streamlines between cortical and subcortical nodes derived from the Desikan-Killiany atlas. Between-group analyses included FSL Randomise for voxel-wise statistics and permutation testing for connectivity analyses. Within-group analyses between FA values and graph measures with IQ, language and visual-motor scores as well as history of white matter injury (WMI) and germinal matrix/intraventricular haemorrhage (GMH/IVH) were performed. In the children born VPT, FA values within major white matter tracts were reduced compared to term-born children. Reduced measures of local strength, clustering coefficient, local and global efficiency were present in the children born VPT within nodes in the lateral frontal, middle and superior temporal, cingulate, precuneus and lateral occipital regions. Within-group analyses revealed associations in term-born children between FA, Verbal IQ, Performance IQ and Full scale IQ within regions of the superior longitudinal fasciculus, inferior fronto-occipital fasciculus, forceps minor and forceps major. No associations with outcome

  3. Tri-linear interpolation-based cerebral white matter fiber imaging

    PubMed Central

    Jiang, Shan; Zhang, Pengfei; Han, Tong; Liu, Weihua; Liu, Meixia

    2013-01-01

    Diffusion tensor imaging is a unique method to visualize white matter fibers three-dimensionally, non-invasively and in vivo, and therefore it is an important tool for observing and researching neural regeneration. Different diffusion tensor imaging-based fiber tracking methods have been already investigated, but making the computing faster, fiber tracking longer and smoother and the details shown clearer are needed to be improved for clinical applications. This study proposed a new fiber tracking strategy based on tri-linear interpolation. We selected a patient with acute infarction of the right basal ganglia and designed experiments based on either the tri-linear interpolation algorithm or tensorline algorithm. Fiber tracking in the same regions of interest (genu of the corpus callosum) was performed separately. The validity of the tri-linear interpolation algorithm was verified by quantitative analysis, and its feasibility in clinical diagnosis was confirmed by the contrast between tracking results and the disease condition of the patient as well as the actual brain anatomy. Statistical results showed that the maximum length and average length of the white matter fibers tracked by the tri-linear interpolation algorithm were significantly longer. The tracking images of the fibers indicated that this method can obtain smoother tracked fibers, more obvious orientation and clearer details. Tracking fiber abnormalities are in good agreement with the actual condition of patients, and tracking displayed fibers that passed though the corpus callosum, which was consistent with the anatomical structures of the brain. Therefore, the tri-linear interpolation algorithm can achieve a clear, anatomically correct and reliable tracking result. PMID:25206524

  4. White matter hyperintensities in migraine: Clinical significance and central pulsatile hemodynamic correlates.

    PubMed

    Cheng, Chun-Yu; Cheng, Hao-Min; Chen, Shih-Pin; Chung, Chih-Ping; Lin, Yung-Yang; Hu, Han-Hwa; Chen, Chen-Huan; Wang, Shuu-Jiun

    2018-06-01

    Background The role of central pulsatile hemodynamics in the pathogenesis of white matter hyperintensities in migraine patients has not been clarified. Methods Sixty patients with migraine (20-50 years old; women, 68%) without overt vascular risk factors and 30 demographically-matched healthy controls were recruited prospectively. Cerebral white matter hyperintensities volume was determined by T1-weighted magnetic resonance imaging with CUBE-fluid-attenuated-inversion-recovery sequences. Central systolic blood pressure, carotid-femoral pulse wave velocity, and carotid augmentation index were measured by applanation tonometry. Carotid pulsatility index was derived from Doppler ultrasound carotid artery flow analysis. Results Compared to the controls, the migraine patients had higher white matter hyperintensities frequency (odds ratio, 2.75; p = 0.04) and greater mean white matter hyperintensities volume (0.174 vs. 0.049, cm 3 , p = 0.04). Multivariable regression analysis showed that white matter hyperintensities volume in migraine patients was positively associated with central systolic blood pressure ( p = 0.04) and carotid-femoral pulse wave velocity ( p < 0.001), but negatively associated with carotid pulsatility index ( p = 0.04) after controlling for potential confounding factors. The interaction effects observed indicated that the influence of carotid-femoral pulse wave velocity ( p = 0.004) and central systolic blood pressure ( p = 0.03) on white matter hyperintensities formation was greater for the lower-carotid pulsatility index subgroup of migraine patients. White matter hyperintensities volume in migraine patients increased with decreasing carotid pulsatility index and with increasing central systolic blood pressure or carotid-femoral pulse wave velocity. Conclusions White matter hyperintensities are more common in patients with migraine than in healthy controls. Increased aortic stiffness or central systolic blood pressure in

  5. Effects of exercise on capillaries in the white matter of transgenic AD mice

    PubMed Central

    Zhang, Yi; Chao, Feng-Lei; Zhou, Chun-Ni; Jiang, Lin; Zhang, Lei; Chen, Lin-Mu; Luo, Yan-Min; Xiao, Qian; Tang, Yong

    2017-01-01

    Previous studies have shown that exercise can prevent white matter atrophy in APP/PS1 transgenic Alzheimer’s disease (AD) mice. However, the mechanism of this protective effect remains unknown. To further understand this issue, we investigated the effects of exercise on the blood supply of white matter in transgenic AD mice. Six-month-old male APP/PS1 mice were randomly divided into a control group and a running group, and age-matched non-transgenic littermates were used as a wild-type control group. Mice in the running group ran on a treadmill at low intensity for four months. Then, spatial learning and memory abilities, white matter and white matter capillaries were examined in all mice. The 10-month-old AD mice exhibited deficits in cognitive function, and 4 months of exercise improved these deficits. The white matter volume and the total length, total volume and total surface area of the white matter capillaries were decreased in the 10-month-old AD mice, and 4 months of exercise dramatically delayed the changes in these parameters in the AD mice. Our results demonstrate that even low-intensity running exercise can improve spatial learning and memory abilities, delay white matter atrophy and protect white matter capillaries in early-stage AD mice. Protecting capillaries might be an important structural basis for the exercise-induced protection of the structural integrity of white matter in AD. PMID:29029478

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

    PubMed

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

    2016-04-15

    Financial literacy, the ability to understand, access, and utilize information in ways that contribute to optimal financial outcomes, is important for independence and wellbeing in old age. We previously reported that financial literacy is associated with greater functional connectivity between brain regions in old age. Here, we tested the hypothesis that higher financial literacy would be associated with greater white matter integrity in old age. Participants included 346 persons without dementia (mean age=81.36, mean education=15.39, male/female=79/267, mean MMSE=28.52) from the Rush Memory and Aging Project. Financial literacy was assessed using a series of questions imbedded as part of an ongoing decision making study. White matter integrity was assessed with diffusion anisotropy measured with diffusion tensor magnetic resonance imaging (DTI). We tested the hypothesis that higher financial literacy is associated with higher diffusion anisotropy in white matter, adjusting for the effects of age, education, sex, and white matter hyperintense lesions. We then repeated the analysis also adjusting for cognitive function. Analyses revealed regions with significant positive associations between financial literacy and diffusion anisotropy, and many remained significant after accounting for cognitive function. White matter tracts connecting right hemisphere temporal-parietal brain regions were particularly implicated. Greater financial literacy is associated with higher diffusion anisotropy in white matter of nondemented older adults after adjusting for important covariates. These results suggest that financial literacy is positively associated with white matter integrity in old age. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  7. The Impact of Sex, Puberty, and Hormones on White Matter Microstructure in Adolescents

    PubMed Central

    Herting, Megan M.; Maxwell, Emily C.; Irvine, Christy

    2012-01-01

    Background: During adolescence, numerous factors influence the organization of the brain. It is unclear what influence sex and puberty have on white matter microstructure, as well as the role that rapidly increasing sex steroids play. Methods: White matter microstructure was examined in 77 adolescents (ages 10–16) using diffusion tensor imaging. Multiple regression analyses were performed to examine the relationships between fractional anisotropy (FA) and mean diffusivity (MD) and sex, puberty, and their interaction, controlling for age. Follow-up analyses determined if sex steroids predicted microstructural characteristics in sexually dimorphic and pubertal-related white matter regions, as well as in whole brain. Results: Boys had higher FA in white matter carrying corticospinal, long-range association, and cortico-subcortical fibers, and lower MD in frontal and temporal white matter compared with girls. Pubertal development was related to higher FA in the insula, while a significant sex-by-puberty interaction was seen in superior frontal white matter. In boys, testosterone predicted white matter integrity in sexually dimorphic regions as well as whole brain FA, whereas estradiol showed a negative relationship with FA in girls. Conclusions: Sex differences and puberty uniquely relate to white matter microstructure in adolescents, which can partially be explained by sex steroids. PMID:22002939

  8. The dimensionality of between-person differences in white matter microstructure in old age.

    PubMed

    Lövdén, Martin; Laukka, Erika Jonsson; Rieckmann, Anna; Kalpouzos, Grégoria; Li, Tie-Qiang; Jonsson, Tomas; Wahlund, Lars-Olof; Fratiglioni, Laura; Bäckman, Lars

    2013-06-01

    Between-person differences in white matter microstructure may partly generalize across the brain and partly play out differently for distinct tracts. We used diffusion-tensor imaging and structural equation modeling to investigate this issue in a sample of 260 adults aged 60-87 years. Mean fractional anisotropy and mean diffusivity of seven white matter tracts in each hemisphere were quantified. Results showed good fit of a model positing that individual differences in white matter microstructure are structured according to tracts. A general factor, although accounting for variance in the measures, did not adequately represent the individual differences. This indicates the presence of a substantial amount of tract-specific individual differences in white matter microstructure. In addition, individual differences are to a varying degree shared between tracts, indicating that general factors also affect white matter microstructure. Age-related differences in white matter microstructure were present for all tracts. Correlations among tract factors did not generally increase as a function of age, suggesting that aging is not a process with homogenous effects on white matter microstructure across the brain. These findings highlight the need for future research to examine whether relations between white matter microstructure and diverse outcomes are specific or general. Copyright © 2011 Wiley Periodicals, Inc.

  9. Plasticity of white matter connectivity in phonetics experts.

    PubMed

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

    2016-09-01

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

  10. Association of Retinopathy and Retinal Microvascular Abnormalities with Stroke and Cerebrovascular Disease

    PubMed Central

    Hughes, Alun D; Falaschetti, Emanuela; Witt, Nicholas; Wijetunge, Sumangali; Thom, Simon A McG; Tillin, Therese; Aldington, Steve J; Chaturvedi, Nish

    2016-01-01

    Background and purpose Abnormalities of the retinal circulation may be associated with cerebrovascular disease. We investigated associations between retinal microvascular abnormalities and 1) strokes and subclinical cerebral infarcts and 2) cerebral white matter lesions in a UK-based tri-ethnic population-based cohort. Methods 1185 participants (age 68.8±6.1y; 77% male) underwent retinal imaging and cerebral MRI. Cerebral infarcts and white matter hyperintensities (WMH) were identified on MRI, retinopathy was graded and retinal vessels were measured. Results Higher retinopathy grade (odds ratio (OR) = 1.40 (1.16, 1.70)), narrower arteriolar diameter (OR = 0.98 (0.97, 0.99)), fewer symmetrical arteriolar bifurcations (OR = 0.84 (0.75, 0.95)), higher arteriolar optimality deviation (OR = 1.16 (1.00, 1.34)) and more tortuous venules (OR = 1.20(1.09, 1.32)) were associated with strokes/infarcts and WMH. Associations with quantitative retinal microvascular measures were independent of retinopathy. Conclusions Abnormalities of the retinal microvasculature are independently associated with stroke, cerebral infarcts and white matter lesions. PMID:27729577

  11. White matter abnormalities in Gulf War veterans with posttraumatic stress disorder: A pilot study.

    PubMed

    Bierer, Linda M; Ivanov, Iliyan; Carpenter, David M; Wong, Edmund W; Golier, Julia A; Tang, Cheuk Y; Yehuda, Rachel

    2015-01-01

    Gulf War veterans were exposed to environmental toxins not present in other combat theaters resulting in a unique biological signature that only partially resembles that seen in other combat veterans with PTSD. Thus it is important to determine if brain abnormalities seen in non-Gulf War veterans with PTSD are also present in Gulf War veterans. In this pilot study, diffusion tensor imaging (DTI) tractography was used to assess the ultra-structural integrity of fronto-limbic white matter connections in Gulf War veterans with and without PTSD. The effects of chronic multisymptom illness on DTI measures was also evaluated. Subjects were 20 previously studied Gulf War veterans on whom MRIs had been obtained. Mean diffusivity (MD) and fractional anisotropy (FA) were determined for left and right cingulum bundle by DTI tractography and compared in separate analyses for 12 veterans with, and 8 without PTSD. The effect of chronic multisymptom illness and it's interaction with PTSD, were similarly investigated using multivariate ACOVA. Partial correlations were used to test the associations of both DTI indices with PTSD severity and plasma cortisol, controlling for whole brain volume. Significantly lower MD was demonstrated in the right cingulum bundle among Gulf War veterans with PTSD. There were no significant differences in MD or FA in the left cingulum bundle. The presence of chronic multisymptom illness significantly attenuated the PTSD associated decrement in right cingulum MD. Clinician and self-rated PTSD symptom severity scores were significantly associated with reduced MD and increased FA in the right cingulum. Similar associations were observed for 8am plasma cortisol in a subset of participants. The preliminary findings indicate increased structural integrity - supporting enhanced connectivity - between right amygdala and anterior cingulate cortex in PTSD. This effect was strongest among Gulf War veterans without chronic multisymptom illness. The association of

  12. White Matter Integrity, Substance Use, and Risk Taking in Adolescence

    PubMed Central

    Jacobus, Joanna; Thayer, Rachel E.; Trim, Ryan S.; Bava, Sunita; Frank, Lawrence R.; Tapert, Susan F.

    2012-01-01

    White matter development is important for efficient communication between brain regions, higher order cognitive functioning, and complex behaviors. Adolescents have a higher propensity for engaging in risky behaviors, yet few studies have explored associations between white matter integrity and risk taking directly. Altered white matter integrity in mid-adolescence was hypothesized to predict subsequent risk taking behaviors 1.5 years later. Adolescent substance users (predominantly alcohol and marijuana, n=47) and demographically similar non-users (n=49) received diffusion tensor imaging at baseline (ages 16–19), and risk taking measures at both baseline and an 18-month follow-up (i.e., at ages 17–20). Brain regions of interest were: fornix, superior corona radiata, superior longitudinal fasciculus, and superior fronto-occipital fasciculus. In substance using youth (n=47), lower white matter integrity at baseline in the fornix and superior corona radiata predicted follow-up substance use (ΔR2 =10–12%, ps < .01), and baseline fornix integrity predicted follow-up delinquent behaviors (ΔR2 = 10%, p < .01) 1.5 years later. Poorer fronto-limbic white matter integrity was linked to a greater propensity for future risk taking behaviors among youth who initiated heavy substance use by mid-adolescence. Most notable were relationships between projection and limbic system fibers and future substance use frequency. Subcortical white matter coherence along with an imbalance between the maturation levels in cognitive control and reward systems may disadvantage the resistance to engage in risk taking behaviors during adolescence. PMID:22564204

  13. White matter integrity, substance use, and risk taking in adolescence.

    PubMed

    Jacobus, Joanna; Thayer, Rachel E; Trim, Ryan S; Bava, Sunita; Frank, Lawrence R; Tapert, Susan F

    2013-06-01

    White matter development is important for efficient communication between brain regions, higher order cognitive functioning, and complex behaviors. Adolescents have a higher propensity for engaging in risky behaviors, yet few studies have explored associations between white matter integrity and risk taking directly. Altered white matter integrity in mid-adolescence was hypothesized to predict subsequent risk taking behaviors 1.5 years later. Adolescent substance users (predominantly alcohol and marijuana, n = 47) and demographically similar nonusers (n = 49) received diffusion tensor imaging at baseline (ages 16-19), and risk taking measures at both baseline and an 18-month follow-up (i.e., at ages 17-20). Brain regions of interest were the fornix, superior corona radiata, superior longitudinal fasciculus, and superior fronto-occipital fasciculus. In substance-using youth (n = 47), lower white matter integrity at baseline in the fornix and superior corona radiata predicted follow-up substance use (ΔR2 = 10-12%, ps < .01), and baseline fornix integrity predicted follow-up delinquent behaviors (ΔR2 = 10%, p < .01) 1.5 years later. Poorer fronto-limbic white matter integrity was linked to a greater propensity for future risk taking behaviors among youth who initiated heavy substance use by mid-adolescence. Most notable were relationships between projection and limbic-system fibers and future substance-use frequency. Subcortical white matter coherence, along with an imbalance between the maturation levels in cognitive control and reward systems, may disadvantage the resistance to engage in risk taking behaviors during adolescence. 2013 APA, all rights reserved

  14. White Matter Hyperintensities and Changes in White Matter Integrity in Patients with Alzheimer’s Disease

    PubMed Central

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

    2012-01-01

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

  15. Delayed White Matter Growth Trajectory in Young Nonpsychotic Siblings of Patients With Childhood-Onset Schizophrenia

    PubMed Central

    Gogtay, Nitin; Hua, Xue; Stidd, Reva; Boyle, Christina P.; Lee, Suh; Weisinger, Brian; Chavez, Alex; Giedd, Jay N.; Clasen, Liv; Toga, Arthur W.; Rapoport, Judith L.; Thompson, Paul M.

    2013-01-01

    Context Nonpsychotic siblings of patients with childhood-onset schizophrenia (COS) share cortical gray matter abnormalities with their probands at an early age; these normalize by the time the siblings are aged 18 years, suggesting that the gray matter abnormalities in schizophrenia could be an age-specific endophenotype. Patients with COS also show significant white matter (WM) growth deficits, which have not yet been explored in nonpsychotic siblings. Objective To study WM growth differences in non-psychotic siblings of patients with COS. Design Longitudinal (5-year) anatomic magnetic resonance imaging study mapping WM growth using a novel tensor-based morphometry analysis. Setting National Institutes of Health Clinical Center, Bethesda, Maryland. Participants Forty-nine healthy siblings of patients with COS (mean [SD] age, 16.1[5.3] years; 19 male, 30 female) and 57 healthy persons serving as controls (age, 16.9[5.3] years; 29 male, 28 female). Intervention Magnetic resonance imaging. Main Outcome Measure White matter growth rates. Results We compared the WM growth rates in 3 age ranges. In the youngest age group (7 to <14 years), we found a significant difference in growth rates, with siblings of patients with COS showing slower WM growth rates in the parietal lobes of the brain than age-matched healthy controls (false discovery rate, q = 0.05; critical P = .001 in the bilateral parietal WM; a post hoc analysis identified growth rate differences only on the left side, critical P =.004). A growth rate difference was not detectable at older ages. In 3-dimensional maps, growth rates in the siblings even appeared to surpass those of healthy individuals at later ages, at least locally in the brain, but this effect did not survive a multiple comparisons correction. Conclusions In this first longitudinal study of nonpsychotic siblings of patients with COS, the siblings showed early WM growth deficits, which normalized with age. As reported before for gray matter, WM

  16. 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

  17. Limitations of ultrasonography for diagnosing white matter damage in preterm infants.

    PubMed

    Debillon, T; N'Guyen, S; Muet, A; Quere, M P; Moussaly, F; Roze, J C

    2003-07-01

    To compare the accuracy of ultrasonography (US) and magnetic resonance imaging (MRI) in diagnosing white matter abnormalities in preterm infants and to determine the specific indications for MRI. Prospective cohort study. A neonatal intensive care unit in France. All preterm infants (white matter in preterm infants, but MRI seems to be necessary for the diagnosis of less severe damage. MRI performed at about the third week of life is highly predictive of the final diagnosis at term.

  18. Age-related white matter integrity differences in oldest-old without dementia.

    PubMed

    Bennett, Ilana J; Greenia, Dana E; Maillard, Pauline; Sajjadi, S Ahmad; DeCarli, Charles; Corrada, Maria M; Kawas, Claudia H

    2017-08-01

    Aging is known to have deleterious effects on cerebral white matter, yet little is known about these white matter alterations in advanced age. In this study, 94 oldest-old adults without dementia (90-103 years) underwent diffusion tensor imaging to assess relationships between chronological age and multiple measures of integrity in 18 white matter regions across the brain. Results revealed significant age-related declines in integrity in regions previously identified as being sensitive to aging in younger-old adults (corpus callosum, fornix, cingulum, external capsule). For the corpus callosum, the effect of age on genu fractional anisotropy was significantly weaker than the relationship between age and splenium fractional anisotropy. Importantly, age-related declines in white matter integrity did not differ in cognitively normal and cognitively impaired not demented oldest-old, suggesting that they were not solely driven by cognitive dysfunction or preclinical dementia in this advanced age group. Instead, white matter in these regions appears to remain vulnerable to normal aging processes through the 10th decade of life. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2010-01-01

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

  20. Alterations of white matter integrity in adults with major depressive disorder: a magnetic resonance imaging study

    PubMed Central

    Zou, Ke; Huang, Xiaoqi; Li, Tao; Gong, Qiyong; Li, Zhe; Ou-yang, Luo; Deng, Wei; Chen, Qin; Li, Chunxiao; Ding, Yi; Sun, Xueli

    2008-01-01

    Objective The purpose of our study was to investigate alterations of white matter integrity in adults with major depressive disorder (MDD) using magnetic resonance imaging (MRI). Methods We performed diffusion tensor imaging with a 3T MRI scanner on 45 patients with major depression and 45 healthy controls matched for age, sex and education. Using a voxel-based analysis, we measured the fractional anisotropy (FA), and we investigated the differences between the patient and control groups. We examined the correlations between the microstructure abnormalities of white matter and symptom severity, age of illness onset and cumulative illness duration, respectively. Results We found a significant decrease in FA in the left hemisphere, including the anterior limb of the internal capsule and the inferior parietal portion of the superior longitudinal fasciculus, in patients with MDD compared with healthy controls. Diffusion tensor imaging measures in the left anterior limb of the internal capsule were negatively related to the severity of depressive symptoms, even after we controlled for age and sex. Conclusion Our findings provide new evidence of microstructural changes of white matter in non–late-onset adult depression. Our results complement those observed in late-life depression and support the hypothesis that the disruption of cortical– subcortical circuit integrity may be involved in the etiology of major depressive disorder. PMID:18982175

  1. 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…

  2. Effects of white matter lesions on brain perfusion in patients with mild cognitive impairment.

    PubMed

    Ishibashi, Masato; Kimura, Noriyuki; Aso, Yasuhiro; Matsubara, Etsuro

    2018-05-01

    To evaluate the effects of white matter lesions on regional cerebral blood flow in subjects with amnestic mild cognitive impairment. Seventy-five subjects with mild cognitive impairment (36 men and 39 women; mean age, 78.1 years) were included in the study. We used the Mini-Mental State Examination to assess cognitive function. All subjects underwent brain magnetic resonance imaging and 99m Tc ethylcysteinate dimer single photon emission computed tomography. Subjects were stratified based on the presence or absence of white matter lesions on magnetic resonance imaging. Statistical parametric mapping of differences in regional cerebral blood flow between the two groups were assessed by voxel-by-voxel group analysis using SPM8. Of all 75 subjects with mild cognitive impairment, 46 (61.3%) had mild to moderate white matter lesions. The prevalence of hypertension tended to be higher in subjects with white matter lesions than in those without white matter lesions. Mini-Mental State Examination scores were significantly lower in subjects with white matter lesions than in those without white matter lesions. Subjects with white matter lesions had decreased regional cerebral blood flow mainly in the frontal, parietal, and medial temporal lobes, as well as the putamen, compared to those without white matter lesions. In subjects with mild cognitive impairment, white matter lesions were associated with cognitive impairment and mainly frontal lobe brain function. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Fiber tracking of brain white matter based on graph theory.

    PubMed

    Lu, Meng

    2015-01-01

    Brain white matter tractography is reconstructed via diffusion-weighted magnetic resonance images. Due to the complex structure of brain white matter fiber bundles, fiber crossing and fiber branching are abundant in human brain. And regular methods with diffusion tensor imaging (DTI) can't accurately handle this problem. the biggest problems of the brain tractography. Therefore, this paper presented a novel brain white matter tractography method based on graph theory, so the fiber tracking between two voxels is transformed into locating the shortest path in a graph. Besides, the presented method uses Q-ball imaging (QBI) as the source data instead of DTI, because QBI can provide accurate information about multiple fiber crossing and branching in one voxel using orientation distribution function (ODF). Experiments showed that the presented method can accurately handle the problem of brain white matter fiber crossing and branching, and reconstruct brain tractograhpy both in phantom data and real brain data.

  4. Maternal adiposity negatively influences infant brain white matter development.

    PubMed

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

    2015-05-01

    To study potential effects of maternal body composition on central nervous system (CNS) development of newborn infants. Diffusion tensor imaging (DTI) was used to evaluate brain white matter development in 2-week-old, full-term, appropriate for gestational age (AGA) infants from uncomplicated pregnancies of normal-weight (BMI < 25 at conception) or obese ( BMI = 30 at conception) and otherwise healthy mothers. Tract-based spatial statistics (TBSS) analyses were used for voxel-wise group comparison of fractional anisotropy (FA), a sensitive measure of white matter integrity. DNA methylation analyses of umbilical cord tissue focused on genes known to be important in CNS development were also performed. Newborns from obese women had significantly lower FA values in multiple white matter regions than those born of normal-weight mothers. Global and regional FA values negatively correlated (P < 0.05) with maternal fat mass percentage. Linear regression analysis followed by gene ontology enrichment showed that methylation status of 68 CpG sites representing 57 genes with GO terms related to CNS development was significantly associated with maternal adiposity status. These results suggest a negative association between maternal adiposity and white matter development in offspring. © 2015 The Obesity Society.

  5. Utility of a Multiparametric Quantitative MRI Model That Assesses Myelin and Edema for Evaluating Plaques, Periplaque White Matter, and Normal-Appearing White Matter in Patients with Multiple Sclerosis: A Feasibility Study.

    PubMed

    Hagiwara, A; Hori, M; Yokoyama, K; Takemura, M Y; Andica, C; Kumamaru, K K; Nakazawa, M; Takano, N; Kawasaki, H; Sato, S; Hamasaki, N; Kunimatsu, A; Aoki, S

    2017-02-01

    T1 and T2 values and proton density can now be quantified on the basis of a single MR acquisition. The myelin and edema in a voxel can also be estimated from these values. The purpose of this study was to evaluate a multiparametric quantitative MR imaging model that assesses myelin and edema for characterizing plaques, periplaque white matter, and normal-appearing white matter in patients with MS. We examined 3T quantitative MR imaging data from 21 patients with MS. The myelin partial volume, excess parenchymal water partial volume, the inverse of T1 and transverse T2 relaxation times (R1, R2), and proton density were compared among plaques, periplaque white matter, and normal-appearing white matter. All metrics differed significantly across the 3 groups ( P < .001). Those in plaques differed most from those in normal-appearing white matter. The percentage changes of the metrics in plaques and periplaque white matter relative to normal-appearing white matter were significantly more different from zero for myelin partial volume (mean, -61.59 ± 20.28% [plaque relative to normal-appearing white matter], and mean, -10.51 ± 11.41% [periplaque white matter relative to normal-appearing white matter]), and excess parenchymal water partial volume (13.82 × 10 3 ± 49.47 × 10 3 % and 51.33 × 10 2 ± 155.31 × 10 2 %) than for R1 (-35.23 ± 13.93% and -6.08 ± 8.66%), R2 (-21.06 ± 11.39% and -4.79 ± 6.79%), and proton density (23.37 ± 10.30% and 3.37 ± 4.24%). Multiparametric quantitative MR imaging captures white matter damage in MS. Myelin partial volume and excess parenchymal water partial volume are more sensitive to the MS disease process than R1, R2, and proton density. © 2017 by American Journal of Neuroradiology.

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

    PubMed Central

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

    2013-01-01

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

  7. Neuroimaging evidence of gray and white matter damage and clinical correlates in progressive supranuclear palsy.

    PubMed

    Piattella, Maria Cristina; Upadhyay, N; Bologna, M; Sbardella, E; Tona, F; Formica, A; Petsas, N; Berardelli, A; Pantano, P

    2015-08-01

    To evaluate gray matter (GM) and white matter (WM) abnormalities and their clinical correlates in patients with progressive supranuclear palsy (PSP). Sixteen PSP patients and sixteen age-matched healthy subjects underwent a clinical evaluation and multimodal magnetic resonance imaging, including three-dimensional T1-weighted imaging and diffusion tensor imaging (DTI). Volumetric and DTI analyses were computed using SPM and FSL tools. PSP patients showed GM volume decrease, involving the frontal cortex, putamen, pallidum, thalamus and accumbens nucleus, cerebellum, and brainstem. Additionally, they had widespread changes in WM bundles, mainly affecting cerebellar peduncles, thalamic radiations, corticospinal tracts, corpus callosum, and longitudinal fasciculi. GM volumes did not correlate with WM abnormalities. DTI indices of WM damage, but not GM volumes, correlated with clinical scores of disease severity and cognitive impairment. The neurodegenerative changes that occur in PSP involve both GM and WM structures and develop concurrently though independently. WM damage in PSP correlates with clinical scores of disease severity and cognitive impairment, thus providing further insight into the pathophysiology of the disease.

  8. ApoE influences regional white-matter axonal density loss in Alzheimer's disease.

    PubMed

    Slattery, Catherine F; Zhang, Jiaying; Paterson, Ross W; Foulkes, Alexander J M; Carton, Amelia; Macpherson, Kirsty; Mancini, Laura; Thomas, David L; Modat, Marc; Toussaint, Nicolas; Cash, David M; Thornton, John S; Henley, Susie M D; Crutch, Sebastian J; Alexander, Daniel C; Ourselin, Sebastien; Fox, Nick C; Zhang, Hui; Schott, Jonathan M

    2017-09-01

    Mechanisms underlying phenotypic heterogeneity in young onset Alzheimer disease (YOAD) are poorly understood. We used diffusion tensor imaging and neurite orientation dispersion and density imaging (NODDI) with tract-based spatial statistics to investigate apolipoprotein (APOE) ε4 modulation of white-matter damage in 37 patients with YOAD (22, 59% APOE ε4 positive) and 23 age-matched controls. Correlation between neurite density index (NDI) and neuropsychological performance was assessed in 4 white-matter regions of interest. White-matter disruption was more widespread in ε4+ individuals but more focal (posterior predominant) in the absence of an ε4 allele. NODDI metrics indicate fractional anisotropy changes are underpinned by combinations of axonal loss and morphological change. Regional NDI in parieto-occipital white matter correlated with visual object and spatial perception battery performance (right and left, both p = 0.02), and performance (nonverbal) intelligence (WASI matrices, right, p = 0.04). NODDI provides tissue-specific microstructural metrics of white-matter tract damage in YOAD, including NDI which correlates with focal cognitive deficits, and APOEε4 status is associated with different patterns of white-matter neurodegeneration. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Design and validation of diffusion MRI models of white matter

    NASA Astrophysics Data System (ADS)

    Jelescu, Ileana O.; Budde, Matthew D.

    2017-11-01

    Diffusion MRI is arguably the method of choice for characterizing white matter microstructure in vivo. Over the typical duration of diffusion encoding, the displacement of water molecules is conveniently on a length scale similar to that of the underlying cellular structures. Moreover, water molecules in white matter are largely compartmentalized which enables biologically-inspired compartmental diffusion models to characterize and quantify the true biological microstructure. A plethora of white matter models have been proposed. However, overparameterization and mathematical fitting complications encourage the introduction of simplifying assumptions that vary between different approaches. These choices impact the quantitative estimation of model parameters with potential detriments to their biological accuracy and promised specificity. First, we review biophysical white matter models in use and recapitulate their underlying assumptions and realms of applicability. Second, we present up-to-date efforts to validate parameters estimated from biophysical models. Simulations and dedicated phantoms are useful in assessing the performance of models when the ground truth is known. However, the biggest challenge remains the validation of the “biological accuracy” of estimated parameters. Complementary techniques such as microscopy of fixed tissue specimens have facilitated direct comparisons of estimates of white matter fiber orientation and densities. However, validation of compartmental diffusivities remains challenging, and complementary MRI-based techniques such as alternative diffusion encodings, compartment-specific contrast agents and metabolites have been used to validate diffusion models. Finally, white matter injury and disease pose additional challenges to modeling, which are also discussed. This review aims to provide an overview of the current state of models and their validation and to stimulate further research in the field to solve the remaining open

  10. Design and validation of diffusion MRI models of white matter

    PubMed Central

    Jelescu, Ileana O.; Budde, Matthew D.

    2018-01-01

    Diffusion MRI is arguably the method of choice for characterizing white matter microstructure in vivo. Over the typical duration of diffusion encoding, the displacement of water molecules is conveniently on a length scale similar to that of the underlying cellular structures. Moreover, water molecules in white matter are largely compartmentalized which enables biologically-inspired compartmental diffusion models to characterize and quantify the true biological microstructure. A plethora of white matter models have been proposed. However, overparameterization and mathematical fitting complications encourage the introduction of simplifying assumptions that vary between different approaches. These choices impact the quantitative estimation of model parameters with potential detriments to their biological accuracy and promised specificity. First, we review biophysical white matter models in use and recapitulate their underlying assumptions and realms of applicability. Second, we present up-to-date efforts to validate parameters estimated from biophysical models. Simulations and dedicated phantoms are useful in assessing the performance of models when the ground truth is known. However, the biggest challenge remains the validation of the “biological accuracy” of estimated parameters. Complementary techniques such as microscopy of fixed tissue specimens have facilitated direct comparisons of estimates of white matter fiber orientation and densities. However, validation of compartmental diffusivities remains challenging, and complementary MRI-based techniques such as alternative diffusion encodings, compartment-specific contrast agents and metabolites have been used to validate diffusion models. Finally, white matter injury and disease pose additional challenges to modeling, which are also discussed. This review aims to provide an overview of the current state of models and their validation and to stimulate further research in the field to solve the remaining open

  11. 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

  12. Patterns of magnetic resonance imaging abnormalities in symptomatic patients with Krabbe disease correspond to phenotype.

    PubMed

    Abdelhalim, Ahmed N; Alberico, Ronald A; Barczykowski, Amy L; Duffner, Patricia K

    2014-02-01

    Initial magnetic resonance imaging studies of individuals with Krabbe disease were analyzed to determine whether the pattern of abnormalities corresponded to the phenotype. This was a retrospective, nonblinded study. Families/patients diagnosed with Krabbe disease submitted medical records and magnetic resonance imaging discs for central review. Institutional review board approval/informed consents were obtained. Sixty-four magnetic resonance imaging scans were reviewed by two neuroradiologists and a child neurologist according to phenotype: early infantile (onset 0-6 months) = 39 patients; late infantile (onset 7-12 months) = 10 patients; later onset (onset 13 months-10 years) = 11 patients; adolescent (onset 11-20 years) = one patient; and adult (21 years or greater) = three patients. Local interpretations were compared with central review. Magnetic resonance imaging abnormalities differed among phenotypes. Early infantile patients had a predominance of increased intensity in the dentate/cerebellar white matter as well as changes in the deep cerebral white matter. Later onset patients did not demonstrate involvement in the dentate/cerebellar white matter but had extensive involvement of the deep cerebral white matter, parieto-occipital region, and posterior corpus callosum. Late infantile patients exhibited a mixed pattern; 40% had dentate/cerebellar white matter involvement while all had involvement of the deep cerebral white matter. Adolescent/adult patients demonstrated isolated corticospinal tract involvement. Local and central reviews primarily differed in interpretation of the early infantile phenotype. Analysis of magnetic resonance imaging in a large cohort of symptomatic patients with Krabbe disease demonstrated imaging abnormalities correspond to specific phenotypes. Knowledge of these patterns along with typical clinical signs/symptoms should promote earlier diagnosis and facilitate treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Total Homocysteine Is Associated With White Matter Hyperintensity Volume

    PubMed Central

    Wright, Clinton B.; Paik, Myunghee C.; Brown, Truman R.; Stabler, Sally P.; Allen, Robert H.; Sacco, Ralph L.; DeCarli, Charles

    2005-01-01

    Background Total homocysteine (tHcy) has been implicated as a risk factor for stroke and dementia, but the mechanism is unclear. White matter hyperintensities may be a risk factor for both, but studies of the relationship between tHcy and quantitative measures of white matter hyperintensity volume (WMHV) are lacking, especially in minority populations. Methods A community-based sample of 259 subjects with baseline tHcy levels underwent pixel-based quantitative measurement of WMHV. We examined the relationship between tHcy and WMHV adjusting for age, sociodemographics, vascular risk factors, and B12 deficiency. Results Higher levels of tHcy were associated with WMHV adjusting for sociodemographics and vascular risk factors. Conclusions These cross-sectional data provide evidence that tHcy is a risk factor for white matter damage. PMID:15879345

  14. White matter lesion extension to automatic brain tissue segmentation on MRI.

    PubMed

    de Boer, Renske; Vrooman, Henri A; van der Lijn, Fedde; Vernooij, Meike W; Ikram, M Arfan; van der Lugt, Aad; Breteler, Monique M B; Niessen, Wiro J

    2009-05-01

    A fully automated brain tissue segmentation method is optimized and extended with white matter lesion segmentation. Cerebrospinal fluid (CSF), gray matter (GM) and white matter (WM) are segmented by an atlas-based k-nearest neighbor classifier on multi-modal magnetic resonance imaging data. This classifier is trained by registering brain atlases to the subject. The resulting GM segmentation is used to automatically find a white matter lesion (WML) threshold in a fluid-attenuated inversion recovery scan. False positive lesions are removed by ensuring that the lesions are within the white matter. The method was visually validated on a set of 209 subjects. No segmentation errors were found in 98% of the brain tissue segmentations and 97% of the WML segmentations. A quantitative evaluation using manual segmentations was performed on a subset of 6 subjects for CSF, GM and WM segmentation and an additional 14 for the WML segmentations. The results indicated that the automatic segmentation accuracy is close to the interobserver variability of manual segmentations.

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

    PubMed

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

    2017-01-01

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

  16. Quantification of diffusion tensor imaging in normal white matter maturation of early childhood using an automated processing pipeline.

    PubMed

    Loh, K B; Ramli, N; Tan, L K; Roziah, M; Rahmat, K; Ariffin, H

    2012-07-01

    The degree and status of white matter myelination can be sensitively monitored using diffusion tensor imaging (DTI). This study looks at the measurement of fractional anistropy (FA) and mean diffusivity (MD) using an automated ROI with an existing DTI atlas. Anatomical MRI and structural DTI were performed cross-sectionally on 26 normal children (newborn to 48 months old), using 1.5-T MRI. The automated processing pipeline was implemented to convert diffusion-weighted images into the NIfTI format. DTI-TK software was used to register the processed images to the ICBM DTI-81 atlas, while AFNI software was used for automated atlas-based volumes of interest (VOIs) and statistical value extraction. DTI exhibited consistent grey-white matter contrast. Triphasic temporal variation of the FA and MD values was noted, with FA increasing and MD decreasing rapidly early in the first 12 months. The second phase lasted 12-24 months during which the rate of FA and MD changes was reduced. After 24 months, the FA and MD values plateaued. DTI is a superior technique to conventional MR imaging in depicting WM maturation. The use of the automated processing pipeline provides a reliable environment for quantitative analysis of high-throughput DTI data. Diffusion tensor imaging outperforms conventional MRI in depicting white matter maturation. • DTI will become an important clinical tool for diagnosing paediatric neurological diseases. • DTI appears especially helpful for developmental abnormalities, tumours and white matter disease. • An automated processing pipeline assists quantitative analysis of high throughput DTI data.

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

    PubMed Central

    Bennett, Ilana J.; Madden, David J.

    2013-01-01

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

  18. Mapping white-matter functional organization at rest and during naturalistic visual perception.

    PubMed

    Marussich, Lauren; Lu, Kun-Han; Wen, Haiguang; Liu, Zhongming

    2017-02-01

    Despite the wide applications of functional magnetic resonance imaging (fMRI) to mapping brain activation and connectivity in cortical gray matter, it has rarely been utilized to study white-matter functions. In this study, we investigated the spatiotemporal characteristics of fMRI data within the white matter acquired from humans both in the resting state and while watching a naturalistic movie. By using independent component analysis and hierarchical clustering, resting-state fMRI data in the white matter were de-noised and decomposed into spatially independent components, which were further assembled into hierarchically organized axonal fiber bundles. Interestingly, such components were partly reorganized during natural vision. Relative to resting state, the visual task specifically induced a stronger degree of temporal coherence within the optic radiations, as well as significant correlations between the optic radiations and multiple cortical visual networks. Therefore, fMRI contains rich functional information about the activity and connectivity within white matter at rest and during tasks, challenging the conventional practice of taking white-matter signals as noise or artifacts. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Increased White Matter Inflammation in Aging- and Alzheimer’s Disease Brain

    PubMed Central

    Raj, Divya; Yin, Zhuoran; Breur, Marjolein; Doorduin, Janine; Holtman, Inge R.; Olah, Marta; Mantingh-Otter, Ietje J.; Van Dam, Debby; De Deyn, Peter P.; den Dunnen, Wilfred; Eggen, Bart J. L.; Amor, Sandra; Boddeke, Erik

    2017-01-01

    Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer’s disease (AD)-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis. Particularly in white matter microglia of 24-month-old mice, abundant expression of phagocytic markers including Mac-2, Axl, CD16/32, Dectin1, CD11c, and CD36 was detected. Interestingly, in white matter of human brain tissue the first signs of inflammatory activity were already detected during middle age. Thus quantification of microglial proteins, such as CD68 (commonly associated with phagocytosis) and HLA-DR (associated with antigen presentation), in postmortem human white matter brain tissue showed an age-dependent increase in immunoreactivity already in middle-aged people (53.2 ± 2.0 years). This early inflammation was also detectable by non-invasive positron emission tomography imaging using [11C]-(R)-PK11195, a ligand that binds to activated microglia. Increased microglia activity was also prominently present in the white matter of human postmortem early-onset AD (EOAD) brain tissue. Interestingly, microglia activity in the white matter of late-onset AD (LOAD) CNS was similar to that of the aged clinically silent AD cases. These data indicate that microglia-induced neuroinflammation is predominant in the white matter of aging mice and humans as well as in EOAD brains. This white matter inflammation may contribute to the progression of neurodegeneration, and have prognostic value for detecting the onset and progression of aging and neurodegeneration. PMID:28713239

  20. Frontostriatal white matter integrity mediates adult age differences in probabilistic reward learning.

    PubMed

    Samanez-Larkin, Gregory R; Levens, Sara M; Perry, Lee M; Dougherty, Robert F; Knutson, Brian

    2012-04-11

    Frontostriatal circuits have been implicated in reward learning, and emerging findings suggest that frontal white matter structural integrity and probabilistic reward learning are reduced in older age. This cross-sectional study examined whether age differences in frontostriatal white matter integrity could account for age differences in reward learning in a community life span sample of human adults. By combining diffusion tensor imaging with a probabilistic reward learning task, we found that older age was associated with decreased reward learning and decreased white matter integrity in specific pathways running from the thalamus to the medial prefrontal cortex and from the medial prefrontal cortex to the ventral striatum. Further, white matter integrity in these thalamocorticostriatal paths could statistically account for age differences in learning. These findings suggest that the integrity of frontostriatal white matter pathways critically supports reward learning. The findings also raise the possibility that interventions that bolster frontostriatal integrity might improve reward learning and decision making.

  1. Cerebral White Matter Integrity and Cognitive Aging: Contributions from Diffusion Tensor Imaging

    PubMed Central

    Madden, David J.; Bennett, Ilana J.; Song, Allen W.

    2009-01-01

    The integrity of cerebral white matter is critical for efficient cognitive functioning, but little is known regarding the role of white matter integrity in age-related differences in cognition. Diffusion tensor imaging (DTI) measures the directional displacement of molecular water and as a result can characterize the properties of white matter that combine to restrict diffusivity in a spatially coherent manner. This review considers DTI studies of aging and their implications for understanding adult age differences in cognitive performance. Decline in white matter integrity contributes to a disconnection among distributed neural systems, with a consistent effect on perceptual speed and executive functioning. The relation between white matter integrity and cognition varies across brain regions, with some evidence suggesting that age-related effects exhibit an anterior-posterior gradient. With continued improvements in spatial resolution and integration with functional brain imaging, DTI holds considerable promise, both for theories of cognitive aging and for translational application. PMID:19705281

  2. Exploring the multiple-hit hypothesis of preterm white matter damage using diffusion MRI.

    PubMed

    Barnett, Madeleine L; Tusor, Nora; Ball, Gareth; Chew, Andrew; Falconer, Shona; Aljabar, Paul; Kimpton, Jessica A; Kennea, Nigel; Rutherford, Mary; David Edwards, A; Counsell, Serena J

    2018-01-01

    Preterm infants are at high risk of diffuse white matter injury and adverse neurodevelopmental outcome. The multiple hit hypothesis suggests that the risk of white matter injury increases with cumulative exposure to multiple perinatal risk factors. Our aim was to test this hypothesis in a large cohort of preterm infants using diffusion weighted magnetic resonance imaging (dMRI). We studied 491 infants (52% male) without focal destructive brain lesions born at < 34 weeks, who underwent structural and dMRI at a specialist Neonatal Imaging Centre. The median (range) gestational age (GA) at birth was 30 + 1 (23 + 2 -33 + 5 ) weeks and median postmenstrual age at scan was 42 + 1 (38-45) weeks. dMRI data were analyzed using tract based spatial statistics and the relationship between dMRI measures in white matter and individual perinatal risk factors was assessed. We tested the hypothesis that increased exposure to perinatal risk factors was associated with lower fractional anisotropy (FA), and higher radial, axial and mean diffusivity (RD, AD, MD) in white matter. Neurodevelopmental performance was investigated using the Bayley Scales of Infant and Toddler Development, Third Edition (BSITD-III) in a subset of 381 infants at 20 months corrected age. We tested the hypothesis that lower FA and higher RD, AD and MD in white matter were associated with poorer neurodevelopmental performance. Identified risk factors for diffuse white matter injury were lower GA at birth, fetal growth restriction, increased number of days requiring ventilation and parenteral nutrition, necrotizing enterocolitis and male sex. Clinical chorioamnionitis and patent ductus arteriosus were not associated with white matter injury. Multivariate analysis demonstrated that fetal growth restriction, increased number of days requiring ventilation and parenteral nutrition were independently associated with lower FA values. Exposure to cumulative risk factors was associated with reduced white matter FA

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

    PubMed

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

    2014-10-01

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

  4. White and Gray Matter Abnormalities After Cranial Radiation in Children and Mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nieman, Brian J., E-mail: brian.nieman@utoronto.ca; Department of Medical Biophysics, University of Toronto, Toronto, Ontario; Ontario Institute for Cancer Research, Toronto, Ontario

    Purpose: Pediatric patients treated with cranial radiation are at high risk of developing lasting cognitive impairments. We sought to identify anatomical changes in both gray matter (GM) and white matter (WM) in radiation-treated patients and in mice, in which the effect of radiation can be isolated from other factors, the time course of anatomical change can be established, and the effect of treatment age can be more fully characterized. Anatomical results were compared between species. Methods and Materials: Patients were imaged with T{sub 1}-weighted magnetic resonance imaging (MRI) after radiation treatment. Nineteen radiation-treated patients were divided into groups of 7 yearsmore » of age and younger (7−) and 8 years and older (8+) and were compared to 41 controls. C57BL6 mice were treated with radiation (n=52) or sham treated (n=52) between postnatal days 16 and 36 and then assessed with in vivo and/or ex vivo MRI. In both cases, measurements of WM and GM volume, cortical thickness, area and volume, and hippocampal volume were compared between groups. Results: WM volume was significantly decreased following treatment in 7− and 8+ treatment groups. GM volume was unchanged overall, but cortical thickness was slightly increased in the 7− group. Results in mice mostly mirrored these changes and provided a time course of change, showing early volume loss and normal growth. Hippocampal volume showed a decreasing trend with age in patients, an effect not observed in the mouse hippocampus but present in the olfactory bulb. Conclusions: Changes in mice treated with cranial radiation are similar to those in humans, including significant WM and GM alterations. Because mice did not receive any other treatment, the similarity across species supports the expectation that radiation is causative and suggests mice provide a representative model for studying impaired brain development after cranial radiation and testing novel treatments.« less

  5. Quantitative susceptibility mapping as a biomarker for evaluating white matter alterations in Parkinson's disease.

    PubMed

    Guan, Xiaojun; Huang, Peiyu; Zeng, Qiaoling; Liu, Chunlei; Wei, Hongjiang; Xuan, Min; Gu, Quanquan; Xu, Xiaojun; Wang, Nian; Yu, Xinfeng; Luo, Xiao; Zhang, Minming

    2018-02-07

    Myelinated white matter showing diamagnetic susceptibility is important for information transfer in the brain. In Parkinson's disease (PD), the white matter is also suffering degenerative alterations. Quantitative susceptibility mapping (QSM) is a novel technique for noninvasive assessment of regional white matter ultrastructure, and provides different information of white matter in addition to standard diffusion tensor imaging (DTI). In this study, we used QSM to detect spatial white matter alterations in PD patients (n = 65) and age- and sex-matched normal controls (n = 46). Voxel-wise tract-based spatial statistics were performed to analyze QSM and DTI data. QSM showed extensive white matter involvement-including regions adjacent to the frontal, parietal, and temporal lobes-in PD patients, which was more widespread than that observed using DTI. Both QSM and DTI showed similar alterations in the left inferior longitudinal fasciculus and right cerebellar hemisphere. Further, alterations in the white matter were correlated with motor impairment and global disease severity in PD patients. We suggest that QSM may provide a novel approach for detecting white matter alterations and underlying network disruptions in PD. Further, the combination of QSM and DTI would provide a more complete evaluation of the diseased brain by analyzing different biological tissue properties.

  6. 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

  7. Experience-dependent plasticity in white matter microstructure: reasoning training alters structural connectivity

    PubMed Central

    Mackey, Allyson P.; Whitaker, Kirstie J.; Bunge, Silvia A.

    2012-01-01

    Diffusion tensor imaging (DTI) techniques have made it possible to investigate white matter plasticity in humans. Changes in DTI measures, principally increases in fractional anisotropy (FA), have been observed following training programs as diverse as juggling, meditation, and working memory. Here, we sought to test whether three months of reasoning training could alter white matter microstructure. We recruited participants (n = 23) who were enrolled in a course to prepare for the Law School Admission Test (LSAT), a test that places strong demands on reasoning skills, as well as age- and IQ-matched controls planning to take the LSAT in the future (n = 22). DTI data were collected at two scan sessions scheduled three months apart. In trained participants but not controls, we observed decreases in radial diffusivity (RD) in white matter connecting frontal cortices, and in mean diffusivity (MD) within frontal and parietal lobe white matter. Further, participants exhibiting larger gains on the LSAT exhibited greater decreases in MD in the right internal capsule. In summary, reasoning training altered multiple measures of white matter structure in young adults. While the cellular underpinnings are unknown, these results provide evidence of experience-dependent white matter changes that may not be limited to myelination. PMID:22936899

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

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

    PubMed

    Meijer, K A; Cercignani, M; Muhlert, N; Sethi, V; Chard, D; Geurts, J J G; Ciccarelli, O

    2016-01-01

    In multiple sclerosis (MS), white matter damage is thought to contribute to cognitive dysfunction, which is especially prominent in secondary progressive MS (SPMS). While studies in healthy subjects have revealed patterns of correlated fractional anisotropy (FA) across white matter tracts, little is known about the underlying patterns of white matter damage in MS. In the present study, we aimed to map the SPMS-related covariance patterns of microstructural white matter changes, and investigated whether or not these patterns were associated with cognitive dysfunction. Diffusion MRI was acquired from 30 SPMS patients and 32 healthy controls (HC). A tensor model was fitted and FA maps were processed using tract-based spatial statistics (TBSS) in order to obtain a skeletonised map for each subject. The skeletonised FA maps of patients only were decomposed into 18 spatially independent components (ICs) using independent component analysis. Comprehensive cognitive assessment was conducted to evaluate five cognitive domains. Correlations between cognitive performance and (1) severity of FA abnormalities of the extracted ICs (i.e. z-scores relative to FA values of HC) and (2) IC load (i.e. FA covariance of a particular IC) were examined. SPMS patients showed lower FA values of all examined patterns of correlated FA (i.e. spatially independent components) than HC (p < 0.01). Tracts visually assigned to the supratentorial commissural class were most severely damaged (z = - 3.54; p < 0.001). Reduced FA was significantly correlated with reduced IC load (i.e. FA covariance) (r = 0.441; p < 0.05). Lower mean FA and component load of the supratentorial projection tracts and limbic association tracts classes were associated with worse cognitive function, including executive function, working memory and verbal memory. Despite the presence of white matter damage, it was possible to reveal patterns of FA covariance across SPMS patients. This could indicate that white

  10. BIANCA (Brain Intensity AbNormality Classification Algorithm): A new tool for automated segmentation of white matter hyperintensities.

    PubMed

    Griffanti, Ludovica; Zamboni, Giovanna; Khan, Aamira; Li, Linxin; Bonifacio, Guendalina; Sundaresan, Vaanathi; Schulz, Ursula G; Kuker, Wilhelm; Battaglini, Marco; Rothwell, Peter M; Jenkinson, Mark

    2016-11-01

    Reliable quantification of white matter hyperintensities of presumed vascular origin (WMHs) is increasingly needed, given the presence of these MRI findings in patients with several neurological and vascular disorders, as well as in elderly healthy subjects. We present BIANCA (Brain Intensity AbNormality Classification Algorithm), a fully automated, supervised method for WMH detection, based on the k-nearest neighbour (k-NN) algorithm. Relative to previous k-NN based segmentation methods, BIANCA offers different options for weighting the spatial information, local spatial intensity averaging, and different options for the choice of the number and location of the training points. BIANCA is multimodal and highly flexible so that the user can adapt the tool to their protocol and specific needs. We optimised and validated BIANCA on two datasets with different MRI protocols and patient populations (a "predominantly neurodegenerative" and a "predominantly vascular" cohort). BIANCA was first optimised on a subset of images for each dataset in terms of overlap and volumetric agreement with a manually segmented WMH mask. The correlation between the volumes extracted with BIANCA (using the optimised set of options), the volumes extracted from the manual masks and visual ratings showed that BIANCA is a valid alternative to manual segmentation. The optimised set of options was then applied to the whole cohorts and the resulting WMH volume estimates showed good correlations with visual ratings and with age. Finally, we performed a reproducibility test, to evaluate the robustness of BIANCA, and compared BIANCA performance against existing methods. Our findings suggest that BIANCA, which will be freely available as part of the FSL package, is a reliable method for automated WMH segmentation in large cross-sectional cohort studies. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  11. 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. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Selective white matter pathology induces a specific impairment in spatial working memory.

    PubMed

    Coltman, Robin; Spain, Aisling; Tsenkina, Yanina; Fowler, Jill H; Smith, Jessica; Scullion, Gillian; Allerhand, Mike; Scott, Fiona; Kalaria, Rajesh N; Ihara, Masafumi; Daumas, Stephanie; Deary, Ian J; Wood, Emma; McCulloch, James; Horsburgh, Karen

    2011-12-01

    The integrity of the white matter is critical in regulating efficient neuronal communication and maintaining cognitive function. Damage to brain white matter putatively contributes to age-related cognitive decline. There is a growing interest in animal models from which the mechanistic basis of white matter pathology in aging can be elucidated but to date there has been a lack of systematic behavior and pathology in the same mice. Anatomically widespread, diffuse white matter damage was induced, in 3 different cohorts of C57Bl/6J mice, by chronic hypoperfusion produced by bilateral carotid stenosis. A comprehensive assessment of spatial memory (spatial reference learning and memory; cohort 1) and serial spatial learning and memory (cohort 2) using the water maze, and spatial working memory (cohort 3) using the 8-arm radial arm maze, was conducted. In parallel, a systematic assessment of white matter components (myelin, axon, glia) was conducted using immunohistochemical markers (myelin-associated glycoprotein [MAG], degraded myelin basic protein [dMBP], anti-amyloid precursor protein [APP], anti-ionized calcium-binding adapter molecule [Iba-1]). Ischemic neuronal perikarya damage, assessed using histology (hematoxylin and eosin; H&E), was absent in all shams but was present in some hypoperfused mice (2/11 in cohort 1, 4/14 in cohort 2, and 17/24 in cohort 3). All animals with neuronal perikaryal damage were excluded from further study. Diffuse white matter damage occurred, throughout the brain, in all hypoperfused mice in each cohort and was essentially absent in sham-operated controls. There was a selective impairment in spatial working memory, with all other measures of spatial memory remaining intact, in hypoperfused mice with selective white matter damage. The results demonstrate that diffuse white matter pathology, in the absence of gray matter damage, induces a selective impairment of spatial working memory. This highlights the importance of assessing

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

    PubMed

    Lockwood Estrin, G; Kyriakopoulou, V; Makropoulos, A; Ball, G; Kuhendran, L; Chew, A; Hagberg, B; Martinez-Biarge, M; Allsop, J; Fox, M; Counsell, S J; Rutherford, M A

    2016-01-01

    Ventriculomegaly (VM) is the most common central nervous system abnormality diagnosed antenatally, and is associated with developmental delay in childhood. We tested the hypothesis that antenatally diagnosed isolated VM represents a biological marker for altered white matter (WM) and cortical grey matter (GM) development in neonates. 25 controls and 21 neonates with antenatally diagnosed isolated VM had magnetic resonance imaging at 41.97(± 2.94) and 45.34(± 2.14) weeks respectively. T2-weighted scans were segmented for volumetric analyses of the lateral ventricles, WM and cortical GM. Diffusion tensor imaging (DTI) measures were assessed using voxel-wise methods in WM and cortical GM; comparisons were made between cohorts. Ventricular and cortical GM volumes were increased, and WM relative volume was reduced in the VM group. Regional decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were demonstrated in WM of the VM group compared to controls. No differences in cortical DTI metrics were observed. At 2 years, neurodevelopmental delays, especially in language, were observed in 6/12 cases in the VM cohort. WM alterations in isolated VM cases may be consistent with abnormal development of WM tracts involved in language and cognition. Alterations in WM FA and MD may represent neural correlates for later neurodevelopmental deficits.

  14. Developmental differences in white matter architecture between boys and girls.

    PubMed

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

    2008-06-01

    Previous studies have found developmental differences between males and females in brain structure. During childhood and adolescence, relative white matter volume increases faster in boys than in girls. Sex differences in the development of white matter microstructure were investigated in a cohort of normal children ages 5-18 in a cross-sectional diffusion tensor imaging (DTI) study. Greater fractional anisotropy (FA) in boys was shown in associative white matter regions (including the frontal lobes), while greater FA in girls was shown in the splenium of the corpus callosum. Greater mean diffusivity (MD) in boys was shown in the corticospinal tract and in frontal white matter in the right hemisphere; greater MD in girls was shown in occipito-parietal regions and the most superior aspect of the corticospinal tract in the right hemisphere. Significant sex-age interactions on FA and MD were also shown. Girls displayed a greater rate of fiber density increase with age when compared with boys in associative regions (reflected in MD values). However, girls displayed a trend toward increased organization with age (reflected in FA values) only in the right hemisphere, while boys displayed this trend only in the left hemisphere. These results indicate differing developmental trajectories in white matter for boys and girls and the importance of taking sex into account in developmental DTI studies. The results also may have implications for the study of the relationship of brain architecture with intelligence. Copyright 2007 Wiley-Liss, Inc.

  15. Vulnerability of white matter tracts and cognition to the SOD2 polymorphism: A preliminary study of antioxidant defense genes in brain aging.

    PubMed

    Salminen, Lauren E; Schofield, Peter R; Pierce, Kerrie D; Bruce, Steven E; Griffin, Michael G; Tate, David F; Cabeen, Ryan P; Laidlaw, David H; Conturo, Thomas E; Bolzenius, Jacob D; Paul, Robert H

    2017-06-30

    Oxidative stress is a key mechanism of the aging process that can cause damage to brain white matter and cognitive functions. Polymorphisms in the superoxide dismutase 2 (SOD2) and catalase (CAT) genes have been associated with abnormalities in antioxidant enzyme activity in the aging brain, suggesting a risk for enhanced oxidative damage to white matter and cognition among older individuals with these genetic variants. The present study compared differences in white matter microstructure and cognition among 96 older adults with and without genetic risk factors of SOD2 (rs4880) and CAT (rs1001179). Results revealed higher radial diffusivity in the anterior thalamic radiation among SOD2 CC genotypes compared to CT/TT genotypes. Further, the CC genotype moderated the relationship between the hippocampal cingulum and processing speed, though this did not survive multiple test correction. The CAT polymorphism was not associated with brain outcomes in this cohort. These results suggest that the CC genotype of SOD2 is an important genetic marker of suboptimal brain aging in healthy individuals. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Astrocytes Promote Oligodendrogenesis after White Matter Damage via Brain-Derived Neurotrophic Factor.

    PubMed

    Miyamoto, Nobukazu; Maki, Takakuni; Shindo, Akihiro; Liang, Anna C; Maeda, Mitsuyo; Egawa, Naohiro; Itoh, Kanako; Lo, Evan K; Lok, Josephine; Ihara, Masafumi; Arai, Ken

    2015-10-14

    Oligodendrocyte precursor cells (OPCs) in the adult brain contribute to white matter homeostasis. After white matter damage, OPCs compensate for oligodendrocyte loss by differentiating into mature oligodendrocytes. However, the underlying mechanisms remain to be fully defined. Here, we test the hypothesis that, during endogenous recovery from white matter ischemic injury, astrocytes support the maturation of OPCs by secreting brain-derived neurotrophic factor (BDNF). For in vitro experiments, cultured primary OPCs and astrocytes were prepared from postnatal day 2 rat cortex. When OPCs were subjected to chemical hypoxic stress by exposing them to sublethal CoCl2 for 7 d, in vitro OPC differentiation into oligodendrocytes was significantly suppressed. Conditioned medium from astrocytes (astro-medium) restored the process of OPC maturation even under the stressed conditions. When astro-medium was filtered with TrkB-Fc to remove BDNF, the BDNF-deficient astro-medium no longer supported OPC maturation. For in vivo experiments, we analyzed a transgenic mouse line (GFAP(cre)/BDNF(wt/fl)) in which BDNF expression is downregulated specifically in GFAP(+) astrocytes. Both wild-type (GFAP(wt)/BDNF(wt/fl) mice) and transgenic mice were subjected to prolonged cerebral hypoperfusion by bilateral common carotid artery stenosis. As expected, compared with wild-type mice, the transgenic mice exhibited a lower number of newly generated oligodendrocytes and larger white matter damage. Together, these findings demonstrate that, during endogenous recovery from white matter damage, astrocytes may promote oligodendrogenesis by secreting BDNF. The repair of white matter after brain injury and neurodegeneration remains a tremendous hurdle for a wide spectrum of CNS disorders. One potentially important opportunity may reside in the response of residual oligodendrocyte precursor cells (OPCs). OPCs may serve as a back-up for generating mature oligodendrocytes in damaged white matter. However

  17. Episodic memory function is associated with multiple measures of white matter integrity in cognitive aging

    PubMed Central

    Lockhart, Samuel N.; Mayda, Adriane B. V.; Roach, Alexandra E.; Fletcher, Evan; Carmichael, Owen; Maillard, Pauline; Schwarz, Christopher G.; Yonelinas, Andrew P.; Ranganath, Charan; DeCarli, Charles

    2011-01-01

    Previous neuroimaging research indicates that white matter injury and integrity, measured respectively by white matter hyperintensities (WMH) and fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI), differ with aging and cerebrovascular disease (CVD) and are associated with episodic memory deficits in cognitively normal older adults. However, knowledge about tract-specific relationships between WMH, FA, and episodic memory in aging remains limited. We hypothesized that white matter connections between frontal cortex and subcortical structures as well as connections between frontal and temporo-parietal cortex would be most affected. In the current study, we examined relationships between WMH, FA and episodic memory in 15 young adults, 13 elders with minimal WMH and 15 elders with extensive WMH, using an episodic recognition memory test for object-color associations. Voxel-based statistics were used to identify voxel clusters where white matter measures were specifically associated with variations in episodic memory performance, and white matter tracts intersecting these clusters were analyzed to examine white matter-memory relationships. White matter injury and integrity measures were significantly associated with episodic memory in extensive regions of white matter, located predominantly in frontal, parietal, and subcortical regions. Template based tractography indicated that white matter injury, as measured by WMH, in the uncinate and inferior longitudinal fasciculi were significantly negatively associated with episodic memory performance. Other tracts such as thalamo-frontal projections, superior longitudinal fasciculus, and dorsal cingulum bundle demonstrated strong negative associations as well. The results suggest that white matter injury to multiple pathways, including connections of frontal and temporal cortex and frontal-subcortical white matter tracts, plays a critical role in memory differences seen in older individuals. PMID:22438841

  18. Functional connectivity and activity of white matter in somatosensory pathways under tactile stimulations.

    PubMed

    Wu, Xi; Yang, Zhipeng; Bailey, Stephen K; Zhou, Jiliu; Cutting, Laurie E; Gore, John C; Ding, Zhaohua

    2017-05-15

    Functional MRI has proven to be effective in detecting neural activity in brain cortices on the basis of blood oxygenation level dependent (BOLD) contrast, but has relatively poor sensitivity for detecting neural activity in white matter. To demonstrate that BOLD signals in white matter are detectable and contain information on neural activity, we stimulated the somatosensory system and examined distributions of BOLD signals in related white matter pathways. The temporal correlation profiles and frequency contents of BOLD signals were compared between stimulation and resting conditions, and between relevant white matter fibers and background regions, as well as between left and right side stimulations. Quantitative analyses show that, overall, MR signals from white matter fiber bundles in the somatosensory system exhibited significantly greater temporal correlations with the primary sensory cortex and greater signal power during tactile stimulations than in a resting state, and were stronger than corresponding measurements for background white matter both during stimulations and in a resting state. The temporal correlation and signal power under stimulation were found to be twice those observed from the same bundle in a resting state, and bore clear relations with the side of stimuli. These indicate that BOLD signals in white matter fibers encode neural activity related to their functional roles connecting cortical volumes, which are detectable with appropriate methods. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. [Analysis of mechanism of transition zones among β, δ and γ dispersions in brain white matter and grey matter].

    PubMed

    Tian, Rui; Lu, Mai

    2017-08-01

    In order to explore the application of the dielectric properties of white matter and grey matter in β, δ and γ dispersion transition zones used in clinical medicine and microwave imaging technology, we calculated the dielectric constant and its increment by using Cole-Cole equation. Based on the mutation of the increment of dielectric constant, the frequency range of three dispersions were evaluated. The dominate dispersion and the corresponding polarization mechanism were analyzed by using Cole-Cole circle. The results showed that there are 3 transition zones in brain white matter, which occur between β and δ dispersion, δ and γ dispersion and β and γ dispersion respectively. In grey matter, there are only 2 transition zones, which are between β and δ dispersion and δ and γ dispersion respectively. By comparing the frequency range of white matter and grey matter, the frequency range in white matter is broader than that in grey matter for the transition zone of β and δ dispersion with the β dispersion occupying dominate position in both tissues, and the corresponding polarization mechanism is interfacial polarization. For the transition zone of δ and γ dispersion, the frequency range in white matter is also broader than that in grey matter with the δ dispersion occupying dominate position in both tissues, and the corresponding polarization mechanism is orientation polarization. This study can provide basic theory and reference for diagnosis of brain diseases and microwave imaging technology.

  20. Modality-Spanning Deficits in Attention-Deficit/Hyperactivity Disorder in Functional Networks, Gray Matter, and White Matter

    PubMed Central

    Kessler, Daniel; Angstadt, Michael; Welsh, Robert C.

    2014-01-01

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

  1. Early and extensive spinal white matter involvement in neuromyelitis optica.

    PubMed

    Hayashida, Shotaro; Masaki, Katsuhisa; Yonekawa, Tomomi; Suzuki, Satoshi O; Hiwatashi, Akio; Matsushita, Takuya; Watanabe, Mitsuru; Yamasaki, Ryo; Suenaga, Toshihiko; Iwaki, Toru; Murai, Hiroyuki; Kira, Jun-Ichi

    2017-05-01

    Studies of longitudinally extensive spinal cord lesions (LESCLs) in neuromyelitis optica (NMO) have focused on gray matter, where the relevant antigen, aquaporin-4 (AQP4), is abundant. Because spinal white matter pathology in NMO is not well characterized, we aimed to clarify spinal white matter pathology of LESCLs in NMO. We analyzed 50 spinal cord lesions from eleven autopsied NMO/NMO spectrum disorder (NMOSD) cases. We also evaluated LESCLs with three or fewer spinal cord attacks by 3-tesla MRI in 15 AQP4 antibody-positive NMO/NMOSD patients and in 15 AQP4 antibody-negative multiple sclerosis (MS) patients. Pathological analysis revealed seven cases of AQP4 loss and four predominantly demyelinating cases. Forty-four lesions from AQP4 loss cases involved significantly more frequently posterior columns (PC) and lateral columns (LC) than anterior columns (AC) (59.1%, 63.6%, and 34.1%, respectively). The posterior horn (PH), central portion (CP), and anterior horn (AH) were similarly affected (38.6%, 36.4% and 31.8%, respectively). Isolated perivascular inflammatory lesions with selective loss of astrocyte endfoot proteins, AQP4 and connexin 43, were present only in white matter and were more frequent in PC and LC than in AC (22.7%, 29.5% and 2.3%, P corr  = 0.020, and P corr  = 0.004, respectively). MRI indicated LESCLs more frequently affected PC and LC than AC in anti-AQP4 antibody-seropositive NMO/NMOSD (86.7%, 60.0% and 20.0%, P corr  = 0.005, and P corr  = 0.043, respectively) and AQP4 antibody-seronegative MS patients (86.7%, 73.3% and 33.3%, P corr  = 0.063, and P corr  = 0.043, respectively). PH, CP and AH were involved in 93.3%, 86.7% and 73.3% of seropositive patients, respectively, and in 53.3%, 60.0% and 40.0% of seronegative patients, respectively. NMO frequently and extensively affects spinal white matter in addition to central gray matter, especially in PC and LC, where isolated perivascular lesions with astrocyte endfoot

  2. Limitations of ultrasonography for diagnosing white matter damage in preterm infants

    PubMed Central

    Debillon, T; N'Guyen, S; Muet, A; Quere, M; Moussaly, F; Roze, J

    2003-01-01

    Objectives: To compare the accuracy of ultrasonography (US) and magnetic resonance imaging (MRI) in diagnosing white matter abnormalities in preterm infants and to determine the specific indications for MRI. Design: Prospective cohort study. Setting: A neonatal intensive care unit in France. Patients: All preterm infants (≤ 33 weeks gestation) without severe respiratory distress syndrome precluding MRI. Main outcome measures: US and MRI performed contemporaneously during the third postnatal week were analysed by an independent observer. The findings were compared with those of a term MRI scan, the results of which were taken as the final diagnosis. Statistical analysis was performed to determine which early imaging study best predicted the term MRI findings. Results: The early US and MRI findings (79 infants) correlated closely for severe lesions (cystic periventricular leucomalacia and parenchymal infarction; κ coefficient = 0.86) but not for moderate lesions (non-cystic leucomalacia and parenchymal punctate haemorrhages; κ = 0.62). Overall, early MRI findings predicted late MRI findings in 98% of patients (95% confidence interval (CI) 89.5 to 99.9) compared with only 68% for early US (95% CI 52.1 to 79.2). Conclusions: US is highly effective in detecting severe lesions of the white matter in preterm infants, but MRI seems to be necessary for the diagnosis of less severe damage. MRI performed at about the third week of life is highly predictive of the final diagnosis at term. PMID:12819157

  3. White matter pathways and social cognition.

    PubMed

    Wang, Yin; Metoki, Athanasia; Alm, Kylie H; Olson, Ingrid R

    2018-04-20

    There is a growing consensus that social cognition and behavior emerge from interactions across distributed regions of the "social brain". Researchers have traditionally focused their attention on functional response properties of these gray matter networks and neglected the vital role of white matter connections in establishing such networks and their functions. In this article, we conduct a comprehensive review of prior research on structural connectivity in social neuroscience and highlight the importance of this literature in clarifying brain mechanisms of social cognition. We pay particular attention to three key social processes: face processing, embodied cognition, and theory of mind, and their respective underlying neural networks. To fully identify and characterize the anatomical architecture of these networks, we further implement probabilistic tractography on a large sample of diffusion-weighted imaging data. The combination of an in-depth literature review and the empirical investigation gives us an unprecedented, well-defined landscape of white matter pathways underlying major social brain networks. Finally, we discuss current problems in the field, outline suggestions for best practice in diffusion-imaging data collection and analysis, and offer new directions for future research. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Diffusion measures indicate fight exposure-related damage to cerebral white matter in boxers and mixed martial arts fighters.

    PubMed

    Shin, W; Mahmoud, S Y; Sakaie, K; Banks, S J; Lowe, M J; Phillips, M; Modic, M T; Bernick, C

    2014-02-01

    Traumatic brain injury is common in fighting athletes such as boxers, given the frequency of blows to the head. Because DTI is sensitive to microstructural changes in white matter, this technique is often used to investigate white matter integrity in patients with traumatic brain injury. We hypothesized that previous fight exposure would predict DTI abnormalities in fighting athletes after controlling for individual variation. A total of 74 boxers and 81 mixed martial arts fighters were included in the analysis and scanned by use of DTI. Individual information and data on fight exposures, including number of fights and knockouts, were collected. A multiple hierarchical linear regression model was used in region-of-interest analysis to test the hypothesis that fight-related exposure could predict DTI values separately in boxers and mixed martial arts fighters. Age, weight, and years of education were controlled to ensure that these factors would not account for the hypothesized effects. We found that the number of knockouts among boxers predicted increased longitudinal diffusivity and transversal diffusivity in white matter and subcortical gray matter regions, including corpus callosum, isthmus cingulate, pericalcarine, precuneus, and amygdala, leading to increased mean diffusivity and decreased fractional anisotropy in the corresponding regions. The mixed martial arts fighters had increased transversal diffusivity in the posterior cingulate. The number of fights did not predict any DTI measures in either group. These findings suggest that the history of fight exposure in a fighter population can be used to predict microstructural brain damage.

  5. Deviant white matter structure in adults with attention-deficit/hyperactivity disorder points to aberrant myelination and affects neuropsychological performance.

    PubMed

    Onnink, A Marten H; Zwiers, Marcel P; Hoogman, Martine; Mostert, Jeanette C; Dammers, Janneke; Kan, Cornelis C; Vasquez, Alejandro Arias; Schene, Aart H; Buitelaar, Jan; Franke, Barbara

    2015-12-03

    Attention-deficit/hyperactivity disorder (ADHD) in childhood is characterized by gray and white matter abnormalities in several brain areas. Considerably less is known about white matter microstructure in adults with ADHD and its relation with clinical symptoms and cognitive performance. In 107 adult ADHD patients and 109 gender-, age- and IQ-matched controls, we used diffusion tensor imaging (DTI) with tract-based spatial statistics (TBSS) to investigate whole-skeleton changes of fractional anisotropy (FA) and mean, axial, and radial diffusivity (MD, AD, RD). Additionally, we studied the relation of FA and MD values with symptom severity and cognitive performance on tasks measuring working memory, attention, inhibition, and delay discounting. In comparison to controls, participants with ADHD showed reduced FA in corpus callosum, bilateral corona radiata, and thalamic radiation. Higher MD and RD were found in overlapping and even more widespread areas in both hemispheres, also encompassing internal and external capsule, sagittal stratum, fornix, and superior lateral fasciculus. Values of FA and MD were not associated with symptom severity. However, within some white matter clusters that distinguished patients from controls, worse inhibition performance was associated with reduced FA and more impulsive decision making was associated with increased MD. This study shows widespread differences in white matter integrity between adults with persistent ADHD and healthy individuals. Changes in RD suggest aberrant myelination as a pathophysiological factor in persistent ADHD. The microstructural differences in adult ADHD may contribute to poor inhibition and greater impulsivity but appear to be independent of disease severity. Copyright © 2015. Published by Elsevier Inc.

  6. Emotional and neutral declarative memory impairments and associated white matter microstructural abnormalities in adults with type 2 diabetes.

    PubMed

    Yau, Po Lai; Javier, David; Tsui, Wai; Sweat, Victoria; Bruehl, Hannah; Borod, Joan C; Convit, Antonio

    2009-12-30

    Declarative memory impairment is frequently reported among adults with type 2 diabetes mellitus (T2DM), who also demonstrate hippocampal volume reduction. Our goals were to ascertain whether emotional memory, which is mediated by neural circuits overlapping those of declarative memory, is also affected. In addition we wanted to characterize cerebral white matter (WM) involvement in T2DM. We studied 24 middle-aged and elderly patients with T2DM who were free of obvious vascular pathology or a psychiatric disorder, and 17 age- and education-matched healthy individuals with no evidence of insulin resistance. We examined emotional and neutral memory and performed a whole-brain voxelwise WM assessment utilizing diffusion tensor imaging (DTI). We found clear evidence of impairment in declarative memory among diabetic subjects and in addition found some preliminary support to suggest a possible blunting of the memory facilitation by emotional material among female but not male diabetics. This report is also the first DTI assessment among individuals with T2DM, which after accounting for overt WM damage, revealed diffuse but predominantly frontal and temporal WM microstructural abnormalities, with extensive involvement of the temporal stem. Hierarchical regression analyses demonstrated that immediate, but not delayed, emotional memory performance was explained by temporal stem FA, independent of age, poor metabolic regulation, and systolic blood pressure. Given that the temporal lobe memory networks appear to be particularly vulnerable to the deleterious effects of T2DM, this may help explain the observed memory impairments among diabetics. Future efforts should better clarify, with a larger sample, whether emotional memory is affected in adults with T2DM and whether there are clear gender effects.

  7. 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

  8. Structural brain abnormalities in Cushing's syndrome.

    PubMed

    Bauduin, Stephanie E E C; van der Wee, Nic J A; van der Werff, Steven J A

    2018-05-08

    Alongside various physical symptoms, patients with Cushing's disease and Cushing's syndrome display a wide variety of neuropsychiatric and cognitive symptoms, which are indicative of involvement of the central nervous system. The aim of this review is to provide an overview of the structural brain abnormalities that are associated with Cushing's disease and Cushing's syndrome and their relation to behavioral and cognitive symptomatology. In this review, we discuss the gray matter structural abnormalities found in patients with active Cushing's disease and Cushing's syndrome, the reversibility and persistence of these changes and the white matter structural changes related to Cushing's syndrome. Recent findings are of particular interest because they provide more detailed information on localization of the structural changes as well as possible insights into the underlying biological processes. Active Cushing's disease and Cushing's syndrome is related to volume reductions of the hippocampus and in a prefrontal region involving the anterior cingulate cortex (ACC) and medial frontal gyrus (MFG). Whilst there are indications that the reductions in hippocampal volume are partially reversible, the changes in the ACC and MFG appear to be more persistent. In contrast to the volumetric findings, changes in white matter connectivity are typically widespread involving multiple tracts.

  9. Morphological and Glucose Metabolism Abnormalities in Alcoholic Korsakoff's Syndrome: Group Comparisons and Individual Analyses

    PubMed Central

    Pitel, Anne-Lise; Aupée, Anne-Marie; Chételat, Gaël; Mézenge, Florence; Beaunieux, Hélène; de la Sayette, Vincent; Viader, Fausto; Baron, Jean-Claude; Eustache, Francis; Desgranges, Béatrice

    2009-01-01

    Background Gray matter volume studies have been limited to few brain regions of interest, and white matter and glucose metabolism have received limited research attention in Korsakoff's syndrome (KS). Because of the lack of brain biomarkers, KS was found to be underdiagnosed in postmortem studies. Methodology/Principal Findings Nine consecutively selected patients with KS and 22 matched controls underwent both structural magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography examinations. Using a whole-brain analysis, the between-group comparisons of gray matter and white matter density and relative glucose uptake between patients with KS and controls showed the involvement of both the frontocerebellar and the Papez circuits, including morphological abnormalities in their nodes and connection tracts and probably resulting hypometabolism. The direct comparison of the regional distribution and degree of gray matter hypodensity and hypometabolism within the KS group indicated very consistent gray matter distribution of both abnormalities, with a single area of significant difference in the middle cingulate cortex showing greater hypometabolism than hypodensity. Finally, the analysis of the variability in the individual patterns of brain abnormalities within our sample of KS patients revealed that the middle cingulate cortex was the only brain region showing significant GM hypodensity and hypometabolism in each of our 9 KS patients. Conclusions/Significance These results indicate widespread brain abnormalities in KS including both gray and white matter damage mainly involving two brain networks, namely, the fronto-cerebellar circuit and the Papez circuit. Furthermore, our findings suggest that the middle cingulate cortex may play a key role in the pathophysiology of KS and could be considered as a potential in vivo brain biomarker. PMID:19936229

  10. 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

  11. A multivariate pattern analysis study of the HIV-related white matter anatomical structural connections alterations

    NASA Astrophysics Data System (ADS)

    Tang, Zhenchao; Liu, Zhenyu; Li, Ruili; Cui, Xinwei; Li, Hongjun; Dong, Enqing; Tian, Jie

    2017-03-01

    It's widely known that HIV infection would cause white matter integrity impairments. Nevertheless, it is still unclear that how the white matter anatomical structural connections are affected by HIV infection. In the current study, we employed a multivariate pattern analysis to explore the HIV-related white matter connections alterations. Forty antiretroviraltherapy- naïve HIV patients and thirty healthy controls were enrolled. Firstly, an Automatic Anatomical Label (AAL) atlas based white matter structural network, a 90 × 90 FA-weighted matrix, was constructed for each subject. Then, the white matter connections deprived from the structural network were entered into a lasso-logistic regression model to perform HIV-control group classification. Using leave one out cross validation, a classification accuracy (ACC) of 90% (P=0.002) and areas under the receiver operating characteristic curve (AUC) of 0.96 was obtained by the classification model. This result indicated that the white matter anatomical structural connections contributed greatly to HIV-control group classification, providing solid evidence that the white matter connections were affected by HIV infection. Specially, 11 white matter connections were selected in the classification model, mainly crossing the regions of frontal lobe, Cingulum, Hippocampus, and Thalamus, which were reported to be damaged in previous HIV studies. This might suggest that the white matter connections adjacent to the HIV-related impaired regions were prone to be damaged.

  12. Blocked, delayed, or obstructed: What causes poor white matter development in intrauterine growth restricted infants?

    PubMed

    Tolcos, Mary; Petratos, Steven; Hirst, Jonathan J; Wong, Flora; Spencer, Sarah J; Azhan, Aminath; Emery, Ben; Walker, David W

    2017-07-01

    Poor white matter development in intrauterine growth restricted (IUGR) babies remains a major, untreated problem in neonatology. New therapies, guided by an understanding of the mechanisms that underlie normal and abnormal oligodendrocyte development and myelin formation, are required. Much of our knowledge of the mechanisms that underlie impaired myelination come from studies in adult demyelinating disease, preterm brain injury, or experimental models of hypoxia-ischemia. However, relatively less is known for IUGR which is surprising because IUGR is a leading cause of perinatal mortality and morbidity, second only to premature birth. IUGR is also a significant risk factor for the later development of cerebral palsy, and is a greater risk compared to some of the more traditionally researched antecedents - asphyxia and inflammation. Recent evidence suggests that the white matter injury and reduced myelination in the brains of some preterm babies is due to impaired maturation of oligodendrocytes thereby resulting in the reduced capacity to synthesize myelin. Therefore, it is not surprising that the hypomyelination observable in the central nervous system of IUGR infants has similarly lead to investigations identifying a delay or blockade in the progress of maturation of oligodendrocytes in these infants. This review will discuss current ideas thought to account for the poor myelination often present in the neonate's brain following IUGR, and discuss novel interventions that are promising as treatments that promote oligodendrocyte maturation, and thereby repair the myelination deficits that otherwise persist into infancy and childhood and lead to neurodevelopmental abnormalities. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Visceral adiposity predicts subclinical white matter hyperintensities in middle-aged adults.

    PubMed

    Pasha, Evan P; Birdsill, Alex; Parker, Paige; Elmenshawy, Ahmed; Tanaka, Hirofumi; Haley, Andreana P

    Growing prevalence of neuropathology and cognitive impairment are emerging consequences of the obesity epidemic. Adiposity indices used in examining the relationships between obesity, neuropathology, and cognition vary substantially in the literature leading to incongruent findings. Our aim was to determine the anthropometric measures most strongly associated with early white matter disease and cognitive function at midlife. Multiple adiposity indices were measured in 126 adults aged 40-62 who also completed a magnetic resonance imaging (MRI) scan to quantify white matter disease and a cognitive test battery. Anthropometric indices of obesity were compared to image-based estimates of visceral adipose tissue with dual-energy X-ray absorptiometry (DEXA) as predictors of current white matter disease and cognitive function. We also explored sex as a potential moderator of these relationships. Waist circumference (WC) was most strongly correlated with DEXA estimates of visceral adipose tissue (r=0.871, p<0.001). Increasing WC (β=0.231, p=0.034), percent body fat (β=0.230, p=0.045), and VAT (β=0.247, p=0.027) significantly predicted subclinical white matter hyperintensities in the absence of cognitive impairment after accounting for age, sex, years of education, and cardiovascular risk factors. Sex was not a significant moderator of any of the observed relationships. Of the anthropometric indices used in this study, WC, BF, and VAT successfully predicted subclinical white matter disease in cognitively normal adults at midlife. Increasing VAT may independently insidiously affect cerebral white matter prior to detectable cognitive changes, necessitating early intervention. Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  14. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Left-Hemispheric Microstructural Abnormalities in Children With High Functioning Autism Spectrum Disorder

    PubMed Central

    Peterson, Daniel; Mahajan, Rajneesh; Crocetti, Deana; Mejia, Amanda; Mostofsky, Stewart

    2014-01-01

    Current theories of the neurobiological basis of Autism Spectrum Disorder (ASD) posit an altered pattern of connectivity in large-scale brain networks. Here we used Diffusion Tensor Imaging to investigate the microstructural properties of the white matter that mediates inter-regional connectivity in 36 high-functioning children with ASD (HF-ASD), as compared to 37 controls. By employing an atlas-based analysis using LDDMM registration, a widespread, but left-lateralized pattern of abnormalities was revealed. The Mean Diffusivity (MD) of water in the white matter of HF-ASD children was significantly elevated throughout the left hemisphere, particularly in the outer-zone cortical white matter. Across diagnostic groups there was a significant effect of age on left hemisphere MD, with a similar reduction in MD during childhood in both TD and HF-ASD children. The increased MD in children with HF-ASD suggests hypomyelination, and may reflect increased short-range cortico-cortical connections subsequent to early white matter overgrowth. These findings also highlight left hemispheric connectivity as relevant to the pathophysiology of ASD, and indicate that the spatial distribution of microstructural abnormalities in HF-ASD is widespread, and left-lateralized. This altered left-hemispheric connectivity may contribute to deficits in communication and praxis observed in ASD. PMID:25256103

  16. Comparison of brain volume abnormalities between ADHD and conduct disorder in adolescence

    PubMed Central

    Stevens, Michael C.; Haney-Caron, Emily

    2012-01-01

    Background Previous studies of brain structure abnormalities in conduct disorder and attention-deficit/hyperactivity disorder (ADHD) samples have been limited owing to cross-comorbidity, preventing clear understanding of which structural brain abnormalities might be specific to or shared by each disorder. To our knowledge, this study was the first direct comparison of grey and white matter volumes in diagnostically “pure” (i.e., no comorbidities) conduct disorder and ADHD samples. Methods Groups of adolescents with noncormobid conduct disorder and with noncomorbid, combined-subtype ADHD were compared with age- and sex-matched controls using DARTEL voxel-based analysis of T1-weighted brain structure images. Analysis of variance with post hoc analyses compared whole brain grey and white matter volumes among the groups. Results We included 24 adolescents in each study group. There was an overall 13% reduction in grey matter volume in adolescents with conduct disorder, reflecting numerous frontal, temporal, parietal and subcortical deficits. The same grey matter regions typically were not abnormal in those with ADHD. Deficits in frontal lobe regions previously identified in studies of patients with ADHD either were not detected, or group differences from controls were not as strong as those between the conduct disorder and control groups. White matter volume measurements did not differentiate conduct disorder and ADHD. Limitations Our modest sample sizes prevented meaningful examination of individual features of ADHD or conduct disorder, such as aggression, callousness, or hyperactive versus inattentive symptom subtypes. Conclusion The evidence supports theories of frontotemporal abnormalities in adolescents with conduct disorder, but raises questions about the prominence of frontal lobe and striatal structural abnormalities in those with noncomorbid, combined-subtype ADHD. The latter point is clinically important, given the widely held belief that ADHD is

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

    PubMed

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

    2012-08-01

    Traditional models hold that the plastic reorganization of brain structures occurs mainly during childhood and adolescence, leaving adults with limited means to learn new knowledge and skills. Research within the last decade has begun to overturn this belief, documenting changes in the brain's gray and white matter as healthy adults learn simple motor and cognitive skills [Lövdén, M., Bodammer, N. C., Kühn, S., Kaufmann, J., Schütze, H., Tempelmann, C., et al. Experience-dependent plasticity of white-matter microstructure extends into old age. Neuropsychologia, 48, 3878-3883, 2010; Taubert, M., Draganski, B., Anwander, A., Müller, K., Horstmann, A., Villringer, A., et al. Dynamic properties of human brain structure: Learning-related changes in cortical areas and associated fiber connections. The Journal of Neuroscience, 30, 11670-11677, 2010; Scholz, J., Klein, M. C., Behrens, T. E. J., & Johansen-Berg, H. Training induces changes in white-matter architecture. Nature Neuroscience, 12, 1370-1371, 2009; Draganski, B., Gaser, C., Busch, V., Schuirer, G., Bogdahn, U., & May, A. Changes in grey matter induced by training. Nature, 427, 311-312, 2004]. Although the significance of these changes is not fully understood, they reveal a brain that remains plastic well beyond early developmental periods. Here we investigate the role of adult structural plasticity in the complex, long-term learning process of foreign language acquisition. We collected monthly diffusion tensor imaging scans of 11 English speakers who took a 9-month intensive course in written and spoken Modern Standard Chinese as well as from 16 control participants who did not study a language. We show that white matter reorganizes progressively across multiple sites as adults study a new language. Language learners exhibited progressive changes in white matter tracts associated with traditional left hemisphere language areas and their right hemisphere analogs. Surprisingly, the most significant changes

  18. Prefrontal white matter pathology in air pollution exposed Mexico City young urbanites and their potential impact on neurovascular unit dysfunction and the development of Alzheimer's disease

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Calderón-Garcidueñas, Lilian, E-mail: lilian.calderon-garciduenas@umontana.edu; Universidad del Valle de México, Mexico City 04850, México; Reynoso-Robles, Rafael

    Millions of urban children are chronically exposed to high concentrations of air pollutants, i.e., fine particulate matter (PM{sub 2.5}) and ozone, associated with increased risk for Alzheimer's disease. Compared with children living with clear air those in Mexico City (MC) exhibit systemic, brain and intrathecal inflammation, low CSF Aβ{sub 42,} breakdown of the BBB, attention and short-term memory deficits, prefrontal white matter hyperintensities, damage to epithelial and endothelial barriers, tight junction and neural autoantibodies, and Alzheimer and Parkinson's hallmarks. The prefrontal white matter is a target of air pollution. We examined by light and electron microscopy the prefrontal white mattermore » of MC dogs (n: 15, age 3.17±0.74 years), children and teens (n: 34, age: 12.64±4.2 years) versus controls. Major findings in MC residents included leaking capillaries and small arterioles with extravascular lipids and erythrocytes, lipofuscin in pericytes, smooth muscle and endothelial cells (EC), thickening of cerebrovascular basement membranes with small deposits of amyloid, patchy absence of the perivascular glial sheet, enlarged Virchow–Robin spaces and nanosize particles (20–48 nm) in EC, basement membranes, axons and dendrites. Tight junctions, a key component of the neurovascular unit (NVU) were abnormal in MC versus control dogs (χ{sup 2}<0.0001), and white matter perivascular damage was significantly worse in MC dogs (p=0.002). The integrity of the NVU, an interactive network of vascular, glial and neuronal cells is compromised in MC young residents. Characterizing the early NVU damage and identifying biomarkers of neurovascular dysfunction may provide a fresh insight into Alzheimer pathogenesis and open opportunities for pediatric neuroprotection. - Highlights: • The prefrontal white matter is a target of air pollution. • Tight junctions, key neurovascular unit elements, are abnormal in young urbanites. • Identifying neurovascular

  19. Immediate remote ischemic postconditioning after hypoxia ischemia in piglets protects cerebral white matter but not grey matter.

    PubMed

    Ezzati, Mojgan; Bainbridge, Alan; Broad, Kevin D; Kawano, Go; Oliver-Taylor, Aaron; Rocha-Ferreira, Eridan; Alonso-Alconada, Daniel; Fierens, Igor; Rostami, Jamshid; Jane Hassell, K; Tachtsidis, Ilias; Gressens, Pierre; Hristova, Mariya; Bennett, Kate; Lebon, Sophie; Fleiss, Bobbi; Yellon, Derek; Hausenloy, Derek J; Golay, Xavier; Robertson, Nicola J

    2016-08-01

    Remote ischemic postconditioning (RIPostC) is a promising therapeutic intervention whereby brief episodes of ischemia/reperfusion of one organ (limb) mitigate damage in another organ (brain) that has experienced severe hypoxia-ischemia. Our aim was to assess whether RIPostC is protective following cerebral hypoxia-ischemia in a piglet model of neonatal encephalopathy (NE) using magnetic resonance spectroscopy (MRS) biomarkers and immunohistochemistry. After hypoxia-ischemia (HI), 16 Large White female newborn piglets were randomized to: (i) no intervention (n = 8); (ii) RIPostC - with four, 10-min cycles of bilateral lower limb ischemia/reperfusion immediately after HI (n = 8). RIPostC reduced the hypoxic-ischemic-induced increase in white matter proton MRS lactate/N acetyl aspartate (p = 0.005) and increased whole brain phosphorus-31 MRS ATP (p = 0.039) over the 48 h after HI. Cell death was reduced with RIPostC in the periventricular white matter (p = 0.03), internal capsule (p = 0.002) and corpus callosum (p = 0.021); there was reduced microglial activation in corpus callosum (p = 0.001) and more surviving oligodendrocytes in corpus callosum (p = 0.029) and periventricular white matter (p = 0.001). Changes in gene expression were detected in the white matter at 48 h, including KATP channel and endothelin A receptor. Immediate RIPostC is a potentially safe and promising brain protective therapy for babies with NE with protection in white but not grey matter. © The Author(s) 2015.

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

    ERIC Educational Resources Information Center

    Paus, Tomas

    2010-01-01

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

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  2. Quantitative ultrasonography of the periventricular white and grey matter of the developing brain.

    PubMed

    Mullaart, R A; Thijssen, J M; Rotteveel, J J; Valckx, F M; van Geemen, A J

    1999-05-01

    This study addresses the value of operator-independent computer processing of ultrasonograms of the developing brain. With this aim, routine cranial ultrasonograms obtained from 39 term and preterm infants without clinical or sonographic evidence of brain damage were analyzed by five observers. The procedure, respectively, included: 1. the definition of four regions of interest (ROI), one white matter and one grey matter area on each side of the brain; 2. digitization of the sonogram data within these ROIs; 3. correction for the equipment settings, using data from a tissue-mimicking phantom as a reference; and 4. calculation of four sonogram characteristics (i.e., mean echo level, MEAN, signal-to-noise ratio, SNR, and axial and lateral correlation, CORAX and CORLAT, of the echo level co-occurrence matrix). Significant differences between both sides of the brain or a significant influence of ROI size were not found. The interobserver spread was considerable, but less than the intersubject spread. Two sonogram characteristics seemed strongly correlated in white and grey matter (CORAX and CORLAT) and another only in white matter (SNR with CORAX and CORLAT). MEAN seemed not to be correlated with any other characteristic. Furthermore, it was found that maturation equally decreases white and grey matter MEAN and, thus, hardly affects the ratio between the two. An effect on the other sonogram characteristics was only found in the white matter (i.e., an increase of SNR and a decrease of CORAX and CORLAT). Except for MEAN, the grey matter sonogram characteristics seem hardly affected by maturation. In view of these findings, we conclude that quantitative ultrasonography reveals white and grey matter maturation and, furthermore, provides a conceptional-age-independent reference (MEAN white:grey matter ratio) that might be found to facilitate the detection of pathologic brain alterations.

  3. Global and Targeted Pathway Impact of Gliomas on White Matter Integrity Based on Lobar Localization.

    PubMed

    Ormond, David R; D'Souza, Shawn; Thompson, John A

    2017-09-07

    Primary brain tumors comprise 28% of all tumors and 80% of malignant tumors. Pathophysiology of high-grade gliomas includes significant distortion of white matter architecture, necrosis, the breakdown of the blood brain barrier, and increased intracranial pressure. Diffusion tensor imaging (DTI), a diffusion weighted imaging technique, can be used to assess white matter architecture. Use of DTI as a non-invasive pathophysiological tool to analyze glioma impact on white matter microstructure has yet to be fully explored. Preliminary assessment of DTI tractography was done as a measure of intracranial tumor impact on white matter architecture. Specifically, we addressed three questions: 1) whether glioma differentially affects local white matter structure compared to metastasis, 2) whether glioma affects tract integrity of major white matter bundles, 3) whether glioma lobe localization affects tract integrity of different white matter bundles. In this study, we retrospectively investigated preoperative DTI scans from 24 patients undergoing tumor resection. Fiber tractography was estimated using a deterministic fiber tracking algorithm in DSI (diffusion spectrum imaging) Studio. The automatic anatomical labeling (AAL) atlas was used to define the left and right (L/R)   hemisphere regions of interest (ROI). In addition, the John Hopkins University (JHU) White Matter Atlas was used to auto-segment major white matter bundle ROIs. For all tracts derived from ROI seed targets, we computed the following parameters: tract number, tract length, fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD). The DTI tractography analysis revealed that white matter integrity in the hemisphere ipsilateral to intracranial tumor was significantly compromised compared to the control contralateral hemisphere. No differences were observed between high vs low-grade gliomas, however, gliomas induced significantly greater white matter

  4. Strength of Temporal White Matter Pathways Predicts Semantic Learning.

    PubMed

    Ripollés, Pablo; Biel, Davina; Peñaloza, Claudia; Kaufmann, Jörn; Marco-Pallarés, Josep; Noesselt, Toemme; Rodríguez-Fornells, Antoni

    2017-11-15

    Learning the associations between words and meanings is a fundamental human ability. Although the language network is cortically well defined, the role of the white matter pathways supporting novel word-to-meaning mappings remains unclear. Here, by using contextual and cross-situational word learning, we tested whether learning the meaning of a new word is related to the integrity of the language-related white matter pathways in 40 adults (18 women). The arcuate, uncinate, inferior-fronto-occipital and inferior-longitudinal fasciculi were virtually dissected using manual and automatic deterministic fiber tracking. Critically, the automatic method allowed assessing the white matter microstructure along the tract. Results demonstrate that the microstructural properties of the left inferior-longitudinal fasciculus predict contextual learning, whereas the left uncinate was associated with cross-situational learning. In addition, we identified regions of special importance within these pathways: the posterior middle temporal gyrus, thought to serve as a lexical interface and specifically related to contextual learning; the anterior temporal lobe, known to be an amodal hub for semantic processing and related to cross-situational learning; and the white matter near the hippocampus, a structure fundamental for the initial stages of new-word learning and, remarkably, related to both types of word learning. No significant associations were found for the inferior-fronto-occipital fasciculus or the arcuate. While previous results suggest that learning new phonological word forms is mediated by the arcuate fasciculus, these findings show that the temporal pathways are the crucial neural substrate supporting one of the most striking human abilities: our capacity to identify correct associations between words and meanings under referential indeterminacy. SIGNIFICANCE STATEMENT The language-processing network is cortically (i.e., gray matter) well defined. However, the role of the

  5. Age-related decline in oligodendrogenesis retards white matter repair in mice.

    PubMed

    Miyamoto, Nobukazu; Pham, Loc-Duyen D; Hayakawa, Kazuhide; Matsuzaki, Toshinori; Seo, Ji Hae; Magnain, Caroline; Ayata, Cenk; Kim, Kyu-Won; Boas, David; Lo, Eng H; Arai, Ken

    2013-09-01

    Aging is one of the major risk factors for white matter injury in cerebrovascular disease. However, the effects of age on the mechanisms of injury/repair in white matter remain to be fully elucidated. Here, we ask whether, compared with young brains, white matter regions in older brains may be more vulnerable in part because of decreased rates of compensatory oligodendrogenesis after injury. A mouse model of prolonged cerebral hypoperfusion was prepared by bilateral common carotid artery stenosis in 2-month and 8-month-old mice. Matching in vitro studies were performed by subjecting oligodendrocyte precursor cells to sublethal 7-day CoCl2 treatment to induce chemical hypoxic stress. Baseline myelin density in the corpus callosum was similar in 2-month and 8-month-old mice. But after induction of prolonged cerebral hypoperfusion, older mice showed more severe white matter injury together with worse deficits in working memory. The numbers of newborn oligodendrocytes and their precursors were increased by cerebral hypoperfusion in young mice, whereas these endogenous responses were significantly dampened in older mice. Defects in cyclic AMP response element-binding protein signaling may be involved because activating cyclic AMP response element-binding protein with the type-III phosphodiesterase inhibitor cilostazol in older mice restored the differentiation of oligodendrocyte precursor cells, alleviated myelin loss, and improved cognitive dysfunction during cerebral hypoperfusion. Cell culture systems confirmed that cilostazol promoted the differentiation of oligodendrocyte precursor cells. An age-related decline in cyclic AMP response element-binding protein-mediated oligodendrogenesis may compromise endogenous white matter repair mechanisms, and therefore, drugs that activate cyclic AMP response element-binding protein signaling provide a potential therapeutic approach for treating white matter injury in aging brains.

  6. 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

  7. Delayed increases in microvascular pathology after experimental traumatic brain injury are associated with prolonged inflammation, blood-brain barrier disruption, and progressive white matter damage.

    PubMed

    Glushakova, Olena Y; Johnson, Danny; Hayes, Ronald L

    2014-07-01

    Traumatic brain injury (TBI) is a significant risk factor for chronic traumatic encephalopathy (CTE), Alzheimer's disease (AD), and Parkinson's disease (PD). Cerebral microbleeds, focal inflammation, and white matter damage are associated with many neurological and neurodegenerative disorders including CTE, AD, PD, vascular dementia, stroke, and TBI. This study evaluates microvascular abnormalities observed at acute and chronic stages following TBI in rats, and examines pathological processes associated with these abnormalities. TBI in adult rats was induced by controlled cortical impact (CCI) of two magnitudes. Brain pathology was assessed in white matter of the corpus callosum for 24 h to 3 months following injury using immunohistochemistry (IHC). TBI resulted in focal microbleeds that were related to the magnitude of injury. At the lower magnitude of injury, microbleeds gradually increased over the 3 month duration of the study. IHC revealed TBI-induced focal abnormalities including blood-brain barrier (BBB) damage (IgG), endothelial damage (intercellular adhesion molecule 1 [ICAM-1]), activation of reactive microglia (ionized calcium binding adaptor molecule 1 [Iba1]), gliosis (glial fibrillary acidic protein [GFAP]) and macrophage-mediated inflammation (cluster of differentiation 68 [CD68]), all showing different temporal profiles. At chronic stages (up to 3 months), apparent myelin loss (Luxol fast blue) and scattered deposition of microbleeds were observed. Microbleeds were surrounded by glial scars and co-localized with CD68 and IgG puncta stainings, suggesting that localized BBB breakdown and inflammation were associated with vascular damage. Our results indicate that evolving white matter degeneration following experimental TBI is associated with significantly delayed microvascular damage and focal microbleeds that are temporally and regionally associated with development of punctate BBB breakdown and progressive inflammatory responses. Increased

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

    PubMed

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

    2015-09-01

    Amblyopia is a visual disorder caused by poorly coordinated binocular input during development. Little is known about the impact of amblyopia on the white matter within the visual system. We studied the properties of six major visual white-matter pathways in a group of adults with amblyopia (n=10) and matched controls (n=10) using diffusion weighted imaging (DWI) and fiber tractography. While we did not find significant differences in diffusion properties in cortico-cortical pathways, patients with amblyopia exhibited increased mean diffusivity in thalamo-cortical visual pathways. These findings suggest that amblyopia may systematically alter the white matter properties of early visual pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Early dynamics of white matter deficits in children developing dyslexia.

    PubMed

    Vanderauwera, Jolijn; Wouters, Jan; Vandermosten, Maaike; Ghesquière, Pol

    2017-10-01

    Neural anomalies have been demonstrated in dyslexia. Recent studies in pre-readers at risk for dyslexia and in pre-readers developing poor reading suggest that these anomalies might be a cause of their reading impairment. Our study goes one step further by exploring the neurodevelopmental trajectory of white matter anomalies in pre-readers with and without a familial risk for dyslexia (n=61) of whom a strictly selected sample develops dyslexia later on (n=15). We collected longitudinal diffusion MRI and behavioural data until grade 3. The results provide evidence that children with dyslexia exhibit pre-reading white matter anomalies in left and right long segment of the arcuate fasciculus (AF), with predictive power of the left segment above traditional cognitive measures and familial risk. Whereas white matter differences in the left AF seem most strongly related to the development of dyslexia, differences in the left IFOF and in the right AF seem driven by both familial risk and later reading ability. Moreover, differences in the left AF appeared to be dynamic. This study supports and expands recent insights into the neural basis of dyslexia, pointing towards pre-reading anomalies related to dyslexia, as well as underpinning the dynamic character of white matter. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Integrity of normal-appearing white matter: Influence of age, visible lesion burden and hypertension in patients with small-vessel disease.

    PubMed

    Muñoz Maniega, Susana; Chappell, Francesca M; Valdés Hernández, Maria C; Armitage, Paul A; Makin, Stephen D; Heye, Anna K; Thrippleton, Michael J; Sakka, Eleni; Shuler, Kirsten; Dennis, Martin S; Wardlaw, Joanna M

    2017-02-01

    White matter hyperintensities accumulate with age and occur in patients with stroke, but their pathogenesis is poorly understood. We measured multiple magnetic resonance imaging biomarkers of tissue integrity in normal-appearing white matter and white matter hyperintensities in patients with mild stroke, to improve understanding of white matter hyperintensities origins. We classified white matter into white matter hyperintensities and normal-appearing white matter and measured fractional anisotropy, mean diffusivity, water content (T1-relaxation time) and blood-brain barrier leakage (signal enhancement slope from dynamic contrast-enhanced magnetic resonance imaging). We studied the effects of age, white matter hyperintensities burden (Fazekas score) and vascular risk factors on each biomarker, in normal-appearing white matter and white matter hyperintensities, and performed receiver-operator characteristic curve analysis. Amongst 204 patients (34.3-90.9 years), all biomarkers differed between normal-appearing white matter and white matter hyperintensities ( P < 0.001). In normal-appearing white matter and white matter hyperintensities, mean diffusivity and T1 increased with age ( P < 0.001), all biomarkers varied with white matter hyperintensities burden ( P < 0.001; P = 0.02 signal enhancement slope), but only signal enhancement slope increased with hypertension ( P = 0.028). Fractional anisotropy showed complex age-white matter hyperintensities-tissue interactions; enhancement slope showed white matter hyperintensities-tissue interactions. Mean diffusivity distinguished white matter hyperintensities from normal-appearing white matter best at all ages. Blood-brain barrier leakage increases with hypertension and white matter hyperintensities burden at all ages in normal-appearing white matter and white matter hyperintensities, whereas water mobility and content increase as tissue damage accrues, suggesting that blood-brain barrier leakage

  11. Correlation Between White Matter Lesions and Intelligence Quotient in Patients With Congenital Cytomegalovirus Infection.

    PubMed

    Inaba, Yuji; Motobayashi, Mitsuo; Nishioka, Makoto; Kaneko, Tomoki; Yamauchi, Shoko; Kawasaki, Yoichiro; Shiba, Naoko; Nishio, Shin-ya; Moteki, Hideaki; Miyagawa, Maiko; Takumi, Yutaka; Usami, Shin-ichi; Koike, Kenichi

    2016-02-01

    It is well known that congenital cytomegalovirus infection exhibits white matter and other types of lesions in magnetic resonance imaging (MRI), but little is known on the clinical significance of white matter lesions because they are also present in asymptomatic congenital cytomegalovirus infection. We investigated for relationships among white matter lesions, intelligence quotient, and other neurodevelopmental features. Nine children (five boys and four girls; mean age: 87.4 months, range: 63-127 months) with sensorineural hearing loss (five bilateral and four unilateral) had been diagnosed as having congenital cytomegalovirus infection by positive polymerase chain reaction findings of dried umbilical cords. They were evaluated for the presence of autistic features, tested using Wechsler Intelligence Scale for Children-Fourth Edition for intelligence quotient, and underwent brain MRI to measure white matter lesion localization and volume. At the time of MRI examination (mean age: 69.4 months, range: 19-92 months), white matter lesions were detected in eight of nine patients. Five subjects were diagnosed as having autism spectrum disorders. We observed increased white matter lesion volume was associated with lower intelligence quotient scores (R(2) = 0.533, P = 0.026) but not with autism spectrum disorders. In individuals with congenital cytomegalovirus, an increased white matter lesion volume is associated with lower intelligence quotient scores but not with an increased likelihood of autistic behavior. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2016-03-01

    White matter microstructural integrity has been related to cognition. Yet, the potential role of specific white matter tracts on top of a global white matter effect remains unclear, especially when considering specific cognitive domains. Therefore, we determined the tract-specific effect of white matter microstructure on global cognition and specific cognitive domains. In 4400 nondemented and stroke-free participants (mean age 63.7 years, 55.5% women), we obtained diffusion magnetic resonance imaging parameters (fractional anisotropy and mean diffusivity) in 14 white matter tracts using probabilistic tractography and assessed cognitive performance with a cognitive test battery. Tract-specific white matter microstructure in all supratentorial tracts was associated with poorer global cognition. Lower fractional anisotropy in association tracts, primarily the inferior fronto-occipital fasciculus, and higher mean diffusivity in projection tracts, in particular the posterior thalamic radiation, most strongly related to poorer cognition. Altered white matter microstructure related to poorer information processing speed, executive functioning, and motor speed, but not to memory. Tract-specific microstructural changes may aid in better understanding the mechanism of cognitive impairment and neurodegenerative diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Joint source based morphometry identifies linked gray and white matter group differences.

    PubMed

    Xu, Lai; Pearlson, Godfrey; Calhoun, Vince D

    2009-02-01

    We present a multivariate approach called joint source based morphometry (jSBM), to identify linked gray and white matter regions which differ between groups. In jSBM, joint independent component analysis (jICA) is used to decompose preprocessed gray and white matter images into joint sources and statistical analysis is used to determine the significant joint sources showing group differences and their relationship to other variables of interest (e.g. age or sex). The identified joint sources are groupings of linked gray and white matter regions with common covariation among subjects. In this study, we first provide a simulation to validate the jSBM approach. To illustrate our method on real data, jSBM is then applied to structural magnetic resonance imaging (sMRI) data obtained from 120 chronic schizophrenia patients and 120 healthy controls to identify group differences. JSBM identified four joint sources as significantly associated with schizophrenia. Linked gray-white matter regions identified in each of the joint sources included: 1) temporal--corpus callosum, 2) occipital/frontal--inferior fronto-occipital fasciculus, 3) frontal/parietal/occipital/temporal--superior longitudinal fasciculus and 4) parietal/frontal--thalamus. Age effects on all four joint sources were significant, but sex effects were significant only for the third joint source. Our findings demonstrate that jSBM can exploit the natural linkage between gray and white matter by incorporating them into a unified framework. This approach is applicable to a wide variety of problems to study linked gray and white matter group differences.

  14. Joint source based morphometry identifies linked gray and white matter group differences

    PubMed Central

    Xu, Lai; Pearlson, Godfrey; Calhoun, Vince D.

    2009-01-01

    We present a multivariate approach called joint source based morphometry (jSBM), to identify linked gray and white matter regions which differ between groups. In jSBM, joint independent component analysis (jICA) is used to decompose preprocessed gray and white matter images into joint sources and statistical analysis is used to determine the significant joint sources showing group differences and their relationship to other variables of interest (e.g. age or sex). The identified joint sources are groupings of linked gray and white matter regions with common covariation among subjects. In this study, we first provide a simulation to validate the jSBM approach. To illustrate our method on real data, jSBM is then applied to structural magnetic resonance imaging (sMRI) data obtained from 120 chronic schizophrenia patients and 120 healthy controls to identify group differences. JSBM identified four joint sources as significantly associated with schizophrenia. Linked gray–white matter regions identified in each of the joint sources included: 1) temporal — corpus callosum, 2) occipital/frontal — inferior fronto-occipital fasciculus, 3) frontal/parietal/occipital/temporal —superior longitudinal fasciculus and 4) parietal/frontal — thalamus. Age effects on all four joint sources were significant, but sex effects were significant only for the third joint source. Our findings demonstrate that jSBM can exploit the natural linkage between gray and white matter by incorporating them into a unified framework. This approach is applicable to a wide variety of problems to study linked gray and white matter group differences. PMID:18992825

  15. Longitudinal changes in microstructural white matter metrics in Alzheimer's disease.

    PubMed

    Mayo, Chantel D; Mazerolle, Erin L; Ritchie, Lesley; Fisk, John D; Gawryluk, Jodie R

    2017-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Current avenues of AD research focus on pre-symptomatic biomarkers that will assist with early diagnosis of AD. The majority of magnetic resonance imaging (MRI) based biomarker research to date has focused on neuronal loss in grey matter and there is a paucity of research on white matter. Longitudinal DTI data from the Alzheimer's Disease Neuroimaging Initiative 2 database were used to examine 1) the within-group microstructural white matter changes in individuals with AD and healthy controls at baseline and year one; and 2) the between-group microstructural differences in individuals with AD and healthy controls at both time points. 1) Within-group: longitudinal Tract-Based Spatial Statistics revealed that individuals with AD and healthy controls both had widespread reduced fractional anisotropy (FA) and increased mean diffusivity (MD) with changes in the hippocampal cingulum exclusive to the AD group. 2) Between-group: relative to healthy controls, individuals with AD had lower FA and higher MD in the hippocampal cingulum, as well as the corpus callosum, internal and external capsule; corona radiata; posterior thalamic radiation; superior and inferior longitudinal fasciculus; fronto-occipital fasciculus; cingulate gyri; fornix; uncinate fasciculus; and tapetum. The current results indicate that sensitivity to white matter microstructure is a promising avenue for AD biomarker research. Additional longitudinal studies on both white and grey matter are warranted to further evaluate potential clinical utility.

  16. Influence of White and Gray Matter Connections on Endogenous Human Cortical Oscillations

    PubMed Central

    Hawasli, Ammar H.; Kim, DoHyun; Ledbetter, Noah M.; Dahiya, Sonika; Barbour, Dennis L.; Leuthardt, Eric C.

    2016-01-01

    Brain oscillations reflect changes in electrical potentials summated across neuronal populations. Low- and high-frequency rhythms have different modulation patterns. Slower rhythms are spatially broad, while faster rhythms are more local. From this observation, we hypothesized that low- and high-frequency oscillations reflect white- and gray-matter communications, respectively, and synchronization between low-frequency phase with high-frequency amplitude represents a mechanism enabling distributed brain-networks to coordinate local processing. Testing this common understanding, we selectively disrupted white or gray matter connections to human cortex while recording surface field potentials. Counter to our original hypotheses, we found that cortex consists of independent oscillatory-units (IOUs) that maintain their own complex endogenous rhythm structure. IOUs are differentially modulated by white and gray matter connections. White-matter connections maintain topographical anatomic heterogeneity (i.e., separable processing in cortical space) and gray-matter connections segregate cortical synchronization patterns (i.e., separable temporal processing through phase-power coupling). Modulation of distinct oscillatory modules enables the functional diversity necessary for complex processing in the human brain. PMID:27445767

  17. Origins of R2∗ and white matter

    PubMed Central

    Rudko, David A.; Klassen, L. Martyn; de Chickera, Sonali N.; Gati, Joseph S.; Dekaban, Gregory A.; Menon, Ravi S.

    2014-01-01

    Estimates of the apparent transverse relaxation rate () can be used to quantify important properties of biological tissue. Surprisingly, the mechanism of dependence on tissue orientation is not well understood. The primary goal of this paper was to characterize orientation dependence of in gray and white matter and relate it to independent measurements of two other susceptibility based parameters: the local Larmor frequency shift (fL) and quantitative volume magnetic susceptibility (Δχ). Through this comparative analysis we calculated scaling relations quantifying (reversible contribution to the transverse relaxation rate from local field inhomogeneities) in a voxel given measurements of the local Larmor frequency shift. is a measure of both perturber geometry and density and is related to tissue microstructure. Additionally, two methods (the Generalized Lorentzian model and iterative dipole inversion) for calculating Δχ were compared in gray and white matter. The value of Δχ derived from fitting the Generalized Lorentzian model was then connected to the observed orientation dependence using image-registered optical density measurements from histochemical staining. Our results demonstrate that the and fL of white and cortical gray matter are well described by a sinusoidal dependence on the orientation of the tissue and a linear dependence on the volume fraction of myelin in the tissue. In deep brain gray matter structures, where there is no obvious symmetry axis, and fL have no orientation dependence but retain a linear dependence on tissue iron concentration and hence Δχ. PMID:24374633

  18. Substance-use initiation moderates the effect of stress on white-matter microstructure in adolescents.

    PubMed

    Zhai, Zu Wei; Yip, Sarah W; Morie, Kristen P; Sinha, Rajita; Mayes, Linda C; Potenza, Marc N

    2018-04-01

    While childhood stress may contribute risk to substance-use initiation and differences in brain white-matter development, understanding of the potential impact of substance-use initiation on the relationship between experienced stress and white-matter microstructure remains limited. This study examined whether substance-use initiation moderated the effect of perceived stress on white-matter differences using measures of primary white-matter fiber anisotropy. Forty adolescents (age 14.75 ± .87 years) were assessed on the Perceived Stress Scale, and 50% were determined to have presence of substance-use initiation. White-matter microstructure was examined using primary-fiber orientations anisotropy, which may reflect white-matter integrity, modeled separately from other fiber orientations in the same voxels. Analyses were conducted on regions of interest previously associated with childhood stress and substance use. Lower perceived stress and presence of substance-use initiation were related to greater right cingulum primary-fiber measures. Substance-use-initiation status moderated the association between perceived stress and right cingulum primary-fiber measures, such that higher perceived stress was associated with lower right cingulum primary-fiber anisotropy in adolescents without substance-use initiation, but not in those with substance-use initiation. Findings in primary-fiber anisotropy suggest differences in right cingulum white-matter integrity is associated with substance-use initiation in higher-stress adolescents. This reflects a possible pre-existing risk factor, an impact of early substance use, or a combination thereof. Examination of potential markers associated with substance-use initiation in white-matter microstructure among stress-exposed youth warrant additional investigation as such biomarkers may inform efforts relating to tailored interventions. (Am J Addict 2018;27:217-224). © 2018 American Academy of Addiction Psychiatry.

  19. Exercise protects myelinated fibers of white matter in a rat model of depression.

    PubMed

    Xiao, Qian; Wang, Feifei; Luo, Yanmin; Chen, Linmu; Chao, Fenglei; Tan, Chuanxue; Gao, Yuan; Huang, Chunxia; Zhang, Lei; Liang, Xin; Tang, Jing; Qi, Yingqing; Jiang, Lin; Zhang, Yi; Zhou, Chunni; Tang, Yong

    2018-02-15

    The antidepressive effects of exercise have been a focus of research and are hypothesized to remodel the brain networks constructed by myelinated fibers. However, whether the antidepressant effects of exercise are dependent on changes in white matter myelination are unknown. Therefore, we chose chronic unpredictable stress (CUS) as a model of depression and designed an experiment. After a 4-week CUS period, 40 animals were tested using the sucrose preference test (SPT) and the open field test (OFT). The depressed rats then underwent 4-week running exercise. Next, electron microscopy and unbiased stereological methods were used to investigate white matter changes in the rats. After the 4-week CUS stimulation, body weight, sucrose preference and scores on the OFT were significantly lower in the depression rats than in the unstressed rats (p < .05). After undergoing a 4-week running exercise, the depression rats showed a significantly greater sucrose preference than the depression control rats without running exercise (p < .05). Furthermore, the white matter parameters of the depression rats (including the white matter volumes, the length and volumes of myelinated fibers, and the volumes and thickness of the myelin sheaths) were significantly reduced after the CUS period (p < .05). However, these white matter parameters were significantly increased after running exercise (p < .05). The present study is the first to provide evidence that running exercise has positive effects on white matter and the myelinated fibers of white matter in depressed rats, and this evidence might provide an important theoretical basis for the exercise-mediated treatment of depression. © 2017 Wiley Periodicals, Inc.

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

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

    PubMed Central

    Downey, Laura E.; Mahoney, Colin J.; Buckley, Aisling H.; Golden, Hannah L.; Henley, Susie M.; Schmitz, Nicole; Schott, Jonathan M.; Simpson, Ivor J.; Ourselin, Sebastien; Fox, Nick C.; Crutch, Sebastian J.; Warren, Jason D.

    2015-01-01

    Impairments of social cognition are often leading features in frontotemporal lobar degeneration (FTLD) and likely to reflect large-scale brain network disintegration. However, the neuroanatomical basis of impaired social cognition in FTLD and the role of white matter connections have not been defined. Here we assessed social cognition in a cohort of patients representing two core syndromes of FTLD, behavioural variant frontotemporal dementia (bvFTD; n = 29) and semantic variant primary progressive aphasia (svPPA; n = 15), relative to healthy older individuals (n = 37) using two components of the Awareness of Social Inference Test, canonical emotion identification and sarcasm identification. Diffusion tensor imaging (DTI) was used to derive white matter tract correlates of social cognition performance and compared with the distribution of grey matter atrophy on voxel-based morphometry. The bvFTD and svPPA groups showed comparably severe deficits for identification of canonical emotions and sarcasm, and these deficits were correlated with distributed and overlapping white matter tract alterations particularly affecting frontotemporal connections in the right cerebral hemisphere. The most robust DTI associations were identified in white matter tracts linking cognitive and evaluative processing with emotional responses: anterior thalamic radiation, fornix (emotion identification) and uncinate fasciculus (sarcasm identification). DTI associations of impaired social cognition were more consistent than corresponding grey matter associations. These findings delineate a brain network substrate for the social impairment that characterises FTLD syndromes. The findings further suggest that DTI can generate sensitive and functionally relevant indexes of white matter damage in FTLD, with potential to transcend conventional syndrome boundaries. PMID:26236629

  2. Ageing and brain white matter structure in 3,513 UK Biobank participants

    PubMed Central

    Cox, Simon R.; Ritchie, Stuart J.; Tucker-Drob, Elliot M.; Liewald, David C.; Hagenaars, Saskia P.; Davies, Gail; Wardlaw, Joanna M.; Gale, Catharine R.; Bastin, Mark E.; Deary, Ian J.

    2016-01-01

    Quantifying the microstructural properties of the human brain's connections is necessary for understanding normal ageing and disease. Here we examine brain white matter magnetic resonance imaging (MRI) data in 3,513 generally healthy people aged 44.64–77.12 years from the UK Biobank. Using conventional water diffusion measures and newer, rarely studied indices from neurite orientation dispersion and density imaging, we document large age associations with white matter microstructure. Mean diffusivity is the most age-sensitive measure, with negative age associations strongest in the thalamic radiation and association fibres. White matter microstructure across brain tracts becomes increasingly correlated in older age. This may reflect an age-related aggregation of systemic detrimental effects. We report several other novel results, including age associations with hemisphere and sex, and comparative volumetric MRI analyses. Results from this unusually large, single-scanner sample provide one of the most extensive characterizations of age associations with major white matter tracts in the human brain. PMID:27976682

  3. Accelerated Gray and White Matter Deterioration With Age in Schizophrenia.

    PubMed

    Cropley, Vanessa L; Klauser, Paul; Lenroot, Rhoshel K; Bruggemann, Jason; Sundram, Suresh; Bousman, Chad; Pereira, Avril; Di Biase, Maria A; Weickert, Thomas W; Weickert, Cynthia Shannon; Pantelis, Christos; Zalesky, Andrew

    2017-03-01

    Although brain changes in schizophrenia have been proposed to mirror those found with advancing age, the trajectory of gray matter and white matter changes during the disease course remains unclear. The authors sought to measure whether these changes in individuals with schizophrenia remain stable, are accelerated, or are diminished with age. Gray matter volume and fractional anisotropy were mapped in 326 individuals diagnosed with schizophrenia or schizoaffective disorder and in 197 healthy comparison subjects aged 20-65 years. Polynomial regression was used to model the influence of age on gray matter volume and fractional anisotropy at a whole-brain and voxel level. Between-group differences in gray matter volume and fractional anisotropy were regionally localized across the lifespan using permutation testing and cluster-based inference. Significant loss of gray matter volume was evident in schizophrenia, progressively worsening with age to a maximal loss of 8% in the seventh decade of life. The inferred rate of gray matter volume loss was significantly accelerated in schizophrenia up to middle age and plateaued thereafter. In contrast, significant reductions in fractional anisotropy emerged in schizophrenia only after age 35, and the rate of fractional anisotropy deterioration with age was constant and best modeled with a straight line. The slope of this line was 60% steeper in schizophrenia relative to comparison subjects, indicating a significantly faster rate of white matter deterioration with age. The rates of reduction of gray matter volume and fractional anisotropy were significantly faster in males than in females, but an interaction between sex and diagnosis was not evident. The findings suggest that schizophrenia is characterized by an initial, rapid rate of gray matter loss that slows in middle life, followed by the emergence of a deficit in white matter that progressively worsens with age at a constant rate.

  4. White and gray matter damage in primary progressive MS: The chicken or the egg?

    PubMed

    Bodini, Benedetta; Chard, Declan; Altmann, Daniel R; Tozer, Daniel; Miller, David H; Thompson, Alan J; Wheeler-Kingshott, Claudia; Ciccarelli, Olga

    2016-01-12

    The temporal relationship between white matter (WM) and gray matter (GM) damage in vivo in early primary progressive multiple sclerosis (PPMS) was investigated testing 2 hypotheses: (1) WM tract abnormalities predict subsequent changes in the connected cortex ("primary WM damage model"); and (2) cortical abnormalities predict later changes in connected WM tracts ("primary GM damage model"). Forty-seven patients with early PPMS and 18 healthy controls had conventional and magnetization transfer imaging at baseline; a subgroup of 35 patients repeated the protocol after 2 years. Masks of the corticospinal tracts, genu of the corpus callosum and optic radiations, and of connected cortical regions, were used for extracting the mean magnetization transfer ratio (MTR). Multiple regressions within each of 5 tract-cortex pairs were performed, adjusting for the dependent variable's baseline MTR; tract lesion load and MTR, spinal cord area, age, and sex were examined for potential confounding. The baseline MTR of most regions was lower in patients than in healthy controls. The tract-cortex pair relationships in the primary WM damage model were significant for the bilateral motor pair and right visual pair, while those in the primary GM damage model were only significant for the right motor pair. Lower lesion MTR at baseline was associated with lower MTR in the same tract normal-appearing WM at 2 years in 3 tracts. These results are consistent with the hypothesis that in early PPMS, cortical damage is for the most part a sequela of normal-appearing WM pathology, which, in turn, is predicted by abnormalities within WM lesions. © 2015 American Academy of Neurology.

  5. 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

  6. 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

  7. 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.…

  8. 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

  9. White matter lesions in Parkinson disease

    PubMed Central

    Bohnen, Nicolaas I.; Albin, Roger L.

    2013-01-01

    Pure vascular parkinsonism without evidence of nigral Lewy body pathology may occur as a distinct clinicopathological entity, but a much more frequent occurrence is the comorbid presence of age-associated white matter lesions (WMLs) in idiopathic Parkinson disease (PD). WMLs are associated with motor and cognitive symptoms in otherwise normal elderly individuals. Comorbid WMLs are, therefore, expected to contribute to clinical symptoms in PD. Studies of WMLs in PD differ with regard to methods of assessment of WML burden and the patient populations selected for analysis, but converging evidence suggests that postural stability and gait motor functions are predominantly affected. WMLs are described to contribute to dementia in Alzheimer disease, and emerging but inconclusive evidence indicates similar effects in PD. In this article, we review the literature addressing the occurrence and impact of WMLs in PD, and suggest that WMLs may exacerbate or contribute to some motor and cognitive deficits associated with PD. We review existing and emerging methods for studying white matter pathology in vivo, and propose future research directions. PMID:21343896

  10. White-Matter Structural Connectivity Underlying Human Laughter-Related Traits Processing.

    PubMed

    Wu, Ching-Lin; Zhong, Suyu; Chan, Yu-Chen; Chen, Hsueh-Chih; Gong, Gaolang; He, Yong; Li, Ping

    2016-01-01

    Most research into the neural mechanisms of humor has not explicitly focused on the association between emotion and humor on the brain white matter networks mediating this connection. However, this connection is especially salient in gelotophobia (the fear of being laughed at), which is regarded as the presentation of humorlessness, and two related traits, gelotophilia (the enjoyment of being laughed at) and katagelasticism (the enjoyment of laughing at others). Here, we explored whether the topological properties of white matter networks can account for the individual differences in the laughter-related traits of 31 healthy adults. We observed a significant negative correlation between gelotophobia scores and the clustering coefficient, local efficiency and global efficiency, but a positive association between gelotophobia scores and path length in the brain's white matter network. Moreover, the current study revealed that with increasing individual fear of being laughed at, the linking efficiencies in superior frontal gyrus, anterior cingulate cortex, parahippocampal gyrus, and middle temporal gyrus decreased. However, there were no significant correlations between either gelotophilia or katagelasticism scores or the topological properties of the brain white matter network. These findings suggest that the fear of being laughed at is directly related to the level of local and global information processing of the brain network, which might provide new insights into the neural mechanisms of the humor information processing.

  11. Structural white matter differences underlying heterogeneous learning abilities after TBI.

    PubMed

    Chiou, Kathy S; Genova, Helen M; Chiaravalloti, Nancy D

    2016-12-01

    The existence of learning deficits after traumatic brain injury (TBI) is generally accepted; however, our understanding of the structural brain mechanisms underlying learning impairment after TBI is limited. Furthermore, our understanding of learning after TBI is often at risk for overgeneralization, as research often overlooks within sample heterogeneity in learning abilities. The present study examined differences in white matter integrity in a sample of adults with moderate to severe TBI who differed in learning abilities. Adults with moderate to severe TBI were grouped into learners and non-learners based upon achievement of the learning criterion of the open-trial Selective Reminding Test (SRT). Diffusion tensor imaging (DTI) was used to identify white matter differences between the learners and non-learners. Adults with TBI who were able to meet the learning criterion had greater white matter integrity (as indicated by higher fractional anisotropy [FA] values) in the right anterior thalamic radiation, forceps minor, inferior fronto-occipital fasciculus, and forceps minor than non-learners. The results of the study suggest that differences in white matter integrity may explain the observed heterogeneity in learning ability after moderate to severe TBI. This also supports emerging evidence for the involvement of the thalamus in higher order cognition, and the role of thalamo-cortical tracts in connecting functional networks associated with learning.

  12. White-Matter Structural Connectivity Underlying Human Laughter-Related Traits Processing

    PubMed Central

    Wu, Ching-Lin; Zhong, Suyu; Chan, Yu-Chen; Chen, Hsueh-Chih; Gong, Gaolang; He, Yong; Li, Ping

    2016-01-01

    Most research into the neural mechanisms of humor has not explicitly focused on the association between emotion and humor on the brain white matter networks mediating this connection. However, this connection is especially salient in gelotophobia (the fear of being laughed at), which is regarded as the presentation of humorlessness, and two related traits, gelotophilia (the enjoyment of being laughed at) and katagelasticism (the enjoyment of laughing at others). Here, we explored whether the topological properties of white matter networks can account for the individual differences in the laughter-related traits of 31 healthy adults. We observed a significant negative correlation between gelotophobia scores and the clustering coefficient, local efficiency and global efficiency, but a positive association between gelotophobia scores and path length in the brain's white matter network. Moreover, the current study revealed that with increasing individual fear of being laughed at, the linking efficiencies in superior frontal gyrus, anterior cingulate cortex, parahippocampal gyrus, and middle temporal gyrus decreased. However, there were no significant correlations between either gelotophilia or katagelasticism scores or the topological properties of the brain white matter network. These findings suggest that the fear of being laughed at is directly related to the level of local and global information processing of the brain network, which might provide new insights into the neural mechanisms of the humor information processing. PMID:27833572

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

  14. Ischemic tolerance in pre-myelinated white matter: the role of astrocyte glycogen in brain pathology.

    PubMed

    Fern, Robert

    2015-06-01

    In isolated white matter, ischemic tolerance changes dramatically in the period immediately before the onset of myelination. In the absence of an extrinsic energy source, postnatal day 0 to 2 (P0 to P2) white matter axons are here shown to maintain excitability for over twice as long as axons >P2, a differential that was dependent on glycogen metabolism. Prolonged withdrawal of extrinsic energy supply tended to spare axons in zones around astrocytes, which are shown to be the sole repository for glycogen particles in developing white matter. Analysis of mitochondrial volume fraction revealed that neither axons nor astrocytes had a low metabolic rate in neonatal white matter, while oligodendroglia at older ages had an elevated metabolism. The astrocyte population is established early in neural development, and exhibits reduced cell density as maturation progresses and white matter expands. The findings show that this event establishes the necessary conditions for ischemia sensitivity in white matter and indicates that astrocyte proximity may be significant for the survival of neuronal elements in conditions associated with compromised energy supply.

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

    PubMed

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

    2015-06-03

    Understanding aging-related cognitive decline is of growing importance in aging societies, but relatively little is known about its neural substrates. Measures of white matter microstructure are known to correlate cross-sectionally with cognitive ability measures, but only a few small studies have tested for longitudinal relations among these variables. We tested whether there were coupled changes in brain white matter microstructure indexed by fractional anisotropy (FA) and three broad cognitive domains (fluid intelligence, processing speed, and memory) in a large cohort of human participants with longitudinal diffusion tensor MRI and detailed cognitive data taken at ages 73 years (n = 731) and 76 years (n = 488). Longitudinal changes in white matter microstructure were coupled with changes in fluid intelligence, but not with processing speed or memory. Individuals with higher baseline white matter FA showed less subsequent decline in processing speed. Our results provide evidence for a longitudinal link between changes in white matter microstructure and aging-related cognitive decline during the eighth decade of life. They are consistent with theoretical perspectives positing that a corticocortical "disconnection" partly explains cognitive aging. Copyright © 2015 Ritchie et al.

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

    PubMed

    Kuznetsova, Ksenia A; Maniega, Susana Muñoz; Ritchie, Stuart J; Cox, Simon R; Storkey, Amos J; Starr, John M; Wardlaw, Joanna M; Deary, Ian J; Bastin, Mark E

    2016-07-01

    Cognitive decline, especially the slowing of information processing speed, is associated with normal ageing. This decline may be due to brain cortico-cortical disconnection caused by age-related white matter deterioration. We present results from a large, narrow age range cohort of generally healthy, community-dwelling subjects in their seventies who also had their cognitive ability tested in youth (age 11 years). We investigate associations between older age brain white matter structure, several measures of information processing speed and childhood cognitive ability in 581 subjects. Analysis of diffusion tensor MRI data using Tract-based Spatial Statistics (TBSS) showed that all measures of information processing speed, as well as a general speed factor composed from these tests (g speed), were significantly associated with fractional anisotropy (FA) across the white matter skeleton rather than in specific tracts. Cognitive ability measured at age 11 years was not associated with older age white matter FA, except for the g speed-independent components of several individual processing speed tests. These results indicate that quicker and more efficient information processing requires global connectivity in older age, and that associations between white matter FA and information processing speed (both individual test scores and g speed), unlike some other aspects of later life brain structure, are generally not accounted for by cognitive ability measured in youth.

  17. Fiberprint: A subject fingerprint based on sparse code pooling for white matter fiber analysis.

    PubMed

    Kumar, Kuldeep; Desrosiers, Christian; Siddiqi, Kaleem; Colliot, Olivier; Toews, Matthew

    2017-09-01

    White matter characterization studies use the information provided by diffusion magnetic resonance imaging (dMRI) to draw cross-population inferences. However, the structure, function, and white matter geometry vary across individuals. Here, we propose a subject fingerprint, called Fiberprint, to quantify the individual uniqueness in white matter geometry using fiber trajectories. We learn a sparse coding representation for fiber trajectories by mapping them to a common space defined by a dictionary. A subject fingerprint is then generated by applying a pooling function for each bundle, thus providing a vector of bundle-wise features describing a particular subject's white matter geometry. These features encode unique properties of fiber trajectories, such as their density along prominent bundles. An analysis of data from 861 Human Connectome Project subjects reveals that a fingerprint based on approximately 3000 fiber trajectories can uniquely identify exemplars from the same individual. We also use fingerprints for twin/sibling identification, our observations consistent with the twin data studies of white matter integrity. Our results demonstrate that the proposed Fiberprint can effectively capture the variability in white matter fiber geometry across individuals, using a compact feature vector (dimension of 50), making this framework particularly attractive for handling large datasets. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Local White Matter Geometry from Diffusion Tensor Gradients

    PubMed Central

    Savadjiev, Peter; Kindlmann, Gordon L.; Bouix, Sylvain; Shenton, Martha E.; Westin, Carl-Fredrik

    2009-01-01

    We introduce a mathematical framework for computing geometrical properties of white matter fibres directly from diffusion tensor fields. The key idea is to isolate the portion of the gradient of the tensor field corresponding to local variation in tensor orientation, and to project it onto a coordinate frame of tensor eigenvectors. The resulting eigenframe-centered representation then makes it possible to define scalar indices (or measures) that describe the local white matter geometry directly from the diffusion tensor field and its gradient, without requiring prior tractography. We derive new scalar indices of (1) fibre dispersion and (2) fibre curving, and we demonstrate them on synthetic and in vivo data. Finally, we illustrate their applicability to a group study on schizophrenia. PMID:19896542

  19. Local White Matter Geometry from Diffusion Tensor Gradients

    PubMed Central

    Savadjiev, Peter; Kindlmann, Gordon L.; Bouix, Sylvain; Shenton, Martha E.; Westin, Carl-Fredrik

    2010-01-01

    We introduce a mathematical framework for computing geometrical properties of white matter fibres directly from diffusion tensor fields. The key idea is to isolate the portion of the gradient of the tensor field corresponding to local variation in tensor orientation, and to project it onto a coordinate frame of tensor eigenvectors. The resulting eigenframe-centered representation then makes it possible to define scalar indices (or measures) that describe the local white matter geometry directly from the diffusion tensor field and its gradient, without requiring prior tractography. We derive new scalar indices of (1) fibre dispersion and (2) fibre curving, and we demonstrate them on synthetic and in vivo data. Finally, we illustrate their applicability to a group study on schizophrenia. PMID:20426006

  20. Chronic kidney disease, cerebral blood flow, and white matter volume in hypertensive adults.

    PubMed

    Tamura, Manjula Kurella; Pajewski, Nicholas M; Bryan, R Nick; Weiner, Daniel E; Diamond, Matthew; Van Buren, Peter; Taylor, Addison; Beddhu, Srinivasan; Rosendorff, Clive; Jahanian, Hesamoddin; Zaharchuk, Greg

    2016-03-29

    To determine the relation between markers of kidney disease-estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR)-with cerebral blood flow (CBF) and white matter volume (WMV) in hypertensive adults. We used baseline data collected from 665 nondiabetic hypertensive adults aged ≥50 years participating in the Systolic Blood Pressure Intervention Trial (SPRINT). We used arterial spin labeling to measure CBF and structural 3T images to segment tissue into normal and abnormal WMV. We used quantile regression to estimate the association between eGFR and UACR with CBF and abnormal WMV, adjusting for sociodemographic and clinical characteristics. There were 218 participants (33%) with eGFR <60 mL/min/1.73 m(2) and 146 participants (22%) with UACR ≥30 mg/g. Reduced eGFR was independently associated with higher adjusted median CBF, but not with abnormal WMV. Conversely, in adjusted analyses, there was a linear independent association between UACR and larger abnormal WMV, but not with CBF. Compared to participants with neither marker of CKD (eGFR ≥60 mL/min/1.73 m(2) and UACR <30 mg/g), median CBF was 5.03 mL/100 g/min higher (95% confidence interval [CI] 0.78, 9.29) and abnormal WMV was 0.63 cm(3) larger (95% CI 0.08, 1.17) among participants with both markers of CKD (eGFR <60 mL/min/1.73 m(2) and UACR ≥30 mg/g). Among nondiabetic hypertensive adults, reduced eGFR was associated with higher CBF and higher UACR was associated with larger abnormal WMV. © 2016 American Academy of Neurology.

  1. White matter connectivity and Internet gaming disorder

    PubMed Central

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

    2017-01-01

    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

  2. Abnormal hubs of white matter networks in the frontal-parieto circuit contribute to depression discrimination via pattern classification.

    PubMed

    Qin, Jiaolong; Wei, Maobin; Liu, Haiyan; Chen, Jianhuai; Yan, Rui; Hua, Lingling; Zhao, Ke; Yao, Zhijian; Lu, Qing

    2014-12-01

    Previous studies had explored the diagnostic and prognostic value of the structural neuroimaging data of MDD and treated the whole brain voxels, the fractional anisotropy and the structural connectivity as classification features. To our best knowledge, no study examined the potential diagnostic value of the hubs of anatomical brain networks in MDD. The purpose of the current study was to provide an exploratory examination of the potential diagnostic and prognostic values of hubs of white matter brain networks in MDD discrimination and the corresponding impaired hub pattern via a multi-pattern analysis. We constructed white matter brain networks from 29 depressions and 30 healthy controls based on diffusion tensor imaging data, calculated nodal measures and identified hubs. Using these measures as features, two types of feature architectures were established, one only included hubs (HUB) and the other contained both hubs and non hubs. The support vector machine classifiers with Gaussian radial basis kernel were used after the feature selection. Moreover, the relative contribution of the features was estimated by means of the consensus features. Our results presented that the hubs (including the bilateral dorsolateral part of superior frontal gyrus, the left middle frontal gyrus, the bilateral middle temporal gyrus, and the bilateral inferior temporal gyrus) played an important role in distinguishing the depressions from healthy controls with the best accuracy of 83.05%. Moreover, most of the HUB consensus features located in the frontal-parieto circuit. These findings provided evidence that the hubs could be served as valuable potential diagnostic measure for MDD, and the hub-concentrated lesion distribution of MDD was primarily anchored within the frontal-parieto circuit. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Spaceflight-induced changes in white matter hyperintensity burden in astronauts.

    PubMed

    Alperin, Noam; Bagci, Ahmet M; Lee, Sang H

    2017-11-21

    To assess the effect of weightlessness and the respective roles of CSF and vascular fluid on changes in white matter hyperintensity (WMH) burden in astronauts. We analyzed prespaceflight and postspaceflight brain MRI scans from 17 astronauts, 10 who flew a long-duration mission on the International Space Station (ISS) and 7 who flew a short-duration mission on the Space Shuttle. Automated analysis methods were used to determine preflight to postflight changes in periventricular and deep WMH, CSF, and brain tissue volumes in fluid-attenuated inversion recovery and high-resolution 3-dimensional T1-weighted imaging. Differences between cohorts and associations between individual measures were assessed. The short-term reversibility of the identified preflight to postflight changes was tested in a subcohort of 5 long-duration astronauts who had a second postflight MRI scan 1 month after the first postflight scan. Significant preflight to postflight changes were measured only in the long-duration cohort and included only the periventricular WMH and ventricular CSF volumes. Changes in deep WMH and brain tissue volumes were not significant in either cohort. The increase in periventricular WMH volume was significantly associated with an increase in ventricular CSF volume (ρ = 0.63, p = 0.008). A partial reversal of these increases was observed in the long-duration subcohort with a 1-month follow-up scan. Long-duration exposure to microgravity is associated with an increase in periventricular WMH in astronauts. This increase was linked to an increase in ventricular CSF volume documented in ISS astronauts. There was no associated change in or abnormal levels of WMH volumes in deep white matter as reported in U-2 high-altitude pilots. © 2017 American Academy of Neurology.

  4. Evaluation of cortical local field potential diffusion in stereotactic electro-encephalography recordings: A glimpse on white matter signal.

    PubMed

    Mercier, Manuel R; Bickel, Stephan; Megevand, Pierre; Groppe, David M; Schroeder, Charles E; Mehta, Ashesh D; Lado, Fred A

    2017-02-15

    While there is a strong interest in meso-scale field potential recording using intracranial electroencephalography with penetrating depth electrodes (i.e. stereotactic EEG or S-EEG) in humans, the signal recorded in the white matter remains ignored. White matter is generally considered electrically neutral and often included in the reference montage. Moreover, re-referencing electrophysiological data is a critical preprocessing choice that could drastically impact signal content and consequently the results of any given analysis. In the present stereotactic electroencephalography study, we first illustrate empirically the consequences of commonly used references (subdermal, white matter, global average, local montage) on inter-electrode signal correlation. Since most of these reference montages incorporate white matter signal, we next consider the difference between signals recorded in cortical gray matter and white matter. Our results reveal that electrode contacts located in the white matter record a mixture of activity, with part arising from the volume conduction (zero time delay) of activity from nearby gray matter. Furthermore, our analysis shows that white matter signal may be correlated with distant gray matter signal. While residual passive electrical spread from nearby matter may account for this relationship, our results suggest the possibility that this long distance correlation arises from the white matter fiber tracts themselves (i.e. activity from distant gray matter traveling along axonal fibers with time lag larger than zero); yet definitive conclusions about the origin of the white matter signal would require further experimental substantiation. By characterizing the properties of signals recorded in white matter and in gray matter, this study illustrates the importance of including anatomical prior knowledge when analyzing S-EEG data. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2011-01-01

    Myotonic dystrophy types 1 and 2 are progressive multisystemic disorders with potential brain involvement. We compared 22 myotonic dystrophy type 1 and 22 myotonic dystrophy type 2 clinically and neuropsychologically well-characterized patients and a corresponding healthy control group using structural brain magnetic resonance imaging at 3 T (T1/T2/diffusion-weighted). Voxel-based morphometry and diffusion tensor imaging with tract-based spatial statistics were applied for voxel-wise analysis of cerebral grey and white matter affection (Pcorrected < 0.05). We further examined the association of structural brain changes with clinical and neuropsychological data. White matter lesions rated visually were more prevalent and severe in myotonic dystrophy type 1 compared with controls, with frontal white matter most prominently affected in both disorders, and temporal lesions restricted to myotonic dystrophy type 1. Voxel-based morphometry analyses demonstrated extensive white matter involvement in all cerebral lobes, brainstem and corpus callosum in myotonic dystrophy types 1 and 2, while grey matter decrease (cortical areas, thalamus, putamen) was restricted to myotonic dystrophy type 1. Accordingly, we found more prominent white matter affection in myotonic dystrophy type 1 than myotonic dystrophy type 2 by diffusion tensor imaging. Association fibres throughout the whole brain, limbic system fibre tracts, the callosal body and projection fibres (e.g. internal/external capsules) were affected in myotonic dystrophy types 1 and 2. Central motor pathways were exclusively impaired in myotonic dystrophy type 1. We found mild executive and attentional deficits in our patients when neuropsychological tests were corrected for manual motor dysfunctioning. Regression analyses revealed associations of white matter affection with several clinical parameters in both disease entities, but not with neuropsychological performance. We showed that depressed mood and fatigue were

  6. 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

  7. Preterm birth leads to hyper-reactive cognitive control processing and poor white matter organization in adulthood.

    PubMed

    Olsen, Alexander; Dennis, Emily L; Evensen, Kari Anne I; Husby Hollund, Ingrid Marie; Løhaugen, Gro C C; Thompson, Paul M; Brubakk, Ann-Mari; Eikenes, Live; Håberg, Asta K

    2018-02-15

    Individuals born preterm with very low birth weight (VLBW; birth weight ≤ 1500 g) are at high risk for perinatal brain injuries and deviant brain development, leading to increased chances of later cognitive, emotional, and behavioral problems. Here we investigated the neuronal underpinnings of both reactive and proactive cognitive control processes in adults with VLBW. We included 32 adults born preterm with VLBW (before 37th week of gestation) and 32 term-born controls (birth weight ≥10th percentile for gestational age) between 22 and 24 years of age that have been followed prospectively since birth. Participants performed a well-validated Not-X continuous performance test (CPT) adapted for use in a mixed block- and event-related fMRI protocol. BOLD fMRI and DTI data was acquired on a 3T scanner. Performance on the Not-X CPT was highly similar between groups. However, the VLBW group demonstrated hyper-reactive cognitive control processing and disrupted white matter organization. The hyper-reactive brain activation signature in VLBW adults was associated with lower gestational age, lower fluid intelligence score, and anxiety problems. Automated Multi-Atlas Tract Extraction (AutoMATE) analyses revealed that this disruption of normal brain function was accompanied by poorer white matter organization in the anterior thalamic radiation and the cingulum, as reflected in both reduced fractional anisotropy and increased mean diffusivity. These findings show that the preterm behavioral phenotype is associated with predominantly reactive-, rather than proactive cognitive control processing, as well as white matter abnormalities, that may underlie common difficulties that many preterm born individuals experience in everyday life. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Seven-Tesla Magnetization Transfer Imaging to Detect Multiple Sclerosis White Matter Lesions.

    PubMed

    Chou, I-Jun; Lim, Su-Yin; Tanasescu, Radu; Al-Radaideh, Ali; Mougin, Olivier E; Tench, Christopher R; Whitehouse, William P; Gowland, Penny A; Constantinescu, Cris S

    2018-03-01

    Fluid-attenuated inversion recovery (FLAIR) imaging at 3 Tesla (T) field strength is the most sensitive modality for detecting white matter lesions in multiple sclerosis. While 7T FLAIR is effective in detecting cortical lesions, it has not been fully optimized for visualization of white matter lesions and thus has not been used for delineating lesions in quantitative magnetic resonance imaging (MRI) studies of the normal appearing white matter in multiple sclerosis. Therefore, we aimed to evaluate the sensitivity of 7T magnetization-transfer-weighted (MT w ) images in the detection of white matter lesions compared with 3T-FLAIR. Fifteen patients with clinically isolated syndrome, 6 with multiple sclerosis, and 10 healthy participants were scanned with 7T 3-dimensional (D) MT w and 3T-2D-FLAIR sequences on the same day. White matter lesions visible on either sequence were delineated. Of 662 lesions identified on 3T-2D-FLAIR images, 652 were detected on 7T-3D-MT w images (sensitivity, 98%; 95% confidence interval, 97% to 99%). The Spearman correlation coefficient between lesion loads estimated by the two sequences was .910. The intrarater and interrater reliability for 7T-3D-MT w images was good with an intraclass correlation coefficient (ICC) of 98.4% and 81.8%, which is similar to that for 3T-2D-FLAIR images (ICC 96.1% and 96.7%). Seven-Tesla MT w sequences detected most of the white matter lesions identified by FLAIR at 3T. This suggests that 7T-MT w imaging is a robust alternative for detecting demyelinating lesions in addition to 3T-FLAIR. Future studies need to compare the roles of optimized 7T-FLAIR and of 7T-MT w imaging. © 2017 The Authors. Journal of Neuroimaging published by Wiley Periodicals, Inc. on behalf of American Society of Neuroimaging.

  9. Multiple sclerosis-related white matter microstructural change alters the BOLD hemodynamic response.

    PubMed

    Hubbard, Nicholas A; Turner, Monroe; Hutchison, Joanna L; Ouyang, Austin; Strain, Jeremy; Oasay, Larry; Sundaram, Saranya; Davis, Scott; Remington, Gina; Brigante, Ryan; Huang, Hao; Hart, John; Frohman, Teresa; Frohman, Elliot; Biswal, Bharat B; Rypma, Bart

    2016-11-01

    Multiple sclerosis (MS) results in inflammatory damage to white matter microstructure. Prior research using blood-oxygen-level dependent (BOLD) imaging indicates MS-related alterations to brain function. What is currently unknown is the extent to which white matter microstructural damage influences BOLD signal in MS. Here we assessed changes in parameters of the BOLD hemodynamic response function (HRF) in patients with relapsing-remitting MS compared to healthy controls. We also used diffusion tensor imaging to assess whether MS-related changes to the BOLD-HRF were affected by changes in white matter microstructural integrity. Our results showed MS-related reductions in BOLD-HRF peak amplitude. These MS-related amplitude decreases were influenced by individual differences in white matter microstructural integrity. Other MS-related factors including altered reaction time, limited spatial extent of BOLD activity, elevated lesion burden, or lesion proximity to regions of interest were not mediators of group differences in BOLD-HRF amplitude. Results are discussed in terms of functional hyperemic mechanisms and implications for analysis of BOLD signal differences. © The Author(s) 2015.

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

    NASA Astrophysics Data System (ADS)

    Pham, Tuan D.; Salvetti, Federica; Wang, Bing; Diani, Marco; Heindel, Walter; Knecht, Stefan; Wersching, Heike; Baune, Bernhard T.; Berger, Klaus

    2011-02-01

    Rating and quantification of cerebral white matter hyperintensities on magnetic resonance imaging (MRI) are important tasks in various clinical and scientific settings. As manual evaluation is time consuming and imprecise, much effort has been made to automate the quantification of white matter hyperintensities. There is rarely any report that attempts to study the similarity/dissimilarity of white matter hyperintensity patterns that have different sizes, shapes and spatial localizations on the MRI. This paper proposes an original computational neuroscience framework for such a conceptual study with a standpoint that the prior knowledge about white matter hyperintensities can be accumulated and utilized to enable a reliable inference of the rating of a new white matter hyperintensity observation. This computational approach for rating inference of white matter hyperintensities, which appears to be the first study, can be utilized as a computerized rating-assisting tool and can be very economical for diagnostic evaluation of brain tissue lesions.

  11. Microstructural Abnormalities Were Found in Brain Gray Matter from Patients with Chronic Myofascial Pain

    PubMed Central

    Xie, Peng; Qin, Bangyong; Song, Ganjun; Zhang, Yi; Cao, Song; Yu, Jin; Wu, Jianjiang; Wang, Jiang; Zhang, Tijiang; Zhang, Xiaoming; Yu, Tian; Zheng, Hong

    2016-01-01

    Myofascial pain, presented as myofascial trigger points (MTrPs)-related pain, is a common, chronic disease involving skeletal muscle, but its underlying mechanisms have been poorly understood. Previous studies have revealed that chronic pain can induce microstructural abnormalities in the cerebral gray matter. However, it remains unclear whether the brain gray matters of patients with chronic MTrPs-related pain undergo alteration. In this study, we employed the Diffusion Kurtosis Imaging (DKI) technique, which is particularly sensitive to brain microstructural perturbation, to monitor the MTrPs-related microstructural alterations in brain gray matter of patients with chronic pain. Our results revealed that, in comparison with the healthy controls, patients with chronic myofascial pain exhibited microstructural abnormalities in the cerebral gray matter and these lesions were mainly distributed in the limbic system and the brain areas involved in the pain matrix. In addition, we showed that microstructural abnormalities in the right anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC) had a significant negative correlation with the course of disease and pain intensity. The results of this study demonstrated for the first time that there are microstructural abnormalities in the brain gray matter of patients with MTrPs-related chronic pain. Our findings may provide new insights into the future development of appropriate therapeutic strategies to this disease. PMID:28066193

  12. Increased PK11195-PET binding in normal-appearing white matter in clinically isolated syndrome

    PubMed Central

    Politis, Marios; Su, Paul; Turkheimer, Federico E.; Malik, Omar; Keihaninejad, Shiva; Wu, Kit; Waldman, Adam; Reynolds, Richard; Nicholas, Richard; Piccini, Paola

    2015-01-01

    The most accurate predictor of the subsequent development of multiple sclerosis in clinically isolated syndrome is the presence of lesions at magnetic resonance imaging. We used in vivo positron emission tomography with 11C-(R)-PK11195, a biomarker of activated microglia, to investigate the normal-appearing white matter and grey matter of subjects with clinically isolated syndrome to explore its role in the development of multiple sclerosis. Eighteen clinically isolated syndrome and eight healthy control subjects were recruited. Baseline assessment included: history, neurological examination, expanded disability status scale, magnetic resonance imaging and PK11195-positron emission tomography scans. All assessments except the PK11195-positron emission tomography scan were repeated over 2 years. SUPERPK methodology was used to measure the binding potential relative to the non-specific volume, BPND. We show a global increase of normal-appearing white matter PK11195 BPND in clinically isolated syndrome subjects compared with healthy controls (P = 0.014). Clinically isolated syndrome subjects with T2 magnetic resonance imaging lesions had higher PK11195 BPND in normal-appearing white matter (P = 0.009) and their normal-appearing white matter PK11195 BPND correlated with the Expanded Disability Status Scale (P = 0.007; r = 0.672). At 2 years those who developed dissemination in space or multiple sclerosis, had higher PK11195 BPND in normal-appearing white matter at baseline (P = 0.007 and P = 0.048, respectively). Central grey matter PK11195 BPND was increased in subjects with clinically isolated syndrome compared to healthy controls but no difference was found in cortical grey matter PK11195 BPND. Microglial activation in clinically isolated syndrome normal-appearing white matter is diffusely increased compared with healthy control subjects and is further increased in those who have magnetic resonance imaging lesions. Furthermore microglial activation in clinically

  13. White matter lesions relate to tract-specific reductions in functional connectivity.

    PubMed

    Langen, Carolyn D; Zonneveld, Hazel I; White, Tonya; Huizinga, Wyke; Cremers, Lotte G M; de Groot, Marius; Ikram, Mohammad Arfan; Niessen, Wiro J; Vernooij, Meike W

    2017-03-01

    White matter lesions play a role in cognitive decline and dementia. One presumed pathway is through disconnection of functional networks. Little is known about location-specific effects of lesions on functional connectivity. This study examined location-specific effects within anatomically-defined white matter tracts in 1584 participants of the Rotterdam Study, aged 50-95. Tracts were delineated from diffusion magnetic resonance images using probabilistic tractography. Lesions were segmented on fluid-attenuated inversion recovery images. Functional connectivity was defined across each tract on resting-state functional magnetic resonance images by using gray matter parcellations corresponding to the tract ends and calculating the correlation of the mean functional activity between the gray matter regions. A significant relationship between both local and brain-wide lesion load and tract-specific functional connectivity was found in several tracts using linear regressions, also after Bonferroni correction. Indirect connectivity analyses revealed that tract-specific functional connectivity is affected by lesions in several tracts simultaneously. These results suggest that local white matter lesions can decrease tract-specific functional connectivity, both in direct and indirect connections. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Whole genome grey and white matter DNA methylation profiles in dorsolateral prefrontal cortex.

    PubMed

    Sanchez-Mut, Jose Vicente; Heyn, Holger; Vidal, Enrique; Delgado-Morales, Raúl; Moran, Sebastian; Sayols, Sergi; Sandoval, Juan; Ferrer, Isidre; Esteller, Manel; Gräff, Johannes

    2017-06-01

    The brain's neocortex is anatomically organized into grey and white matter, which are mainly composed by neuronal and glial cells, respectively. The neocortex can be further divided in different Brodmann areas according to their cytoarchitectural organization, which are associated with distinct cortical functions. There is increasing evidence that brain development and function are governed by epigenetic processes, yet their contribution to the functional organization of the neocortex remains incompletely understood. Herein, we determined the DNA methylation patterns of grey and white matter of dorsolateral prefrontal cortex (Brodmann area 9), an important region for higher cognitive skills that is particularly affected in various neurological diseases. For avoiding interindividual differences, we analyzed white and grey matter from the same donor using whole genome bisulfite sequencing, and for validating their biological significance, we used Infinium HumanMethylation450 BeadChip and pyrosequencing in ten and twenty independent samples, respectively. The combination of these analysis indicated robust grey-white matter differences in DNA methylation. What is more, cell type-specific markers were enriched among the most differentially methylated genes. Interestingly, we also found an outstanding number of grey-white matter differentially methylated genes that have previously been associated with Alzheimer's, Parkinson's, and Huntington's disease, as well as Multiple and Amyotrophic lateral sclerosis. The data presented here thus constitute an important resource for future studies not only to gain insight into brain regional as well as grey and white matter differences, but also to unmask epigenetic alterations that might underlie neurological and neurodegenerative diseases. © 2017 Wiley Periodicals, Inc.

  15. White matter pathways in persistent developmental stuttering: Lessons from tractography.

    PubMed

    Kronfeld-Duenias, Vered; Civier, Oren; Amir, Ofer; Ezrati-Vinacour, Ruth; Ben-Shachar, Michal

    2018-03-01

    Fluent speech production relies on the coordinated processing of multiple brain regions. This highlights the role of neural pathways that connect distinct brain regions in producing fluent speech. Here, we aim to investigate the role of the white matter pathways in persistent developmental stuttering (PDS), where speech fluency is disrupted. We use diffusion weighted imaging and tractography to compare the white matter properties between adults who do and do not stutter. We compare the diffusion properties along 18 major cerebral white matter pathways. We complement the analysis with an overview of the methodology and a roadmap of the pathways implicated in PDS according to the existing literature. We report differences in the microstructural properties of the anterior callosum, the right inferior longitudinal fasciculus and the right cingulum in people who stutter compared with fluent controls. Persistent developmental stuttering is consistently associated with differences in bilateral distributed networks. We review evidence showing that PDS involves differences in bilateral dorsal fronto-temporal and fronto-parietal pathways, in callosal pathways, in several motor pathways and in basal ganglia connections. This entails an important role for long range white matter pathways in this disorder. Using a wide-lens analysis, we demonstrate differences in additional, right hemispheric pathways, which go beyond the replicable findings in the literature. This suggests that the affected circuits may extend beyond the known language and motor pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Disrupted white matter structure underlies cognitive deficit in hypertensive patients.

    PubMed

    Li, Xin; Ma, Chao; Sun, Xuan; Zhang, Junying; Chen, Yaojing; Chen, Kewei; Zhang, Zhanjun

    2016-09-01

    Hypertension is considered a risk factor of cognitive impairments and could result in white matter changes. Current studies on hypertension-related white matter (WM) changes focus only on regional changes, and the information about global changes in WM structure network is limited. We assessed the cognitive function in 39 hypertensive patients and 37 healthy controls with a battery of neuropsychological tests. The WM structural networks were constructed by utilizing diffusion tensor tractography and calculated topological properties of the networks using a graph theoretical method. The direct and indirect correlations among cognitive impairments, brain WM network disruptions and hypertension were analyzed with structural equation modelling (SEM). Hypertensive patients showed deficits in executive function, memory and attention compared with controls. An aberrant connectivity of WM networks was found in the hypertensive patients (P Eglob = 0.005, P Lp = 0.005), especially in the frontal and parietal regions. Importantly, SEM analysis showed that the decline of executive function resulted from aberrant WM networks in hypertensive patients (p = 0.3788, CFI = 0.99). These results suggest that the cognitive decline in hypertensive patients was due to frontal and parietal WM disconnections. Our findings highlight the importance of brain protection in hypertension patients. • Hypertension has a negative effect on the performance of the cognitive domains • Reduced efficiencies of white matter networks were shown in hypertension • Disrupted white matter networks are responsible for poor cognitive function in hypertension.

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

    PubMed Central

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

    2015-01-01

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

  18. Maternal Dietary Choline Status Influences Brain Gray and White Matter Development in Young Pigs

    PubMed Central

    Mudd, Austin T; Getty, Caitlyn M; Dilger, Ryan N

    2018-01-01

    Abstract Background Choline is an essential nutrient that is pivotal to proper brain development. Research in animal models suggests that perinatal choline deficiency influences neuron development in the hippocampus and cortex, yet these observations require invasive techniques. Objective This study aimed to characterize the effects of perinatal choline deficiency on gray and white matter development with the use of noninvasive neuroimaging techniques in young pigs. Methods During the last 64 d of the 114-d gestation period Yorkshire sows were provided with a choline-sufficient (CS) or choline-deficient (CD) diet, analyzed to contain 1214 mg or 483 mg total choline/kg diet, respectively. Upon farrowing, pigs (Sus scrofa domesticus) were allowed colostrum consumption for ≤48 h, were further stratified into postnatal treatment groups, and were provided either CS or CD milk replacers, analyzed to contain 1591 or 518 mg total choline/kg diet, respectively, for 28 d. At 30 d of age, pigs were subjected to MRI procedures to assess brain development. Gray and white matter development was assessed through voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) to assess the effects of prenatal and postnatal dietary choline status. Results VBM analysis indicated that prenatally CS pigs exhibited increased (P < 0.01) gray matter in the left and right cortex compared with prenatally CD pigs. Analysis of white matter indicated that prenatally CS pigs exhibited increased (P < 0.01) white matter in the internal capsule, putamen–globus pallidus, and right cortex compared with prenatally CD pigs. No postnatal effects (P > 0.05) of choline status were noted for VBM analyses of gray and white matter. TBSS also showed no significant effects (P > 0.05) of prenatal or postnatal choline status for diffusion values along white matter tracts. Conclusions Observations from this study suggest that prenatal choline deficiency results in altered cortical gray

  19. Effects of Aerobic Capacity on Thrombin-Induced Hydrocephalus and White Matter Injury.

    PubMed

    Ni, Wei; Gao, Feng; Zheng, Mingzhe; Koch, Lauren G; Britton, Steven L; Keep, Richard F; Xi, Guohua; Hua, Ya

    2016-01-01

    We have previously shown that intracerebral hemorrhage-induced brain injury is less in rats bred for high aerobic capacity (high capacity runners; HCR) compared with those bred for low aerobic capacity (low capacity runners; LCRs). Thrombin, an essential component in the coagulation cascade, is produced after cerebral hemorrhage. Intraventricular injection of thrombin causes significant hydrocephalus and white matter damage. In the present study, we examined the effect of exercise capacity on thrombin-induced hydrocephalus and white matter damage. Mid-aged (13-month-old) female LCRs (n = 13) and HCRs (n = 12) rats were used in this study. Rats received an intraventricular injection of thrombin (3 U, 50 μl). All rats underwent magnetic resonance imaging (MRI) at 24 h and were then euthanized for brain histology and Western blot. The mortalities were 20 % in LCRs and 33 % in HCRs after thrombin injection (p > 0.05). No rats died after saline injection. Intraventricular thrombin injection resulted in hydrocephalus and periventricular white matter damage as determined on MRI. In LCR rats, thrombin induced significant ventricle enlargement (23.0 ± 2.3 vs12.8 ± 1.9 mm(3) in LCR saline group; p < 0.01) and white matter lesion (9.3 ± 7.6 vs 0.6 ± 0.5 mm(3) in LCR saline group, p < 0.05). In comparison, in HCR rats thrombin induced less ventricular enlargement (17.3 ± 3.9 vs 23.0 ± 2.3 mm(3) in LCRs, p < 0.01) and smaller white matter lesions (2.6 ± 1.2 mm(3) vs 9.3 ± 7.6 mm(3) in LCRs, p < 0.05). In LCR rats, there was also upregulation of heat shock protein-32, a stress marker, and microglial activation in the periventricular white matter. These changes were significantly reduced in HCR rats. Intraventricular injection of thrombin caused more white matter damage and hydrocephalus in rats with low aerobic capacity. A differential effect of thrombin may contribute to differences in the effects of cerebral

  20. Sex differences in white matter development during adolescence: a DTI study.

    PubMed

    Wang, Yingying; Adamson, Chris; Yuan, Weihong; Altaye, Mekibib; Rajagopal, Akila; Byars, Anna W; Holland, Scott K

    2012-10-10

    Adolescence is a complex transitional period in human development, composing physical maturation, cognitive and social behavioral changes. The objective of this study is to investigate sex differences in white matter development and the associations between intelligence and white matter microstructure in the adolescent brain using diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS). In a cohort of 16 typically-developing adolescents aged 13 to 17 years, longitudinal DTI data were recorded from each subject at two time points that were one year apart. We used TBSS to analyze the diffusion indices including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Our results suggest that boys (13-18 years) continued to demonstrate white matter maturation, whereas girls appeared to reach mature levels earlier. In addition, we identified significant positive correlations between FA and full-scale intelligence quotient (IQ) in the right inferior fronto-occipital fasciculus when both sexes were looked at together. Only girls showed significant positive correlations between FA and verbal IQ in the left cortico-spinal tract and superior longitudinal fasciculus. The preliminary evidence presented in this study supports that boys and girls have different developmental trajectories in white matter microstructure. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. DEWS (DEep White matter hyperintensity Segmentation framework): A fully automated pipeline for detecting small deep white matter hyperintensities in migraineurs.

    PubMed

    Park, Bo-Yong; Lee, Mi Ji; Lee, Seung-Hak; Cha, Jihoon; Chung, Chin-Sang; Kim, Sung Tae; Park, Hyunjin

    2018-01-01

    Migraineurs show an increased load of white matter hyperintensities (WMHs) and more rapid deep WMH progression. Previous methods for WMH segmentation have limited efficacy to detect small deep WMHs. We developed a new fully automated detection pipeline, DEWS (DEep White matter hyperintensity Segmentation framework), for small and superficially-located deep WMHs. A total of 148 non-elderly subjects with migraine were included in this study. The pipeline consists of three components: 1) white matter (WM) extraction, 2) WMH detection, and 3) false positive reduction. In WM extraction, we adjusted the WM mask to re-assign misclassified WMHs back to WM using many sequential low-level image processing steps. In WMH detection, the potential WMH clusters were detected using an intensity based threshold and region growing approach. For false positive reduction, the detected WMH clusters were classified into final WMHs and non-WMHs using the random forest (RF) classifier. Size, texture, and multi-scale deep features were used to train the RF classifier. DEWS successfully detected small deep WMHs with a high positive predictive value (PPV) of 0.98 and true positive rate (TPR) of 0.70 in the training and test sets. Similar performance of PPV (0.96) and TPR (0.68) was attained in the validation set. DEWS showed a superior performance in comparison with other methods. Our proposed pipeline is freely available online to help the research community in quantifying deep WMHs in non-elderly adults.

  2. Altered white matter microstructure in adolescent substance users.

    PubMed

    Bava, Sunita; Frank, Lawrence R; McQueeny, Tim; Schweinsburg, Brian C; Schweinsburg, Alecia D; Tapert, Susan F

    2009-09-30

    Chronic marijuana use during adolescence is frequently comorbid with heavy alcohol consumption and associated with CNS alterations, yet the influence of early cannabis and alcohol use on microstructural white matter integrity is unclear. Building on evidence that cannabinoid receptors are present in myelin precursors and affect glial cell processing, and that excessive ethanol exposure is associated with persistently impaired myelination, we used diffusion tensor imaging (DTI) to characterize white matter integrity in heavy substance using and non-using adolescents. We evaluated 36 marijuana and alcohol-using (MJ+ALC) adolescents (ages 16-19) and 36 demographically similar non-using controls with DTI. The diffusion parameters fractional anisotropy (FA) and mean diffusivity (MD) were subjected to whole-brain voxelwise group comparisons using tract-based spatial statistics (Smith, S.M., Jenkinson, M., Johansen-Berg, H., Rueckert, D., Nichols, T.E., Mackay, C.E., Watkins, K.E., Ciccarelli, O., Cader, M.Z., Matthews, P.M., Behrens, T.E., 2006. Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 31, 1487-1505). MJ+ALC teens had significantly lower FA than controls in 10 regions, including left superior longitudinal fasciculus (SLF), left postcentral gyrus, bilateral crus cerebri, and inferior frontal and temporal white matter tracts. These diminutions occurred in the context of increased FA in right occipital, internal capsule, and SLF regions. Changes in MD were less distributed, but increased MD was evident in the right occipital lobe, whereas the left inferior longitudinal fasciculus showed lower MD in MJ+ALC users. Findings suggest that fronto-parietal circuitry may be particularly impacted in adolescent users of the most prevalent intoxicants: marijuana and alcohol. Disruptions to white matter in this young group could indicate aberrant axonal and myelin maturation with resultant compromise of fiber integrity. Findings of

  3. Severe cerebral white matter involvement in a case of dentatorubropallidoluysian atrophy studied at autopsy.

    PubMed

    Muñoz, Esteban; Campdelacreu, Jaume; Ferrer, Isidre; Rey, María J; Cardozo, Adriana; Gómez, Beatriz; Tolosa, Eduardo

    2004-06-01

    The pathophysiology of white matter involvement in dentatorubropallidoluysian atrophy (DRPLA) is controversial. Moreover, the clinical repercussions and evolution of these lesions have not been well documented. To describe a case of DRPLA with severe cerebellar white matter involvement. Case report. Patient A 62-year-old woman with DRPLA. When the genetic diagnosis was made, the patient manifested severe ataxia, slight dysarthria, and subcortical cognitive impairment. Cranial magnetic resonance imaging showed atrophy of the cerebellum and brainstem and moderate high-intensity signal alterations in the periventricular cerebral white matter in T2-weighted sequences. In the following 5 years, she developed uncontrolled head movements associated with severe bruxism and tetraparesis, and became deeply demented. New magnetic resonance imaging showed severe diffuse cerebral white matter alterations in T2 sequences with only slight progression of brainstem and cerebellar atrophy. After her death at 67 years of age, the autopsy study showed diffuse myelin pallor, axonal preservation, and reactive astrogliosis in the cerebral white matter, with only mild atherosclerotic changes, and moderate neuronal loss in the cerebellum and brainstem. Leukoencephalopathy could be a prominent finding in some patients with DRPLA, explaining, at least in part, their clinical evolution. In our case, the disproportion between the severity of white matter damage and vascular changes does not support a cardinal role for ischemic mechanisms in leukoencephalopathy.

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  5. 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. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  6. Axon-glia Synapses Are Highly Vulnerable to White Matter Injury in the Developing Brain

    PubMed Central

    Shen, Yan; Liu, Xiao-Bo; Pleasure, David E.; Deng, Wenbin

    2011-01-01

    The biology of cerebral white matter injury is woefully understudied, in part due to the difficulty to reliably model this type of injury in rodents. Periventricular leukomalacia (PVL) is the predominant form of brain injury and the most common cause of cerebral palsy in premature infants. PVL is characterized by predominant white matter injury. No specific therapy for PVL is presently available because the pathogenesis is not well understood. Here we report that two types of mouse PVL models have been created by hypoxia-ischemia with or without systemic co-administration of lipopolysaccharide (LPS). LPS co-administration exacerbated hypoxic-ischemic white matter injury and led to enhanced microglial activation and astrogliosis. Drug trials with the anti-inflammatory agent minocycline, the anti-excitotoxic agent NBQX and the antioxidant agent edaravone showed various degrees of protection in the two models, indicating that excitotoxic, oxidative and inflammatory forms of injury are involved in the pathogenesis of injury to immature white matter. We then applied immune-electron microscopy to reveal fine structural changes in the injured white matter, and found that synapses between axons and oligodendroglial precursor cells (OPCs) are quickly and profoundly damaged. Hypoxia-ischemia caused a drastic decrease in the number of postsynaptic densities associated with the glutamatergic axon-OPC synapses defined by the expression of vesicular glutamate transporters, vGluT1 and vGluT2, on axon terminals that formed contacts with OPCs in the periventricular white matter, resulted in selective shrinkage of the postsynaptic OPCs contacted by vGluT2 labeled synapses, and led to excitotoxicity mediated by GluR2-lacking, Ca2+-permeable AMPA receptors. Taken together, the present study provides novel mechanistic insights into the pathogenesis of PVL, and reveals that axon-glia synapses are highly vulnerable to white matter injury in the developing brain. More broadly, the study

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

    PubMed

    Deniz Can, Dilara; 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. Early gray-matter concentration in the right cerebellum, early white-matter concentration in the right cerebellum, and early white-matter concentration in the left posterior limb of the internal capsule (PLIC)/cerebral peduncle were positively and strongly associated with infants' receptive language ability at 12 months. Early gray-matter concentration in the right hippocampus was positively and strongly correlated with infants' expressive language ability at 12 months. Our results suggest that the cerebellum, PLIC/cerebral peduncle, and the hippocampus may be associated with early language development. Potential links between these structural predictors and infants' linguistic functions are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Aging of Cerebral White Matter

    PubMed Central

    Liu, Huan; Yang, Yuanyuan; Xia, Yuguo; Zhu, Wen; Leak, Rehana K.; Wei, Zhishuo; Wang, Jianyi; Hu, Xiaoming

    2016-01-01

    White matter (WM) occupies a large volume of the human cerebrum and is mainly composed of myelinated axons and myelin-producing glial cells. The myelinated axons within WM are the structural foundation for efficient neurotransmission between cortical and subcortical areas. Similar to neuron-enriched gray matter areas, WM undergoes a series of changes during the process of aging. WM malfunction can induce serious neurobehavioral and cognitive impairments. Thus, age-related changes in WM may contribute to the functional decline observed in the elderly. In addition, aged WM becomes more susceptible to neurological disorders, such as stroke, traumatic brain injury (TBI), and neurodegeneration. In this review, we summarize the structural and functional alterations of WM in natural aging and speculate on the underlying mechanisms. We also discuss how age-related WM changes influence the progression of various brain disorders, including ischemic and hemorrhagic stroke, TBI, Alzheimer’s disease, and Parkinson’s disease. Although the physiology of WM is still poorly understood relative to gray matter, WM is a rational therapeutic target for a number of neurological and psychiatric conditions. PMID:27865980

  9. Fronto-Parietal gray matter and white matter efficiency differentially predict intelligence in males and females.

    PubMed

    Ryman, Sephira G; Yeo, Ronald A; Witkiewitz, Katie; Vakhtin, Andrei A; van den Heuvel, Martijn; de Reus, Marcel; Flores, Ranee A; Wertz, Christopher R; Jung, Rex E

    2016-11-01

    While there are minimal sex differences in overall intelligence, males, on average, have larger total brain volume and corresponding regional brain volumes compared to females, measures that are consistently related to intelligence. Limited research has examined which other brain characteristics may differentially contribute to intelligence in females to facilitate equal performance on intelligence measures. Recent reports of sex differences in the neural characteristics of the brain further highlight the need to differentiate how the structural neural characteristics relate to intellectual ability in males and females. The current study utilized a graph network approach in conjunction with structural equation modeling to examine potential sex differences in the relationship between white matter efficiency, fronto-parietal gray matter volume, and general cognitive ability (GCA). Participants were healthy adults (n = 244) who completed a battery of cognitive testing and underwent structural neuroimaging. Results indicated that in males, a latent factor of fronto-parietal gray matter was significantly related to GCA when controlling for total gray matter volume. In females, white matter efficiency and total gray matter volume were significantly related to GCA, with no specificity of the fronto-parietal gray matter factor over and above total gray matter volume. This work highlights that different neural characteristics across males and females may contribute to performance on intelligence measures. Hum Brain Mapp 37:4006-4016, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

    PubMed

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

    2012-12-01

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

  11. Cerebrovascular reactivity and white matter integrity.

    PubMed

    Sam, Kevin; Peltenburg, Boris; Conklin, John; Sobczyk, Olivia; Poublanc, Julien; Crawley, Adrian P; Mandell, Daniel M; Venkatraghavan, Lakshmikumar; Duffin, James; Fisher, Joseph A; Black, Sandra E; Mikulis, David J

    2016-11-29

    To compare the diffusion and perfusion MRI metrics of normal-appearing white matter (NAWM) with and without impaired cerebrovascular reactivity (CVR). Seventy-five participants with moderate to severe leukoaraiosis underwent blood oxygen level-dependent CVR mapping using a 3T MRI system with precise carbon dioxide stimulus manipulation. Several MRI metrics were statistically compared between areas of NAWM with positive and negative CVR using one-way analysis of variance with Bonferroni correction for multiple comparisons. Areas of NAWM with negative CVR showed a significant reduction in fractional anisotropy by a mean (SD) of 3.7% (2.4), cerebral blood flow by 22.1% (8.2), regional cerebral blood volume by 22.2% (7.0), and a significant increase in mean diffusivity by 3.9% (3.1) and time to maximum by 10.9% (13.2) (p < 0.01), compared to areas with positive CVR. Impaired CVR is associated with subtle changes in the tissue integrity of NAWM, as evaluated using several quantitative diffusion and perfusion MRI metrics. These findings suggest that impaired CVR may contribute to the progression of white matter disease. © 2016 American Academy of Neurology.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Keller, Timothy A.; Just, Marcel Adam

    2009-01-01

    SUMMARY Neuroimaging studies using diffusion tensor imaging (DTI) have revealed regions of cerebral white matter with decreased microstructural organization (lower fractional anisotropy or FA) among poor readers. We examined whether 100 hours of intensive remedial instruction affected the white matter of 8–10-year-old poor readers. Prior to instruction, poor readers had significantly lower FA than good readers in a region of the left anterior centrum semiovale. The instruction resulted in a change in white matter (significantly increased FA), and in the very same region. The FA increase was correlated with a decrease in radial diffusivity (but not with a change in axial diffusivity), suggesting that myelination had increased. Furthermore, the FA increase was correlated with improvement in phonological decoding ability, clarifying the cognitive locus of the effect. The results demonstrate for the first time the capability of a behavioral intervention to bring about a positive change in cortico-cortical white matter tracts. PMID:20005820

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

    PubMed Central

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

    2014-01-01

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

  15. Quantifying cerebellum grey matter and white matter perfusion using pulsed arterial spin labeling.

    PubMed

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

    2014-01-01

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

  16. Impaired white matter connectivity between regions containing mirror neurons, and relationship to negative symptoms and social cognition, in patients with first-episode schizophrenia.

    PubMed

    Saito, Yukiko; Kubicki, Marek; Koerte, Inga; Otsuka, Tatsui; Rathi, Yogesh; Pasternak, Ofer; Bouix, Sylvain; Eckbo, Ryan; Kikinis, Zora; von Hohenberg, Christian Clemm; Roppongi, Tomohide; Del Re, Elisabetta; Asami, Takeshi; Lee, Sang-Hyuk; Karmacharya, Sarina; Mesholam-Gately, Raquelle I; Seidman, Larry J; Levitt, James; McCarley, Robert W; Shenton, Martha E; Niznikiewicz, Margaret A

    2018-02-01

    In schizophrenia, abnormalities in structural connectivity between brain regions known to contain mirror neurons and their relationship to negative symptoms related to a domain of social cognition are not well understood. Diffusion tensor imaging (DTI) scans were acquired in 16 patients with first episode schizophrenia and 16 matched healthy controls. FA and Trace of the tracts interconnecting regions known to be rich in mirror neurons, i.e., anterior cingulate cortex (ACC), inferior parietal lobe (IPL) and premotor cortex (PMC) were evaluated. A significant group effect for Trace was observed in IPL-PMC white matter fiber tract (F (1, 28) = 7.13, p = .012), as well as in the PMC-ACC white matter fiber tract (F (1, 28) = 4.64, p = .040). There were no group differences in FA. In addition, patients with schizophrenia showed a significant positive correlation between the Trace of the left IPL-PMC white matter fiber tract, and the Ability to Feel Intimacy and Closeness score (rho = .57, p = 0.034), and a negative correlation between the Trace of the left PMC-ACC and the Relationships with Friends and Peers score (rho = remove -.54, p = 0.049). We have demonstrated disrupted white mater microstructure within the white matter tracts subserving brain regions containing mirror neurons. We further showed that such structural disruptions might impact negative symptoms and, more specifically, contribute to the inability to feel intimacy (a measure conceptually related to theory of mind) in first episode schizophrenia. Further studies are needed to understand the potential of our results for diagnosis, prognosis and therapeutic interventions.

  17. Macrostructural abnormalities in Korsakoff syndrome compared with uncomplicated alcoholism.

    PubMed

    Pitel, A-L; Chételat, G; Le Berre, A P; Desgranges, B; Eustache, F; Beaunieux, H

    2012-04-24

    To distinguish, in patients with Korsakoff syndrome (KS), the structural brain abnormalities shared with alcoholic patients without KS (AL), from those specific to KS. MRI data were collected in 11 alcoholic patients with KS, 34 alcoholic patients without KS, and 25 healthy control subjects (CS). Gray and white matter volumes were compared in the 3 groups using a voxel-based approach. A conjunction analysis indicated a large pattern of shared gray and white matter volume deficits in AL and KS. There were graded effects of volume deficits (KS < AL < CS) in the medial portion of the thalami, hypothalamus (mammillary bodies), left insula, and genu of the corpus callosum. Abnormalities in the left thalamic radiation were observed only in KS. Our results indicate considerable similarities in the pattern of gray and white matter damage in AL and KS. This finding confirms the widespread neurotoxic effect of chronic alcohol consumption. Only a few cerebral regions, including the medial thalami, mammillary bodies, and corpus callosum, were more severely damaged in KS than in AL. The continuum of macrostructural damage from AL to KS is therefore restricted to key brain structures. Longitudinal investigations are required to determine whether alcoholic patients with medial thalamic volumes that are comparable to those of patients with KS are at increased risk of developing KS.

  18. White matter integrity as a predictor of response to treatment in first episode psychosis.

    PubMed

    Reis Marques, Tiago; Taylor, Heather; Chaddock, Chris; Dell'acqua, Flavio; Handley, Rowena; Reinders, A A T Simone; Mondelli, Valeria; Bonaccorso, Stefania; Diforti, Marta; Simmons, Andrew; David, Anthony S; Murray, Robin M; Pariante, Carmine M; Kapur, Shitij; Dazzan, Paola

    2014-01-01

    The integrity of brain white matter connections is central to a patient's ability to respond to pharmacological interventions. This study tested this hypothesis using a specific measure of white matter integrity, and examining its relationship to treatment response using a prospective design in patients within their first episode of psychosis. Diffusion tensor imaging data were acquired in 63 patients with first episode psychosis and 52 healthy control subjects (baseline). Response was assessed after 12 weeks and patients were classified as responders or non-responders according to treatment outcome. At this second time-point, they also underwent a second diffusion tensor imaging scan. Tract-based spatial statistics were used to assess fractional anisotropy as a marker of white matter integrity. At baseline, non-responders showed lower fractional anisotropy than both responders and healthy control subjects (P < 0.05; family-wise error-corrected), mainly in the uncinate, cingulum and corpus callosum, whereas responders were indistinguishable from healthy control subjects. After 12 weeks, there was an increase in fractional anisotropy in both responders and non-responders, positively correlated with antipsychotic exposure. This represents one of the largest, controlled investigations of white matter integrity and response to antipsychotic treatment early in psychosis. These data, together with earlier findings on cortical grey matter, suggest that grey and white matter integrity at the start of treatment is an important moderator of response to antipsychotics. These findings can inform patient stratification to anticipate care needs, and raise the possibility that antipsychotics may restore white matter integrity as part of the therapeutic response.

  19. White Matter Structural Connectivity and Episodic Memory in Early Childhood

    PubMed Central

    Ngo, Chi T.; Alm, Kylie H.; Metoki, Athanasia; Hampton, William; Riggins, Tracy; Newcombe, Nora S.; Olson, Ingrid R.

    2018-01-01

    Episodic memory undergoes dramatic improvement in early childhood; the reason for this is poorly understood. In adults, episodic memory relies on a distributed neural network. Key brain regions that supporting these processes include the hippocampus, portions of the parietal cortex, and portions of prefrontal cortex, each of which shows different developmental profiles. Here we asked whether developmental differences in the axonal pathways connecting these regions may account for the robust gains in episodic memory in young children. Using diffusion weighted imaging, we examined whether white matter connectivity between brain regions implicated in episodic memory differed with age, and were associated with memory performance differences in 4- and 6-year-old children. Results revealed that white matter connecting the hippocampus to the inferior parietal lobule significantly predicted children’s performance on episodic memory tasks. In contrast, variation in the white matter connecting the hippocampus to the medial prefrontal cortex did not relate to memory performance. These findings suggest that structural connectivity between the hippocampus and lateral parietal regions is relevant to the development of episodic memory PMID:29175538

  20. Toll-like Receptor 2: A Novel Therapeutic Target for Ischemic White Matter Injury and Oligodendrocyte Death

    PubMed Central

    Choi, Jun Young

    2017-01-01

    Despite paramount clinical significance of white matter stroke, there is a paucity of researches on the pathomechanism of ischemic white matter damage and accompanying oligodendrocyte (OL) death. Therefore, a large gap exists between clinical needs and laboratory researches in this disease entity. Recent works have started to elucidate cellular and molecular basis of white matter injury under ischemic stress. In this paper, we briefly introduce white matter stroke from a clinical point of view and review pathophysiology of ischemic white matter injury characterized by OL death and demyelination. We present a series of evidence that Toll-like receptor 2 (TLR2), one of the membranous pattern recognition receptors, plays a cell-autonomous protective role in ischemic OL death and ensuing demyelination. Moreover, we also discuss our recent findings that its endogenous ligand, high-mobility group box 1 (HMGB1), is released from dying OLs and exerts autocrine trophic effects on OLs and myelin sheath under ischemic condition. We propose that modulation of TLR2 and its endogenous ligand HMGB1 can be a novel therapeutic target for ischemic white matter disease. PMID:28912641

  1. White-matter microstructure and hearing acuity in older adults: a population-based cross-sectional DTI study.

    PubMed

    Rigters, Stephanie C; Cremers, Lotte G M; Ikram, M Arfan; van der Schroeff, Marc P; de Groot, Marius; Roshchupkin, Gennady V; Niessen, Wiro J N; Baatenburg de Jong, Robert J; Goedegebure, André; Vernooij, Meike W

    2018-01-01

    To study the relation between the microstructure of white matter in the brain and hearing function in older adults we carried out a population-based, cross-sectional study. In 2562 participants of the Rotterdam Study, we conducted diffusion tensor imaging to determine the microstructure of the white-matter tracts. We performed pure-tone audiogram and digit-in-noise tests to quantify hearing acuity. Poorer white-matter microstructure, especially in the association tracts, was related to poorer hearing acuity. After differentiating the separate white-matter tracts in the left and right hemisphere, poorer white-matter microstructure in the right superior longitudinal fasciculus and the right uncinate fasciculus remained significantly associated with worse hearing. These associations did not significantly differ between middle-aged (51-69 years old) and older (70-100 years old) participants. Progressing age was thus not found to be an effect modifier. In a voxel-based analysis no voxels in the white matter were significantly associated with hearing impairment. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Microstructural White Matter Alterations in the Corpus Callosum of Girls With Conduct Disorder.

    PubMed

    Menks, Willeke Martine; Furger, Reto; Lenz, Claudia; Fehlbaum, Lynn Valérie; Stadler, Christina; Raschle, Nora Maria

    2017-03-01

    Diffusion tensor imaging (DTI) studies in adolescent conduct disorder (CD) have demonstrated white matter alterations of tracts connecting functionally distinct fronto-limbic regions, but only in boys or mixed-gender samples. So far, no study has investigated white matter integrity in girls with CD on a whole-brain level. Therefore, our aim was to investigate white matter alterations in adolescent girls with CD. We collected high-resolution DTI data from 24 girls with CD and 20 typically developing control girls using a 3T magnetic resonance imaging system. Fractional anisotropy (FA) and mean diffusivity (MD) were analyzed for whole-brain as well as a priori-defined regions of interest, while controlling for age and intelligence, using a voxel-based analysis and an age-appropriate customized template. Whole-brain findings revealed white matter alterations (i.e., increased FA) in girls with CD bilaterally within the body of the corpus callosum, expanding toward the right cingulum and left corona radiata. The FA and MD results in a priori-defined regions of interest were more widespread and included changes in the cingulum, corona radiata, fornix, and uncinate fasciculus. These results were not driven by age, intelligence, or attention-deficit/hyperactivity disorder comorbidity. This report provides the first evidence of white matter alterations in female adolescents with CD as indicated through white matter reductions in callosal tracts. This finding enhances current knowledge about the neuropathological basis of female CD. An increased understanding of gender-specific neuronal characteristics in CD may influence diagnosis, early detection, and successful intervention strategies. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Disrupted White Matter Microstructure and Mood Disorders after Traumatic Brain Injury.

    PubMed

    Spitz, Gershon; Alway, Yvette; Gould, Kate Rachel; Ponsford, Jennie L

    2017-02-15

    Traumatic brain injury (TBI) is associated with an elevated frequency of mood disorders that may, in part, be explained by changes in white-matter microstructure. This study is the first to examine the relationship between mood disorders and white-matter pathology in a sample of patients with mild to severe TBI using a standardized psychiatric interview. This study reports on a sub-sample of 29 individuals recruited from a large prospective study that examined the evolution of psychiatric disorders following complicated, mild to severe TBI. Individuals with TBI were also compared with 23 healthy control participants. Individuals were invited to complete the Structured Clinical Interview for DSM-IV Disorders (SCID) to diagnose psychiatric disorders. Participants who developed a mood disorder within the first 3 years were categorized into a TBI-Mood group. Diffusion tensor tractography assessed white matter microstructure using atlas-based tract-averaged and along-tract approaches. Fractional anisotropy (FA) was used as the measure of white-matter microstructure. TBI participants with and without a mood disorder did not differ in regard to injury severity and other background factors. Nevertheless, TBI participants diagnosed with a mood disorder displayed significantly lower tract-averaged FA values for the right arcuate fasciculus (p = 0.011), right inferior longitudinal fasciculus (p = 0.009), and anterior segments I (p = 0.0004) and II (p = 0.007) of the corpus callosum, as well as the left (p = 0.014) and right (p = 0.015) fronto-occipital longitudinal fasciculi. The pattern of white matter disruption identified in the current study provides further support for a neurobiological basis of post-TBI mood disorders. Greater understanding of individuals' underlying neuropathology may enable better characterization and prediction of mood disorders. Integration of neuropathology may also inform the potential efficacy of pharmacological and

  4. Diffusion tensor imaging and myelin composition analysis reveal abnormal myelination in corpus callosum of canine mucopolysaccharidosis I

    PubMed Central

    Provenzale, James M.; Nestrasil, Igor; Chen, Steven; Kan, Shih-hsin; Le, Steven Q.; Jens, Jacqueline K.; Snella, Elizabeth M.; Vondrak, Kristen N.; Yee, Jennifer K.; Vite, Charles H.; Elashoff, David; Duan, Lewei; Wang, Raymond Y.; Ellinwood, N. Matthew; Guzman, Miguel A.; Shapiro, Elsa G.; Dickson, Patricia I.

    2015-01-01

    Children with mucopolysaccharidosis I (MPS I) develop hyperintense white matter foci on T2-weighted brain magnetic resonance (MR) imaging that are associated clinically with cognitive impairment. We report here a diffusion tensor imaging (DTI) and tissue evaluation of white matter in a canine model of MPS I. We found that two DTI parameters, fractional anisotropy (a measure of white matter integrity) and radial diffusivity (which reflects degree of myelination) were abnormal in the corpus callosum of MPS I dogs compared to carrier controls. Tissue studies of the corpus callosum showed reduced expression of myelin-related genes and an abnormal composition of myelin in MPS I dogs. We treated MPS I dogs with recombinant alpha-l-iduronidase, which is the enzyme that is deficient in MPS I disease. The recombinant alpha-l-iduronidase was administered by intrathecal injection into the cisterna magna. Treated dogs showed partial correction of corpus callosum myelination. Our findings suggest that abnormal myelination occurs in the canine MPS I brain, that it may underlie clinically-relevant brain imaging findings in human MPS I patients, and that it may respond to treatment. PMID:26222335

  5. The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis.

    PubMed

    Debette, Stéphanie; Markus, H S

    2010-07-26

    To review the evidence for an association of white matter hyperintensities with risk of stroke, cognitive decline, dementia, and death. Systematic review and meta-analysis. PubMed from 1966 to 23 November 2009. Prospective longitudinal studies that used magnetic resonance imaging and assessed the impact of white matter hyperintensities on risk of incident stroke, cognitive decline, dementia, and death, and, for the meta-analysis, studies that provided risk estimates for a categorical measure of white matter hyperintensities, assessing the impact of these lesions on risk of stroke, dementia, and death. Population studied, duration of follow-up, method used to measure white matter hyperintensities, definition of the outcome, and measure of the association of white matter hyperintensities with the outcome. 46 longitudinal studies evaluated the association of white matter hyperintensities with risk of stroke (n=12), cognitive decline (n=19), dementia (n=17), and death (n=10). 22 studies could be included in a meta-analysis (nine of stroke, nine of dementia, eight of death). White matter hyperintensities were associated with an increased risk of stroke (hazard ratio 3.3, 95% confidence interval 2.6 to 4.4), dementia (1.9, 1.3 to 2.8), and death (2.0, 1.6 to 2.7). An association of white matter hyperintensities with a faster decline in global cognitive performance, executive function, and processing speed was also suggested. White matter hyperintensities predict an increased risk of stroke, dementia, and death. Therefore white matter hyperintensities indicate an increased risk of cerebrovascular events when identified as part of diagnostic investigations, and support their use as an intermediate marker in a research setting. Their discovery should prompt detailed screening for risk factors of stroke and dementia.

  6. Integration of white matter network is associated with interindividual differences in psychologically mediated placebo response in migraine patients.

    PubMed

    Liu, Jixin; Ma, Shaohui; Mu, Junya; Chen, Tao; Xu, Qing; Dun, Wanghuan; Tian, Jie; Zhang, Ming

    2017-10-01

    Individual differences of brain changes of neural communication and integration in the modular architecture of the human brain network exist for the repeated migraine attack and physical or psychological stressors. However, whether the interindividual variability in the migraine brain connectome predicts placebo response to placebo treatment is still unclear. Using DTI and graph theory approaches, we systematically investigated the topological organization of white matter networks in 71 patients with migraine without aura (MO) and 50 matched healthy controls at three levels: global network measure, nodal efficiency, and nodal intramodule/intermodule efficiency. All patients participated in an 8-week sham acupuncture treatment to induce analgesia. In our results, 30% (n = 21) of patients had 50% change in migraine days from baseline after placebo treatment. At baseline, abnormal increased network integration was found in MO patients as compared with the HC group, and the increased global efficiency before starting clinical treatment was associated with their following placebo response. For nodal efficiency, significantly increased within-subnetwork nodal efficiency and intersubnetwork connectivity of the hippocampus and middle frontal gyrus in patients' white matter network were correlated with the responses of follow-up placebo treatment. Our findings suggested that the trait-like individual differences in pain-related maladaptive stress interfered with and diminished the capacity of chronic pain modulation differently, and the placebo response for treatment could be predicted from a prior white matter network modular structure in migraineurs. Hum Brain Mapp 38:5250-5259, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. White matter compromise predicts poor intellectual outcome in survivors of pediatric low-grade glioma.

    PubMed

    Liu, Fang; Scantlebury, Nadia; Tabori, Uri; Bouffet, Eric; Laughlin, Suzanne; Strother, Douglas; McConnell, Dina; Hukin, Juliette; Fryer, Chris; Brière, Marie-Eve; Montour-Proulx, Isabelle; Keene, Daniel; Wang, Frank; Mabbott, Donald J

    2015-04-01

    While the impact of cranial radiation on white matter following treatment for pediatric brain tumor has been the focus of many recent studies, the effect of treatment in the absence of radiation has received little attention. The relations between white matter and cognitive outcome have not been explored in patients who have undergone radiation-free treatment. As most patients treated without cranial radiation survive long after their diagnosis, it is critical to identify factors that may impact structural and neurocognitive outcomes. Using diffusion tensor imaging, we examined white matter structure in 32 patients with pediatric low-grade glioma (PLGG) (19 with subtentorial location and 13 with supratentorial location) and 32 healthy participants. Indices of intellectual functioning were also evaluated. Radiation was not used to treat this cohort, aged 8-19 years. We detected evidence of deficits in IQ and compromised supra- and subtentorial white matter in patients relative to healthy children (P < .05). Compromise of supratentorial white matter mediated the impact of treatment for PLGG on IQ. Greater white matter compromise was observed in patients who presented without multiple symptoms, were treated with biopsy/no surgery, had positive neurofibromatosis 1 status, were younger age at diagnosis, and whose parents had lower levels of education (P < .05). Our findings provide evidence of increased risk of intellectual and white matter compromise in patients treated for PLGG without radiation. We identify a neural origin of cognitive deficit useful for predicting outcome and mitigating long-term adverse effects in pediatric brain tumor patients treated without cranial radiation. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

    PubMed

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

    2015-01-01

    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. 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. Myelin controls axon speed, and the synchrony of impulse traffic between distant cortical regions appears to be critical for optimal mental performance and learning. 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. 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. 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. Copyright © 2014 International Federation of Clinical Neurophysiology. All rights reserved.

  9. White versus gray matter: fMRI hemodynamic responses show similar characteristics, but differ in peak amplitude

    PubMed Central

    2012-01-01

    Background There is growing evidence for the idea of fMRI activation in white matter. In the current study, we compared hemodynamic response functions (HRF) in white matter and gray matter using 4 T fMRI. White matter fMRI activation was elicited in the isthmus of the corpus callosum at both the group and individual levels (using an established interhemispheric transfer task). Callosal HRFs were compared to HRFs from cingulate and parietal activation. Results Examination of the raw HRF revealed similar overall response characteristics. Finite impulse response modeling confirmed that the WM HRF characteristics were comparable to those of the GM HRF, but had significantly decreased peak response amplitudes. Conclusions Overall, the results matched a priori expectations of smaller HRF responses in white matter due to the relative drop in cerebral blood flow (CBF) and cerebral blood volume (CBV). Importantly, the findings demonstrate that despite lower CBF and CBV, white matter fMRI activation remained within detectable ranges at 4 T. PMID:22852798

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

    PubMed

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

    2016-01-01

    While brain gray matter is primarily associated with sensorimotor processing and cognition, white matter modulates the distribution of action potentials, coordinates communication between different brain regions, and acts as a relay for input/output signals. Previous studies have described morphological changes in gray and white matter during childhood and adolescence, which are consistent with cellular genesis and maturation, but corresponding events in infants are poorly documented. In the present study, we estimated the total number of cells (neurons, oligodendrocytes, astrocytes, and microglia) in the cerebral white matter of 9 infants aged 0-33 months, using design-based stereological methods to obtain quantitative data about brain development. There were linear increases with age in the numbers of oligodendrocytes (7-28 billion) and astrocytes (1.5-6.7 billion) during the first 3 years of life, thus attaining two-thirds of the corresponding numbers in adults. The numbers of neurons (0.7 billion) and microglia (0.2 billion) in the white matter did not increase during the first 3 years of life, but showed large biological variation. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. Network specific change in white matter integrity in mesial temporal lobe epilepsy.

    PubMed

    Imamura, Hisaji; Matsumoto, Riki; Takaya, Shigetoshi; Nakagawa, Tomokazu; Shimotake, Akihiro; Kikuchi, Takayuki; Sawamoto, Nobukatsu; Kunieda, Takeharu; Mikuni, Nobuhiro; Miyamoto, Susumu; Fukuyama, Hidenao; Takahashi, Ryosuke; Ikeda, Akio

    2016-02-01

    To identify the specific change of white matter integrity that occurs in the brain network related to epileptic activity in patients with mesial temporal lobe epilepsy (MTLE). We recruited 18 patients with MTLE and 18 healthy subjects. In MTLE patients, the remote functional-deficit zone was delineated using fluorodeoxyglucose positron emission tomography as an extratemporal region showing glucose hypometabolism. Using diffusion magnetic resonance imaging tractography, we defined a seizure propagation tract (PT) as a white matter pathway that connects the focus with a remote functional deficit zone. We also used the corticospinal tract (CST) and inferior longitudinal fasciculus (ILF) as control tracts in the hemisphere ipsilateral to the focus. Fractional anisotropy (FA), mean diffusivity (MD), and volume of the tracts were compared among PT, CST, and ILF. Tractographic analysis identified the uncinate fasciculus, arcuate fasciculus, and fornix as PTs. A decrease in FA was found in MTLE patients compared with healthy subjects in all tracts, but PTs showed a more significant decrease in FA than did the two control tracts. Although the change in MD was also found in MTLE patients compared with healthy controls, a tract-specific change was not observed. Although white-matter damage was observed in all candidate tracts examined, the integrity of white matter was most significantly decreased in PTs in MTLE. The change in white matter integrity occurs specifically in the pathways that connect the focus and remote functional deficit zones in patients with MTLE, i.e., the pathways that are assume to be associated with seizure propagation. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    PubMed

    Privado, Jesús; Román, Francisco J; Saénz-Urturi, Carlota; Burgaleta, Miguel; Colom, Roberto

    2017-05-04

    Personality neuroscience defines the scientific study of the neurobiological basis of personality. This field assumes that individual differences in personality traits are related with structural and functional variations of the human brain. Gray and white matters are structural properties considered separately in previous research. Available findings in this regard are largely disparate. Here we analyze the relationships between gray matter (cortical thickness (CT), cortical surface area (CSA), and cortical volume) and integrity scores obtained after several white matter tracts connecting different brain regions, with individual differences in the personality traits comprised by the Five-Factor Model (extraversion, agreeableness, conscientiousness, neuroticism, and openness to experience). These psychological and biological data were obtained from young healthy women. The main findings showed statistically significant associations between occipital CSA variations and extraversion, as well as between parietal CT variations and neuroticism. Regarding white matter integrity, openness showed positive correlations with tracts connecting posterior and anterior brain regions. Therefore, variations in discrete gray matter clusters were associated with temperamental traits (extraversion and neuroticism), whereas long-distance structural connections were related with the dimension of personality that has been associated with high-level cognitive processes (openness). Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Increased PK11195-PET binding in normal-appearing white matter in clinically isolated syndrome.

    PubMed

    Giannetti, Paolo; Politis, Marios; Su, Paul; Turkheimer, Federico E; Malik, Omar; Keihaninejad, Shiva; Wu, Kit; Waldman, Adam; Reynolds, Richard; Nicholas, Richard; Piccini, Paola

    2015-01-01

    The most accurate predictor of the subsequent development of multiple sclerosis in clinically isolated syndrome is the presence of lesions at magnetic resonance imaging. We used in vivo positron emission tomography with (11)C-(R)-PK11195, a biomarker of activated microglia, to investigate the normal-appearing white matter and grey matter of subjects with clinically isolated syndrome to explore its role in the development of multiple sclerosis. Eighteen clinically isolated syndrome and eight healthy control subjects were recruited. Baseline assessment included: history, neurological examination, expanded disability status scale, magnetic resonance imaging and PK11195-positron emission tomography scans. All assessments except the PK11195-positron emission tomography scan were repeated over 2 years. SUPERPK methodology was used to measure the binding potential relative to the non-specific volume, BPND. We show a global increase of normal-appearing white matter PK11195 BPND in clinically isolated syndrome subjects compared with healthy controls (P = 0.014). Clinically isolated syndrome subjects with T2 magnetic resonance imaging lesions had higher PK11195 BPND in normal-appearing white matter (P = 0.009) and their normal-appearing white matter PK11195 BPND correlated with the Expanded Disability Status Scale (P = 0.007; r = 0.672). At 2 years those who developed dissemination in space or multiple sclerosis, had higher PK11195 BPND in normal-appearing white matter at baseline (P = 0.007 and P = 0.048, respectively). Central grey matter PK11195 BPND was increased in subjects with clinically isolated syndrome compared to healthy controls but no difference was found in cortical grey matter PK11195 BPND. Microglial activation in clinically isolated syndrome normal-appearing white matter is diffusely increased compared with healthy control subjects and is further increased in those who have magnetic resonance imaging lesions. Furthermore microglial activation in clinically

  14. Characterization of neurons in the cortical white matter in human temporal lobe epilepsy.

    PubMed

    Richter, Zsófia; Janszky, József; Sétáló, György; Horváth, Réka; Horváth, Zsolt; Dóczi, Tamás; Seress, László; Ábrahám, Hajnalka

    2016-10-01

    The aim of the present work was to characterize neurons in the archi- and neocortical white matter, and to investigate their distribution in mesial temporal sclerosis. Immunohistochemistry and quantification of neurons were performed on surgically resected tissue sections of patients with therapy-resistant temporal lobe epilepsy. Temporal lobe tissues of patients with tumor but without epilepsy and that from autopsy were used as controls. Neurons were identified with immunohistochemistry using antibodies against NeuN, calcium-binding proteins, transcription factor Tbr1 and neurofilaments. We found significantly higher density of neurons in the archi- and neocortical white matter of patients with temporal lobe epilepsy than in that of controls. Based on their morphology and neurochemical content, both excitatory and inhibitory cells were present among these neurons. A subset of neurons in the white matter was Tbr-1-immunoreactive and these neurons coexpressed NeuN and neurofilament marker SMI311R. No colocalization of Tbr1 was observed with the inhibitory neuronal markers, calcium-binding proteins. We suggest that a large population of white matter neurons comprises remnants of the subplate. Furthermore, we propose that a subset of white matter neurons was arrested during migration, highlighting the role of cortical maldevelopment in epilepsy associated with mesial temporal sclerosis. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Characterizing white matter tissue in large strain via asymmetric indentation and inverse finite element modeling.

    PubMed

    Feng, Yuan; Lee, Chung-Hao; Sun, Lining; Ji, Songbai; Zhao, Xuefeng

    2017-01-01

    Characterizing the mechanical properties of white matter is important to understand and model brain development and injury. With embedded aligned axonal fibers, white matter is typically modeled as a transversely isotropic material. However, most studies characterize the white matter tissue using models with a single anisotropic invariant or in a small-strain regime. In this study, we combined a single experimental procedure - asymmetric indentation - with inverse finite element (FE) modeling to estimate the nearly incompressible transversely isotropic material parameters of white matter. A minimal form comprising three parameters was employed to simulate indentation responses in the large-strain regime. The parameters were estimated using a global optimization procedure based on a genetic algorithm (GA). Experimental data from two indentation configurations of porcine white matter, parallel and perpendicular to the axonal fiber direction, were utilized to estimate model parameters. Results in this study confirmed a strong mechanical anisotropy of white matter in large strain. Further, our results suggested that both indentation configurations are needed to estimate the parameters with sufficient accuracy, and that the indenter-sample friction is important. Finally, we also showed that the estimated parameters were consistent with those previously obtained via a trial-and-error forward FE method in the small-strain regime. These findings are useful in modeling and parameterization of white matter, especially under large deformation, and demonstrate the potential of the proposed asymmetric indentation technique to characterize other soft biological tissues with transversely isotropic properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. 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.

  17. Differential microstructural and morphological abnormalities in mild cognitive impairment and Alzheimer's disease: Evidence from cortical and deep gray matter.

    PubMed

    Gong, Nan-Jie; Chan, Chun-Chung; Leung, Lam-Ming; Wong, Chun-Sing; Dibb, Russell; Liu, Chunlei

    2017-05-01

    One aim of this study is to use non-Gaussian diffusion kurtosis imaging (DKI) for capturing microstructural abnormalities in gray matter of Alzheimer's disease (AD). The other aim is to compare DKI metrics against thickness of cortical gray matter and volume of deep gray matter, respectively. A cohort of 18 patients with AD, 18 patients with amnestic mild cognitive impairment (MCI), and 18 normal controls underwent morphological and DKI MR imaging. Images were investigated using regions-of-interest-based analyses for deep gray matter and vertex-wise analyses for cortical gray matter. In deep gray matter, more regions showed DKI parametric abnormalities than atrophies at the early MCI stage. Mean kurtosis (MK) exhibited the largest number of significant abnormalities among all DKI metrics. At the later AD stage, diffusional abnormalities were observed in fewer regions than atrophies. In cortical gray matter, abnormalities in thickness were mainly in the medial and lateral temporal lobes, which fit the locations of known early pathological changes. Microstructural abnormalities were predominantly in the parietal and even frontal lobes, which fit the locations of known late pathological changes. In conclusion, MK can complement conventional diffusion metrics for detecting microstructural changes, especially in deep gray matter. This study also provides evidence supporting the notion that microstructural changes predate morphological changes. Hum Brain Mapp 38:2495-2508, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. In Vivo Evidence of Reduced Integrity of the Gray-White Matter Boundary in Autism Spectrum Disorder.

    PubMed

    Andrews, Derek Sayre; Avino, Thomas A; Gudbrandsen, Maria; Daly, Eileen; Marquand, Andre; Murphy, Clodagh M; Lai, Meng-Chuan; Lombardo, Michael V; Ruigrok, Amber N V; Williams, Steven C; Bullmore, Edward T; The Mrc Aims Consortium; Suckling, John; Baron-Cohen, Simon; Craig, Michael C; Murphy, Declan G M; Ecker, Christine

    2017-02-01

    Atypical cortical organization and reduced integrity of the gray-white matter boundary have been reported by postmortem studies in individuals with autism spectrum disorder (ASD). However, there are no in vivo studies that examine these particular features of cortical organization in ASD. Hence, we used structural magnetic resonance imaging to examine differences in tissue contrast between gray and white matter in 98 adults with ASD and 98 typically developing controls, to test the hypothesis that individuals with ASD have significantly reduced tissue contrast. More specifically, we examined contrast as a percentage between gray and white matter tissue signal intensities (GWPC) sampled at the gray-white matter boundary, and across different cortical layers. We found that individuals with ASD had significantly reduced GWPC in several clusters throughout the cortex (cluster, P < 0.05). As expected, these reductions were greatest when tissue intensities were sampled close to gray-white matter interface, which indicates a less distinct gray-white matter boundary in ASD. Our in vivo findings of reduced GWPC in ASD are therefore consistent with prior postmortem findings of a less well-defined gray-white matter boundary in ASD. Taken together, these results indicate that GWPC might be utilized as an in vivo proxy measure of atypical cortical microstructural organization in future studies. © The Author 2017. Published by Oxford University Press.

  19. In vivo characterization of cortical and white matter neuroaxonal pathology in early multiple sclerosis.

    PubMed

    Granberg, Tobias; Fan, Qiuyun; Treaba, Constantina Andrada; Ouellette, Russell; Herranz, Elena; Mangeat, Gabriel; Louapre, Céline; Cohen-Adad, Julien; Klawiter, Eric C; Sloane, Jacob A; Mainero, Caterina

    2017-11-01

    Neuroaxonal pathology is a main determinant of disease progression in multiple sclerosis; however, its underlying pathophysiological mechanisms, including its link to inflammatory demyelination and temporal occurrence in the disease course are still unknown. We used ultra-high field (7 T), ultra-high gradient strength diffusion and T1/T2-weighted myelin-sensitive magnetic resonance imaging to characterize microstructural changes in myelin and neuroaxonal integrity in the cortex and white matter in early stage multiple sclerosis, their distribution in lesional and normal-appearing tissue, and their correlations with neurological disability. Twenty-six early stage multiple sclerosis subjects (disease duration ≤5 years) and 24 age-matched healthy controls underwent 7 T T2*-weighted imaging for cortical lesion segmentation and 3 T T1/T2-weighted myelin-sensitive imaging and neurite orientation dispersion and density imaging for assessing microstructural myelin, axonal and dendrite integrity in lesional and normal-appearing tissue of the cortex and the white matter. Conventional mean diffusivity and fractional anisotropy metrics were also assessed for comparison. Cortical lesions were identified in 92% of early multiple sclerosis subjects and they were characterized by lower intracellular volume fraction (P = 0.015 by paired t-test), lower myelin-sensitive contrast (P = 0.030 by related-samples Wilcoxon signed-rank test) and higher mean diffusivity (P = 0.022 by related-samples Wilcoxon signed-rank test) relative to the contralateral normal-appearing cortex. Similar findings were observed in white matter lesions relative to normal-appearing white matter (all P < 0.001), accompanied by an increased orientation dispersion (P < 0.001 by paired t-test) and lower fractional anisotropy (P < 0.001 by related-samples Wilcoxon signed-rank test) suggestive of less coherent underlying fibre orientation. Additionally, the normal-appearing white matter in multiple sclerosis

  20. White Matter Hyperintensities and Hypobaric Exposure

    DTIC Science & Technology

    2014-11-01

    at the Research Imaging Institute, University of Texas Health Science Center, San Antonio, Texas , using a Siemens (Erlangen, Germany) 3T Tim Trio... Research Department 2510 Fifth St. Wright-Patterson AFB, OH 45433-7913 8. PERFORMING ORGANIZATION REPORT NUMBER AFRL-SA-WP-JA-2014-0008...Prescribed by ANSI Std. Z39.18 RESEARCH ARTICLE White Matter Hyperintensities and Hypobaric Exposure Stephen A. McGuire, MD,1,2,3 Paul M

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

    PubMed

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

    2016-08-01

    Spatial and functional gradients of development have been described for the maturation of cerebral gray and white matter using histological and radiological approaches. We evaluated these patterns in very preterm (VPT) infants using diffusion tensor imaging. Data were obtained from 3 groups: 1) 22 VPT infants without white matter injury (WMI), of whom all had serial MRI studies during the neonatal period, 2) 19 VPT infants with WMI, of whom 3 had serial MRI studies and 3) 12 healthy, term-born infants. Regions of interest were placed in the cortical gray and adjacent white matter in primary motor, primary visual, visual association, and prefrontal regions. From the MRI data at term-equivalent postmenstrual age, differences in mean diffusivity were found in all areas between VPT infants with WMI and the other 2 groups. In contrast, minimal differences in fractional anisotropy were found between the 3 groups. These findings suggest that cortical maturation is delayed in VPT infants with WMI when compared with term control infants and VPT infants without WMI. From the serial MRI data from VPT infants, synchronous development between gray and white matter was evident in all areas and all groups, with maturation in primary motor and sensory regions preceding that of association areas. This finding highlights the regionally varying but locally synchronous nature of the development of cortical gray matter and its adjacent white matter. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Individual white matter fractional anisotropy analysis on patients with MRI negative partial epilepsy.

    PubMed

    Duning, Thomas; Kellinghaus, Christoph; Mohammadi, Siawoosh; Schiffbauer, Hagen; Keller, Simon; Ringelstein, E Bernd; Knecht, Stefan; Deppe, Michael

    2010-02-01

    Conventional structural MRI fails to identify a cerebral lesion in 25% of patients with cryptogenic partial epilepsy (CPE). Diffusion tensor imaging is an MRI technique sensitive to microstructural abnormalities of cerebral white matter (WM) by quantification of fractional anisotropy (FA). The objectives of the present study were to identify focal FA abnormalities in patients with CPE who were deemed MRI negative during routine presurgical evaluation. Diffusion tensor imaging at 3 T was performed in 12 patients with CPE and normal conventional MRI and in 67 age matched healthy volunteers. WM integrity was compared between groups on the basis of automated voxel-wise statistics of FA maps using an analysis of covariance. Volumetric measurements from high resolution T1-weighted images were also performed. Significant FA reductions in WM regions encompassing diffuse areas of the brain were observed when all patients as a group were compared with controls. On an individual basis, voxel based analyses revealed widespread symmetrical FA reduction in CPE patients. Furthermore, asymmetrical temporal lobe FA reduction was consistently ipsilateral to the electroclinical focus. No significant correlations were found between FA alterations and clinical data. There were no differences in brain volumes of CPE patients compared with controls. Despite normal conventional MRI, WM integrity abnormalities in CPE patients extend far beyond the epileptogenic zone. Given that unilateral temporal lobe FA abnormalities were consistently observed ipsilateral to the seizure focus, analysis of temporal FA may provide an informative in vivo investigation into the localisation of the epileptogenic zone in MRI negative patients.

  3. APOL1 renal-risk variants associate with reduced cerebral white matter lesion volume and increased gray matter volume.

    PubMed

    Freedman, Barry I; Gadegbeku, Crystal A; Bryan, R Nick; Palmer, Nicholette D; Hicks, Pamela J; Ma, Lijun; Rocco, Michael V; Smith, S Carrie; Xu, Jianzhao; Whitlow, Christopher T; Wagner, Benjamin C; Langefeld, Carl D; Hawfield, Amret T; Bates, Jeffrey T; Lerner, Alan J; Raj, Dominic S; Sadaghiani, Mohammad S; Toto, Robert D; Wright, Jackson T; Bowden, Donald W; Williamson, Jeff D; Sink, Kaycee M; Maldjian, Joseph A; Pajewski, Nicholas M; Divers, Jasmin

    2016-08-01

    To assess apolipoprotein L1 gene (APOL1) renal-risk-variant effects on the brain, magnetic resonance imaging (MRI)-based cerebral volumes and cognitive function were assessed in 517 African American-Diabetes Heart Study (AA-DHS) Memory IN Diabetes (MIND) and 2568 hypertensive African American Systolic Blood Pressure Intervention Trial (SPRINT) participants without diabetes. Within these cohorts, 483 and 197 had cerebral MRI, respectively. AA-DHS participants were characterized as follows: 60.9% female, mean age of 58.6 years, diabetes duration 13.1 years, estimated glomerular filtration rate of 88.2 ml/min/1.73 m(2), and a median spot urine albumin to creatinine ratio of 10.0 mg/g. In additive genetic models adjusting for age, sex, ancestry, scanner, intracranial volume, body mass index, hemoglobin A1c, statins, nephropathy, smoking, hypertension, and cardiovascular disease, APOL1 renal-risk-variants were positively associated with gray matter volume (β = 3.4 × 10(-3)) and negatively associated with white matter lesion volume (β = -0.303) (an indicator of cerebral small vessel disease) and cerebrospinal fluid volume (β= -30707) (all significant), but not with white matter volume or cognitive function. Significant associations corresponding to adjusted effect sizes (β/SE) were observed with gray matter volume (0.16) and white matter lesion volume (-0.208), but not with cerebrospinal fluid volume (-0.251). Meta-analysis results with SPRINT Memory and Cognition in Decreased Hypertension (MIND) participants who had cerebral MRI were confirmatory. Thus, APOL1 renal-risk-variants are associated with larger gray matter volume and lower white matter lesion volume suggesting lower intracranial small vessel disease. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

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

    USDA-ARS?s Scientific Manuscript database

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

  5. Supervised learning technique for the automated identification of white matter hyperintensities in traumatic brain injury.

    PubMed

    Stone, James R; Wilde, Elisabeth A; Taylor, Brian A; Tate, David F; Levin, Harvey; Bigler, Erin D; Scheibel, Randall S; Newsome, Mary R; Mayer, Andrew R; Abildskov, Tracy; Black, Garrett M; Lennon, Michael J; York, Gerald E; Agarwal, Rajan; DeVillasante, Jorge; Ritter, John L; Walker, Peter B; Ahlers, Stephen T; Tustison, Nicholas J

    2016-01-01

    White matter hyperintensities (WMHs) are foci of abnormal signal intensity in white matter regions seen with magnetic resonance imaging (MRI). WMHs are associated with normal ageing and have shown prognostic value in neurological conditions such as traumatic brain injury (TBI). The impracticality of manually quantifying these lesions limits their clinical utility and motivates the utilization of machine learning techniques for automated segmentation workflows. This study develops a concatenated random forest framework with image features for segmenting WMHs in a TBI cohort. The framework is built upon the Advanced Normalization Tools (ANTs) and ANTsR toolkits. MR (3D FLAIR, T2- and T1-weighted) images from 24 service members and veterans scanned in the Chronic Effects of Neurotrauma Consortium's (CENC) observational study were acquired. Manual annotations were employed for both training and evaluation using a leave-one-out strategy. Performance measures include sensitivity, positive predictive value, [Formula: see text] score and relative volume difference. Final average results were: sensitivity = 0.68 ± 0.38, positive predictive value = 0.51 ± 0.40, [Formula: see text] = 0.52 ± 0.36, relative volume difference = 43 ± 26%. In addition, three lesion size ranges are selected to illustrate the variation in performance with lesion size. Paired with correlative outcome data, supervised learning methods may allow for identification of imaging features predictive of diagnosis and prognosis in individual TBI patients.

  6. Optimization of white matter tractography for pre-surgical planning and image-guided surgery.

    PubMed

    Arfanakis, Konstantinos; Gui, Minzhi; Lazar, Mariana

    2006-01-01

    Accurate localization of white matter fiber tracts in relation to brain tumors is a goal of critical importance to the neurosurgical community. White matter fiber tractography by means of diffusion tensor magnetic resonance imaging (DTI) is the only non-invasive method that can provide estimates of brain connectivity. However, conventional tractography methods are based on data acquisition techniques that suffer from image distortions and artifacts. Thus, a large percentage of white matter fiber bundles are distorted, and/or terminated early, while others are completely undetected. This severely limits the potential of fiber tractography in pre-surgical planning and image-guided surgery. In contrast, Turboprop-DTI is a technique that provides images with significantly fewer distortions and artifacts than conventional DTI data acquisition methods. The purpose of this study was to evaluate fiber tracking results obtained from Turboprop-DTI data. It was demonstrated that Turboprop may be a more appropriate DTI data acquisition technique for tracing white matter fibers than conventional DTI methods, especially in applications such as pre-surgical planning and image-guided surgery.

  7. Development of Tract-Specific White Matter Pathways During Early Reading Development in At-Risk Children and Typical Controls.

    PubMed

    Wang, Yingying; Mauer, Meaghan V; Raney, Talia; Peysakhovich, Barbara; Becker, Bryce L C; Sliva, Danielle D; Gaab, Nadine

    2017-04-01

    Developmental dyslexia is a neurodevelopmental disorder with a strong genetic basis. Previous studies observed white matter alterations in the left posterior brain regions in adults and school-age children with dyslexia. However, no study yet has examined the development of tract-specific white matter pathways from the pre-reading to the fluent reading stage in children at familial risk for dyslexia (FHD+) versus controls (FHD-). This study examined white matter integrity at pre-reading, beginning, and fluent reading stages cross-sectionally ( n = 78) and longitudinally (n = 45) using an automated fiber-tract quantification method. Our findings depict white matter alterations and atypical lateralization of the arcuate fasciculus at the pre-reading stage in FHD+ versus FHD- children. Moreover, we demonstrate faster white matter development in subsequent good versus poor readers and a positive association between white matter maturation and reading development using a longitudinal design. Additionally, the combination of white matter maturation, familial risk, and psychometric measures best predicted later reading abilities. Furthermore, within FHD+ children, subsequent good readers exhibited faster white matter development in the right superior longitudinal fasciculus compared with subsequent poor readers, suggesting a compensatory mechanism. Overall, our findings highlight the importance of white matter pathway maturation in the development of typical and atypical reading skills. Published by Oxford University Press 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  8. Aging of cerebral white matter.

    PubMed

    Liu, Huan; Yang, Yuanyuan; Xia, Yuguo; Zhu, Wen; Leak, Rehana K; Wei, Zhishuo; Wang, Jianyi; Hu, Xiaoming

    2017-03-01

    White matter (WM) occupies a large volume of the human cerebrum and is mainly composed of myelinated axons and myelin-producing glial cells. The myelinated axons within WM are the structural foundation for efficient neurotransmission between cortical and subcortical areas. Similar to neuron-enriched gray matter areas, WM undergoes a series of changes during the process of aging. WM malfunction can induce serious neurobehavioral and cognitive impairments. Thus, age-related changes in WM may contribute to the functional decline observed in the elderly. In addition, aged WM becomes more susceptible to neurological disorders, such as stroke, traumatic brain injury (TBI), and neurodegeneration. In this review, we summarize the structural and functional alterations of WM in natural aging and speculate on the underlying mechanisms. We also discuss how age-related WM changes influence the progression of various brain disorders, including ischemic and hemorrhagic stroke, TBI, Alzheimer's disease, and Parkinson's disease. Although the physiology of WM is still poorly understood relative to gray matter, WM is a rational therapeutic target for a number of neurological and psychiatric conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    PubMed Central

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

    2015-01-01

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

  10. White matter structural connectivity and episodic memory in early childhood.

    PubMed

    Ngo, Chi T; Alm, Kylie H; Metoki, Athanasia; Hampton, William; Riggins, Tracy; Newcombe, Nora S; Olson, Ingrid R

    2017-12-01

    Episodic memory undergoes dramatic improvement in early childhood; the reason for this is poorly understood. In adults, episodic memory relies on a distributed neural network. Key brain regions that supporting these processes include the hippocampus, portions of the parietal cortex, and portions of prefrontal cortex, each of which shows different developmental profiles. Here we asked whether developmental differences in the axonal pathways connecting these regions may account for the robust gains in episodic memory in young children. Using diffusion weighted imaging, we examined whether white matter connectivity between brain regions implicated in episodic memory differed with age, and were associated with memory performance differences in 4- and 6-year-old children. Results revealed that white matter connecting the hippocampus to the inferior parietal lobule significantly predicted children's performance on episodic memory tasks. In contrast, variation in the white matter connecting the hippocampus to the medial prefrontal cortex did not relate to memory performance. These findings suggest that structural connectivity between the hippocampus and lateral parietal regions is relevant to the development of episodic memory. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    PubMed Central

    Perobelli, Sandra; Alessandrini, Franco; Zoccatelli, Giada; Nicolis, Elena; Beltramello, Alberto; Assael, Baroukh M.; Cipolli, Marco

    2015-01-01

    Shwachman–Diamond syndrome is a rare recessive genetic disease caused by mutations in SBDS gene, at chromosome 7q11. Phenotypically, the syndrome is characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, skeletal dysplasia and variable cognitive impairments. Structural brain abnormalities (smaller head circumference and decreased brain volume) have also been reported. No correlation studies between brain abnormalities and neuropsychological features have yet been performed. In this study we investigate neuroanatomical findings, neurofunctional pathways and cognitive functioning of Shwachman–Diamond syndrome subjects compared with healthy controls. To be eligible for inclusion, participants were required to have known SBDS mutations on both alleles, no history of cranial trauma or any standard contraindication to magnetic resonance imaging. Appropriate tests were used to assess cognitive functions. The static images were acquired on a 3 × 0 T magnetic resonance scanner and blood oxygen level-dependent functional magnetic resonance imaging data were collected both during the execution of the Stroop task and at rest. Diffusion tensor imaging was used to assess brain white matter. The Tract-based Spatial Statistics package and probabilistic tractography were used to characterize white matter pathways. Nine participants (5 males), half of all the subjects aged 9–19 years included in the Italian Shwachman–Diamond Syndrome Registry, were evaluated and compared with nine healthy subjects, matched for sex and age. The patients performed less well than norms and controls on cognitive tasks (p = 0.0002). Overall, cortical thickness was greater in the patients, both in the left (+10%) and in the right (+15%) hemisphere, significantly differently increased in the temporal (left and right, p = 0.04), and right parietal (p = 0.03) lobes and in Brodmann area 44 (p = 0.04) of the right frontal lobe. The greatest increases were observed in

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

    PubMed

    Perobelli, Sandra; Alessandrini, Franco; Zoccatelli, Giada; Nicolis, Elena; Beltramello, Alberto; Assael, Baroukh M; Cipolli, Marco

    2015-01-01

    Shwachman-Diamond syndrome is a rare recessive genetic disease caused by mutations in SBDS gene, at chromosome 7q11. Phenotypically, the syndrome is characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, skeletal dysplasia and variable cognitive impairments. Structural brain abnormalities (smaller head circumference and decreased brain volume) have also been reported. No correlation studies between brain abnormalities and neuropsychological features have yet been performed. In this study we investigate neuroanatomical findings, neurofunctional pathways and cognitive functioning of Shwachman-Diamond syndrome subjects compared with healthy controls. To be eligible for inclusion, participants were required to have known SBDS mutations on both alleles, no history of cranial trauma or any standard contraindication to magnetic resonance imaging. Appropriate tests were used to assess cognitive functions. The static images were acquired on a 3 × 0 T magnetic resonance scanner and blood oxygen level-dependent functional magnetic resonance imaging data were collected both during the execution of the Stroop task and at rest. Diffusion tensor imaging was used to assess brain white matter. The Tract-based Spatial Statistics package and probabilistic tractography were used to characterize white matter pathways. Nine participants (5 males), half of all the subjects aged 9-19 years included in the Italian Shwachman-Diamond Syndrome Registry, were evaluated and compared with nine healthy subjects, matched for sex and age. The patients performed less well than norms and controls on cognitive tasks (p = 0.0002). Overall, cortical thickness was greater in the patients, both in the left (+10%) and in the right (+15%) hemisphere, significantly differently increased in the temporal (left and right, p = 0.04), and right parietal (p = 0.03) lobes and in Brodmann area 44 (p = 0.04) of the right frontal lobe. The greatest increases were observed in the left

  13. Tract-based analysis of white matter integrity in psychotic and nonpsychotic bipolar disorder.

    PubMed

    Ji, Andrew; Godwin, Douglass; Rutlin, Jerrel; Kandala, Sridhar; Shimony, Joshua S; Mamah, Daniel

    2017-02-01

    At least 50% of individuals with bipolar disorder (BD) present with psychosis during their lifetime. Psychotic symptoms have sometimes been linked to specific genetic and phenotypic markers. This study aims to explore potential differences between bipolar disorder subtypes by measuring white matter integrity of the brain and relationships with clinical measures. Diffusion tensor imaging and clinical measures were acquired from 102 participants, grouped as psychotic bipolar disorder (PBD) (n=48), non-psychotic bipolar disorder (NBD) (n=24), and healthy controls (n=30). We utilized a powerful, automated tool (TRACULA: Tracts Constrained by Underlying Anatomy) to analyze the fractional anisotropy (FA) and mean diffusivity (MD) of 18 white matter tracts. Decreased FA in numerous tracts was observed in bipolar disorder groups compared to healthy controls: bilateral cingulum-cingulate gyrus bundles, corticospinal tracts, and superior longitudinal fasciculi as well as the right hemisphere cingulum-angular bundle. Only left uncinate fasciculus FA differed between PBD and NPBD groups. We found no group differences in MD. Positive symptoms correlated with FA in the superior (inversely) and inferior (directly) longitudinal fasciculi. Negative symptoms directly correlated with mean FA of the corticospinal tract and cingulum-angular bundle. Neurotropic, mood-stabilizing medication prescribed for individuals with BD may interact with measures of white matter integrity in our BD participants. Our results indicate decreased white matter coherence in BD. Minimal differences in white matter FA between PBD and NPBD participants suggest related underlying neurobiology. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Sources of Disconnection in Neurocognitive Aging: Cerebral White Matter Integrity, Resting-state Functional Connectivity, and White Matter Hyperintensity Volume

    PubMed Central

    Madden, David J.; Parks, Emily L.; Tallman, Catherine W.; Boylan, Maria A.; Hoagey, David A.; Cocjin, Sally B.; Packard, Lauren E.; Johnson, Micah A.; Chou, Ying-hui; Potter, Guy G.; Chen, Nan-kuei; Siciliano, Rachel E.; Monge, Zachary A.; Honig, Jesse A.; Diaz, Michele T.

    2017-01-01

    Age-related decline in fluid cognition can be characterized as a disconnection among specific brain structures, leading to a decline in functional efficiency. The potential sources of disconnection, however, are unclear. We investigated imaging measures of cerebral white matter integrity, resting-state functional connectivity, and white matter hyperintensity (WMH) volume as mediators of the relation between age and fluid cognition, in 145 healthy, community-dwelling adults 19–79 years of age. At a general level of analysis, with a single composite measure of fluid cognition and single measures of each of the three imaging modalities, age exhibited an independent influence on the cognitive and imaging measures, and the imaging variables did not mediate the age-cognition relation. At a more specific level of analysis, resting-state functional connectivity of sensorimotor networks was a significant mediator of the age-related decline in executive function. These findings suggest that different levels of analysis lead to different models of neurocognitive disconnection, and that resting-state functional connectivity, in particular, may contribute to age-related decline in executive function. PMID:28389085

  15. Pathophysiology of Glia in Perinatal White Matter Injury

    PubMed Central

    Back, Stephen A.; Rosenberg, Paul A.

    2014-01-01

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

  16. White matter maturation profiles through early childhood predict general cognitive ability.

    PubMed

    Deoni, Sean C L; O'Muircheartaigh, Jonathan; Elison, Jed T; Walker, Lindsay; Doernberg, Ellen; Waskiewicz, Nicole; Dirks, Holly; Piryatinsky, Irene; Dean, Doug C; Jumbe, N L

    2016-03-01

    Infancy and early childhood are periods of rapid brain development, during which brain structure and function mature alongside evolving cognitive ability. An important neurodevelopmental process during this postnatal period is the maturation of the myelinated white matter, which facilitates rapid communication across neural systems and networks. Though prior brain imaging studies in children (4 years of age and above), adolescents, and adults have consistently linked white matter development with cognitive maturation and intelligence, few studies have examined how these processes are related throughout early development (birth to 4 years of age). Here, we show that the profile of white matter myelination across the first 5 years of life is strongly and specifically related to cognitive ability. Using a longitudinal design, coupled with advanced magnetic resonance imaging, we demonstrate that children with above-average ability show differential trajectories of myelin development compared to average and below average ability children, even when controlling for socioeconomic status, gestation, and birth weight. Specifically, higher ability children exhibit slower but more prolonged early development, resulting in overall increased myelin measures by ~3 years of age. These results provide new insight into the early neuroanatomical correlates of cognitive ability, and suggest an early period of prolonged maturation with associated protracted white matter plasticity may result in strengthened neural networks that can better support later development. Further, these results reinforce the necessity of a longitudinal perspective in investigating typical or suspected atypical cognitive maturation.

  17. 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

  18. White Matter Glial Pathology in Autism

    DTIC Science & Technology

    2015-11-01

    AWARD NUMBER: W81XWH-12-1-0302 TITLE: White Matter Glial Pathology in Autism PRINCIPAL INVESTIGATOR: Gregory A. Ordway, Ph.D. CONTRACTING...Pathology in Autism 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0302 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Gregory A. Ordway, Ph.D...Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Methods used to directly study the autism brain include brain

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

    PubMed Central

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

    2015-01-01

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

  20. White matter tract abnormalities are associated with cognitive dysfunction in secondary progressive multiple sclerosis.

    PubMed

    Meijer, Kim A; Muhlert, Nils; Cercignani, Mara; Sethi, Varun; Ron, Maria A; Thompson, Alan J; Miller, David H; Chard, Declan; Geurts, Jeroen Jg; Ciccarelli, Olga

    2016-10-01

    While our knowledge of white matter (WM) pathology underlying cognitive impairment in relapsing remitting multiple sclerosis (MS) is increasing, equivalent understanding in those with secondary progressive (SP) MS lags behind. The aim of this study is to examine whether the extent and severity of WM tract damage differ between cognitively impaired (CI) and cognitively preserved (CP) secondary progressive multiple sclerosis (SPMS) patients. Conventional magnetic resonance imaging (MRI) and diffusion MRI were acquired from 30 SPMS patients and 32 healthy controls (HC). Cognitive domains commonly affected in MS patients were assessed. Linear regression was used to predict cognition. Diffusion measures were compared between groups using tract-based spatial statistics (TBSS). A total of 12 patients were classified as CI, and processing speed was the most commonly affected domain. The final regression model including demographic variables and radial diffusivity explained the greatest variance of cognitive performance (R 2  = 0.48, p = 0.002). SPMS patients showed widespread loss of WM integrity throughout the WM skeleton when compared with HC. When compared with CP patients, CI patients showed more extensive and severe damage of several WM tracts, including the fornix, superior longitudinal fasciculus and forceps major. Loss of WM integrity assessed using TBSS helps to explain cognitive decline in SPMS patients. © The Author(s), 2016.

  1. White matter connectivity and aerobic fitness in male adolescents.

    PubMed

    Herting, Megan M; Colby, John B; Sowell, Elizabeth R; Nagel, Bonnie J

    2014-01-01

    Exercise has been shown to have positive effects on the brain and behavior throughout various stages of the lifespan. However, little is known about the impact of exercise on neurodevelopment during the adolescent years, particularly with regard to white matter microstructure, as assessed by diffusion tensor imaging (DTI). Both tract-based spatial statistics (TBSS) and tractography-based along-tract statistics were utilized to examine the relationship between white matter microstructure and aerobic exercise in adolescent males, ages 15-18. Furthermore, we examined the data by both (1) grouping individuals based on aerobic fitness self-reports (high fit (HF) vs. low fit (LF)), and (2) using VO2 peak as a continuous variable across the entire sample. Results showed that HF youth had an overall higher number of streamline counts compared to LF peers, which was driven by group differences in corticospinal tract (CST) and anterior corpus callosum (Fminor). In addition, VO2 peak was negatively related to FA in the left CST. Together, these results suggest that aerobic fitness relates to white matter connectivity and microstructure in tracts carrying frontal and motor fibers during adolescence. Furthermore, the current study highlights the importance of considering the environmental factor of aerobic exercise when examining adolescent brain development. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Brain Growth Rate Abnormalities Visualized in Adolescents with Autism

    PubMed Central

    Hua, Xue; Thompson, Paul M.; Leow, Alex D.; Madsen, Sarah K.; Caplan, Rochelle; Alger, Jeffry R.; O’Neill, Joseph; Joshi, Kishori; Smalley, Susan L.; Toga, Arthur W.; Levitt, Jennifer G.

    2014-01-01

    Autism spectrum disorder (ASD) is a heterogeneous disorder of brain development with wide-ranging cognitive deficits. Typically diagnosed before age 3, ASD is behaviorally defined but patients are thought to have protracted alterations in brain maturation. With longitudinal magnetic resonance imaging (MRI), we mapped an anomalous developmental trajectory of the brains of autistic compared to those of typically developing children and adolescents. Using tensor-based morphometry (TBM), we created 3D maps visualizing regional tissue growth rates based on longitudinal brain MRI scans of 13 autistic and 7 typically developing boys (mean age/inter-scan interval: autism 12.0 ± 2.3 years/2.9 ± 0.9 years; control 12.3 ± 2.4/2.8 ± 0.8). The typically developing boys demonstrated strong whole-brain white matter growth during this period, but the autistic boys showed abnormally slowed white matter development (p = 0.03, corrected), especially in the parietal (p = 0.008), temporal (p = 0.03) and occipital lobes (p =0.02). We also visualized abnormal overgrowth in autism in some gray matter structures, such as the putamen and anterior cingulate cortex. Our findings reveal aberrant growth rates in brain regions implicated in social impairment, communication deficits and repetitive behaviors in autism, suggesting that growth rate abnormalities persist into adolescence. TBM revealed persisting growth rate anomalies long after diagnosis, which has implications for evaluation of therapeutic effects. PMID:22021093

  3. Brain growth rate abnormalities visualized in adolescents with autism.

    PubMed

    Hua, Xue; Thompson, Paul M; Leow, Alex D; Madsen, Sarah K; Caplan, Rochelle; Alger, Jeffry R; O'Neill, Joseph; Joshi, Kishori; Smalley, Susan L; Toga, Arthur W; Levitt, Jennifer G

    2013-02-01

    Autism spectrum disorder is a heterogeneous disorder of brain development with wide ranging cognitive deficits. Typically diagnosed before age 3, autism spectrum disorder is behaviorally defined but patients are thought to have protracted alterations in brain maturation. With longitudinal magnetic resonance imaging (MRI), we mapped an anomalous developmental trajectory of the brains of autistic compared with those of typically developing children and adolescents. Using tensor-based morphometry, we created 3D maps visualizing regional tissue growth rates based on longitudinal brain MRI scans of 13 autistic and seven typically developing boys (mean age/interscan interval: autism 12.0 ± 2.3 years/2.9 ± 0.9 years; control 12.3 ± 2.4/2.8 ± 0.8). The typically developing boys demonstrated strong whole brain white matter growth during this period, but the autistic boys showed abnormally slowed white matter development (P = 0.03, corrected), especially in the parietal (P = 0.008), temporal (P = 0.03), and occipital lobes (P = 0.02). We also visualized abnormal overgrowth in autism in gray matter structures such as the putamen and anterior cingulate cortex. Our findings reveal aberrant growth rates in brain regions implicated in social impairment, communication deficits and repetitive behaviors in autism, suggesting that growth rate abnormalities persist into adolescence. Tensor-based morphometry revealed persisting growth rate anomalies long after diagnosis, which has implications for evaluation of therapeutic effects. Copyright © 2011 Wiley Periodicals, Inc.

  4. Neonatal brain abnormalities and memory and learning outcomes at 7 years in children born very preterm.

    PubMed

    Omizzolo, Cristina; Scratch, Shannon E; Stargatt, Robyn; Kidokoro, Hiroyuki; Thompson, Deanne K; Lee, Katherine J; Cheong, Jeanie; Neil, Jeffrey; Inder, Terrie E; Doyle, Lex W; Anderson, Peter J

    2014-01-01

    Using prospective longitudinal data from 198 very preterm and 70 full term children, this study characterised the memory and learning abilities of very preterm children at 7 years of age in both verbal and visual domains. The relationship between the extent of brain abnormalities on neonatal magnetic resonance imaging (MRI) and memory and learning outcomes at 7 years of age in very preterm children was also investigated. Neonatal MRI scans were qualitatively assessed for global, white-matter, cortical grey-matter, deep grey-matter, and cerebellar abnormalities. Very preterm children performed less well on measures of immediate memory, working memory, long-term memory, and learning compared with term-born controls. Neonatal brain abnormalities, and in particular deep grey-matter abnormality, were associated with poorer memory and learning performance at 7 years in very preterm children. Findings support the importance of cerebral neonatal pathology for predicting later memory and learning function.

  5. Blood Pressure Control in Aging Predicts Cerebral Atrophy Related to Small-Vessel White Matter Lesions.

    PubMed

    Kern, Kyle C; Wright, Clinton B; Bergfield, Kaitlin L; Fitzhugh, Megan C; Chen, Kewei; Moeller, James R; Nabizadeh, Nooshin; Elkind, Mitchell S V; Sacco, Ralph L; Stern, Yaakov; DeCarli, Charles S; Alexander, Gene E

    2017-01-01

    Cerebral small-vessel damage manifests as white matter hyperintensities and cerebral atrophy on brain MRI and is associated with aging, cognitive decline and dementia. We sought to examine the interrelationship of these imaging biomarkers and the influence of hypertension in older individuals. We used a multivariate spatial covariance neuroimaging technique to localize the effects of white matter lesion load on regional gray matter volume and assessed the role of blood pressure control, age and education on this relationship. Using a case-control design matching for age, gender, and educational attainment we selected 64 participants with normal blood pressure, controlled hypertension or uncontrolled hypertension from the Northern Manhattan Study cohort. We applied gray matter voxel-based morphometry with the scaled subprofile model to (1) identify regional covariance patterns of gray matter volume differences associated with white matter lesion load, (2) compare this relationship across blood pressure groups, and (3) relate it to cognitive performance. In this group of participants aged 60-86 years, we identified a pattern of reduced gray matter volume associated with white matter lesion load in bilateral temporal-parietal regions with relative preservation of volume in the basal forebrain, thalami and cingulate cortex. This pattern was expressed most in the uncontrolled hypertension group and least in the normotensives, but was also more evident in older and more educated individuals. Expression of this pattern was associated with worse performance in executive function and memory. In summary, white matter lesions from small-vessel disease are associated with a regional pattern of gray matter atrophy that is mitigated by blood pressure control, exacerbated by aging, and associated with cognitive performance.

  6. Gestational Age at Birth and Brain White Matter Development in Term-Born Infants and Children.

    PubMed

    Ou, X; Glasier, C M; Ramakrishnaiah, R H; Kanfi, A; Rowell, A C; Pivik, R T; Andres, A; Cleves, M A; Badger, T M

    2017-12-01

    Studies on infants and children born preterm have shown that adequate gestational length is critical for brain white matter development. Less is known regarding how variations in gestational age at birth in term infants and children affect white matter development, which was evaluated in this study. Using DTI tract-based spatial statistics methods, we evaluated white matter microstructures in 2 groups of term-born (≥37 weeks of gestation) healthy subjects: 2-week-old infants ( n = 44) and 8-year-old children ( n = 63). DTI parameters including fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were calculated by voxelwise and ROI methods and were correlated with gestational age at birth, with potential confounding factors such as postnatal age and sex controlled. Fractional anisotropy values, which are markers for white matter microstructural integrity, positively correlated ( P < .05, corrected) with gestational age at birth in most major white matter tracts/regions for the term infants. Mean diffusivity values, which are measures of water diffusivities in the brain, and axial and radial diffusivity values, which are markers for axonal growth and myelination, respectively, negatively correlated ( P < .05, corrected) with gestational age at birth in all major white matter tracts/regions excluding the body and splenium of the corpus callosum for the term infants. No significant correlations with gestational age were observed for any tracts/regions for the term-born 8-year-old children. Our results indicate that longer gestation during the normal term period is associated with significantly greater infant white matter development (as reflected by higher fractional anisotropy and lower mean diffusivity, axial diffusivity, and radial diffusivity values); however, similar associations were not observable in later childhood. © 2017 by American Journal of Neuroradiology.

  7. Predictors of Memory in Healthy Aging: Polyunsaturated Fatty Acid Balance and Fornix White Matter Integrity.

    PubMed

    Zamroziewicz, Marta K; Paul, Erick J; Zwilling, Chris E; Barbey, Aron K

    2017-07-01

    Recent evidence demonstrates that age and disease-related decline in cognition depends not only upon degeneration in brain structure and function, but also on dietary intake and nutritional status. Memory, a potential preclinical marker of Alzheimer's disease, is supported by white matter integrity in the brain and dietary patterns high in omega-3 and omega-6 polyunsaturated fatty acids. However, the extent to which memory is supported by specific omega-3 and omega-6 polyunsaturated fatty acids, and the degree to which this relationship is reliant upon microstructure of particular white matter regions is not known. This study therefore examined the cross-sectional relationship between empirically-derived patterns of omega-3 and omega-6 polyunsaturated fatty acids (represented by nutrient biomarker patterns), memory, and regional white matter microstructure in healthy, older adults. We measured thirteen plasma phospholipid omega-3 and omega-6 polyunsaturated fatty acids, memory, and regional white matter microstructure in 94 cognitively intact older adults (65 to 75 years old). A three-step mediation analysis was implemented using multivariate linear regressions, adjusted for age, gender, education, income, depression status, and body mass index. The mediation analysis revealed that a mixture of plasma phospholipid omega-3 and omega-6 polyunsaturated fatty acids is linked to memory and that white matter microstructure of the fornix fully mediates the relationship between this pattern of plasma phospholipid polyunsaturated fatty acids and memory. These results suggest that memory may be optimally supported by a balance of plasma phospholipid omega-3 and omega-6 polyunsaturated fatty acids through the preservation of fornix white matter microstructure in cognitively intact older adults. This report provides novel evidence for the benefits of plasma phospholipid omega-3 and omega-6 polyunsaturated fatty acid balance on memory and underlying white matter microstructure.

  8. Asymmetrical flow field-flow fractionation of white wine chromophoric colloidal matter.

    PubMed

    Coelho, Christian; Parot, Jérémie; Gonsior, Michael; Nikolantonaki, Maria; Schmitt-Kopplin, Philippe; Parlanti, Edith; Gougeon, Régis D

    2017-04-01

    Two analytical separation methods-size-exclusion chromatography and asymmetrical flow field-flow fractionation-were implemented to evaluate the integrity of the colloidal composition of Chardonnay white wine and the impact of pressing and fermentations on the final macromolecular composition. Wine chromophoric colloidal matter, representing UV-visible-absorbing wine macromolecules, was evaluated by optical and structural measurements combined with the description of elution profiles obtained by both separative techniques. The objective of this study was to apply these two types of fractionation on a typical Chardonnay white wine produced in Burgundy and to evaluate how each of them impacted the determination of the macromolecular chromophoric content of wine. UV-visible and fluorescence measurements of collected fractions were successfully applied. An additional proteomic study revealed that grape and microorganism proteins largely impacted the composition of chromophoric colloidal matter of Chardonnay wines. Asymmetrical flow field-flow fractionation appeared to be more reliable and less invasive with respect to the native chemical environment of chromophoric wine macromolecules, and hence is recommended as a tool to fractionate chromophoric colloidal matter in white wines. Graphical Abstract An innovative macromolecular separation method based on Asymmetrical Flow Field-Flow Fractionation was developed to better control colloidal dynamics across Chardonnay white winemaking.

  9. In vivo diffusion tensor imaging and ex vivo histologic characterization of white matter pathology in a post-status epilepticus model of temporal lobe epilepsy.

    PubMed

    van Eijsden, Pieter; Otte, Wim M; van der Hel, W Saskia; van Nieuwenhuizen, Onno; Dijkhuizen, Rick M; de Graaf, Robin A; Braun, Kees P J

    2011-04-01

    Although epilepsy is historically considered a disease of gray matter, recent diffusion tensor imaging (DTI) studies have shown white matter abnormalities in patients with epilepsy. The histopathologic correlate of these findings, and whether they are a cause or consequence of epilepsy, remains unclear. To characterize these changes and their underlying histopathology, DTI was performed in juvenile rats, 4 and 8 weeks after pilocarpine-induced status epilepticus (SE). In the medial corpus callosum (CC), mean diffusivity and axial diffusivity (MD and λ₁) as well as a myelin staining were significantly reduced at 4 weeks. Only the λ₁ decrease persisted at 8 weeks. In the fornix fimbriae (FF), λ₁ and myelin staining were decreased at both time points, whereas fractional anisotropy (FA) and MD were significantly reduced at 8 weeks only. We conclude that SE induces both transient and chronic white matter changes in the medial CC and FF that are to some degree related to myelin pathology. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

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

    PubMed Central

    Rokem, Ariel; Takemura, Hiromasa; Bock, Andrew S.; Scherf, K. Suzanne; Behrmann, Marlene; Wandell, Brian A.; Fine, Ione; Bridge, Holly; Pestilli, Franco

    2017-01-01

    Visual neuroscience has traditionally focused much of its attention on understanding the response properties of single neurons or neuronal ensembles. The visual white matter and the long-range neuronal connections it supports are fundamental in establishing such neuronal response properties and visual function. This review article provides an introduction to measurements and methods to study the human visual white matter using diffusion MRI. These methods allow us to measure the microstructural and macrostructural properties of the white matter in living human individuals; they allow us to trace long-range connections between neurons in different parts of the visual system and to measure the biophysical properties of these connections. We also review a range of findings from recent studies on connections between different visual field maps, the effects of visual impairment on the white matter, and the properties underlying networks that process visual information supporting visual face recognition. Finally, we discuss a few promising directions for future studies. These include new methods for analysis of MRI data, open datasets that are becoming available to study brain connectivity and white matter properties, and open source software for the analysis of these data. PMID:28196374

  11. 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,…

  12. White matter fiber integrity of the saccadic eye movement network differs between schizophrenia and healthy groups.

    PubMed

    Schaeffer, David J; Rodrigue, Amanda L; Burton, Courtney R; Pierce, Jordan E; Murphy, Megan N; Clementz, Brett A; McDowell, Jennifer E

    2017-12-01

    Recent diffusion tensor imaging (DTI) studies suggest that altered white matter fiber integrity is a pathophysiological feature of schizophrenia. Lower white matter integrity is associated with poor cognitive control, a characteristic of schizophrenia that can be measured using antisaccade tasks. Although the functional neural correlates of poor antisaccade performance have been well documented, fewer studies have investigated the extent to which white matter fibers connecting the functional nodes of this network contribute to antisaccade performance. The aim of the present study was to assess the white matter structural integrity of fibers connecting two functional nodes (putamen and medial frontal eye fields) of the saccadic eye movement network implicated in poor antisaccade performance in schizophrenia. To evaluate white matter integrity, DTI was acquired on subjects with schizophrenia and two comparison groups: (a) behaviorally matched healthy comparison subjects with low levels of cognitive control (LCC group), and (b) healthy subjects with high levels of cognitive control (HCC group). White matter fibers were tracked between functional regions of interest generated from antisaccade fMRI activation maps, and measures of diffusivity were quantified. The results demonstrated lower white matter integrity in the schizophrenia group than in the HCC group, but not the LCC group who showed similarly poor cognitive control performance. Overall, the results suggest that these alterations are not specific to the disease process of schizophrenia, but may rather be a function of uncontrolled cognitive factors that are concomitant with the disease but also observed in some healthy people. © 2017 Society for Psychophysiological Research.

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

    NASA Astrophysics Data System (ADS)

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

    2013-02-01

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

  14. APOE/TOMM 40 genetic loci, white matter hyperintensities, and cerebral microbleeds

    PubMed Central

    Lyall, Donald M.; Muñoz Maniega, Susana; Harris, Sarah E.; Bastin, Mark E.; Murray, Catherine; Lutz, Michael W.; Saunders, Ann M.; Roses, Allen D.; Valdés Hernández, Maria del C.; Royle, Natalie A.; Starr, John M.; Porteous, David J.; Deary, Ian J.

    2015-01-01

    Background Two markers of cerebral small vessel disease are white matter hyperintensities and cerebral microbleeds, which commonly occur in people with Alzheimer's disease. Aim and/or hypothesis To test for independent associations between two Alzheimer's disease‐susceptibility gene loci – APOE ε and the TOMM 40 ‘523’ poly‐T repeat – and white matter hyperintensities/cerebral microbleed burden in community‐dwelling older adults. Methods Participants in the Lothian Birth Cohort 1936 underwent genotyping for APOE ε and TOMM 40 523, and detailed structural brain magnetic resonance imaging at a mean age of 72·70 years (standard deviation = 0·7; range = 71–74). Results No significant effects of APOE ε or TOMM 40 523 genotypes on white matter hyperintensities or cerebral microbleed burden were found amongst 624 participants. Conclusions Lack of association between two Alzheimer's disease susceptibility gene loci and markers of cerebral small vessel disease may reflect the relative health of this population compared with those in other studies in the literature. PMID:26310205

  15. APOE/TOMM40 genetic loci, white matter hyperintensities, and cerebral microbleeds.

    PubMed

    Lyall, Donald M; Muñoz Maniega, Susana; Harris, Sarah E; Bastin, Mark E; Murray, Catherine; Lutz, Michael W; Saunders, Ann M; Roses, Allen D; Valdés Hernández, Maria del C; Royle, Natalie A; Starr, John M; Porteous, David J; Deary, Ian J; Wardlaw, Joanna M

    2015-12-01

    Two markers of cerebral small vessel disease are white matter hyperintensities and cerebral microbleeds, which commonly occur in people with Alzheimer's disease. To test for independent associations between two Alzheimer's disease-susceptibility gene loci--APOE ε and the TOMM40 '523' poly-T repeat--and white matter hyperintensities/cerebral microbleed burden in community-dwelling older adults. Participants in the Lothian Birth Cohort 1936 underwent genotyping for APOE ε and TOMM40 523, and detailed structural brain magnetic resonance imaging at a mean age of 72·70 years (standard deviation = 0·7; range = 71-74). No significant effects of APOE ε or TOMM40 523 genotypes on white matter hyperintensities or cerebral microbleed burden were found amongst 624 participants. Lack of association between two Alzheimer's disease susceptibility gene loci and markers of cerebral small vessel disease may reflect the relative health of this population compared with those in other studies in the literature. © 2015 The Authors. International Journal of Stroke published by John Wiley & Sons Ltd on behalf of World Stroke Organization.

  16. Microstructure Imaging of Crossing (MIX) White Matter Fibers from diffusion MRI

    PubMed Central

    Farooq, Hamza; Xu, Junqian; Nam, Jung Who; Keefe, Daniel F.; Yacoub, Essa; Georgiou, Tryphon; Lenglet, Christophe

    2016-01-01

    Diffusion MRI (dMRI) reveals microstructural features of the brain white matter by quantifying the anisotropic diffusion of water molecules within axonal bundles. Yet, identifying features such as axonal orientation dispersion, density, diameter, etc., in complex white matter fiber configurations (e.g. crossings) has proved challenging. Besides optimized data acquisition and advanced biophysical models, computational procedures to fit such models to the data are critical. However, these procedures have been largely overlooked by the dMRI microstructure community and new, more versatile, approaches are needed to solve complex biophysical model fitting problems. Existing methods are limited to models assuming single fiber orientation, relevant to limited brain areas like the corpus callosum, or multiple orientations but without the ability to extract detailed microstructural features. Here, we introduce a new and versatile optimization technique (MIX), which enables microstructure imaging of crossing white matter fibers. We provide a MATLAB implementation of MIX, and demonstrate its applicability to general microstructure models in fiber crossings using synthetic as well as ex-vivo and in-vivo brain data. PMID:27982056

  17. Running exercise protects the capillaries in white matter in a rat model of depression.

    PubMed

    Chen, Lin-Mu; Zhang, Ai-Pin; Wang, Fei-Fei; Tan, Chuan-Xue; Gao, Yuan; Huang, Chun-Xia; Zhang, Yi; Jiang, Lin; Zhou, Chun-Ni; Chao, Feng-Lei; Zhang, Lei; Tang, Yong

    2016-12-01

    Running has been shown to improve depressive symptoms when used as an adjunct to medication. However, the mechanisms underlying the antidepressant effects of running are not fully understood. Changes of capillaries in white matter have been discovered in clinical patients and depression model rats. Considering the important part of white matter in depression, running may cause capillary structural changes in white matter. Chronic unpredictable stress (CUS) rats were provided with a 4-week running exercise (from the fifth week to the eighth week) for 20 minutes each day for 5 consecutive days each week. Anhedonia was measured by a behavior test. Furthermore, capillary changes were investigated in the control group, the CUS/Standard group, and the CUS/Running group using stereological methods. The 4-week running increased sucrose consumption significantly in the CUS/Running group and had significant effects on the total volume, total length, and total surface area of the capillaries in the white matter of depression rats. These results demonstrated that exercise-induced protection of the capillaries in white matter might be one of the structural bases for the exercise-induced treatment of depression. It might provide important parameters for further study of the vascular mechanisms of depression and a new research direction for the development of clinical antidepressant means. J. Comp. Neurol. 524:3577-3586, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Hemoglobin and mean platelet volume predicts diffuse T1-MRI white matter volume decrease in sickle cell disease patients.

    PubMed

    Choi, Soyoung; Bush, Adam M; Borzage, Matthew T; Joshi, Anand A; Mack, William J; Coates, Thomas D; Leahy, Richard M; Wood, John C

    2017-01-01

    Sickle cell disease (SCD) is a life-threatening genetic condition. Patients suffer from chronic systemic and cerebral vascular disease that leads to early and cumulative neurological damage. Few studies have quantified the effects of this disease on brain morphometry and even fewer efforts have been devoted to older patients despite the progressive nature of the disease. This study quantifies global and regional brain volumes in adolescent and young adult patients with SCD and racially matched controls with the aim of distinguishing between age related changes associated with normal brain maturation and damage from sickle cell disease. T1 weighted images were acquired on 33 clinically asymptomatic SCD patients (age = 21.3 ± 7.8; F = 18, M = 15) and 32 racially matched control subjects (age = 24.4 ± 7.5; F = 22, M = 10). Exclusion criteria included pregnancy, previous overt stroke, acute chest, or pain crisis hospitalization within one month. All brain volume comparisons were corrected for age and sex. Globally, grey matter volume was not different but white matter volume was 8.1% lower (p = 0.0056) in the right hemisphere and 6.8% (p = 0.0068) in the left hemisphere in SCD patients compared with controls. Multivariate analysis retained hemoglobin (β = 0.33; p = 0.0036), sex (β = 0.35; p = 0.0017) and mean platelet volume (β = 0.27; p = 0.016) as significant factors in the final prediction model for white matter volume for a combined r 2 of 0.37 (p < 0.0001). Lower white matter volume was confined to phylogenetically younger brain regions in the anterior and middle cerebral artery distributions. Our findings suggest that there are diffuse white matter abnormalities in SCD patients, especially in the frontal, parietal and temporal lobes, that are associated with low hemoglobin levels and mean platelet volume. The pattern of brain loss suggests chronic microvascular insufficiency and tissue hypoxia as the causal mechanism

  19. Chronic cigarette smoking and the microstructural integrity of white matter in healthy adults

    PubMed Central

    Paul, Robert H.; Grieve, Stuart M.; Niaura, Raymond; David, Sean P.; Laidlaw, David H.; Cohen, Ronald; Sweet, Lawrence; Taylor, George; Clark, C. Richard; Pogun, Sakire; Gordon, Evian

    2008-01-01

    Results from recent studies suggest that chronic cigarette smoking is associated with increased white matter volume in the brain as determined by in vivo neuroimaging. We used diffusion tensor imaging to examine the microstructural integrity of the white matter in 10 chronic smokers and 10 nonsmokers. All individuals were healthy, without histories of medical or psychiatric illness. Fractional anisotropy (FA) and trace were measured in the genu, body, and splenium of the corpus callosum. FA provides a measure of directional versus nondirectional water diffusion, whereas trace provides a measure of nondirectional water diffusion. Lower FA and higher trace values are considered to reflect less brain integrity. Voxel-based morphometry was used to define volumes in each of these regions of the corpus callosum. Chronic smokers exhibited significantly higher FA in the body and whole corpus callosum and a strong trend for higher FA in the splenium compared with nonsmokers. FA did not differ between groups in the genu, and neither trace nor white matter volumes differed between groups in any of the regions of interest. When subdivided by Fagerström score (low vs. high), the low Fagerström group exhibited significantly higher FA in the body of the corpus callosum compared with the high Fagerström group and the nonsmokers. These results suggest that, among healthy adults, lower exposure to cigarette smoking is associated with increased microstructural integrity of the white matter compared with either no exposure or higher exposure. Additional studies are needed to further explore differences in white matter integrity between smokers and nonsmokers. PMID:18188754

  20. The Relationship between Intelligence and Anxiety: An Association with Subcortical White Matter Metabolism.

    PubMed

    Coplan, Jeremy D; Hodulik, Sarah; Mathew, Sanjay J; Mao, Xiangling; Hof, Patrick R; Gorman, Jack M; Shungu, Dikoma C

    2011-01-01

    We have demonstrated in a previous study that a high degree of worry in patients with generalized anxiety disorder (GAD) correlates positively with intelligence and that a low degree of worry in healthy subjects correlates positively with intelligence. We have also shown that both worry and intelligence exhibit an inverse correlation with certain metabolites in the subcortical white matter. Here we re-examine the relationships among generalized anxiety, worry, intelligence, and subcortical white matter metabolism in an extended sample. Results from the original study were combined with results from a second study to create a sample comprised of 26 patients with GAD and 18 healthy volunteers. Subjects were evaluated using the Penn State Worry Questionnaire, the Wechsler Brief intelligence quotient (IQ) assessment, and proton magnetic resonance spectroscopic imaging ((1)H-MRSI) to measure subcortical white matter metabolism of choline and related compounds (CHO). Patients with GAD exhibited higher IQ's and lower metabolite concentrations of CHO in the subcortical white matter in comparison to healthy volunteers. When data from GAD patients and healthy controls were combined, relatively low CHO predicted both relatively higher IQ and worry scores. Relatively high anxiety in patients with GAD predicted high IQ whereas relatively low anxiety in controls also predicted high IQ. That is, the relationship between anxiety and intelligence was positive in GAD patients but inverse in healthy volunteers. The collective data suggest that both worry and intelligence are characterized by depletion of metabolic substrate in the subcortical white matter and that intelligence may have co-evolved with worry in humans.

  1. In Vivo Assessment of Brain White Matter Inflammation in Multiple Sclerosis with (18)F-PBR111 PET.

    PubMed

    Colasanti, Alessandro; Guo, Qi; Muhlert, Nils; Giannetti, Paolo; Onega, Mayca; Newbould, Rexford D; Ciccarelli, Olga; Rison, Stuart; Thomas, Charlotte; Nicholas, Richard; Muraro, Paolo A; Malik, Omar; Owen, David R; Piccini, Paola; Gunn, Roger N; Rabiner, Eugenii A; Matthews, Paul M

    2014-07-01

    PET radioligand binding to the 18-kD translocator protein (TSPO) in the brains of patients with multiple sclerosis (MS) primarily reflects activated microglia and macrophages. We previously developed genetic stratification for accurate quantitative estimation of TSPO using second-generation PET radioligands. In this study, we used (18)F-PBR111 PET and MR imaging to measure relative binding in the lesional, perilesional, and surrounding normal-appearing white matter of MS patients, as an index of the innate immune response. (18)F-PBR111 binding was quantified in 11 MS patients and 11 age-matched healthy volunteers, stratified according to the rs6971 TSPO gene polymorphism. Fluid-attenuated inversion recovery and magnetization transfer ratio (MTR) MR imaging were used to segment the white matter in MS patients as lesions, perilesional volumes, nonlesional white matter with reduced MTR, and nonlesional white matter with normal MTR. (18)F-PBR111 binding was higher in the white matter lesions and perilesional volumes of MS patients than in white matter of healthy controls (P < 0.05). Although there was substantial heterogeneity in binding between different lesions, a within-subject analysis showed higher (18)F-PBR111 binding in MS lesions (P < 0.05) and in perilesional (P < 0.05) and nonlesional white matter with reduced MTR (P < 0.005) than in nonlesional white matter with a normal MTR. A positive correlation was observed between the mean (18)F-PBR111 volume of distribution increase in lesions relative to nonlesional white matter with a normal MTR and the MS severity score (Spearman ρ = 0.62, P < 0.05). This study demonstrates that quantitative TSPO PET with a second-generation radioligand can be used to characterize innate immune responses in MS in vivo and provides further evidence supporting an association between the white matter TSPO PET signal in lesions and disease severity. Our approach is practical for extension to studies of the role of the innate immune

  2. Distinct white matter injury associated with medial temporal lobe atrophy in Alzheimer's versus semantic dementia.

    PubMed

    Bejanin, Alexandre; Desgranges, Béatrice; La Joie, Renaud; Landeau, Brigitte; Perrotin, Audrey; Mézenge, Florence; Belliard, Serge; de La Sayette, Vincent; Eustache, Francis; Chételat, Gaël

    2017-04-01

    This study aims at further understanding the distinct vulnerability of brain networks in Alzheimer's disease (AD) versus semantic dementia (SD) investigating the white matter injury associated with medial temporal lobe (MTL) atrophy in both conditions. Twenty-six AD patients, twenty-one SD patients, and thirty-nine controls underwent a high-resolution T1-MRI scan allowing to obtain maps of grey matter volume and white matter density. A statistical conjunction approach was used to identify MTL regions showing grey matter atrophy in both patient groups. The relationship between this common grey matter atrophy and white matter density maps was then assessed within each patient group. Patterns of grey matter atrophy were distinct in AD and SD but included a common region in the MTL, encompassing the hippocampus and amygdala. This common atrophy was associated with alterations in different white matter areas in AD versus SD, mainly including the cingulum and corpus callosum in AD, while restricted to the temporal lobe - essentially the uncinate and inferior longitudinal fasciculi - in SD. Complementary analyses revealed that these relationships remained significant when controlling for global atrophy or disease severity. Overall, this study provides the first evidence that atrophy of the same MTL region is related to damage in distinct white matter fibers in AD and SD. These different patterns emphasize the vulnerability of distinct brain networks related to the MTL in these two disorders, which might underlie the discrepancy in their symptoms. These results further suggest differences between AD and SD in the neuropathological processes occurring in the MTL. Hum Brain Mapp 38:1791-1800, 2017. © 2017 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. White matter integrity in Asperger syndrome: a preliminary diffusion tensor magnetic resonance imaging study in adults.

    PubMed

    Bloemen, Oswald J N; Deeley, Quinton; Sundram, Fred; Daly, Eileen M; Barker, Gareth J; Jones, Derek K; van Amelsvoort, Therese A M J; Schmitz, Nicole; Robertson, Dene; Murphy, Kieran C; Murphy, Declan G M

    2010-10-01

    Autistic Spectrum Disorder (ASD), including Asperger syndrome and autism, is a highly genetic neurodevelopmental disorder. There is a consensus that ASD has a biological basis, and it has been proposed that it is a "connectivity" disorder. Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) allows measurement of the microstructural integrity of white matter (a proxy measure of "connectivity"). However, nobody has investigated the microstructural integrity of whole brain white matter in people with Asperger syndrome. We measured the fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD) of white matter, using DT-MRI, in 13 adults with Asperger syndrome and 13 controls. The groups did not differ significantly in overall intelligence and age. FA, MD and RD were assessed using whole brain voxel-based techniques. Adults with Asperger syndrome had a significantly lower FA than controls in 13 clusters. These were largely bilateral and included white matter in the internal capsule, frontal, temporal, parietal and occipital lobes, cingulum and corpus callosum. Adults with Asperger syndrome have widespread significant differences from controls in white matter microstructural integrity.

  4. 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

  5. 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. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Becker, Mary P.; Collins, Paul F.; Lim, Kelvin O.; Muetzel, R.L.; Luciana, M.

    2015-01-01

    Diffusion tensor imaging (DTI) studies of cannabis users report alterations in brain white matter microstructure, primarily based on cross-sectional research, and etiology of the alterations remains unclear. We report findings from longitudinal voxelwise analyses of DTI data collected at baseline and at a 2-year follow-up on 23 young adult (18-20 years old at baseline) regular cannabis users and 23 age-, sex-, and IQ-matched non-using controls with limited substance use histories. Onset of cannabis use was prior to age 17. Cannabis users displayed reduced longitudinal growth in fractional anisotropy in the central and parietal regions of the right and left superior longitudinal fasciculus, in white matter adjacent to the left superior frontal gyrus, in the left corticospinal tract, and in the right anterior thalamic radiation lateral to the genu of the corpus callosum, along with less longitudinal reduction of radial diffusion in the right central/posterior superior longitudinal fasciculus, corticospinal tract, and posterior cingulum. Greater amounts of cannabis use were correlated with reduced longitudinal growth in FA as was relatively impaired performance on a measure of verbal learning. These findings suggest that continued heavy cannabis use during adolescence and young adulthood alters ongoing development of white matter microstructure, contributing to functional impairment. PMID:26602958

  8. Racial Differences in Gray Matter Integrity by Diffusion Tensor in Black and White Octogenarians.

    PubMed

    Liu, Ge; Allen, Ben; Lopez, Oscar; Aizenstein, Howard; Boudreau, Robert; Newman, Anne; Yaffe, Kristine; Kritchevsky, Stephen; Launer, Lenore; Satterfield, Suzanne; Simonsick, Eleanor; Rosano, Caterina

    2015-01-01

    To quantify racial differences in brain structural characteristics in white and black octogenarians, and to examine whether these characteristics contribute to cognition. Cross-sectional study of 283 adults 79-89 years old (59.4% white;42.0% women) with data on gray matter integrity via diffusion tensor imaging (mean diffusivity), gray matter atrophy (GMA), white matter hyperintensities (WMH), literacy, smoking, drinking, income, hypertension and diabetes. Participants were recruited from an ongoing epidemiological study of older adults living in the community with a range of chronic conditions, physical and cognitive function. Standardized betas (sβ) of neuroimaging markers predicting Digit Symbol Substitution Test (DSST) and Modified Mini-Mental State Examination (3MS) scores were computed in multivariable regression models stratified by race. Compared to whites, blacks had lower DSST (p=0.001) and lower 3MS (p=0.006), but also lower mean diffusivity (i.e. higher gray matter microstructural integrity, p=0.032), independent of gender, income, literacy, body mass index, diabetes and drinking habits. Racial differences were not significant for WMH (p=0.062) or GMA (p=0.4). Among blacks, mean diffusivity and WMH were associated with DSST (sβ=-.209, p=0.037 and -.211, p=.038, respectively) independent of each other and other covariates; among whites, mean diffusivity, but not WMH, was significantly associated with DSST and 3MS (sβ =-.277, p=.002 and -.250, p=0.029, respectively). In this cohort of octogenarians living in the community, blacks appeared to have higher microstructural integrity of gray matter as compared to whites. This neuroimaging marker was related to higher cognition even in the presence of WMH and other cardiovascular conditions. If confirmed, these findings suggest microstructural gray matter integrity may be a target to improve cognition, especially among blacks who survive to very old age with a range of chronic cardiovascular conditions.

  9. Intra-individual variability in information processing speed reflects white matter microstructure in multiple sclerosis.

    PubMed

    Mazerolle, Erin L; Wojtowicz, Magdalena A; Omisade, Antonina; Fisk, John D

    2013-01-01

    Slowed information processing speed is commonly reported in persons with multiple sclerosis (MS), and is typically investigated using clinical neuropsychological tests, which provide sensitive indices of mean-level information processing speed. However, recent studies have demonstrated that within-person variability or intra-individual variability (IIV) in information processing speed may be a more sensitive indicator of neurologic status than mean-level performance on clinical tests. We evaluated the neural basis of increased IIV in mildly affected relapsing-remitting MS patients by characterizing the relation between IIV (controlling for mean-level performance) and white matter integrity using diffusion tensor imaging (DTI). Twenty women with relapsing-remitting MS and 20 matched control participants completed the Computerized Test of Information Processing (CTIP), from which both mean response time and IIV were calculated. Other clinical measures of information processing speed were also collected. Relations between IIV on the CTIP and DTI metrics of white matter microstructure were evaluated using tract-based spatial statistics. We observed slower and more variable responses on the CTIP in MS patients relative to controls. Significant relations between white matter microstructure and IIV were observed for MS patients. Increased IIV was associated with reduced integrity in more white matter tracts than was slowed information processing speed as measured by either mean CTIP response time or other neuropsychological test scores. Thus, despite the common use of mean-level performance as an index of cognitive dysfunction in MS, IIV may be more sensitive to the overall burden of white matter disease at the microstructural level. Furthermore, our study highlights the potential value of considering within-person fluctuations, in addition to mean-level performance, for uncovering brain-behavior relationships in neurologic disorders with widespread white matter pathology.

  10. Calibrated imaging reveals altered grey matter metabolism related to white matter microstructure and symptom severity in multiple sclerosis.

    PubMed

    Hubbard, Nicholas A; Turner, Monroe P; Ouyang, Minhui; Himes, Lyndahl; Thomas, Binu P; Hutchison, Joanna L; Faghihahmadabadi, Shawheen; Davis, Scott L; Strain, Jeremy F; Spence, Jeffrey; Krawczyk, Daniel C; Huang, Hao; Lu, Hanzhang; Hart, John; Frohman, Teresa C; Frohman, Elliot M; Okuda, Darin T; Rypma, Bart

    2017-11-01

    Multiple sclerosis (MS) involves damage to white matter microstructures. This damage has been related to grey matter function as measured by standard, physiologically-nonspecific neuroimaging indices (i.e., blood-oxygen-level dependent signal [BOLD]). Here, we used calibrated functional magnetic resonance imaging and diffusion tensor imaging to examine the extent to which specific, evoked grey matter physiological processes were associated with white matter diffusion in MS. Evoked changes in BOLD, cerebral blood flow (CBF), and oxygen metabolism (CMRO 2 ) were measured in visual cortex. Individual differences in the diffusion tensor measure, radial diffusivity, within occipital tracts were strongly associated with MS patients' BOLD and CMRO 2 . However, these relationships were in opposite directions, complicating the interpretation of the relationship between BOLD and white matter microstructural damage in MS. CMRO 2 was strongly associated with individual differences in patients' fatigue and neurological disability, suggesting that alterations to evoked oxygen metabolic processes may be taken as a marker for primary symptoms of MS. This work demonstrates the first application of calibrated and diffusion imaging together and details the first application of calibrated functional MRI in a neurological population. Results lend support for neuroenergetic hypotheses of MS pathophysiology and provide an initial demonstration of the utility of evoked oxygen metabolism signals for neurology research. Hum Brain Mapp 38:5375-5390, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. Correlating Cognitive Decline with White Matter Lesion and Brain Atrophy Magnetic Resonance Imaging Measurements in Alzheimer's Disease.

    PubMed

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

    2015-01-01

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

  12. Compressive mechanical characterization of non-human primate spinal cord white matter.

    PubMed

    Jannesar, Shervin; Allen, Mark; Mills, Sarah; Gibbons, Anne; Bresnahan, Jacqueline C; Salegio, Ernesto A; Sparrey, Carolyn J

    2018-05-02

    The goal of developing computational models of spinal cord injury (SCI) is to better understand the human injury condition. However, finite element models of human SCI have used rodent spinal cord tissue properties due to a lack of experimental data. Central nervous system tissues in non human primates (NHP) closely resemble that of humans and therefore, it is expected that material constitutive models obtained from NHPs will increase the fidelity and the accuracy of human SCI models. Human SCI most often results from compressive loading and spinal cord white matter properties affect FE predicted patterns of injury; therefore, the objectives of this study were to characterize the unconfined compressive response of NHP spinal cord white matter and present an experimentally derived, finite element tractable constitutive model for the tissue. Cervical spinal cords were harvested from nine male adult NHPs (Macaca mulatta). White matter biopsy samples (3 mm in diameter) were taken from both lateral columns of the spinal cord and were divided into four strain rate groups for unconfined dynamic compression and stress relaxation (post-mortem <1-hour). The NHP spinal cord white matter compressive response was sensitive to strain rate and showed substantial stress relaxation confirming the viscoelastic behavior of the material. An Ogden 1st order model best captured the non-linear behavior of NHP white matter in a quasi-linear viscoelastic material model with 4-term Prony series. This study is the first to characterize NHP spinal cord white matter at high (>10/sec) strain rates typical of traumatic injury. The finite element derived material constitutive model of this study will increase the fidelity of SCI computational models and provide important insights for transferring pre-clinical findings to clinical treatments. Spinal cord injury (SCI) finite element (FE) models provide an important tool to bridge the gap between animal studies and human injury, assess injury

  13. Structural white matter asymmetries in relation to functional asymmetries during speech perception and production.

    PubMed

    Ocklenburg, Sebastian; Hugdahl, Kenneth; Westerhausen, René

    2013-12-01

    Functional hemispheric asymmetries of speech production and perception are a key feature of the human language system, but their neurophysiological basis is still poorly understood. Using a combined fMRI and tract-based spatial statistics approach, we investigated the relation of microstructural asymmetries in language-relevant white matter pathways and functional activation asymmetries during silent verb generation and passive listening to spoken words. Tract-based spatial statistics revealed several leftward asymmetric clusters in the arcuate fasciculus and uncinate fasciculus that were differentially related to activation asymmetries in the two functional tasks. Frontal and temporal activation asymmetries during silent verb generation were positively related to the strength of specific microstructural white matter asymmetries in the arcuate fasciculus. In contrast, microstructural uncinate fasciculus asymmetries were related to temporal activation asymmetries during passive listening. These findings suggest that white matter asymmetries may indeed be one of the factors underlying functional hemispheric asymmetries. Moreover, they also show that specific localized white matter asymmetries might be of greater relevance for functional activation asymmetries than microstructural features of whole pathways. © 2013.

  14. Structural Integrity of Normal Appearing White Matter and Sex-Specific Outcomes After Acute Ischemic Stroke.

    PubMed

    Etherton, Mark R; Wu, Ona; Cougo, Pedro; Giese, Anne-Katrin; Cloonan, Lisa; Fitzpatrick, Kaitlin M; Kanakis, Allison S; Boulouis, Gregoire; Karadeli, Hasan H; Lauer, Arne; Rosand, Jonathan; Furie, Karen L; Rost, Natalia S

    2017-12-01

    Women have worse poststroke outcomes than men. We evaluated sex-specific clinical and neuroimaging characteristics of white matter in association with functional recovery after acute ischemic stroke. We performed a retrospective analysis of acute ischemic stroke patients with admission brain MRI and 3- to 6-month modified Rankin Scale score. White matter hyperintensity and acute infarct volume were quantified on fluid-attenuated inversion recovery and diffusion tensor imaging MRI, respectively. Diffusivity anisotropy metrics were calculated in normal appearing white matter contralateral to the acute ischemia. Among 319 patients with acute ischemic stroke, women were older (68.0 versus 62.7 years; P =0.004), had increased incidence of atrial fibrillation (21.4% versus 12.2%; P =0.04), and lower rate of tobacco use (21.1% versus 35.9%; P =0.03). There was no sex-specific difference in white matter hyperintensity volume, acute infarct volume, National Institutes of Health Stroke Scale, prestroke modified Rankin Scale score, or normal appearing white matter diffusivity anisotropy metrics. However, women were less likely to have an excellent outcome (modified Rankin Scale score <2: 49.6% versus 67.0%; P =0.005). In logistic regression analysis, female sex and the interaction of sex with fractional anisotropy, radial diffusivity, and axial diffusivity were independent predictors of functional outcome. Female sex is associated with decreased likelihood of excellent outcome after acute ischemic stroke. The correlation between markers of white matter integrity and functional outcomes in women, but not men, suggests a potential sex-specific mechanism. © 2017 American Heart Association, Inc.

  15. White matter microstructure and impulsivity in methamphetamine dependence with and without a history of psychosis.

    PubMed

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

    2016-06-01

    Methamphetamine (MA) use may lead to white matter injury and to a range of behavioral problems and psychiatric disorders, including psychosis. The present study sought to assess white matter microstructural impairment as well as impulsive behavior in MA dependence and MA-associated psychosis (MAP). Thirty patients with a history of MAP, 39 participants with MA dependence and 40 healthy controls underwent diffusion tensor imaging (DTI). Participants also completed the UPPS-P impulsive behavior questionnaire. We applied tract-based spatial statistics (TBSS) to investigate group differences in mean diffusivity (MD), fractional anisotropy (FA), axial (λ‖ ) and radial diffusivity (λ⊥ ), and their association with impulsivity scores and psychotic symptoms. The MAP group displayed widespread higher MD, λ‖ and λ⊥ levels compared to both controls and the MA group, and lower FA in extensive white matter areas relative to controls. MD levels correlated positively with negative psychotic symptoms in MAP. No significant DTI group differences were found between the MA group and controls. Both clinical groups showed high levels of impulsivity, and this dysfunction was associated with DTI measures in frontal white matter tracts. MAP patients show distinct patterns of impaired white matter integrity of global nature relative to controls and the MA group. Future work to investigate the precise nature and timing of alterations in MAP is needed. The results are further suggestive of frontal white matter pathology playing a role in impulsivity in MA dependence and MAP. Hum Brain Mapp 37:2055-2067, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. White matter hyperintensities of presumed vascular origin: a population-based study in rural Ecuador (The Atahualpa Project).

    PubMed

    Del Brutto, Oscar H; Mera, Robertino M; Del Brutto, Victor J; Zambrano, Mauricio; Lama, Julio

    2015-04-01

    Cerebral small vessel disease is probably one of the most common pathogenetic mechanisms underlying stroke in Latin America. However, the importance of silent markers of small vessel disease, including white matter hyperintensities of presumed vascular origin, has not been assessed so far. The study aims to evaluate prevalence and correlates of white matter hyperintensities in community-dwelling elders living in Atahualpa (rural Ecuador). Atahualpa residents aged ≥ 60 years were identified during a door-to-door survey and invited to undergo brain magnetic resonance imaging for identification and grading white matter hyperintensities and other markers of small vessel disease. Using multivariate logistic regression models, we evaluated whether white matter hyperintensities is associated with demographics, cardiovascular health status, stroke, cerebral microbleeds, and cortical atrophy, after adjusting for the other variables. Out of 258 enrolled persons (mean age, 70 ± 8 years; 59% women), 172 (67%) had white matter hyperintensities, which were moderate to severe in 63. Analyses showed significant associations of white matter hyperintensities presence and severity with age and cardiovascular health status, as well as with overt and silent strokes, and a trend for association with cerebral microbleeds and cortical atrophy. Prevalence and correlates of white matter hyperintensities in elders living in rural Ecuador is almost comparable with that reported from industrialized nations, reinforcing the concept that the burden of small vessel disease is on the rise in underserved Latin American populations. © 2014 World Stroke Organization.

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

    PubMed Central

    Elitt, Christopher M.; Rosenberg, Paul A.

    2014-01-01

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

  18. Intrahemispheric white matter asymmetries: the missing link between brain structure and functional lateralization?

    PubMed

    Ocklenburg, Sebastian; Friedrich, Patrick; Güntürkün, Onur; Genç, Erhan

    2016-07-01

    Hemispheric asymmetries are a central principle of nervous system architecture and shape the functional organization of most cognitive systems. Structural gray matter asymmetries and callosal interactions have been identified as contributing neural factors but always fell short to constitute a full explanans. Meanwhile, recent advances in in vivo white matter tractography have unrevealed the asymmetrical organization of many intrahemispheric white matter pathways, which might serve as the missing link to explain the substrate of functional lateralization. By taking into account callosal interactions, gray matter asymmetries and asymmetrical interhemispheric pathways, we opt for a new triadic model that has the potential to explain many observations which cannot be elucidated within the current frameworks of lateralized cognition.

  19. 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

  20. Altered white matter integrity and development in children with autism: a combined voxel-based morphometry and diffusion imaging study.

    PubMed

    Mengotti, Paola; D'Agostini, Serena; Terlevic, Robert; De Colle, Cristina; Biasizzo, Elsa; Londero, Danielle; Ferro, Adele; Rambaldelli, Gianluca; Balestrieri, Matteo; Zanini, Sergio; Fabbro, Franco; Molteni, Massimo; Brambilla, Paolo

    2011-02-01

    A combined protocol of voxel-based morphometry (VBM) and diffusion-weighted imaging (DWI) was applied to investigate the neurodevelopment of gray and white matter in autism. Twenty children with autism (mean age= 7 ± 2.75 years old; age range: 4-14; 2 girls) and 22 matched normally developing children (mean age = 7.68 ± 2.03 years old; age range: 4-11; 2 girls) underwent magnetic resonance imaging (MRI). VBM was employed by applying the Template-o-Matic toolbox (TOM), a new approach which constructs the age-matched customized template for tissue segmentation. Also, the apparent diffusion coefficients (ADC) of water molecules were obtained from the analysis of DWI. Regions of interests (ROIs), standardized at 5 pixels, were placed in cortical lobes and corpus callosum on the non-diffusion weighted echo-planar images (b = 0) and were then automatically transferred to the corresponding maps to obtain the ADC values. Compared to normal children, individuals with autism had significantly: (1) increased white matter volumes in the right inferior frontal gyrus, the right fusiform gyrus, the left precentral and supplementary motor area and the left hippocampus, (2) increased gray matter volumes in the inferior temporal gyri bilaterally, the right inferior parietal cortex, the right superior occipital lobe and the left superior parietal lobule, and (3) decreased gray matter volumes in the right inferior frontal gyrus and the left supplementary motor area. Abnormally increased ADC values in the bilateral frontal cortex and in the left side of the genu of the corpus callosum were also reported in autism. Finally, age correlated negatively with lobar and callosal ADC measurements in individuals with autism, but not in children with normal development. These findings suggest cerebral dysconnectivity in the early phases of autism coupled with an altered white matter maturation trajectory during childhood potentially taking place in the frontal and parietal lobes, which may

  1. Relation between brain temperature and white matter damage in subacute carbon monoxide poisoning

    PubMed Central

    Fujiwara, Shunrou; Yoshioka, Yoshichika; Matsuda, Tsuyoshi; Nishimoto, Hideaki; Ogawa, Akira; Ogasawara, Kuniaki; Beppu, Takaaki

    2016-01-01

    In the previous studies, carbon monoxide (CO) poisoning showed an imbalance between cerebral perfusion and metabolism in the acute phase and the brain temperature (BT) in these patients remained abnormally high from the acute to the subacute phase. As observed in chronic ischemic patients, BT can continuously remain high depending on impairments of cerebral blood flow and metabolism; this is because heat removal and production system in the brain may mainly be maintained by the balance of these two factors; thus, cerebral white matter damage (WMD) affecting normal metabolism may affect the BT in patients with CO poisoning. Here, we investigated whether the BT correlates with the degree of WMD in patients with subacute CO-poisoning. In 16 patients with subacute CO-poisoning, the BT and degree of WMD were quantitatively measured by using magnetic resonance spectroscopy and the fractional anisotropy (FA) value from diffusion tensor imaging dataset. Consequently, the BT significantly correlated with the degree of WMD. In particular, BT observed in patients with delayed neuropsychiatric sequelae, a crucial symptom with sudden-onset in the chronic phase after CO exposure, might indicate cerebral hypo-metabolism and abnormal hemodynamics like “matched perfusion,” in which the reduced perfusion matches the reduced metabolism. PMID:27819312

  2. Supratentorial white matter blurring associated with voltage-gated potassium channel-complex limbic encephalitis.

    PubMed

    Urbach, H; Rauer, S; Mader, I; Paus, S; Wagner, J; Malter, M P; Prüss, H; Lewerenz, J; Kassubek, J; Hegen, H; Auer, M; Deisenhammer, F; Ufer, F; Bien, C G; Baumgartner, A

    2015-12-01

    Limbic encephalitis (LE) associated with voltage-gated potassium channel-complex antibodies (VGKC-LE) is frequently non-paraneoplastic and associated with marked improvement following corticosteroid therapy. Mesial temporal lobe abnormalities are present in around 80 % of patients. If associated or preceded by faciobrachial dystonic seizures, basal ganglia signal changes may occur. In some patients, blurring of the supratentorial white matter on T2-weighted images (SWMB) may be seen. The purpose of this study was to evaluate the incidence of SWMB and whether it is specific for VGKC-LE. Two experienced neuroradiologists independently evaluated signal abnormalities on FLAIR MRI in 79 patients with LE while unaware on the antibody type. SWMB was independently assessed as present in 10 of 36 (28 %) compared to 2 (5 %) of 43 non-VGKC patients (p = 0.009). It was not related to the presence of LGI1 or CASPR2 proteins of VGKC antibodies. MRI showed increased temporomesial FLAIR signal in 22 (61 %) VGKC compared to 14 (33 %) non-VGKC patients (p = 0.013), and extratemporomesial structures were affected in one VGKC (3 %) compared to 11 (26 %) non-VGKC patients (p = 0.005). SWMB is a newly described MRI sign rather specific for VGKC-LE.

  3. Age-related cerebral white matter changes and pulse-wave encephalopathy: observations with three-dimensional MRI.

    PubMed

    Henry Feugeas, Marie Cécile; De Marco, Giovanni; Peretti, Ilana Idy; Godon-Hardy, Sylvie; Fredy, Daniel; Claeys, Elisabeth Schouman

    2005-11-01

    Our purpose was to investigate leukoaraïosis (LA) using three-dimensional MR imaging combined with advanced image-processing technology to attempt to group signal abnormalities according to their etiology. Coronal T2-weighted fast fluid-attenuated inversion-recovery (FLAIR) sequences and three-dimensional T1-weighted fast spoiled gradient recalled echo sequences were used to examine cerebral white matter changes in 75 elderly people with memory complaint but no dementia. They were otherwise healthy, community-dwelling subjects. Three subtypes of LA were defined on the basis of their shape, geography and extent: the so-called subependymal/subpial LA, perivascular LA and "bands" along long white matter tracts. Subependymal changes were directly contiguous with ventricular spaces. They showed features of "water hammer" lesions with ventricular systematisation and a more frequent location around the frontal horns than around the bodies (P=.0008). The use of cerebrospinal fluid (CSF) contiguity criterion allowed a classification of splenial changes in the subpial group. Conversely, posterior periventricular lesions in the centrum ovale as well as irregular and extensive periventricular lesions were not directly contiguous with CSF spaces. The so-called perivascular changes showed features of small-vessel-associated disease; they surrounded linear CSF-like signals that followed the direction of perforating vessels. Distribution of these perivascular changes appeared heterogeneous (P ranging from .04 to 5.10(-16)). These findings suggest that subependymal/subpial LA and subcortical LA may be separate manifestations of a single underlying pulse-wave encephalopathy.

  4. Anatomically related gray and white matter alterations in the brains of functional dyspepsia patients.

    PubMed

    Nan, J; Liu, J; Mu, J; Zhang, Y; Zhang, M; Tian, J; Liang, F; Zeng, F

    2015-06-01

    Previous studies summarized altered brain functional patterns in functional dyspepsia (FD) patients, but how the brain structural patterns are related to FD remains largely unclear. The objective of this study was to determine the brain structural characteristics in FD patients. Optimized voxel-based morphometry and tract-based spatial statistics were employed to investigate the changes in gray matter (GM) and white matter (WM) respectively in 34 FD patients with postprandial distress syndrome and 33 healthy controls based on T1-weighted and diffusion-weighted imaging. The Pearson's correlation evaluated the link among GM alterations, WM abnormalities, and clinical variables in FD patients. The optimal brain structural parameters for identifying FD were explored using the receiver operating characteristic curve. Compared to controls, FD patients exhibited a decrease in GM density (GMD) in the right posterior insula/temporal superior cortex (marked as pINS), right inferior frontal cortex (IFC), and left middle cingulate cortex, and an increase in fractional anisotropy (FA) in the posterior limb of the internal capsule, posterior thalamic radiation, and external capsule (EC). Interestingly, the GMD in the pINS was significantly associated with GMD in the IFC and FA in the EC. Moreover, the EC adjacent to the pINS provided the best performance for distinguishing FD patients from controls. Our results showed pINS-related structural abnormalities in FD patients, indicating that GM and WM parameters were not affected independently. These findings would lay the foundation for probing an efficient target in the brain for treating FD. © 2015 John Wiley & Sons Ltd.

  5. Microstructure abnormalities in adolescents with internet addiction disorder.

    PubMed

    Yuan, Kai; Qin, Wei; Wang, Guihong; Zeng, Fang; Zhao, Liyan; Yang, Xuejuan; Liu, Peng; Liu, Jixin; Sun, Jinbo; von Deneen, Karen M; Gong, Qiyong; Liu, Yijun; Tian, Jie

    2011-01-01

    Recent studies suggest that internet addiction disorder (IAD) is associated with structural abnormalities in brain gray matter. However, few studies have investigated the effects of internet addiction on the microstructural integrity of major neuronal fiber pathways, and almost no studies have assessed the microstructural changes with the duration of internet addiction. We investigated the morphology of the brain in adolescents with IAD (N = 18) using an optimized voxel-based morphometry (VBM) technique, and studied the white matter fractional anisotropy (FA) changes using the diffusion tensor imaging (DTI) method, linking these brain structural measures to the duration of IAD. We provided evidences demonstrating the multiple structural changes of the brain in IAD subjects. VBM results indicated the decreased gray matter volume in the bilateral dorsolateral prefrontal cortex (DLPFC), the supplementary motor area (SMA), the orbitofrontal cortex (OFC), the cerebellum and the left rostral ACC (rACC). DTI analysis revealed the enhanced FA value of the left posterior limb of the internal capsule (PLIC) and reduced FA value in the white matter within the right parahippocampal gyrus (PHG). Gray matter volumes of the DLPFC, rACC, SMA, and white matter FA changes of the PLIC were significantly correlated with the duration of internet addiction in the adolescents with IAD. Our results suggested that long-term internet addiction would result in brain structural alterations, which probably contributed to chronic dysfunction in subjects with IAD. The current study may shed further light on the potential brain effects of IAD.

  6. The role of white matter in personality traits and affective processing in bipolar disorder.

    PubMed

    Bauer, Isabelle E; Wu, Mon-Ju; Meyer, Thomas D; Mwangi, Benson; Ouyang, Austin; Spiker, Danielle; Zunta-Soares, Giovana B; Huang, Hao; Soares, Jair C

    2016-09-01

    Bipolar disorder (BD) is characterized by affective processing bias and variations in personality traits. It is still unknown whether these features are linked to the same structural brain alterations. The aim of this study was to investigate relationships between specific personality traits, white matter (WM) properties, and affective processing in BD and HC. 24 healthy controls (HC) and 38 adults with BDI (HC: 29.47 ± 2.23 years, 15 females; BDI: 32.44 ± 1.84 years, 20 females) completed clinical scales and the Big Five Inventory. They were also administered the Affective Go/No-Go (AGN) and the Rapid Visual Processing (RVP) tasks of the Cambridge Neuropsychological Test Automated Battery. Diffusion Tensor Imaging (DTI) assessed the microstructure of WM tracts. In BDI measures of WM properties were reduced across all major brain white matter tracts. As expected, individuals with BDI reported greater neuroticism, lower agreeableness and conscientiousness, and made a greater number of errors in response to affective stimuli in the AGN task compared to HC. High neuroticism scores were associated with faster AGN latency, and overall reduced AGN accuracy in both HC and BDI. Elevated FA values were associated with reduced neuroticism and increased cognitive processing in HC but not in BDI. Our findings showed important potential links between personality, affective processing and WM integrity in BD. In the future therapeutic interventions for BD using brain stimulation protocols might benefit from the use of DTI to target pathways underlying abnormal affective processing. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. High-mobility group box-1 as an autocrine trophic factor in white matter stroke.

    PubMed

    Choi, Jun Young; Cui, Yuexian; Chowdhury, Samma Tasneem; Kim, Byung Gon

    2017-06-20

    Maintenance of white matter integrity in health and disease is critical for a variety of neural functions. Ischemic stroke in the white matter frequently results in degeneration of oligodendrocytes (OLs) and myelin. Previously, we found that toll-like receptor 2 (TLR2) expressed in OLs provides cell-autonomous protective effects on ischemic OL death and demyelination in white matter stroke. Here, we identified high-mobility group box-1 (HMGB1) as an endogenous TLR2 ligand that promotes survival of OLs under ischemic stress. HMGB1 rapidly accumulated in the culture medium of OLs exposed to oxygen-glucose deprivation (OGD). This conditioned medium exhibited a protective activity against ischemic OL death that was completely abolished by immunodepletion of HMGB1. Knockdown of HMGB1 or application of glycyrrhizin, a specific HMGB1 inhibitor, aggravated OGD-induced OL death, and recombinant HMGB1 application reduced the extent of OL death in a TLR2-dependent manner. We confirmed that cytosolic translocation of HMGB1 and activation of TLR2-mediated signaling pathways occurred in a focal white matter stroke model induced by endothelin-1 injection. Animals with glycyrrhizin coinjection showed an expansion of the demyelinating lesion in a TLR2-dependent manner, accompanied by aggravation of sensorimotor behavioral deficits. These results indicate that HMGB1/TLR2 activates an autocrine trophic signaling pathways in OLs and myelin to maintain structural and functional integrity of the white matter under ischemic conditions.

  8. Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain

    PubMed Central

    Al-Mashhadi, Sufana; Simpson, Julie E.; Heath, Paul R.; Dickman, Mark; Forster, Gillian; Matthews, Fiona E.; Brayne, Carol; Ince, Paul G.; Wharton, Stephen B.

    2016-01-01

    White matter lesions (WML) are common in brain aging and are associated with dementia. We aimed to investigate whether oxidative DNA damage and occur in WML and in apparently normal white matter in cases with lesions. Tissue from WML and control white matter from brains with lesions (controls lesional) and without lesions (controls non-lesional) were obtained, using post-mortem magnetic resonance imaging-guided sampling, from the Medical Research Council Cognitive Function and Ageing Study. Oxidative damage was assessed by immunohistochemistry to 8-hydroxy-2′-deoxoguanosine (8-OHdG) and Western blotting for malondialdehyde. DNA response was assessed by phosphorylated histone H2AX (γH2AX), p53, senescence markers and by quantitative Reverse transcription polymerase chain reaction (RT-PCR) panel for candidate DNA damage-associated genes. 8-OHdG was expressed in glia and endothelium, with increased expression in both WML and controls lesional compared with controls non-lesional (P < 0.001). γH2Ax showed a similar, although attenuated difference among groups (P = 0.03). Expression of senescence-associated β-galactosidase and p16 suggested induction of senescence mechanisms in glia. Oxidative DNA damage and a DNA damage response are features of WML pathogenesis and suggest candidate mechanisms for glial dysfunction. Their expression in apparently normal white matter in cases with WML suggests that white matter dysfunction is not restricted to lesions. The role of this field-effect lesion pathogenesis and cognitive impairment are areas to be defined. PMID:25311358

  9. Prefrontal white matter pathology in air pollution exposed Mexico City young urbanites and their potential impact on neurovascular unit dysfunction and the development of Alzheimer's disease.

    PubMed

    Calderón-Garcidueñas, Lilian; Reynoso-Robles, Rafael; Vargas-Martínez, Javier; Gómez-Maqueo-Chew, Aline; Pérez-Guillé, Beatriz; Mukherjee, Partha S; Torres-Jardón, Ricardo; Perry, George; Gónzalez-Maciel, Angélica

    2016-04-01

    Millions of urban children are chronically exposed to high concentrations of air pollutants, i.e., fine particulate matter (PM2.5) and ozone, associated with increased risk for Alzheimer's disease. Compared with children living with clear air those in Mexico City (MC) exhibit systemic, brain and intrathecal inflammation, low CSF Aβ42, breakdown of the BBB, attention and short-term memory deficits, prefrontal white matter hyperintensities, damage to epithelial and endothelial barriers, tight junction and neural autoantibodies, and Alzheimer and Parkinson's hallmarks. The prefrontal white matter is a target of air pollution. We examined by light and electron microscopy the prefrontal white matter of MC dogs (n: 15, age 3.17±0.74 years), children and teens (n: 34, age: 12.64±4.2 years) versus controls. Major findings in MC residents included leaking capillaries and small arterioles with extravascular lipids and erythrocytes, lipofuscin in pericytes, smooth muscle and endothelial cells (EC), thickening of cerebrovascular basement membranes with small deposits of amyloid, patchy absence of the perivascular glial sheet, enlarged Virchow-Robin spaces and nanosize particles (20-48nm) in EC, basement membranes, axons and dendrites. Tight junctions, a key component of the neurovascular unit (NVU) were abnormal in MC versus control dogs (χ(2)<0.0001), and white matter perivascular damage was significantly worse in MC dogs (p=0.002). The integrity of the NVU, an interactive network of vascular, glial and neuronal cells is compromised in MC young residents. Characterizing the early NVU damage and identifying biomarkers of neurovascular dysfunction may provide a fresh insight into Alzheimer pathogenesis and open opportunities for pediatric neuroprotection. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. BDNF Val66Met polymorphism modulates the effect of loneliness on white matter microstructure in young adults.

    PubMed

    Meng, Jie; Hao, Lei; Wei, Dongtao; Sun, Jiangzhou; Li, Yu; Qiu, Jiang

    2017-12-01

    Loneliness is a common experience. Susceptibility to loneliness is a stable trait and is heritable. Previous studies have suggested that loneliness may impact regional gray matter density and brain activation to social stimuli, but its relation to white matter structure and how it may interact with genetic factors remains unclear. In this study, we investigated whether and how a common polymorphism (Val66Met) in the brain-derived neurotrophic factor gene modulated the association between loneliness and white matter microstructure in 162 young adults. The tract-based spatial statistics analyses revealed that the relationships between loneliness and white matter microstructures were significantly different between Val/Met heterozygotes and Val/Val homozygotes. Specifically, loneliness was significantly correlated with reduced fractional anisotropy and increased radial diffusivity in widespread white matter fibers within Val/Met heterozygotes. It was also significantly correlated with increased radial diffusivity in Met/Met genotypes but showed no significant association with white matter measures in Val/Val genotypes. Furthermore, the associations between loneliness and fractional anisotropy (or radial diffusivity) in Val/Met heterozygotes turned out to be global effects. These results provide evidence that loneliness may interact with the BDNF Val66Met polymorphism to shape the microstructures of white matter, and the Val/Met heterozygotes may be more susceptible to social environment. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Gestational age at birth and brain white matter development in term-born infants and children

    USDA-ARS?s Scientific Manuscript database

    Studies on infants and children born preterm have shown that adequate gestational length is critical for brain white matter development. Less is known regarding how variations in gestational age at birth in term infants and children affect white matter development, which was evaluated in this study....

  12. HIV disease and diabetes interact to affect brain white matter hyperintensities and cognition.

    PubMed

    Wu, Minjie; Fatukasi, Omalara; Yang, Shaolin; Alger, Jeffery; Barker, Peter B; Hetherington, Hoby; Kim, Tae; Levine, Andrew; Martin, Eileen; Munro, Cynthia A; Parrish, Todd; Ragin, Ann; Sacktor, Ned; Seaberg, Eric; Becker, James T

    2018-05-22

    Since the onset of combination antiretroviral therapy (cART) use, the incidence of HIV-associated dementia and of HIV encephalitis have fallen dramatically. The present study investigates the extent of white matter hyperintensities (WMHs) among individuals with HIV disease, and factors that predict their presence and their impact on psychomotor speed. 322 men participating in the Multicenter AIDS Cohort Study (MACS) (185 HIV-infected, age: 57.5 ± 6.0) underwent MRI scans of the brain. T1-weighted MP-RAGE and T2-weighted Fluid Attenuated Inversion Recovery (FLAIR) images were obtained and processed using an automated method for identifying and measuring WMHs. WMH burden was expressed as the log10 transformed percentage of total white matter that was abnormal. There were no significant associations between WMHs and HIV disease. However, the extent of WMHs was predicted by age > 60 (β=.17), non-Caucasian race (β=.14), glomerular filtration rate (β= -.11) and the presence of diabetes (β=.12). There were no interactions between HIV status and age (β = -.03) or between age and diabetes (β = .07). However, the interaction between HIV infection and diabetes was significant (β = .26). The extent of WMHs was significantly associated with performance on measures of psychomotor speed (β = .15). In today's therapeutic environment, in HIV-infected and HIV seronegative individuals those factors which affect the cerebrovasculature are the best predictors of WMHs. Diabetes has a specific impact among HIV-infected, but not uninfected men, suggesting the need for more aggressive treatment even in the prediabetes state, especially as WMHs affect cognitive functions.

  13. Adolescent engagement in dangerous behaviors is associated with increased white matter maturity of frontal cortex.

    PubMed

    Berns, Gregory S; Moore, Sara; Capra, C Monica

    2009-08-26

    Myelination of white matter in the brain continues throughout adolescence and early adulthood. This cortical immaturity has been suggested as a potential cause of dangerous and impulsive behaviors in adolescence. We tested this hypothesis in a group of healthy adolescents, age 12-18 (N = 91), who underwent diffusion tensor imaging (DTI) to delineate cortical white matter tracts. As a measure of real-world risk taking, participants completed the Adolescent Risk Questionnaire (ARQ) which measures engagement in dangerous activities. After adjusting for age-related changes in both DTI and ARQ, engagement in dangerous behaviors was found to be positively correlated with fractional anisotropy and negatively correlated with transverse diffusivity in frontal white matter tracts, indicative of increased myelination and/or density of fibers (ages 14-18, N = 60). The direction of correlation suggests that rather than having immature cortices, adolescents who engage in dangerous activities have frontal white matter tracts that are more adult in form than their more conservative peers.

  14. White Matter Maturation Supports the Development of Reasoning Ability Through its Influence on Processing Speed

    PubMed Central

    Ferrer, E.; Whitaker, K.J.; Steele, J.; Green, C.T.; Wendelken, C.; Bunge, S.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 contribute to improved reasoning ability over development. In particular, we sought to understand whether previously reported relationships between white matter microstructure and reasoning are mediated by processing speed. To this end, we analyzed diffusion tensor imaging data as well as data from standard psychometric tests of cognitive abilities from 103 individuals between the ages of 6 and 18. We used structural equation modeling to investigate the network of relationships between brain and behavior variables. Our analyses provide support for the hypothesis that white matter maturation (as indexed either by microstructural organization or volume) supports improved processing speed, which, in turn, supports improved reasoning ability. PMID:24118718

  15. Broad spectrum of neuropsychiatric phenotypes associated with white matter disease in PTEN hamartoma tumor syndrome.

    PubMed

    Balci, Tugce B; Davila, Jorge; Lewis, Denice; Boafo, Addo; Sell, Erick; Richer, Julie; Nikkel, Sarah M; Armour, Christine M; Tomiak, Eva; Lines, Matthew A; Sawyer, Sarah L

    2018-01-01

    White matter lesions have been described in patients with PTEN hamartoma tumor syndrome (PHTS). How these lesions correlate with the neurocognitive features associated with PTEN mutations, such as autism spectrum disorder (ASD) or developmental delay, has not been well established. We report nine patients with PTEN mutations and white matter changes on brain magnetic resonance imaging (MRI), eight of whom were referred for reasons other than developmental delay or ASD. Their clinical presentations ranged from asymptomatic macrocephaly with normal development/intellect, to obsessive compulsive disorder, and debilitating neurological disease. To our knowledge, this report constitutes the first detailed description of PTEN-related white matter changes in adult patients and in children with normal development and intelligence. We present a detailed assessment of the neuropsychological phenotype of our patients and discuss the relationship between the wide array of neuropsychiatric features and observed white matter findings in the context of these individuals. © 2017 Wiley Periodicals, Inc.

  16. White Matter Correlates of Auditory Comprehension Outcomes in Chronic Post-Stroke Aphasia

    PubMed Central

    Xing, Shihui; Lacey, Elizabeth H.; Skipper-Kallal, Laura M.; Zeng, Jinsheng; Turkeltaub, Peter E.

    2017-01-01

    Neuroimaging studies have shown that speech comprehension involves a number of widely distributed regions within the frontal and temporal lobes. We aimed to examine the differential contributions of white matter connectivity to auditory word and sentence comprehension in chronic post-stroke aphasia. Structural and diffusion MRI data were acquired on 40 patients with chronic post-stroke aphasia. A battery of auditory word and sentence comprehension tests were administered to all the patients. Tract-based spatial statistics were used to identify areas in which white matter integrity related to specific comprehension deficits. Relevant tracts were reconstructed using probabilistic tractography in healthy older participants, and the mean values of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of the entire tracts were examined in relation to comprehension scores. Anterior temporal white matter integrity loss and involvement of the uncinate fasciculus related to word-level comprehension deficits (RFA = 0.408, P = 0.012; RMD = −0.429, P = 0.008; RAD = −0.424, P = 0.009; RRD = −0.439, P = 0.007). Posterior temporal white matter integrity loss and involvement of the inferior longitudinal fasciculus related to sentence-level comprehension deficits (RFA = 0.382, P = 0.02; RMD = −0.461, P = 0.004; RAD = −0.457, P = 0.004; RRD = −0.453, P = 0.005). Loss of white matter integrity in the inferior fronto-occipital fasciculus related to both word- and sentence-level comprehension (word-level scores: RFA = 0.41, P = 0.012; RMD = −0.447, P = 0.006; RAD = −0.489, P = 0.002; RRD = −0.432, P = 0.008; sentence-level scores: RFA = 0.409, P = 0.012; RMD = −0.413, P = 0.011; RAD = −0.408, P = 0.012; RRD = −0.413, P = 0.011). Lesion overlap, but not white matter integrity, in the

  17. Abnormal Structure–Function Relationship in Spasmodic Dysphonia

    PubMed Central

    Ludlow, Christy L.

    2012-01-01

    Spasmodic dysphonia (SD) is a primary focal dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. Although recent studies have found abnormal brain function and white matter organization in SD, the extent of gray matter alterations, their structure–function relationships, and correlations with symptoms remain unknown. We compared gray matter volume (GMV) and cortical thickness (CT) in 40 SD patients and 40 controls using voxel-based morphometry and cortical distance estimates. These measures were examined for relationships with blood oxygen level–dependent signal change during symptomatic syllable production in 15 of the same patients. SD patients had increased GMV, CT, and brain activation in key structures of the speech control system, including the laryngeal sensorimotor cortex, inferior frontal gyrus (IFG), superior/middle temporal and supramarginal gyri, and in a structure commonly abnormal in other primary dystonias, the cerebellum. Among these regions, GMV, CT and activation of the IFG and cerebellum showed positive relationships with SD severity, while CT of the IFG correlated with SD duration. The left anterior insula was the only region with decreased CT, which also correlated with SD symptom severity. These findings provide evidence for coupling between structural and functional abnormalities at different levels within the speech production system in SD. PMID:21666131

  18. Relationship between symptom dimensions and white matter alterations in obsessive-compulsive disorder.

    PubMed

    Yagi, Michiyo; Hirano, Yoshiyuki; Nakazato, Michiko; Nemoto, Kiyotaka; Ishikawa, Kazuhiro; Sutoh, Chihiro; Miyata, Haruko; Matsumoto, Junko; Matsumoto, Koji; Masuda, Yoshitada; Obata, Takayuki; Iyo, Masaomi; Shimizu, Eiji; Nakagawa, Akiko

    2017-06-01

    To investigate the relationship between the severities of symptom dimensions in obsessive-compulsive disorder (OCD) and white matter alterations. We applied tract-based spatial statistics for diffusion tensor imaging (DTI) acquired by 3T magnetic resonance imaging. First, we compared fractional anisotropy (FA) between 20 OCD patients and 30 healthy controls (HC). Then, applying whole brain analysis, we searched the brain regions showing correlations between the severities of symptom dimensions assessed by Obsessive-Compulsive Inventory-Revised and FA in all participants. Finally, we calculated the correlations between the six symptom dimensions and multiple DTI measures [FA, axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD)] in a region-of-interest (ROI) analysis and explored the differences between OCD patients and HC. There were no between-group differences in FA or brain region correlations between the severities of symptom dimensions and FA in any of the participants. ROI analysis revealed negative correlations between checking severity and left inferior frontal gyrus white matter and left middle temporal gyrus white matter and a positive correlation between ordering severity and right precuneus in FA in OCD compared with HC. We also found negative correlations between ordering severity and right precuneus in RD, between obsessing severities and right supramarginal gyrus in AD and MD, and between hoarding severity and right insular gyrus in AD. Our study supported the hypothesis that the severities of respective symptom dimensions are associated with different patterns of white matter alterations.

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

    PubMed Central

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

    2010-01-01

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

  20. Disrupted White Matter Network and Cognitive Decline in Type 2 Diabetes Patients.

    PubMed

    Zhang, Junying; Liu, Zhen; Li, Zixiao; Wang, Yunxia; Chen, Yaojing; Li, Xin; Chen, Kewei; Shu, Ni; Zhang, Zhanjun

    2016-05-06

    Type 2 diabetes mellitus is accompanied by cognitive impairment and is associated with an increased risk of dementia. Damage to brain structures such as white matter network disruption may underlie this cognitive disturbance. In the present study, 886 non-diabetic and 163 type 2 diabetic participants completed a battery of neuropsychological tests. Among them, 38 diabetic patients and 34 non-diabetic participants that matched the patients for age/sex/education received a magnetic resonance imaging-based diffusion tensor imaging. Then we calculated the topological properties of the white matter network using a graph theoretical method to investigate network efficiency differences between groups. We found that type 2 diabetic patients had inferior performances compared to the non-diabetic controls, in several cognitive domains involving executive function, spatial processing, memory, and attention. We also found that diabetic patients exhibited a disrupted topological organization of the white matter network (including the global network properties, i.e., network strength, global efficiency, local efficiency and shortest path length, and the nodal efficiency of the right rolandic operculum) in the brain. Moreover, those global network properties and the nodal efficiency of the right rolandic operculum both had positive correlations with executive function in the patient group. The results suggest that type 2 diabetes mellitus leads to an alteration in the topological organization of the cortical white matter network and this alteration may account for the observed cognitive decline.