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Sample records for abnormal white matter

  1. 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

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

    PubMed

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

    2016-06-01

    Here we report whole exome sequencing (WES) on a cohort of 71 patients with persistently unresolved white matter abnormalities with a suspected diagnosis of leukodystrophy or genetic leukoencephalopathy. WES analyses were performed on trio, or greater, family groups. Diagnostic pathogenic variants were identified in 35% (25 of 71) of patients. Potentially pathogenic variants were identified in clinically relevant genes in a further 7% (5 of 71) of cases, giving a total yield of clinical diagnoses in 42% of individuals. These findings provide evidence that WES can substantially decrease the number of unresolved white matter cases. Ann Neurol 2016;79:1031-1037. PMID:27159321

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

    PubMed Central

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

    2014-01-01

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

  4. Age exacerbates HIV-associated white matter abnormalities.

    PubMed

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

    2016-04-01

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

  5. White Matter Abnormalities in Schizophrenia and Schizotypal Personality Disorder

    PubMed Central

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

    2015-01-01

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

  6. Myelin vs Axon Abnormalities in White Matter in Bipolar Disorder

    PubMed Central

    Lewandowski, Kathryn E; Ongür, Dost; Sperry, Sarah H; Cohen, Bruce M; Sehovic, Selma; Goldbach, Jacqueline R; Du, Fei

    2015-01-01

    White matter (WM) abnormalities are among the most commonly reported neuroimaging findings in bipolar disorder. Nonetheless, the specific nature and pathophysiology of these abnormalities remain unclear. Use of a combination of magnetization transfer ratio (MTR) and diffusion tensor spectroscopy (DTS) permits examination of myelin and axon abnormalities separately. We aimed to examine myelination and axon geometry in euthymic patients with bipolar disorder with psychosis (BDP) by combining these two complementary noninvasive MRI techniques. We applied a combined MRI approach using MTR to study myelin content and DTS to study metabolite (N-acetylaspartate, NAA) diffusion within axons in patients with BDP (n=21) and healthy controls (n=24). Data were collected from a 1 × 3 × 3-cm voxel within the right prefrontal cortex WM at 4 Tesla. Clinical and cognitive data were examined in association with MTR and DTS data. MTR was significantly reduced in BDP, suggesting reduced myelin content. The apparent diffusion coefficient of NAA did not differ from healthy controls, suggesting no changes in axon geometry in patients with BDP. These findings suggest that patients with BDP exhibit reduced myelin content, but no changes in axon geometry compared with controls. These findings are in contrast with our recent findings, using the same techniques, in patients with schizophrenia (SZ), which suggest both myelination and axon abnormalities in SZ. This difference may indicate that alterations in WM in BDP may have unique causes and may be less extensive than WM abnormalities seen in SZ. PMID:25409595

  7. Spatial characteristics of white matter abnormalities in schizophrenia.

    PubMed

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

    2013-09-01

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

  8. White and Gray Matter Abnormalities in Narcolepsy with Cataplexy

    PubMed Central

    Scherfler, Christoph; Frauscher, Birgit; Schocke, Michael; Nocker, Michael; Gschliesser, Viola; Ehrmann, Laura; Niederreiter, Markus; Esterhammer, Regina; Seppi, Klaus; Brandauer, Elisabeth; Poewe, Werner; Högl, Birgit

    2012-01-01

    Study Objectives: The authors applied diffusion-tensor imaging including measurements of mean diffusivity (MD), which is a parameter of brain tissue integrity, fractional anisotropy (FA), which is a parameter of neuronal fiber integrity, and voxel-based morphometry, which is a measure of gray and white matter volume, to detect brain tissue changes in patients with narcolepsy-cataplexy. Design: N/A. Patients: Patients with narcolepsy-cataplexy (n = 16) and age-matched healthy control subjects (n = 12) were studied. Interventions: Whole cerebral MD, FA measures, and the volumes of the gray and white matter compartments were analyzed using statistical parametric mapping. Measurement and Results: Significant MD increases and concomitant FA decreases were localized in the fronto-orbital cortex (P < 0.001) and the anterior cingulate (FA, P < 0.001; MD, P = 0.03) in narcolepsy-cataplexy. Additional MD increases without FA changes were detected in the ventral tegmental area, the dorsal raphe nuclei (P < 0.001), and the hypothalamus (P < 0.01). FA signal decreases were observed in the white matter tracts of the inferior frontal and inferior temporal cortices of narcolepsy-cataplexy patients (P < 0.001). Brain volume loss was evident in focal areas of the inferior and superior temporal cortices (P < 0.001) and the cingulate (P = 0.038). Conclusions: Areas of increased diffusivity in the hypothalamus appear consistent with hypocretinergic cell loss reported in narcolepsy-cataplexy. Signal abnormalities in the ventral tegmental area and the dorsal raphe nuclei correspond to major synaptic targets of hypocretin neurons that were associated with the regulation of the sleep-wake cycle. Brain tissue alterations identified in the frontal cortex and cingulate are crucial in the maintenance of attention and reward-dependent decision making, both known to be impaired in narcolepsy-cataplexy. Citation: Scherfler C; Frauscher B; Schocke M; Nocker M; Gschliesser V; Ehrmann L

  9. Clinical Prediction of Fall Risk and White Matter Abnormalities

    PubMed Central

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

    2015-01-01

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

  10. 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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  13. 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

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

    PubMed Central

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

    2012-01-01

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

  15. Brain white matter abnormality in a newborn infant with congenital adrenal hyperplasia.

    PubMed

    Kaga, Akimune; Saito-Hakoda, Akiko; Uematsu, Mitsugu; Kamimura, Miki; Kanno, Junko; Kure, Shigeo; Fujiwara, Ikuma

    2013-10-01

    Several studies have described brain white matter abnormalities on magnetic resonance imaging (MRI) in children and adults with congenital adrenal hyperplasia (CAH), while the brain MRI findings of newborn infants with CAH have not been clarified. We report a newborn boy with CAH who presented brain white matter abnormality on MRI. He was diagnosed as having salt-wasting CAH with a high 17-OHP level at neonatal screening and was initially treated with hydrocortisone at 8 days of age. On day 11 after birth, he had a generalized tonic seizure. No evidence of serum electrolyte abnormalities was observed. Brain MRI revealed white matter abnormalities that consisted of bilateral small diffuse hyperintensities on T1-weighted images with slightly low intensity on T2-weighted images in the watershed area. Several factors associated with brain white matter abnormalities in adults with CAH, such as increasing age, hypertension, diabetes and corticosteroid replacement, were not applicable. Although the cause of the phenomenon in this case is unclear, brain white matter abnormality could be observed in newborn infants with CAH as well as in adult patients. PMID:24170965

  16. Neonatal White Matter Abnormality Predicts Childhood Motor Impairment in Very Preterm Children

    ERIC Educational Resources Information Center

    Spittle, Alicia J.; Cheong, Jeanie; Doyle, Lex W.; Roberts, Gehan; Lee, Katherine J.; Lim, Jeremy; Hunt, Rod W.; Inder, Terrie E.; Anderson, Peter J.

    2011-01-01

    Aim: Children born very preterm are at risk for impaired motor performance ranging from cerebral palsy (CP) to milder abnormalities, such as developmental coordination disorder. White matter abnormalities (WMA) at term have been associated with CP in very preterm children; however, little is known about the impact of WMA on the range of motor…

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2013-01-01

    The purpose of this project was to evaluate white matter degeneration and its impact on hippocampal structural connectivity in patients with amnestic mild cognitive impairment, non-amnestic mild cognitive impairment and Alzheimer's disease. We estimated white matter fractional anisotropy, mean diffusivity and hippocampal structural connectivity in two independent cohorts. The ADNI cohort included 108 subjects [25 cognitively normal, 21 amnestic mild cognitive impairment, 47 non-amnestic mild cognitive impairment and 15 Alzheimer's disease]. A second cohort included 34 subjects [15 cognitively normal and 19 amnestic mild cognitive impairment] recruited in Montreal. All subjects underwent clinical and neuropsychological assessment in addition to diffusion and T1 MRI. Individual fractional anisotropy and mean diffusivity maps were generated using FSL-DTIfit. In addition, hippocampal structural connectivity maps expressing the probability of connectivity between the hippocampus and cortex were generated using a pipeline based on FSL-probtrackX. Voxel-based group comparison statistics of fractional anisotropy, mean diffusivity and hippocampal structural connectivity were estimated using Tract-Based Spatial Statistics. The proportion of abnormal to total white matter volume was estimated using the total volume of the white matter skeleton. We found that in both cohorts, amnestic mild cognitive impairment patients had 27-29% white matter volume showing higher mean diffusivity but no significant fractional anisotropy abnormalities. No fractional anisotropy or mean diffusivity differences were observed between non-amnestic mild cognitive impairment patients and cognitively normal subjects. Alzheimer's disease patients had 66.3% of normalized white matter volume with increased mean diffusivity and 54.3% of the white matter had reduced fractional anisotropy. Reduced structural connectivity was found in the hippocampal connections to temporal, inferior parietal, posterior

  2. Age-related abnormalities in white matter microstructure in autism spectrum disorders

    PubMed Central

    Kleinhans, Natalia M.; Pauley, Gregory; Richards, Todd; Neuhaus, Emily; Martin, Nathalie; Corrigan, Neva M.; Shaw, Dennis W.; Estes, Annette; Dager, Stephen R.

    2012-01-01

    Abnormalities in structural and functional connectivity have been reported in autism spectrum disorders (ASD) across a wide age range. However, developmental changes in white matter microstructure are poorly understood. We used a cross-sectional design to determine whether white matter abnormalities measured using diffusion tensor imaging (DTI) were present in adolescents and adults with ASD and whether age-related changes in white matter microstructure differed between ASD and typically developing (TD) individuals. Participants included 28 individuals with ASD and 33 TD controls matched on age and IQ and assessed at one time point. Widespread decreased fractional anisotropy (FA), and increased radial diffusivity (RaD) and mean diffusivity (MD) were observed in the ASD group compared to the TD group. In addition, significant group-by-age interactions were also observed in FA, RaD, and MD in all major tracts except the brain stem, indicating that age-related changes in white matter microstructure differed between the groups. We propose that white matter microstructural changes in ASD may reflect myelination and/or other structural differences including differences in axonal density/arborization. In addition, we suggest that white matter microstuctural impairments may be normalizing during young adulthood in ASD. Future longitudinal studies that include a wider range of ages and more extensive clinical characterization will be critical for further uncovering the neurodevelopmental processes unfolding during this dynamic time in development. PMID:22902768

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  5. 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;…

  6. White Matter Abnormalities in Early-Onset Schizophrenia: A Voxel-Based Diffusion Tensor Imaging Study

    ERIC Educational Resources Information Center

    Kumra, Sanjiv; Ashtari, Manzar; Cervellione, Kelly L.; Henderson, Inika; Kester, Hana; Roofeh, David; Wu, Jinghui; Clarke, Tana; Thaden, Emily; Kane, John M.; Rhinewine, Joseph; Lencz, Todd; Diamond, Alan; Ardekani, Babak A.; Szeszko, Philip R.

    2005-01-01

    Objective: To investigate abnormalities in the structural integrity of brain white matter as suggested by diffusion tensor imaging in adolescents with early-onset schizophrenia (onset of psychosis by age 18). Method: Twenty-six patients with schizophrenia and 34 age- and gender-matched healthy volunteers received diffusion tensor imaging and…

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  11. White matter abnormalities in an adult patient with l-2-hydroxyglutaric aciduria.

    PubMed

    Yamamoto, Toshiyuki; Yoshioka, Seiichiro; Tsurusaki, Yoshinori; Shino, Shimada; Shimojima, Keiko; Shigematsu, Yosuke; Takeuchi, Yoshihiro; Matsumoto, Naomichi

    2016-01-01

    l-2-Hydroxyglutaric aciduria (l-2-HGA) is a rare inborn error of metabolism. Mainly, patients with this disorder exhibit neurological symptoms and characteristic neuroradiological findings, such as subcortical white matter abnormalities, which are believed to be caused by the toxicity of the accumulation of l-2-hydroxyglutaric acid. A genotype-first approach of the whole exome sequence was used to identify compound heterozygous mutations, c.584A>G (p.Y195C) and c.772T>C (p.C258R), in L2HGDH, the gene responsible for this disorder, in an adult patient with intellectual disability and intractable epilepsy. A retrospective assay confirmed the increased concentrations of 2-hydroxyglutaric acid in the urine. These results suggested that neuroradiological findings of subcortical white matter abnormalities are characteristic of l-2-HGA and that clinical exome sequencing has sufficient power to compensate for insufficient clinical evaluations. PMID:25982940

  12. Posterior brain white matter abnormalities in older adults with probable mild cognitive impairment

    PubMed Central

    Cooley, Sarah A.; Cabeen, Ryan P.; Laidlaw, David H.; Conturo, Thomas E.; Lane, Elizabeth M.; Heaps, Jodi M.; Bolzenius, Jacob D.; Baker, Laurie M.; Salminen, Lauren E.; Scott, Staci E.; Paul, Robert H.

    2014-01-01

    Objective Much of the mild cognitive impairment (MCI) neuroimaging literature has exclusively focused on regions associated with Alzheimer’s disease. Little research has examined white matter abnormalities of other brain regions, including those associated with visual processing, despite evidence that other brain abnormalities appear in these regions in early disease stages. Method Diffusion tensor imaging (DTI) was utilized to examine participants (n = 44) that completed baseline imaging as part of a longitudinal healthy aging study. Participants were divided into two groups based on scores from the Montreal Cognitive Assessment (MoCA), a brief screening tool for MCI. Participants who scored < 26 were defined as “probable MCI” while those who scored ≥ 26 were labled cognitively healthy. Two DTI indices were analyzed including fractional anisotropy (FA) and mean diffusivity (MD). DTI values for white matter in the lingual gyrus, cuneus, pericalcarine, fusiform gyrus and all four lobes were compared using MANOVA. Regression analyses examined the relationship between DTI indices and total MoCA score. Results Results revealed significantly lower FA in the probable MCI group in the cuneus, fusiform, pericalcarine and occipital lobe, and significantly higher MD in the temporal lobe. Fusiform FA and temporal lobe MD were significantly related to total MoCA score after accounting for age and education. Conclusions Results indicate that there are posterior white matter microstructural changes in individuals with probable MCI. These differences demonstrate that white matter abnormalities are evident among individuals with probable MCI in regions beyond those commonly associated with Alzheimer’s disease and anterior brain aging patterns. PMID:25523313

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2009-01-01

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

  16. 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

  17. 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. PMID:26663463

  18. Inferior frontal gyrus white matter abnormalities in obsessive-compulsive disorder.

    PubMed

    Gonçalves, Óscar F; Sousa, Sónia; Maia, Liliana; Carvalho, Sandra; Leite, Jorge; Ganho, Ana; Fernandes-Gonçalves, Ana; Frank, Brandon; Pocinho, Fernando; Carracedo, Angel; Sampaio, Adriana

    2015-06-17

    The aim of the present study is to explore obsessive-compulsive disorder (OCD)-related abnormalities in white matter connectivity in OCD for a core region associated with inhibitory control [i.e. inferior frontal gyrus (IFG)]. Fifteen patients with OCD (11 men) and 15 healthy controls (nine men) underwent diffusion tensor imaging scanning to study four diffusivity indexes of white matter integrity [fractional anisotropy, mean diffusivity (MD), axial diffusivity and radial diffusivity (RD)]. The results showed that persons with OCD manifested significantly lower fractional anisotropy levels in the bilateral IFG as well as its parcellations in the pars opercularis, pars triangularis, and pars orbitalis. Significantly higher levels of MD, RD were evident for the OCD group in the IFG as a whole as well as in the bilateral subregions of the pars triangularis and pars opercularis (for MD and RD), the right side of the pars orbitalis (for RD), and the left side of the pars triangularis and right side pars opercularis (for axial diffusivity). Overall, the results suggest significant alterations in structural connectivity, probably associated with myelination and axonal abnormalities in the IFG of OCD patients. PMID:25945482

  19. Mathematical Difficulties and White Matter Abnormalities in Subacute Pediatric Mild Traumatic Brain Injury.

    PubMed

    Van Beek, Leen; Ghesquière, Pol; Lagae, Lieven; De Smedt, Bert

    2015-10-15

    Mathematical difficulties have been documented following pediatric mild traumatic brain injury (mTBI), yet a precise characterization of these impairments and their neural correlates is currently unavailable. We aimed to characterize these impairments by comparing behavioral and neuroimaging (i.e., diffusion tensor imaging [DTI]) outcomes from children with subacute mTBI to typically-developing controls. Twenty subacute pediatric mTBI patients and 20 well-matched controls underwent cognitive assessment and DTI examination. DTI tractography was used to detect white matter abnormalities in the corpus callosum (CC) and superior and inferior longitudinal fasciculi; these tracts are involved in mathematical performance and they are often damaged after mTBI. Behavioral results revealed that children with mTBI performed significantly more poorly on rapid apprehension of small numbers of objects (or "subitizing"), processing of non-symbolic numerosities, and procedural problem solving. These group differences were explained by differences in visuospatial working memory, which suggests that the observed mathematical difficulties may be a consequence of impairments in visuospatial abilities. DTI analysis revealed subtle group differences in the CC genu and splenium (i.e., higher fractional anisotropy and lower mean and radial diffusivity in children with mTBI) but the observed white matter abnormalities of the CC were not significantly associated with the observed mathematical difficulties in the mTBI patients. PMID:25915107

  20. The role of pre-treatment white matter abnormalities in developing white matter changes following whole brain radiation: a volumetric study.

    PubMed

    Sabsevitz, David S; Bovi, Joseph A; Leo, Peter D; Laviolette, Peter S; Rand, Scott D; Mueller, Wade M; Schultz, Christopher J

    2013-09-01

    White matter injury is a known complication of whole brain radiation (WBRT). Little is known about the factors that predispose a patient to such injury. The current study used MR volumetrics to examine risk factors, in particular the influence of pre-treatment white matter health, in developing white matter change (WMC) following WBRT. Thirty-four patients with unilateral metastatic disease underwent FLAIR MRI pre-treatment and at several time points following treatment. The volume of abnormal FLAIR signal in the white matter was measured in the hemisphere contralateral to the diseased hemisphere at each time point. Analyses were restricted to the uninvolved hemisphere to allow for the measurement of WBRT effects without the potential confounding effects of the disease on imaging findings. The relationship between select pre-treatment clinical variables and the degree of WMC following treatment was examined using correlational and regression based analyses. Age when treated and volume of abnormal FLAIR prior to treatment were significantly associated with WMC following WBRT; however, pre-treatment FLAIR volume was the strongest predictor of post-treatment WMCs. Age did not add any predictive value once white matter status was considered. No significant relationships were found between biological equivalent dose and select cerebrovascular risk factors (total glucose, blood pressure, BMI) and development of WMCs. The findings from this study identify pre-treatment white matter health as an important risk factor in developing WMC following WBRT. This information can be used to make more informed decisions and counsel patients on their risk for treatment effects. PMID:23813291

  1. 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

  2. Abnormal endothelial tight junctions in active lesions and normal-appearing white matter in multiple sclerosis.

    PubMed

    Plumb, Jonnie; McQuaid, Stephen; Mirakhur, Meenakshi; Kirk, John

    2002-04-01

    Blood-brain barrier (BBB) breakdown, demonstrable in vivo by enhanced MRI is characteristic of new and expanding inflammatory lesions in relapsing-remitting and chronic progressive multiple sclerosis (MS). Subtle leakage may also occur in primary progressive MS. However, the anatomical route(s) of BBB leakage have not been demonstrated. We investigated the possible involvement of interendothelial tight junctions (TJ) by examining the expression of TJ proteins (occludin and ZO-1 ) in blood vessels in active MS lesions from 8 cases of MS and in normal-appearing white (NAWM) matter from 6 cases. Blood vessels (10-50 per frozen section) were scanned using confocal laser scanning microscopy to acquire datasets for analysis. TJ abnormalities manifested as beading, interruption, absence or diffuse cytoplasmic localization of fluorescence, or separation of junctions (putative opening) were frequent (affecting 40% of vessels) in oil-red-O-positive active plaques but less frequent in NAWM (15%), and in normal (< 2%) and neurological controls (6%). Putatively "open" junctions were seen in vessels in active lesions and in microscopically inflamed vessels in NAWM. Dual fluorescence revealed abnormal TJs in vessels with pre-mortem serum protein leakage. Abnormal or open TJs, associated with inflammation may contribute to BBB leakage in enhancing MRI lesions and may also be involved in subtle leakage in non-enhancing focal and diffuse lesions in NAWM. BBB disruption due to tight junctional pathology should be regarded as a significant form of tissue injury in MS, alongside demyelination and axonopathy. PMID:11958369

  3. 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

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

    PubMed Central

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

    2013-01-01

    The purpose of this project was to evaluate white matter degeneration and its impact on hippocampal structural connectivity in patients with amnestic mild cognitive impairment, non-amnestic mild cognitive impairment and Alzheimer’s disease. We estimated white matter fractional anisotropy, mean diffusivity and hippocampal structural connectivity in two independent cohorts. The ADNI cohort included 108 subjects [25 cognitively normal, 21 amnestic mild cognitive impairment, 47 non-amnestic mild cognitive impairment and 15 Alzheimer’s disease]. A second cohort included 34 subjects [15 cognitively normal and 19 amnestic mild cognitive impairment] recruited in Montreal. All subjects underwent clinical and neuropsychological assessment in addition to diffusion and T1 MRI. Individual fractional anisotropy and mean diffusivity maps were generated using FSL-DTIfit. In addition, hippocampal structural connectivity maps expressing the probability of connectivity between the hippocampus and cortex were generated using a pipeline based on FSL-probtrackX. Voxel-based group comparison statistics of fractional anisotropy, mean diffusivity and hippocampal structural connectivity were estimated using Tract-Based Spatial Statistics. The proportion of abnormal to total white matter volume was estimated using the total volume of the white matter skeleton. We found that in both cohorts, amnestic mild cognitive impairment patients had 27-29% white matter volume showing higher mean diffusivity but no significant fractional anisotropy abnormalities. No fractional anisotropy or mean diffusivity differences were observed between non-amnestic mild cognitive impairment patients and cognitively normal subjects. Alzheimer’s disease patients had 66.3% of normalized white matter volume with increased mean diffusivity and 54.3% of the white matter had reduced fractional anisotropy. Reduced structural connectivity was found in the hippocampal connections to temporal, inferior parietal

  5. 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…

  6. Abnormal trigeminal nerve microstructure and brain white matter in idiopathic trigeminal neuralgia.

    PubMed

    DeSouza, Danielle D; Hodaie, Mojgan; Davis, Karen D

    2014-01-01

    Idiopathic trigeminal neuralgia (TN) is classically associated with neurovascular compression (NVC) of the trigeminal nerve at the root entry zone (REZ), but NVC-induced structural alterations are not always apparent on conventional imaging. Previous studies report lower fractional anisotropy (FA) in the affected trigeminal nerves of TN patients using diffusion tensor imaging (DTI). However, it is not known if TN patients have trigeminal nerve abnormalities of mean, radial, or axial diffusivity (MD, RD, AD - metrics linked to neuroinflammation and edema) or brain white matter (WM) abnormalities. DTI scans in 18 right-sided TN patients and 18 healthy controls were retrospectively analyzed to extract FA, RD, AD, and MD from the trigeminal nerve REZ, and Tract-Based Spatial Statistics (TBSS) was used to assess brain WM. In patients, the affected trigeminal nerve had lower FA, and higher RD, AD, and MD was found bilaterally compared to controls. Group TBSS (P<0.05, corrected) showed patients had lower FA and increased RD, MD, and AD in brain WM connecting areas involved in the sensory and cognitive-affective dimensions of pain, attention, and motor functions, including the corpus callosum, cingulum, posterior corona radiata, and superior longitudinal fasciculus. These data indicate that TN patients have abnormal tissue microstructure in their affected trigeminal nerves, and as a possible consequence, WM microstructural alterations in the brain. These findings suggest that trigeminal nerve structural abnormalities occur in TN, even if not apparent on gross imaging. Furthermore, MD and RD findings suggest that neuroinflammation and edema may contribute to TN pathophysiology. PMID:23999058

  7. Periventricular white matter abnormalities and restricted repetitive behavior in autism spectrum disorder

    PubMed Central

    Blackmon, Karen; Ben-Avi, Emma; Wang, Xiuyuan; Pardoe, Heath R.; Di Martino, Adriana; Halgren, Eric; Devinsky, Orrin; Thesen, Thomas; Kuzniecky, Ruben

    2015-01-01

    Malformations of cortical development are found at higher rates in autism spectrum disorder (ASD) than in healthy controls on postmortem neuropathological evaluation but are more variably observed on visual review of in-vivo MRI brain scans. This may be due to the visually elusive nature of many malformations on MRI. Here, we utilize a quantitative approach to determine whether a volumetric measure of heterotopic gray matter in the white matter is elevated in people with ASD, relative to typically developing controls (TDC). Data from a primary sample of 48 children/young adults with ASD and 48 age-, and gender-matched TDCs, selected from the Autism Brain Imaging Data Exchange (ABIDE) open-access database, were analyzed to compare groups on (1) blinded review of high-resolution T1-weighted research sequences; and (2) quantitative measurement of white matter hypointensity (WMH) volume calculated from the same T1-weighted scans. Groupwise WMH volume comparisons were repeated in an independent, multi-site sample (80 ASD/80 TDC), also selected from ABIDE. Visual review resulted in equivalent proportions of imaging abnormalities in the ASD and TDC group. However, quantitative analysis revealed elevated periventricular and deep subcortical WMH volumes in ASD. This finding was replicated in the independent, multi-site sample. Periventricular WMH volume was not associated with age but was associated with greater restricted repetitive behaviors on both parent-reported and clinician-rated assessment inventories. Thus, findings demonstrate that periventricular WMH volume is elevated in ASD and associated with a higher degree of repetitive behaviors and restricted interests. Although the etiology of focal WMH clusters is unknown, the absence of age effects suggests that they may reflect a static anomaly. PMID:26693400

  8. Increases in brain white matter abnormalities and subcortical gray matter are linked to CD4 recovery in HIV infection.

    PubMed

    Fennema-Notestine, Christine; Ellis, Ronald J; Archibald, Sarah L; Jernigan, Terry L; Letendre, Scott L; Notestine, Randy J; Taylor, Michael J; Theilmann, Rebecca J; Julaton, Michelle D; Croteau, David J; Wolfson, Tanya; Heaton, Robert K; Gamst, Anthony C; Franklin, Donald R; Clifford, David B; Collier, Ann C; Gelman, Benjamin B; Marra, Christina; McArthur, Justin C; McCutchan, J Allen; Morgello, Susan; Simpson, David M; Grant, Igor

    2013-08-01

    MRI alterations in the cerebral white (WM) and gray matter (GM) are common in HIV infection, even during successful combination antiretroviral therapy (CART), and their pathophysiology and clinical significance are unclear. We evaluated the association of these alterations with recovery of CD4+ T cells. Seventy-five HIV-infected (HIV+) volunteers in the CNS HIV Anti-Retroviral Therapy Effects Research study underwent brain MRI at two visits. Multi-channel morphometry yielded volumes of total cerebral WM, abnormal WM, cortical and subcortical GM, and ventricular and sulcal CSF. Multivariable linear regressions were used to predict volumetric changes with change in current CD4 and detectable HIV RNA. On average, the cohort (79 % initially on CART) demonstrated loss of total cerebral WM alongside increases in abnormal WM and ventricular volumes. A greater extent of CD4 recovery was associated with increases in abnormal WM and subcortical GM volumes. Virologic suppression was associated with increased subcortical GM volume, independent of CD4 recovery. These findings suggest a possible link between brain alterations and immune recovery, distinct from the influence of virologic suppression. The association of increasing abnormal WM and subcortical GM volumes with CD4+ T cell recovery suggests that neuroinflammation may be one mechanism in CNS pathogenesis. PMID:23838849

  9. Abnormal White Matter Blood-Oxygen-Level-Dependent Signals in Chronic Mild Traumatic Brain Injury.

    PubMed

    Astafiev, Serguei V; Shulman, Gordon L; Metcalf, Nicholas V; Rengachary, Jennifer; MacDonald, Christine L; Harrington, Deborah L; Maruta, Jun; Shimony, Joshua S; Ghajar, Jamshid; Diwakar, Mithun; Huang, Ming-Xiong; Lee, Roland R; Corbetta, Maurizio

    2015-08-15

    Concussion, or mild traumatic brain injury (mTBI), can cause persistent behavioral symptoms and cognitive impairment, but it is unclear if this condition is associated with detectable structural or functional brain changes. At two sites, chronic mTBI human subjects with persistent post-concussive symptoms (three months to five years after injury) and age- and education-matched healthy human control subjects underwent extensive neuropsychological and visual tracking eye movement tests. At one site, patients and controls also performed the visual tracking tasks while blood-oxygen-level-dependent (BOLD) signals were measured with functional magnetic resonance imaging. Although neither neuropsychological nor visual tracking measures distinguished patients from controls at the level of individual subjects, abnormal BOLD signals were reliably detected in patients. The most consistent changes were localized in white matter regions: anterior internal capsule and superior longitudinal fasciculus. In contrast, BOLD signals were normal in cortical regions, such as the frontal eye field and intraparietal sulcus, that mediate oculomotor and attention functions necessary for visual tracking. The abnormal BOLD signals accurately differentiated chronic mTBI patients from healthy controls at the single-subject level, although they did not correlate with symptoms or neuropsychological performance. We conclude that subjects with persistent post-concussive symptoms can be identified years after their TBI using fMRI and an eye movement task despite showing normal structural MRI and DTI. PMID:25758167

  10. Abnormal topological organization of the white matter network in Mandarin speakers with congenital amusia

    PubMed Central

    Zhao, Yanxin; Chen, Xizhuo; Zhong, Suyu; Cui, Zaixu; Gong, Gaolang; Dong, Qi; Nan, Yun

    2016-01-01

    Congenital amusia is a neurogenetic disorder that mainly affects the processing of musical pitch. Brain imaging evidence indicates that it is associated with abnormal structural and functional connections in the fronto-temporal region. However, a holistic understanding of the anatomical topology underlying amusia is still lacking. Here, we used probabilistic diffusion tensor imaging tractography and graph theory to examine whole brain white matter structural connectivity in 31 Mandarin-speaking amusics and 24 age- and IQ-matched controls. Amusics showed significantly reduced global connectivity, as indicated by the abnormally decreased clustering coefficient (Cp) and increased normalized shortest path length (λ) compared to the controls. Moreover, amusics exhibited enhanced nodal strength in the right inferior parietal lobule relative to controls. The co-existence of the lexical tone deficits was associated with even more deteriorated global network efficiency in amusics, as suggested by the significant correlation between the increments in normalized shortest path length (λ) and the insensitivity in lexical tone perception. Our study is the first to reveal reduced global connectivity efficiency in amusics as well as an increase in the global connectivity cost due to the co-existed lexical tone deficits. Taken together these results provide a holistic perspective on the anatomical substrates underlying congenital amusia. PMID:27211239

  11. Abnormal topological organization of the white matter network in Mandarin speakers with congenital amusia.

    PubMed

    Zhao, Yanxin; Chen, Xizhuo; Zhong, Suyu; Cui, Zaixu; Gong, Gaolang; Dong, Qi; Nan, Yun

    2016-01-01

    Congenital amusia is a neurogenetic disorder that mainly affects the processing of musical pitch. Brain imaging evidence indicates that it is associated with abnormal structural and functional connections in the fronto-temporal region. However, a holistic understanding of the anatomical topology underlying amusia is still lacking. Here, we used probabilistic diffusion tensor imaging tractography and graph theory to examine whole brain white matter structural connectivity in 31 Mandarin-speaking amusics and 24 age- and IQ-matched controls. Amusics showed significantly reduced global connectivity, as indicated by the abnormally decreased clustering coefficient (Cp) and increased normalized shortest path length (λ) compared to the controls. Moreover, amusics exhibited enhanced nodal strength in the right inferior parietal lobule relative to controls. The co-existence of the lexical tone deficits was associated with even more deteriorated global network efficiency in amusics, as suggested by the significant correlation between the increments in normalized shortest path length (λ) and the insensitivity in lexical tone perception. Our study is the first to reveal reduced global connectivity efficiency in amusics as well as an increase in the global connectivity cost due to the co-existed lexical tone deficits. Taken together these results provide a holistic perspective on the anatomical substrates underlying congenital amusia. PMID:27211239

  12. Multimodal Voxel-Based Meta-Analysis of White Matter Abnormalities in Obsessive–Compulsive Disorder

    PubMed Central

    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

    2014-01-01

    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. PMID:24407265

  13. 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

  14. White matter signal abnormality quality differentiates mild cognitive impairment that converts to Alzheimer's disease from nonconverters.

    PubMed

    Lindemer, Emily R; Salat, David H; Smith, Eric E; Nguyen, Khoa; Fischl, Bruce; Greve, Douglas N

    2015-09-01

    The objective of this study was to assess how longitudinal change in the quantity and quality of white matter signal abnormalities (WMSAs) contributes to the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). The Mahalanobis distance of WMSA from normal-appearing white matter using T1-, T2-, and proton density-weighted MRI was defined as a quality measure for WMSA. Cross-sectional analysis of WMSA volume in 104 cognitively healthy older adults, 116 individuals with MCI who converted to AD within 3 years (mild cognitive impairment converter [MCI-C]), 115 individuals with MCI that did not convert in that time (mild cognitive impairment nonconverter [MCI-NC]), and 124 individuals with AD from the Alzheimer's Disease Neuroimaging Initiative revealed that WMSA volume was substantially greater in AD relative to the other groups but did not differ between MCI-NC and MCI-C. Longitudinally, MCI-C exhibited faster WMSA quality progression but not volume compared with matched MCI-NC beginning 18 months before MCI-C conversion to AD. The strongest difference in rate of change was seen in the time period starting 6 months before MCI-C conversion to AD and ending 6 months after conversion (p < 0.001). The relatively strong effect in this time period relative to AD conversion in the MCI-C was similar to the relative rate of change in hippocampal volume, a traditional imaging marker of AD pathology. These data demonstrate changes in white matter tissue properties that occur within WMSA in individuals with MCI that will subsequently obtain a clinical diagnosis of AD within 18 months. Individuals with AD have substantially greater WMSA volume than all MCI suggesting that there is a progressive accumulation of WMSA with progressive disease severity, and that quality change predates changes in this total volume. Given the timing of the changes in WMSA tissue quality relative to the clinical diagnosis of AD, these findings suggest that WMSAs are a critical

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

    PubMed Central

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

    2015-01-01

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

  16. Improved Sensitivity to Cerebral White Matter Abnormalities in Alzheimer’s Disease with Spherical Deconvolution Based Tractography

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  18. Diffuse white matter tract abnormalities in clinically normal ageing retired athletes with a history of sports-related concussions

    PubMed Central

    Tremblay, Sebastien; Henry, Luke C.; Bedetti, Christophe; Larson-Dupuis, Camille; Gagnon, Jean-François; Evans, Alan C.; Théoret, Hugo; Lassonde, Maryse

    2014-01-01

    Sports-related concussions have been shown to lead to persistent subclinical anomalies of the motor and cognitive systems in young asymptomatic athletes. In advancing age, these latent alterations correlate with detectable motor and cognitive function decline. Until now, the interacting effects of concussions and the normal ageing process on white matter tract integrity remain unknown. Here we used a tract-based spatial statistical method to uncover potential white matter tissue damage in 15 retired athletes with a history of concussions, free of comorbid medical conditions. We also investigated potential associations between white matter integrity and declines in cognitive and motor functions. Compared to an age- and education-matched control group of 15 retired athletes without concussions, former athletes with concussions exhibited widespread white matter anomalies along many major association, interhemispheric, and projection tracts. Group contrasts revealed decreases in fractional anisotropy, as well as increases in mean and radial diffusivity measures in the concussed group. These differences were primarily apparent in fronto-parietal networks as well as in the frontal aspect of the corpus callosum. The white matter anomalies uncovered in concussed athletes were significantly associated with a decline in episodic memory and lateral ventricle expansion. Finally, the expected association between frontal white matter integrity and motor learning found in former non-concussed athletes was absent in concussed participants. Together, these results show that advancing age in retired athletes presenting with a history of sports-related concussions is linked to diffuse white matter abnormalities that are consistent with the effects of traumatic axonal injury and exacerbated demyelination. These changes in white matter integrity might explain the cognitive and motor function declines documented in this population. PMID:25186429

  19. Diffusion Tractography and Neuromotor Outcome in Very Preterm Children with White Matter Abnormalities

    PubMed Central

    Estep, Meredith E.; Smyser, Christopher D.; Anderson, Peter J.; Ortinau, Cynthia M.; Wallendorf, Michael; Katzman, Charles S.; Doyle, Lex W; Thompson, Deanne K.; Neil, Jeffery J.; Inder, Terrie E.; Shimony, Joshua S.

    2014-01-01

    Background Moderate-severe white matter abnormality (WMA) in the newborn has been shown to produce persistent disruptions in cerebral connectivity, but does not universally result in neurodevelopmental disability in very preterm (VPT) children. The aims of this hypothesis driven study were to apply diffusion imaging to: 1) examine whether bilateral WMA detected in VPT children in the newborn period can predict microstructural organization at age 7; 2) compare corticospinal tract (CST) and corpus callosum (CC) measures in VPT children at age 7 with neonatal WMA with normal versus impaired motor functioning. Methods Diffusion parameters of the CST and CC were compared between VPT 7-year-olds with (n=20) and without (n=42) bilateral WMA detected in the newborn period. For those with WMA, diffusion parameters were further examined. Results Microstructural organization of CST and CC tracts at age 7 years were altered in VPT children with moderate-severe WMA detected at term equivalent age compared to those without injury. Furthermore, diffusion parameters differed in the CC for children with WMA categorized by motor outcome (N=8). Conclusions WMA on conventional MRI at term equivalent age is associated with altered microstructural organization of the CST and CC at 7 years of age. PMID:24713814

  20. Abnormal white matter structural networks characterize heroin-dependent individuals: a network analysis.

    PubMed

    Zhang, Ruibin; Jiang, Guihua; Tian, Junzhang; Qiu, Yingwei; Wen, Xue; Zalesky, Andrew; Li, Meng; Ma, Xiaofen; Wang, Junjing; Li, Shumei; Wang, Tianyue; Li, Changhong; Huang, Ruiwang

    2016-05-01

    Neuroimaging studies suggested that drug addiction is linked to abnormal brain functional connectivity. However, little is known about the alteration of brain white matter (WM) connectivity in addictive drug users and nearly no study has been performed to examine the alterations of brain WM connectivity in heroin-dependent individuals (HDIs). Diffusion tensor imaging (DTI) offers a comprehensive technique to map the whole brain WM connectivity in vivo. In this study, we acquired DTI datasets from 20 HDIs and 18 healthy controls and constructed their brain WM structural networks using a deterministic fibre tracking approach. Using graph theoretical analysis, we explored the global and nodal topological parameters of brain network for both groups and adopted a network-based statistic (NBS) approach to assess between-group differences in inter-regional WM connections. Statistical analysis indicated the global efficiency and network strength were significantly increased, but the characteristic path length was significantly decreased in the HDIs compared with the controls. We also found that in the HDIs, the nodal efficiency was significantly increased in the left prefrontal cortex, bilateral orbital frontal cortices and left anterior cingulate gyrus. Moreover, the NBS analysis revealed that in the HDIs, the significant increased connections were located in the paralimbic, orbitofrontal, prefrontal and temporal regions. Our results may reflect the disruption of whole brain WM structural networks in the HDIs. Our findings suggest that mapping brain WM structural network may be helpful for better understanding the neuromechanism of heroin addiction. PMID:25740690

  1. White matter microstructure abnormalities and executive function in adolescents with prenatal cocaine exposure

    PubMed Central

    Lebel, Catherine; Warner, Tamara; Colby, John; Soderberg, Lindsay; Roussotte, Florence; Behnke, Marylou; Davis Eyler, Fonda; Sowell, Elizabeth R.

    2013-01-01

    Children with prenatal exposure to cocaine are at higher risk for negative behavioral function and attention difficulties, and have demonstrated brain diffusion abnormalities in frontal white matter regions. However, brain regions beyond frontal and callosal areas have not been investigated using diffusion tensor imaging (DTI). DTI data were collected on 42 youth aged 14–16 years; subjects were divided into three groups based on detailed exposure histories: those with prenatal exposure to cocaine but not alcohol (PCE, n=12), prenatal exposure to cocaine and alcohol (CAE, n=17), and controls (n=13). Tractography was performed and along-tract diffusion parameters were examined for group differences and correlations with executive function measures. In the right arcuate fasciculus and cingulum, the CAE group had higher fractional anisotropy (FA) and/or lower mean diffusivity (MD) than the other two groups. The PCE group demonstrated lower FA in the right arcuate and higher MD in the splenium of the corpus callosum than controls. Diffusion parameters in tracts with group differences correlated with measures of executive function. In conclusion, these diffusion differences in adolescents with prenatal cocaine exposure suggest localized, long-term structural brain alterations that may underlie attention and response inhibition difficulties. PMID:23769420

  2. White matter abnormalities are associated with chronic postconcussion symptoms in blast-related mild traumatic brain injury.

    PubMed

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

    2016-01-01

    Blast-related mild traumatic brain injury (mTBI) is a common injury among Iraq and Afghanistan military veterans due to the frequent use of improvised explosive devices. A significant minority of individuals with mTBI report chronic postconcussion symptoms (PCS), which include physical, emotional, and cognitive complaints. However, chronic PCS are nonspecific and are also associated with mental health disorders such as posttraumatic stress disorder (PTSD). Identifying the mechanisms that contribute to chronic PCS is particularly challenging in blast-related mTBI, where the incidence of comorbid PTSD is high. In this study, we examined whether blast-related mTBI is associated with diffuse white matter changes, and whether these neural changes are associated with chronic PCS. Ninety Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans were assigned to one of three groups including a blast-exposed no--TBI group, a blast-related mTBI without loss of consciousness (LOC) group (mTBI--LOC), and a blast-related mTBI with LOC group (mTBI + LOC). PCS were measured with the Rivermead Postconcussion Questionnaire. Results showed that participants in the mTBI + LOC group had more spatially heterogeneous white matter abnormalities than those in the no--TBI group. These white matter abnormalities were significantly associated with physical PCS severity even after accounting for PTSD symptoms, but not with cognitive or emotional PCS severity. A mediation analysis revealed that mTBI + LOC significantly influenced physical PCS severity through its effect on white matter integrity. These results suggest that white matter abnormalities are associated with chronic PCS independent of PTSD symptom severity and that these abnormalities are an important mechanism explaining the relationship between mTBI and chronic physical PCS. PMID:26497829

  3. 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

  4. Abnormal white matter microstructure in schizophrenia: a voxelwise analysis of axial and radial diffusivity.

    PubMed

    Seal, Marc L; Yücel, Murat; Fornito, Alex; Wood, Stephen J; Harrison, Ben J; Walterfang, Mark; Pell, Gaby S; Pantelis, Christos

    2008-04-01

    Diffusion Tensor Imaging (DTI) investigations in schizophrenia have provided evidence of impairment in white matter as indicated by reduced fractional anisotropy (FA). However, the neuropathological implications of these findings remain unclear. In the current study, we conducted a voxelwise analysis of the constituent parameters of FA, Axial (lambda(||)) and Radial Diffusivity (lambda( upper left and right quadrants)), in 14 male participants with schizophrenia and 14 age, gender, education, and premorbid intelligence matched healthy controls. Significantly reduced FA and higher Radial Diffusivity were concurrently observed in several major white matter tracts in the schizophrenia group. This finding suggests that the loss of white matter integrity in schizophrenia is the result of demyelination and/or changes to the axonal cytoskeleton rather than gross axonal damage. PMID:18262770

  5. 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

    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

  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. PMID:26620714

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

    PubMed Central

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

    2010-01-01

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

  8. Persistent homological sparse network approach to detecting white matter abnormality in maltreated children: MRI and DTI multimodal study.

    PubMed

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

    2013-01-01

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

  9. Brain metabolite concentrations are associated with illness severity scores and white matter abnormalities in very preterm infants

    PubMed Central

    Card, Dallas; Nossin-Manor, Revital; Moore, Aideen M.; Raybaud, Charles; Sled, John G.; Taylor, Margot J.

    2016-01-01

    Background Magnetic resonance spectroscopy allows for the noninvasive study of brain metabolism and therefore may provide useful information about brain injuries. We examined the associations of brain metabolite ratios in very preterm infants with white matter lesions and overall health status at birth. Methods Spectroscopy data were obtained from 99 very preterm infants (born ≤32wk gestation) imaged shortly after birth and from 67 of these infants at term-equivalent age. These data were processed using LC Model. Multiple regression was used to examine the association of metabolite ratios with focal non cystic white matter lesions visible on conventional magnetic resonance imaging (MRI) and with at-birth illness severity scores. Results Within 2wk of birth, the ratio of N-acetylaspartate + N-acetylaspartylglutamate to creatine + phosphocreatine was significantly lower in those infants showing white matter abnormalities on conventional MRI. Increased lactate to creatine + phosphocreatine and lactate to glycerophosphocholine + phosphocholine ratios were significantly associated with increasing severity of Clinical Risk Index for Babies II and Apgar scores taken at 1 and 5min after birth. Conclusion Both overall health status at birth and white matter injury in preterm neonates are reflected in metabolite ratios measured shortly after birth. Long-term follow-up will provide additional insight into the prognostic value of these measures. PMID:23575877

  10. Subcortical white matter abnormalities related to drug resistance in Wilson disease.

    PubMed

    Aikath, D; Gupta, A; Chattopadhyay, I; Hashmi, M A; Gangopadhyay, P K; Das, S K; Ray, K

    2006-09-12

    Wilson disease (WD) produces typical lesions in the brain, which can aid in diagnosis and therapy. The authors present a drug-resistant WD case with atypical cerebral lesions with marked involvement of white matter as visualized on MRI scans. The diagnosis was confirmed by identification of mutations in the ATP7B gene. The case demonstrates an uncommon pathology-related cerebral copper accumulation and emphasizes the importance of genetic screening in the diagnosis of WD. PMID:16966556

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

    PubMed

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

    2016-02-01

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

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

    PubMed Central

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

    2016-01-01

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

  13. Jugular venous reflux and white matter abnormalities in Alzheimer's disease: a pilot study.

    PubMed

    Chung, Chih-Ping; Beggs, Clive; Wang, Pei-Ning; Bergsland, Niels; Shepherd, Simon; Cheng, Chun-Yu; Ramasamy, Deepa P; Dwyer, Michael G; Hu, Han-Hwa; Zivadinov, Robert

    2014-01-01

    To determine whether jugular venous reflux (JVR) is associated with cerebral white matter changes (WMCs) in individuals with Alzheimer's disease (AD), we studied 12 AD patients 24 mild cognitive impairment (MCI) patients, and 17 elderly age- and gender-matched controls. Duplex ultrasonography and 1.5T MRI scanning was applied to quantify cerebral WMCs [T2 white matter (WM) lesion and dirty-appearing-white-matter (DAWM)]. Subjects with severe JVR had more frequently hypertension (p = 0.044), more severe WMC, including increased total (p = 0.047) and periventricular DAWM volumes (p = 0.008), and a trend for increased cerebrospinal fluid volumes (p = 0.067) compared with the other groups. A significantly decreased (65.8%) periventricular DAWM volume (p = 0.01) in the JVR-positive AD individuals compared with their JVR-negative counterparts was detected. There was a trend for increased periventricular and subcortical T2 WMC lesion volumes in the JVR-positive AD individuals compared with their JVR-negative counterparts (p = 0.073). This phenomenon was not observed in either the control or MCI groups. In multiple regression analysis, the increased periventricular WMC lesion volume and decreased DAWM volume resulted in 85.7% sensitivity and 80% specificity for distinguishing between JVR-positive and JVR-negative AD patients. These JVR-WMC association patterns were not seen in the control and MCI groups. Therefore, this pilot study suggests that there may be an association between JVR and WMCs in AD patients, implying that cerebral venous outflow impairment might play a role in the dynamics of WMCs formation in AD patients, particularly in the periventricular regions. Further longitudinal studies are needed to confirm and validate our findings. PMID:24217278

  14. Symmetric bilateral caudate, hippocampal, cerebellar, and subcortical white matter MRI abnormalities in an adult patient with heat stroke

    PubMed Central

    Schucany, William G.

    2008-01-01

    Heat stroke is the end result of excess heat stress and results in multiorgan dysfunction with a propensity for central nervous system (CNS) injury. Damage to the CNS appears to be the result of multiple mechanisms, including direct heat damage and the initiation of a sepsis-type syndrome. Only a few scattered case reports exist in the literature that document CNS damage via imaging. We present a case with symmetric bilateral magnetic resonance findings in the caudate nuclei, subcortical white matter, hippocampi, and cerebellum. To our knowledge, this is the first case to report symmetric bilateral caudate abnormality and bilateral hippocampal enhancement. PMID:18982090

  15. Gray and white matter volume abnormalities in generalized anxiety disorder by categorical and dimensional characterization.

    PubMed

    Hilbert, Kevin; Pine, Daniel S; Muehlhan, Markus; Lueken, Ulrike; Steudte-Schmiedgen, Susann; Beesdo-Baum, Katja

    2015-12-30

    Increasing efforts have been made to investigate the underlying pathophysiology of generalized anxiety disorder (GAD), but only limited consistent information is available on gray (GM) and white matter (WM) volume changes in affected adults. Additionally, few studies employed dimensional approaches to GAD pathology. This study compares structural brain imaging data from n=19 GAD subjects and n=24 healthy comparison (HC) subjects, all medication-free and matched on age, sex and education. Separate categorical and dimensional models were employed using voxel-based morphometry for GM and WM. Significantly higher GM volumes were found in GAD subjects mainly in basal ganglia structures and less consistently in the superior temporal pole. For WM, GAD subjects showed significantly lower volumes in the dlPFC. Largely consistent findings in dimensional and categorical models point toward these structural alterations being reliable and of importance for GAD. While lower volume in the dlPFC could reflect impaired emotional processing and control over worry in GAD, basal ganglia alterations may be linked to disturbed gain and loss anticipation as implicated in previous functional GAD studies. As perturbations in anticipation processes are central to GAD, these areas may warrant greater attention in future studies. PMID:26490569

  16. Comparison of positron emission tomography, cognition, and brain volume in Alzheimer's disease with and without severe abnormalities of white matter.

    PubMed Central

    DeCarli, C; Grady, C L; Clark, C M; Katz, D A; Brady, D R; Murphy, D G; Haxby, J V; Salerno, J A; Gillette, J A; Gonzalez-Aviles, A; Rapoport, S I

    1996-01-01

    OBJECTIVES--To examine cerebral metabolism, cognitive performance, and brain volumes in healthy controls and two groups of patients with probable Alzheimer's disease, one group with severe abnormalities of white matter (DAT+) and the other group with none, or minimal abnormalities (DAT-). METHODS--Neuropsychological tests, CT, MRI, quantitative MRI, and PET studies were carried out to allow comparison between the DAT+ and DAT- groups and the healthy controls. RESULTS--Compared with the healthy controls, both demented groups had significantly reduced global and regional cerebral metabolism, significant brain atrophy, and significantly lower scores on neuropsychological testing. The DAT- patient group showed a pattern of parietal-temporal cerebral metabolic reductions and neuropsychological performance deficits typical of Alzheimer's disease. In addition, metabolism in the association neocortex (AD ratio) and measures of neuropsychological task performance were significantly correlated in the DAT- patient group. Comparison of DAT+ with DAT- patients showed a significantly higher ratio of parietal to whole brain glucose utilisation for the DAT+ group. Moreover, when comparing group z score differences from the healthy controls, the DAT+ group had, on average, smaller differences from controls in the frontal, parietal, and temporal regions than did the DAT- group. Discriminant analysis using metabolic ratios of the frontal, parietal, and temporal regions showed cerebral metabolic patterns to be significantly different among the DAT+, the DAT-, and the healthy controls. These differences were due primarily to relatively higher frontal, parietal, and temporal metabolic ratios in the DAT+ group which resulted in discriminant scores for the DAT+ group between the healthy controls and the DAT- group. Group mean scores on tests of neuropsychological performance were not significantly different between the DAT- and DAT+ patients. By contrast with the DAT- group, however, no

  17. Abnormal functional connectivity density in patients with ischemic white matter lesions: An observational study.

    PubMed

    Ding, Ju-Rong; Ding, Xin; Hua, Bo; Xiong, Xingzhong; Wang, Qingsong; Chen, Huafu

    2016-09-01

    White matter lesions (WMLs) are frequently detected in elderly people. Previous structural and functional studies have demonstrated that WMLs are associated with cognitive and motor decline. However, the underlying mechanism of how WMLs lead to cognitive decline and motor disturbance remains unclear. We used functional connectivity density mapping (FCDM) to investigate changes in brain functional connectivity in 16 patients with ischemic WMLs and 13 controls. Both short- and long-range FCD maps were computed, and group comparisons were performed between the 2 groups. A correlation analysis was further performed between regions with altered FCD and cognitive test scores (Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]) in the patient group. We found that patients with ischemic WMLs showed reduced short-range FCD in the temporal cortex, primary motor cortex, and subcortical region, which may account for inadequate top-down attention, impaired motor, memory, and executive function associated with WMLs. The positive correlation between primary motor cortex and MoCA scores may provide evidence for the influences of cognitive function on behavioral performance. The inferior parietal cortex exhibited increased short-range FCD, reflecting a hyper bottom-up attention to compensate for the inadequate top-down attention for language comprehension and information retrieval in patients with WMLs. Moreover, the prefrontal and primary motor cortex showed increased long-range FCD and the former positively correlated with MoCA scores, which may suggest a strategy of cortical functional reorganization to compensate for motor and executive deficits. Our findings provide new insights into how WMLs cause cognitive and motor decline from cortical functional connectivity perspective. PMID:27603353

  18. Abnormalities of white matter integrity in the corpus callosum of adolescents with PTSD after childhood sexual abuse: a DTI study.

    PubMed

    Rinne-Albers, Mirjam A W; van der Werff, Steven J A; van Hoof, Marie-José; van Lang, Natasja D; Lamers-Winkelman, Francien; Rombouts, Serge A; Vermeiren, Robert R J M; van der Wee, Nic J A

    2016-08-01

    This study seeks to determine whether white matter integrity in the brain differs between adolescents with post-traumatic stress disorder (PTSD) due to childhood sexual abuse (CSA) and matched healthy adolescents and whether there is a relationship between white matter integrity and symptom severity in the patient group. Using 3T diffusion tensor imaging, we examined fractional anisotropy (FA) in a group of adolescents with CSA-related PTSD (n = 20) and matched healthy controls (n = 20), in a region of interest consisting of the bilateral uncinate fasciculus (UF), the genu, splenium and body of the corpus callosum (CC), and the bilateral cingulum. In addition, we performed an exploratory whole brain analysis. Trauma symptomatology was measured with the Trauma Symptom Checklist for Children (TSCC) to enable correlational analyses between FA differences and trauma symptomatology. The PTSD group had significantly lower FA values in the genu, midbody and splenium of the CC in comparison with controls (p < 0.05, tfce corrected). Post hoc analyses of the eigenvalues of the DTI scan showed increased radial and mean diffusivity in the patient group. In addition, we found a significant negative correlation between scores on the anger subscale of the TSCC and FA values in the left body of the CC in patients (p < 0.05). Adolescents with CSA-related PTSD show decreased FA in the CC, with abnormalities in the integrity of the left body of the CC being related to anger symptoms. These findings suggest that early trauma exposure affects the development of the CC, which may play a role in the pathophysiology of PTSD in adolescents. PMID:26700102

  19. White Matter Signal Abnormalities in Children with suspected HIV-Related Neurologic Disease on Early Combination Antiretroviral Therapy

    PubMed Central

    Ackermann, Christelle; Andronikou, Savvas; Laughton, Barbara; Kidd, Martin; Dobbels, Els; Innes, Steve; van Toorn, Ronald; Cotton, Mark

    2014-01-01

    BACKGROUND The natural history and manifestation of HIV-related neurological disease have been ameliorated by combination antiretroviral therapy (ART). We describe the characteristics of white matter signal abnormalities (WMSA) on magnetic resonance imaging (MRI) in children with HIV-related neurological disease. METHODS We reviewed MRI scans of children with suspected HIV-related neurological disease despite early ART, and correlated with clinical, neurodevelopmental data, virological markers and time on ART. These children were also on the Children with HIV Early Antiretroviral (CHER) trial. RESULTS MRI scans were performed at a mean age 31.9 months (range 8-54) on 44 children: 10 on deferred and 34 on early treatment arms, commencing ART at mean age of 18.5 and 8 weeks respectively. Multiple high signal intensity lesions on T2 /FLAIR were documented in 22 patients (50%), predominantly in frontal (91%) and parietal (82%) white matter. No differences in neurodevelopmental scores comparing children with and without WMSA were found. Neither lesion load nor distribution showed significant correlation with neurodevelopmental scores or neurological examination. Normal head growth was more common in the WMSA group (p=0.01). There was a trend for association of WMSA and longer time on ART (p=0.13) and nadir CD4% (p=0.08). CONCLUSION Half of children referred with HIV-related brain disease had WMSA on T2/FLAIR. Our findings of the association with normal head growth and duration of ART require further study. We suspect that WMSA can occur early and that initiating ART by 8 weeks of life may be too late to prevent HIV from entering the CNS. PMID:24595047

  20. Abnormal white matter integrity in antipsychotic-naïve first-episode psychosis patients assessed by a DTI principal component analysis

    PubMed Central

    Alvarado-Alanis, Patricia; León-Ortiz, Pablo; Reyes-Madrigal, Francisco; Favila, Rafael; Rodríguez-Mayoral, Oscar; Nicolini, Humberto; Azcárraga, Mariana; Graff-Guerrero, Ariel; Rowland, Laura M.; de la Fuente-Sandoval, Camilo

    2015-01-01

    Introduction Diffusion tensor imaging (DTI) studies in patients with schizophrenia have shown abnormalities in the microstructure of white matter tracts. Specifically, reduced fractional anisotropy (FA) has been described across multiple white matter tracts, in studies that have mainly included patients treated with antipsychotic medications. Objective To compare FA in antipsychotic-naïve patients experiencing a first episode of psychosis (FEP) to FA in healthy controls to demonstrate that the variance of FA can be grouped, in a coincidental manner, in four predetermined factors in accordance with a theoretical partition of the white matter tracts, using a principal components analysis (PCA). Methods Thirty-five antipsychotic-naïve FEP patients and 35 age- and gender-matched healthy controls underwent DTI at 3T. Analysis was performed using a tract-based spatial statistics (TBSS) method and exploratory PCA. Results DTI analysis showed extensive FA reduction in white matter tracts in FEP patients compared with the control group. The PCA grouped the white matter tracts into four factors explaining 66% of the total variance. Comparison of the FA values within each factor highlighted the differences between FEP patients and controls. Discussion Our study confirms extensive white matter tracts anomalies in patients with schizophrenia, more specifically, in drug-naïve FEP patients. The results also indicate that a small number of white matter tracts share common FA anomalies that relate to deficit symptoms in FEP patients. Our study adds to a growing body of literature emphasizing the need for treatments targeting white matter function and structure in FEP patients. PMID:25620120

  1. White Matter Abnormalities Track Disease Progression in PSEN1 Autosomal Dominant Alzheimer's Disease.

    PubMed

    Sánchez-Valle, Raquel; Monté, Gemma C; Sala-Llonch, Roser; Bosch, Beatriz; Fortea, Juan; Lladó, Albert; Antonell, Anna; Balasa, Mircea; Bargalló, Nuria; Molinuevo, José Luis

    2016-02-20

    PSEN1 mutations are the most frequent cause of autosomal dominant Alzheimer's disease (ADAD), and show nearly full penetrance. There is presently increasing interest in the study of biomarkers that track disease progression in order to test therapeutic interventions in ADAD. We used white mater (WM) volumetric characteristics and diffusion tensor imaging (DTI) metrics to investigate correlations with the normalized time to expected symptoms onset (relative age ratio) and group differences in a cohort of 36 subjects from PSEN1 ADAD families: 22 mutation carriers, 10 symptomatic (SMC) and 12 asymptomatic (AMC), and 14 non-carriers (NC). Subjects underwent a 3T MRI. WM morphometric data and DTI metrics were analyzed. We found that PSEN1 MC showed significant negative correlation between fractional anisotropy (FA) and the relative age ratio in the genus and body of corpus callosum and corona radiate (p <  0.05 Family-wise error correction (FWE) at cluster level) and positive correlation with mean diffusivity (MD), axial diffusivity (AxD), and radial diffusivity (RD) in the splenium of corpus callosum. SMC presented WM volume loss, reduced FA and increased MD, AxD, and RD in the anterior and posterior corona radiate, corpus callosum (p <  0.05 FWE) compared with NC. No significant differences were observed between AMC and NC in WM volume or DTI measures. These findings suggest that the integrity of the WM deteriorates linearly in PSEN1 ADAD from the early phases of the disease; thus DTI metrics might be useful to monitor the disease progression. However, the lack of significant alterations at the preclinical stages suggests that these indexes might not be good candidates for early markers of the disease. PMID:26923015

  2. 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

  3. Hyperhomocysteinemia and MTHFR Polymorphisms as Antenatal Risk Factors of White Matter Abnormalities in Two Cohorts of Late Preterm and Full Term Newborns

    PubMed Central

    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. PMID:25829992

  4. Abnormal blood–brain barrier permeability in normal appearing white matter in multiple sclerosis investigated by MRI☆☆☆

    PubMed Central

    Cramer, S.P.; Simonsen, H.; Frederiksen, J.L.; Rostrup, E.; Larsson, H.B.W.

    2013-01-01

    Objectives To investigate whether blood–brain barrier (BBB) permeability is disrupted in normal appearing white matter in MS patients, when compared to healthy controls and whether it is correlated with MS clinical characteristics. Methods Dynamic contrast-enhanced MRI was used to measure BBB permeability in 27 patients with MS and compared to 24 matched healthy controls. Results Permeability measured as Ktrans was significantly higher in periventricular normal appearing white matter (NAWM) and thalamic gray matter in MS patients when compared to healthy controls, with periventricular NAWM showing the most pronounced difference. Recent relapse coincided with significantly higher permeability in periventricular NAWM, thalamic gray matter, and MS lesions. Immunomodulatory treatment and recent relapse were significant predictors of permeability in MS lesions and periventricular NAWM. Our results suggest that after an MS relapse permeability gradually decreases, possibly an effect of immunomodulatory treatment. Conclusions Our results emphasize the importance of BBB pathology in MS, which we find to be most prominent in the periventricular NAWM, an area prone to development of MS lesions. Both the facts that recent relapse appears to cause widespread BBB disruption and that immunomodulatory treatment seems to attenuate this effect indicate that BBB permeability is intricately linked to the presence of MS relapse activity. This may reveal further insights into the pathophysiology of MS. PMID:24371801

  5. Density abnormalities in normal-appearing gray matter in the middle-aged brain with white matter hyperintense lesions: a DARTEL-enhanced voxel-based morphometry study

    PubMed Central

    Peng, Yan; Li, Shenhong; Zhuang, Ying; Liu, Xiaojia; Wu, Lin; Gong, Honghan; Liu, Dewu; Zhou, Fuqing

    2016-01-01

    Background and purpose Little is known about the structural alterations within gray matter (GM) in middle-aged subjects with white matter hyperintense (WMH) lesions. Here, we aimed to examine the anatomical changes within the GM and their relationship to WMH lesion loads in middle-aged subjects. Participants and methods Twenty-three middle-aged subjects with WMH lesions (WMH group) and 23 demographically matched healthy control subjects participated in the study. A Diffeomorphic Anatomical Registration Through Exponentiated Liealgebra-enhanced voxel-based morphometry was used to measure the GM density, and the correlations between WMH lesion volume and extracted GM values in abnormal regions were identified by voxel-based morphometry analysis. Results Compared with the healthy control subjects, the WMH group had a significantly decreased GM density in the left middle frontal gyrus, bilateral anterior cingulate cortex, left and right premotor cortex, and left and right middle cingulate cortex and an increased GM density in the bilateral cerebellum anterior lobe, left middle temporal gyrus, right temporoparietal junction, left and right prefrontal cortex (PFC), and left inferior parietal lobule. A relationship was observed between the normalized WMH lesion volume and the decreased GM density, including the left middle frontal gyrus (ρ=−0.629, P=0.002), bilateral anterior cingulate cortex (ρ=−0.507, P=0.019), right middle cingulate cortex (ρ=−0.484, P=0.026), and right premotor cortex (ρ=−0.438, P=0.047). The WMH lesion loads also negatively correlated with increased GM density in the right temporoparietal junction (ρ=−0.484, P=0.026), left PFC (ρ=−0.469, P=0.032), and right PFC (ρ=−0.438, P=0.047). Conclusion We observed that lesion load-associated structural plasticity corresponds to bidirectional changes in regional GM density in the WMH group. PMID:27274211

  6. 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. PMID:27142715

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2010-07-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2013-11-01

    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 14years 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

  11. White Matter Abnormalities and Dystonic Motor Disorder Associated with Mutations in the "SLC16A2" Gene

    ERIC Educational Resources Information Center

    Gika, Artemis D.; Siddiqui, Ata; Hulse, Anthony J.; Edward, Selvakumari; Fallon, Penny; McEntagart, Meriel E.; Jan, Wajanat; Josifova, Dragana; Lerman-Sagie, Tally; Drummond, James; Thompson, Edward; Refetoff, Samuel; Bonnemann, Carsten G.; Jungbluth, Heinz

    2010-01-01

    Aim: Mutations in the "SLC16A2" gene have been implicated in Allan-Herndon-Dudley syndrome (AHDS), an X-linked learning disability syndrome associated with thyroid function test (TFT) abnormalities. Delayed myelination is a non-specific finding in individuals with learning disability whose genetic basis is often uncertain. The aim of this study…

  12. 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 ...

  13. White Matter Abnormalities in Patients with Focal Cortical Dysplasia Revealed by Diffusion Tensor Imaging Analysis in a Voxelwise Approach

    PubMed Central

    Fonseca, Viviane de Carvalho; Yasuda, Clarissa Lin; Tedeschi, Guilherme Garlipp; Betting, Luiz Eduardo; Cendes, Fernando

    2012-01-01

    Background: Diffusion tensor imaging (DTI) allows the analysis of changes in microstructure, through the quantification of the spread and direction of water molecules in tissues. We used fractional anisotropy (FA) maps to compare the integrity of WM between patients and controls. The objective of the present study was to investigate WM abnormalities in patients with frontal lobe epilepsy secondary to focal cortical dysplasia (FCD). Materials and Methods: We included 31 controls (12 women, 33.1 ± 9.6 years, mean ± SD) and 22 patients (11 women, 30.4 ± 10.0 years), recruited from our outpatient clinic. They had clinical and EEG diagnosis of frontal lobe epilepsy, secondary to FCD detected on MRI. Patients and controls underwent 3T MRI, including the DTI sequence, obtained in 32 directions and b value of 1000 s/mm2. To process the DTI we used the following softwares: MRIcroN and FSL/TBSS (tract-based spatial statistics). We used a threshold-free cluster enhancement with significance at p < 0.05, fully corrected for multiple comparisons across space. Results: Areas with FA reduction in patients were identified in both hemispheres, mainly in the frontal lobes, cingulum, and forceps minor (p = 0.014), caudate e anterior thalamic radiation (p = 0.034), superior longitudinal fasciculus (p = 0.044), uncinate fasciculus, and inferior fronto-occipital fasciculus (p = 0.042). Conclusion: Our results showed a widespread pattern of WM microstructural abnormalities extending beyond the main lesion seen on MRI (frontal lobe), which may be related to frequent seizures or to the extent of MRI-invisible portion of FCD. PMID:22855684

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

    PubMed

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

    2016-04-01

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

  15. White Matter Microstructural Abnormalities of the Cingulum Bundle in Youth with 22q11.2 Deletion Syndrome: Associations with Medication, Neuropsychological Function, and Prodromal Symptoms of Psychosis

    PubMed Central

    Kates, Wendy R.; Olszewski, Amy K.; Gnirke, Matthew H.; Kikinis, Zora; Nelson, Joshua; Antshel, Kevin M.; Fremont, Wanda; Radoeva, Petya D.; Middleton, Frank A.; Shenton, Martha E.; Coman, Ioana L.

    2014-01-01

    Background The 22q11.2 Deletion Syndrome (22q11.2DS) is regarded as an etiologically homogenous model for understanding neuroanatomic disruptions associated with a high risk for schizophrenia. This study utilized diffusion tensor imaging (DTI) to analyze white matter microstructure in individuals with 22q11.2DS. We focused on the cingulum bundle (CB), previously shown to be disrupted in patients with schizophrenia and associated with symptoms of psychosis. Methods White matter microstructure was assessed in the anterior, superior, and posterior CB using the tractography algorithm in DTIStudio. Neuropsychological function, presence of prodromal symptoms of psychosis, and medication history were assessed in all participants. Results Relative to controls, young adults with 22q11.2DS showed alterations in most DTI metrics of the CB. Alterations were associated with positive prodromal symptoms of psychosis. However, when individuals with 22q11.2DS were divided by usage of antipsychotics / mood stabilizers, the medicated and non-medicated groups differed significantly in axial diffusivity of the anterior CB and in fractional anisotropy of the superior CB. DTI metrics did not differ between the medicated group and the control group. Conclusions Results suggest that the microstructure of the CB is altered in individuals with 22q11.2DS, and that those alterations may underlie positive prodromal symptoms of psychosis. Our findings further provide preliminary evidence that antipsychotic / mood stabilizer usage may have a reparative effect on white matter microstructure in prodromal 22q11.2DS, independent of the potential effects of psychosis. Future studies of white matter pathology in individuals with 22q11.2DS should test for potential effects of medication on white matter microstructure. PMID:25066496

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

    PubMed

    White, Tonya; Schmidt, Marcus; Karatekin, Canan

    2009-11-30

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

  17. 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.

  18. Cerebral White Matter

    PubMed Central

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

    2013-01-01

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

  19. Bootstrapping white matter segmentation, Eve++

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  20. White matter dementia in CADASIL.

    PubMed

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

    1999-03-01

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

  1. Tryptophan Metabolism and White Matter Integrity in Schizophrenia.

    PubMed

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

    2016-09-01

    Schizophrenia is associated with abnormalities in the structure and functioning of white matter, but the underlying neuropathology is unclear. We hypothesized that increased tryptophan degradation in the kynurenine pathway could be associated with white matter microstructure and biochemistry, potentially contributing to white matter abnormalities in schizophrenia. To test this, fasting plasma samples were obtained from 37 schizophrenia patients and 38 healthy controls and levels of total tryptophan and its metabolite kynurenine were assessed. The ratio of kynurenine to tryptophan was used as an index of tryptophan catabolic activity in this pathway. White matter structure and function were assessed by diffusion tensor imaging (DTI) and (1)H magnetic resonance spectroscopy (MRS). Tryptophan levels were significantly lower (p<0.001), and kynurenine/tryptophan ratios were correspondingly higher (p=0.018) in patients compared with controls. In patients, lower plasma tryptophan levels corresponded to lower structural integrity (DTI fractional anisotropy) (r=0.347, p=0.038). In both patients and controls, the kynurenine/tryptophan ratio was inversely correlated with frontal white matter glutamate level (r=-0.391 and -0.350 respectively, p=0.024 and 0.036). These results provide initial evidence implicating abnormal tryptophan/kynurenine pathway activity in changes to white matter integrity and white matter glutamate in schizophrenia. PMID:27143602

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

    PubMed

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

    2014-12-01

    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

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

    PubMed Central

    White, Tonya; Schmidt, Marcus; Karatekin, Canan

    2009-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  5. White matter injury in ischemic stroke.

    PubMed

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

    2016-06-01

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

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

    PubMed Central

    Yu, Rongjun; Zhao, Liyan; Lu, Lin

    2011-01-01

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

  7. Cardiorespiratory fitness and brain volume and white matter integrity

    PubMed Central

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

    2015-01-01

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

  8. White Matter Microstructure in Idiopathic Craniocervical Dystonia

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2003-06-01

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

  10. White matter involvement in chronic musculoskeletal pain

    PubMed Central

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

    2014-01-01

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

  11. Astrocytes and Developmental White Matter Disorders

    ERIC Educational Resources Information Center

    Sen, Ellora; Levison, Steven W.

    2006-01-01

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

  12. Scalable brain network construction on white matter fibers

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

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

  13. White matter microstructure alterations in bipolar disorder

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

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

    2015-12-01

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

  16. 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.

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

    PubMed Central

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

    2013-01-01

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

  18. White matter of the brain

    MedlinePlus

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

  19. White Matter Diseases with Radiologic-Pathologic Correlation.

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2013-01-01

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

  1. Canavan Disease: A White Matter Disorder

    ERIC Educational Resources Information Center

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

    2006-01-01

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

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

    PubMed

    Maltese, Matthew R; Margulies, Susan S

    2016-11-01

    The finite element (FE) brain model is used increasingly as a design tool for developing technology to mitigate traumatic brain injury. We developed an ultra high-definition FE brain model (>4 million elements) from CT and MRI scans of a 2-month-old pre-adolescent piglet brain, and simulated rapid head rotations. Strain distributions in the thalamus, coronal radiata, corpus callosum, cerebral cortex gray matter, brainstem and cerebellum were evaluated to determine the influence of employing homogeneous brain moduli, or distinct experimentally derived gray and white matter property representations, where some white matter regions are stiffer and others less stiff than gray matter. We find that constitutive heterogeneity significantly lowers white matter deformations in all regions compared with homogeneous properties, and should be incorporated in FE model injury prediction. PMID:27123826

  3. Increased Number of White Matter Lesions in Patients with Familial Cerebral Cavernous Malformations

    PubMed Central

    Golden, Michael J.; Morrison, Leslie A.; Kim, Helen; Hart, Blaine L.

    2015-01-01

    BACKGKROUND AND PURPOSE Familial cerebral cavernous malformations, an autosomal dominant disorder, result in excess morbidity and mortality in affected patients. The disorder is most prevalent in the Southwest United States, where the affected families are most often carriers of the CCM1-KRIT1 Common Hispanic Mutation. The brain and spinal cord parenchyma in these individuals is usually affected by multiple cavernous malformations. Previous studies have shown abnormalities of endothelial cell junctions and the blood-brain barrier in cerebral cavernous malformations. Endothelial cell abnormalities have also been described in pathologic studies of white matter hyperintensities. We compared the prevalence of white matter hyperintensities in a population with known familial cerebral cavernous malformations. MATERIALS AND METHODS We examined 191 subjects with familial cerebral cavernous malformations who were enrolled into an institutional review board-approved study. All carry the same Common Hispanic Mutation in the CCM1 gene. Each subject underwent 3TMR imaging, including gradient recalled-echo, SWI, and FLAIR sequences. The number of cavernous malformations and the number of nonhemorrhagic white matter hyperintensities were counted. Subjects older than 60 yearsof age were excluded due to the high prevalence of white matter lesions in this population, and children younger than 6 were excluded due to potential sedation requirements. Logistic regression analysis was performed to determine the prevalence of abnormal white matter hyperintensities in those with familial cerebral cavernous malformations compared with healthy controls or those with sporadic cerebral cavernous malformation within the familial cerebral cavernous malformations group; it was also performed to evaluate the associations between abnormal white matter hyperintensities and age, sex, headaches, thyroid disease, diabetes, hypertension, hyperlipidemia, seizure history, or modified Rankin Scale score

  4. Diffusion imaging, white matter, and psychopathology.

    PubMed

    Thomason, Moriah E; Thompson, Paul M

    2011-01-01

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

  5. 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. PMID:26610427

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  8. Cerebral white matter deficiencies in pedophilic men.

    PubMed

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

    2008-02-01

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

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

    PubMed

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

    2016-01-01

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

  10. Automated Detection of Lupus White Matter Lesions in MRI

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-06-01

    Diffusion tensor imaging (DTI) has shown poorer microstructural white matter integrity in children with phenylketonuria (PKU), specifically decreases in mean diffusivity (MD), in comparison with healthy children. However, little research has been conducted to investigate the relationship between age and white matter integrity in this population. The present study examined group differences in the relationship between age and MD across a range of brain regions in 31 children with early- and continuously-treated PKU and 51 healthy control children. Relationships among MD, age, and group were explored using hierarchical linear regression and Pearson correlation. Results indicated a stronger age-related decrease in MD for children with PKU in comparison with healthy children in 4 of the 10 brain regions examined, suggesting that the trajectory of white matter development is abnormal in children with PKU. Further research using longitudinal methodology is needed to fully elucidate our understanding of white matter development in children with PKU. PMID:27114916

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

    PubMed Central

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

    2016-01-01

    Diffusion tensor imaging (DTI) has shown poorer microstructural white matter integrity in children with phenylketonuria (PKU), specifically decreases in mean diffusivity (MD), in comparison with healthy children. However, little research has been conducted to investigate the relationship between age and white matter integrity in this population. The present study examined group differences in the relationship between age and MD across a range of brain regions in 31 children with early- and continuously-treated PKU and 51 healthy control children. Relationships among MD, age, and group were explored using hierarchical linear regression and Pearson correlation. Results indicated a stronger age-related decrease in MD for children with PKU in comparison with healthy children in 4 of the 10 brain regions examined, suggesting that the trajectory of white matter development is abnormal in children with PKU. Further research using longitudinal methodology is needed to fully elucidate our understanding of white matter development in children with PKU. PMID:27114916

  13. 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

  14. Microglia of Prefrontal White Matter in Suicide

    PubMed Central

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

    2014-01-01

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

  15. 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

  16. White matter connectivity and Internet gaming disorder.

    PubMed

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

    2016-05-01

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

  17. Age-Related White Matter Changes

    PubMed Central

    Xiong, Yun Yun; Mok, Vincent

    2011-01-01

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

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

    PubMed Central

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

    2008-01-01

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

  19. 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…

  20. 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…

  1. White Matter Neuron Alterations in Schizophrenia and Related Disorders

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2014-01-01

    Atherosclerotic vascular disease (AVD) is endemic to the developed world, with known negative outcomes for cognition and brain health. The effects of AVD on the white matter fibers of the brain have not yet been studied using diffusion tensor imaging (DTI). This study examined differences in fractional anisotropy (FA) between AVD and healthy comparison (HC) participants, and described the regional patterns of FA in each group. AVD participants were hypothesized to have lower FA than HC participants, indicating abnormalities in white matter health or organization. 1.5 tesla diffusion tensor imaging was performed in 35 AVD and 22 HC participants. Mean FA measures were calculated for the white matter of the whole brain, as well for individual lobes. Globally and in every brain region measured except the temporal lobes, there were significant effects of group where AVD participants had lower FA values than their HC counterparts. Group differences in FA remained significant when controlled for white matter hyperintensity (WMH) volume, suggesting that FA detects white matter abnormality above and beyond what is measurable using the older WMH technique. These findings suggest a likely neural substrate underlying the changes in cognition and mood reported in atherosclerotic vascular disease patients. PMID:24144509

  3. Altered White Matter Microstructure in Adolescents and Adults with Bulimia Nervosa.

    PubMed

    He, Xiaofu; Stefan, Mihaela; Terranova, Kate; Steinglass, Joanna; Marsh, Rachel

    2016-06-01

    Previous data suggest structural and functional deficits in frontal control circuits in adolescents and adults with bulimia nervosa (BN), but less is known about the microstructure of white matter in these circuits early in the course of the disorder. Diffusion tensor imaging (DTI) data were acquired from 28 female adolescents and adults with BN and 28 age- and BMI-matched healthy female participants. Tract-based spatial statistics (TBSS) was used to detect group differences in white matter microstructure and explore the differential effects of age on white matter microstructure across groups. Significant reductions in fractional anisotropy (FA) were detected in the BN compared with healthy control group in multiple tracts including forceps minor and major, superior longitudinal, inferior fronto-occipital, and uncinate fasciculi, anterior thalamic radiation, cingulum, and corticospinal tract. FA reductions in forceps and frontotemporal tracts correlated inversely with symptom severity and Stroop interference in the BN group. These findings suggest that white matter microstructure is abnormal in BN in tracts extending through frontal and temporoparietal cortices, especially in those with the most severe symptoms. Age-related differences in both FA and RD in these tracts in BN compared with healthy individuals may represent an abnormal trajectory of white matter development that contributes to the persistence of functional impairments in self-regulation in BN. PMID:26647975

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

    PubMed

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

    2015-03-01

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

  5. 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

  6. 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. PMID:24080382

  7. MELAS with diffuse degeneration of the cerebral white matter: report of an autopsy case.

    PubMed

    Yokoyama, Teruo; Hasegawa, Kazuko; Obama, Runko; Ishihara, Tadayuki; Yagishita, Saburou

    2010-02-01

    Up to now diffuse white matter demyelination of the cerebrum has been reported in only a few cases of mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS). Here we document an autopsy case with this rare neuropathology. Most MELAS cases are diagnosed antemortem by A3243G transition of mitochondrial DNA. While cerebral damage including necrotic foci in the cerebral cortex are common findings in MELAS, prominent white matter involvement best characterizes this MELAS case. There were numerous necrotic foci, varying in size and chronological stage, in the cerebral white matter. In the areas of the white matter without necrotic foci, there was diffuse fibrillary gliosis with the loss of axons and oligodendrocytes. The gliosis was dominant in the deep white matter, sparing the U-fiber. The cerebral cortex showed diffuse cortical atrophy with few scattered necrotic foci. Distribution of the cerebral lesions does not coincide with the territory of blood supply. The vascular wall presented only slight to mild hyalinosis. We assumed a common pathogenesis to the cortical lesions and the white matter change. The pathogenesis of the present diffuse cerebral lesions may not be just secondary to circulatory disturbance but partly due to metabolic abnormality. PMID:19496942

  8. Gray, White Matter Concentration Changes and Their Correlation with Heterotopic Neurons in Temporal Lobe Epilepsy

    PubMed Central

    Tae, Woo Suk; Joo, Eun Yun; Kim, Sung Tae

    2010-01-01

    Objective To identify changes in gray and white matter concentrations (GMC, WMC), and their relation to heterotopic neuron numbers in mesial temporal lobe epilepsy (mTLE). Materials and Methods The gray matter or white matter concentrations of 16 left and 15 right mTLE patients who achieved an excellent surgical outcome were compared with those of 24 healthy volunteers for the left group and with 23 healthy volunteers for the right group, by optimized voxel-based morphometry using unmodulated and modulated images. A histologic count of heterotopic neurons was obtained in the white matter of the anterior temporal lobe originating from the patients' surgical specimens. In addition, the number of heterotopic neurons were tested to determine if there was a correlation with the GMC or WMC. Results The GMCs of the left and right mTLE groups were reduced in the ipsilateral hippocampi, bilateral thalami, precentral gyri, and in the cerebellum. The WMCs were reduced in the ipsilateral white matter of the anterior temporal lobe, bilateral parahippocampal gyri, and internal capsules, but increased in the pons and bilateral precentral gyri. The heterotopic neuron counts in the left mTLE group showed a positive correlation (r = 0.819, p < 0.0001) with GMCs and a negative correlation (r = -0.839, p < 0.0001) with WMCs in the white matter of the anterior temporal lobe. Conclusion The present study shows the abnormalities of the cortico-thalamo-hippocampal network including a gray matter volume reduction in the anterior frontal lobes and an abnormality of brain tissue concentration in the pontine area. Furthermore, heterotopic neuron numbers were significantly correlated with GMC or WMC in the left white matter of anterior temporal lobe. PMID:20046492

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

    PubMed

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

    2015-02-01

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

  10. Pathologic staging of white matter lesions in adult-onset leukoencephalopathy/leukodystrophy with axonal spheroids.

    PubMed

    Alturkustani, Murad; Keith, Julia; Hazrati, Lili-Naz; Rademakers, Rosa; Ang, Lee-Cyn

    2015-03-01

    The pathologic features of adult-onset leukoencephalopathy/leukodystrophy with axonal spheroids (ALAS) are variable, and this has led to different hypotheses as to whether primarily demyelination or axonopathy may underlie this disorder. Typical ALAS pathology is rarely accompanied by focal multiple sclerosis (MS)-like plaques. In ALAS pathology accompanied by focal multiple sclerosis (MS)-like plaques cases, the pathologic features cannot be distinguished from those of progressive MS with diffusely abnormal white matter. To clarify these issues, we examined neuropathologic features in 159 representative samples from 5 ALAS cases (3 men and 2 women aged 39-61 years) and in 95 representative samples from 3 chronic MS cases (1 man and 2 women aged 50-73 years). The white matter abnormalities in ALAS cases were characterized by 3 evolving stages: 1) white matter with numerous spheroids in a background of well-myelinated fibers; 2) moderate loss of myelinated fibers with sparse to moderate number of spheroids; and 3) leukodystrophy-like pattern of confluent axonal and myelin loss. The application of this staging system suggests that myelin loss in ALAS is preceded by axonopathy. In progressive MS cases, the diffusely abnormal white matter pathology could be attributed to both primary demyelination and axonopathy. Some cases with predominant axonopathy are difficult to distinguish from cases with ALAS. PMID:25668567

  11. 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…

  12. 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…

  13. White matter lesions and intra-arterial thrombolysis.

    PubMed

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

    2012-07-01

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

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

    PubMed

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

    2016-08-30

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

  15. 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

  16. Grey matter abnormalities in social anxiety disorder: a pilot study.

    PubMed

    Syal, Supriya; Hattingh, Coenraad J; Fouché, Jean-Paul; Spottiswoode, Bruce; Carey, Paul D; Lochner, Christine; Stein, Dan J

    2012-09-01

    While a number of studies have explored the functional neuroanatomy of social anxiety disorder (SAD), data on grey matter integrity are lacking. We conducted structural MRI scans to examine the cortical thickness of grey matter in individuals with SAD. 13 unmedicated adult patients with a primary diagnosis of generalized social anxiety disorder and 13 demographically (age, gender and education) matched healthy controls underwent 3T structural magnetic resonance imaging. Cortical thickness and subcortical volumes were estimated using an automated algorithm (Freesurfer Version 4.5). Compared to controls, social anxiety disorder patients showed significant bilateral cortical thinning in the fusiform and post central regions. Additionally, right hemisphere specific thinning was found in the frontal, temporal, parietal and insular cortices of individuals with social anxiety disorder. Although uncorrected cortical grey matter volumes were significantly lower in individuals with SAD, we did not detect volumetric differences in corrected amygdala, hippocampal or cortical grey matter volumes across study groups. Structural differences in grey matter thickness between SAD patients and controls highlight the diffuse neuroanatomical networks involved in both social anxiety and social behavior. Additional work is needed to investigate the causal mechanisms involved in such structural abnormalities in SAD. PMID:22527992

  17. White matter changes mimicking a leukodystrophy in a patient with Mucopolysaccharidosis: characterization by MRI.

    PubMed

    Barone, Rita; Parano, Enrico; Trifiletti, Rosario Rich; Fiumara, Agata; Pavone, Piero

    2002-03-30

    Mucopolysaccharidosis (MPS) type I (alpha-iduronidase deficiency) is characterized by storage and massive urinary excretion of dermatan sulfate and heparan sulfate; it may be distinguished into three different subtypes based on age at onset and severity of the clinical symptoms. We report on progressive white matter involvement documented by serial MR imaging in a patient with the MPS type I, severe skeletal involvement and preserved mental capabilities (intermediate phenotype or Hurler/Scheie syndrome).The natural history of white matter abnormalities in patients with MPS is still unclear; based on the present study, it appears that degenerative changes of the white matter mimicking a leukodystrophy may mark the course of MPS type I. We also suggest that the degree of MR changes in patients with MPS does not always reflect their neurological impairment. PMID:11897250

  18. White Matter Hyperintensities and Hypobaric Exposure

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  1. 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

  2. White matter microstructure from nonparametric axon diameter distribution mapping.

    PubMed

    Benjamini, Dan; Komlosh, Michal E; Holtzclaw, Lynne A; Nevo, Uri; Basser, Peter J

    2016-07-15

    We report the development of a double diffusion encoding (DDE) MRI method to estimate and map the axon diameter distribution (ADD) within an imaging volume. A variety of biological processes, ranging from development to disease and trauma, may lead to changes in the ADD in the central and peripheral nervous systems. Unlike previously proposed methods, this ADD experimental design and estimation framework employs a more general, nonparametric approach, without a priori assumptions about the underlying form of the ADD, making it suitable to analyze abnormal tissue. In the current study, this framework was used on an ex vivo ferret spinal cord, while emphasizing the way in which the ADD can be weighted by either the number or the volume of the axons. The different weightings, which result in different spatial contrasts, were considered throughout this work. DDE data were analyzed to derive spatially resolved maps of average axon diameter, ADD variance, and extra-axonal volume fraction, along with a novel sub-micron restricted structures map. The morphological information contained in these maps was then used to segment white matter into distinct domains by using a proposed k-means clustering algorithm with spatial contiguity and left-right symmetry constraints, resulting in identifiable white matter tracks. The method was validated by comparing histological measures to the estimated ADDs using a quantitative similarity metric, resulting in good agreement. With further acquisition acceleration and experimental parameters adjustments, this ADD estimation framework could be first used preclinically, and eventually clinically, enabling a wide range of neuroimaging applications for improved understanding of neurodegenerative pathologies and assessing microstructural changes resulting from trauma. PMID:27126002

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

    PubMed Central

    Bouix, Sylvain; Kubicki, Marek

    2014-01-01

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

  4. Portal-systemic shunt encephalopathy presenting with diffuse cerebral white matter lesion: an autopsy case.

    PubMed

    Kimura, Noriyuki; Kumamoto, Toshihide; Hanaoka, Takuya; Nakamura, Kenichiro; Hazama, Yusuke; Arakawa, Ryuki

    2008-12-01

    We report herein an autopsy case of portal-systemic encephalopathy (PSE) presenting with diffuse tissue rarefaction in the cerebral deep white matter. Clinically, the patient showed recurrent episodes of unconsciousness, abnormal behavior and urinary incontinence, as well as flapping tremor. Cognitive impairment and peripheral neuropathy developed following recurrent episodes. Although conventional arterial portography revealed a small portal-systemic collateral vessel of a left gastro-renal venous shunt, abdominal CT and liver biopsy showed no evidence of liver cirrhosis and serum ammonia level showed a mild increase. T2-weighted MRI demonstrated symmetrical signal hyperintensities in the deep white matter. Neuropathological findings showed Alzheimer type II astrocytes in the deep layers of the cerebral cortices and severe tissue rarefaction with no or slight reactive astrocytosis in the subcortical and deep white matter. These white matter changes have been reported infrequently in patients with PSE. The present case suggests that chronic PSE without liver cirrhosis may develop diffuse white matter lesions. PMID:18384515

  5. Quantitative Tractography Metrics of White Matter Integrity in Diffusion-Tensor MRI

    PubMed Central

    Correia, Stephen; Lee, Stephanie Y.; Voorn, Thom; Tate, David F.; Paul, Robert H.; Zhang, Song; Salloway, Stephen P.; Malloy, Paul F.; Laidlaw, David H.

    2009-01-01

    We present new quantitative diffusion-tensor imaging (DTI) tractography-based metrics for assessing cerebral white matter integrity. These metrics extend prior work in this area. Tractography models of cerebral white matter were produced from each subject's DTI data. The models are a set of curves (e.g., “streamtubes”) derived from DTI data that represent the underlying topography of the cerebral white matter. Nine metrics were calculated in whole brain tractography models and in three “tracts-of-interest” (TOI): transcallosal fibers, and the left and right cingulum bundles. The metrics included the number of streamtubes and several metrics based on the summed length of streamtubes in including some that were weighted by scalar anisotropy metrics and normalized for estimated intracranial volume. We then tested whether patients with subcortical ischemic vascular disease (i.e., vascular cognitive impairment or VCI) vs. healthy controls (HC) differed on the metrics. The metrics were significantly lower in the VCI group in whole brain and in transcallosal TOI but not in the left or right cingulum bundles. The metrics correlated significantly with cognitive functions known to be impacted by white matter abnormalities (e.g., processing speed) but not with those more impacted by cortical disease (e.g., naming). These new metrics help bridge the gap between DTI tractography and scalar analytical methods and provide a potential means for examining group differences in white matter integrity in specific tracts-of-interest. PMID:18617421

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

    PubMed

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

    2009-01-01

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

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

    SciTech Connect

    Quencer, R.M.

    1982-09-01

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

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

    PubMed

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

    2008-06-01

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

  9. Structure-Specific Statistical Mapping of White Matter Tracts

    PubMed Central

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

    2008-01-01

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

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

    PubMed

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

    2016-09-01

    The objective of this study was to investigate the relationship between cardiorespiratory (CR) fitness and the brain's white matter tract integrity using diffusion tensor imaging (DTI) in the Alzheimer's disease (AD) population. We recruited older adults in the early stages of AD (n = 37; CDR = 0.5 and 1) and collected cross-sectional fitness and diffusion imaging data. We examined the association between CR fitness (peak oxygen consumption [VO2peak]) and fractional anisotropy (FA) in AD-related white matter tracts using two processing methodologies: a tract-of-interest approach and tract-based spatial statistic (TBSS). Subsequent diffusivity metrics (radial diffusivity [RD], mean diffusivity [MD], and axial diffusivity [A × D]) were also correlated with VO2peak. The tract-of-interest approach showed that higher VO2peak was associated with preserved white matter integrity as measured by increased FA in the right inferior fronto-occipital fasciculus (p = 0.035, r = 0.36). We did not find a significant correlation using TBSS, though there was a trend for a positive association between white matter integrity and higher VO2peak measures (p < 0.01 uncorrected). Our findings indicate that higher CR fitness levels in early AD participants may be related to preserved white matter integrity. However to draw stronger conclusions, further study on the relationship between fitness and white matter deterioration in AD is necessary. PMID:26239997

  11. Microstructural changes in white matter associated with freezing of gait in Parkinson's disease.

    PubMed

    Vercruysse, Sarah; Leunissen, Inge; Vervoort, Griet; Vandenberghe, Wim; Swinnen, Stephan; Nieuwboer, Alice

    2015-04-01

    In Parkinson's disease (PD), freezing of gait (FOG) is associated with widespread functional and structural gray matter changes throughout the brain. Previous study of freezing-related white matter changes was restricted to brainstem and cerebellar locomotor tracts. This study was undertaken to determine the spatial distribution of white matter damage associated with FOG by combining whole brain and striatofrontal seed-based diffusion tensor imaging. Diffusion-weighted images were collected in 26 PD patients and 16 age-matched controls. Parkinson's disease groups with (n = 11) and without freezing of gait (n = 15) were matched for age and disease severity. We applied tract-based spatial statistics to compare fractional anisotropy and mean diffusivity of white matter structure across the whole brain between groups. Probabilistic tractography was used to evaluate fractional anisotropy and mean diffusivity of key subcortico-cortical tracts. Tract-based spatial statistics revealed decreased fractional anisotropy in PD with FOG in bilateral cerebellar and superior longitudinal fascicle clusters. Increased mean diffusivity values were apparent in the right internal capsule, superior frontal cortex, anterior corona radiata, the left anterior thalamic radiation, and cerebellum. Tractography showed consistent white matter alterations in striatofrontal tracts through the putamen, caudate, pallidum, subthalamic nucleus, and in connections of the cerebellar peduncle with subthalamic nucleus and pedunculopontine nucleus bilaterally. We conclude that FOG is associated with diffuse white matter damage involving major cortico-cortical, corticofugal motor, and several striatofrontal tracts in addition to previously described cerebello-pontine connectivity changes. These distributed white matter abnormalities may contribute to the motor and non-motor correlates of FOG. PMID:25640958

  12. Bayesian model selection for pathological neuroimaging data applied to white matter lesion segmentation.

    PubMed

    Sudre, Carole H; Cardoso, M Jorge; Bouvy, Willem H; Biessels, Geert Jan; Barnes, Josephine; Ourselin, Sebastien

    2015-10-01

    In neuroimaging studies, pathologies can present themselves as abnormal intensity patterns. Thus, solutions for detecting abnormal intensities are currently under investigation. As each patient is unique, an unbiased and biologically plausible model of pathological data would have to be able to adapt to the subject's individual presentation. Such a model would provide the means for a better understanding of the underlying biological processes and improve one's ability to define pathologically meaningful imaging biomarkers. With this aim in mind, this work proposes a hierarchical fully unsupervised model selection framework for neuroimaging data which enables the distinction between different types of abnormal image patterns without pathological a priori knowledge. Its application on simulated and clinical data demonstrated the ability to detect abnormal intensity clusters, resulting in a competitive to improved behavior in white matter lesion segmentation when compared to three other freely-available automated methods. PMID:25850086

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

    PubMed Central

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

    2016-01-01

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

  14. Mapping White Matter Integrity in Elderly People with HIV

    PubMed Central

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

    2013-01-01

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

  15. Diffusion Tensor Imaging, White Matter lesions, the Corpus Callosum and Gait in the Elderly

    PubMed Central

    Bhadelia, Refeeque A.; Price, Lori Lyn; Tedesco, Kurtis L.; Scott, Tammy; Qiu, Wei Qiao; Patz, Samuel; Folstein, Marshal; Rosenberg, Irwin; Caplan, Louis R.; Bergethon, Peter

    2009-01-01

    Background and Purpose Gait impairment is common in the elderly, especially those with stroke and white matter hyperintensities (WMH) on conventional brain MRI. Diffusion Tensor Imaging (DTI) is more sensitive to white matter damage than conventional MRI. The relationship between DTI measures and gait has not been previously evaluated. Our purpose was to investigate the relationship between the integrity of white matter in the corpus callosum as determined by DTI and quantitative measures of gait in the elderly. Methods One hundred seventy-three participants of a community-dwelling elderly cohort had neurological and neuropsychological examinations and brain MRI. Gait function was measured by Tinetti gait (0-12), balance (0-16) and total (0-28) scores. DTI assessed Fractional Anisotropy in the genu and splenium of the corpus callosum. Conventional MRI was used to evaluate for brain infarcts and WMH volume. Results Participants with abnormal gait had low fractional anisotropy in the genu of the corpus callosum but not the splenium. Multiple regressions analyses showed an independent association between these genu abnormalities and all three Tinetti scores (p <0.001). This association remained significant after adding MRI infarcts and WMH volume to the analysis. Conclusions The independent association between quantitative measures of gait function and DTI findings shows that white matter integrity in the genu of corpus callosum is an important marker of gait in the elderly. DTI analyses of white matter tracts in brain and spinal cord may improve knowledge about the pathophysiology of gait impairment and help target clinical interventions. PMID:19797696

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

    PubMed

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

    2014-01-01

    Empathic abilities are impaired in schizophrenia. Although the pathology of schizophrenia is thought to involve disrupted white matter integrity, the relationship between empathic disabilities and altered white matter in the disorder remains unclear. The present study tested associations between empathic disabilities and white matter integrity in order to investigate the neural basis of impaired empathy in schizophrenia. Sixty-nine patients with schizophrenia and 69 age-, gender-, handedness-, education- and IQ level-matched healthy controls underwent diffusion-weighted imaging. Empathic abilities were assessed using the Interpersonal Reactivity Index (IRI). Using tract-based spatial statistics (TBSS), the associations between empathic abilities and white matter fractional anisotropy (FA), a measure of white matter integrity, were examined in the patient group within brain areas that showed a significant FA reduction compared with the controls. The patients with schizophrenia reported lower perspective taking and higher personal distress according to the IRI. The patients showed a significant FA reduction in bilateral deep white matter in the frontal, temporal, parietal and occipital lobes, a large portion of the corpus callosum, and the corona radiata. In schizophrenia patients, fantasy subscales positively correlated with FA in the left inferior fronto-occipital fasciculi and anterior thalamic radiation, and personal distress subscales negatively correlated with FA in the splenium of the corpus callosum. These results suggest that disrupted white matter integrity in these regions constitutes a pathology underpinning specific components of empathic disabilities in schizophrenia, highlighting that different aspects of empathic impairments in the disorder would have, at least partially, distinct neuropathological bases. PMID:24099786

  17. Alterations in White Matter Microstructure in Neurofibromatosis-1

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2012-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  20. 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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2010-06-23

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

  3. Evidence for White Dwarfs with Strange-Matter Cores

    NASA Astrophysics Data System (ADS)

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

    2008-09-01

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

  4. Evidence for White Dwarfs with Strange-Matter Cores

    NASA Astrophysics Data System (ADS)

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

    2006-10-01

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

  5. Analysis of white dwarfs with strange-matter cores

    NASA Astrophysics Data System (ADS)

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

    2006-06-01

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

  6. NMDA receptor antibodies associated with distinct white matter syndromes

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  8. Defective Glial Maturation in Vanishing White Matter Disease

    PubMed Central

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

    2014-01-01

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

  9. 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…

  10. Astrocytes in Oligodendrocyte Lineage Development and White Matter Pathology

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2010-01-01

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

  13. Accelerated decline in white matter integrity in clinically normal individuals at risk for Alzheimer's disease.

    PubMed

    Rieckmann, Anna; Van Dijk, Koene R A; Sperling, Reisa A; Johnson, Keith A; Buckner, Randy L; Hedden, Trey

    2016-06-01

    Prior studies have identified white matter abnormalities in Alzheimer's disease (AD). Yet, cross-sectional studies in normal older individuals show little evidence for an association between markers of AD risk (APOE4 genotype and amyloid deposition), and white matter integrity. Here, 108 normal older adults (age, 66-87) with assessments of apolipoprotein e4 (APOE4) genotype and assessment of amyloid burden by positron emission tomography underwent diffusion tensor imaging scans for measuring white matter integrity at 2 time points, on average 2.6 years apart. Linear mixed-effects models showed that amyloid burden at baseline was associated with steeper decline in fractional anisotropy in the parahippocampal cingulum (p < 0.05). This association was not significant between baseline measures suggesting that longitudinal analyses can provide novel insights that are not detectable in cross-sectional designs. Amyloid-related changes in hippocampus volume did not explain the association between amyloid burden and change in fractional anisotropy. The results suggest that accumulation of cortical amyloid and white matter changes in parahippocampal cingulum are not independent processes in individuals at increased risk for AD. PMID:27143434

  14. Chronic Post-Concussion Neurocognitive Deficits. I. Relationship with White Matter Integrity

    PubMed Central

    Maruta, Jun; Palacios, Eva M.; Zimmerman, Robert D.; Ghajar, Jamshid; Mukherjee, Pratik

    2016-01-01

    We previously identified visual tracking deficits and associated degradation of integrity in specific white matter tracts as characteristics of concussion. We re-explored these characteristics in adult patients with persistent post-concussive symptoms using independent new data acquired during 2009–2012. Thirty-two patients and 126 normal controls underwent cognitive assessments and MR-DTI. After data collection, a subset of control subjects was selected to be individually paired with patients based on gender and age. We identified patients’ cognitive deficits through pairwise comparisons between patients and matched control subjects. Within the remaining 94 normal subjects, we identified white matter tracts whose integrity correlated with metrics that indicated performance degradation in patients. We then tested for reduced integrity in these white matter tracts in patients relative to matched controls. Most patients showed no abnormality in MR images unlike the previous study. Patients’ visual tracking was generally normal. Patients’ response times in an attention task were slowed, but could not be explained as reduced integrity of white matter tracts relating to normal response timing. In the present patient cohort, we did not observe behavioral or anatomical deficits that we previously identified as characteristic of concussion. The recent cohort likely represented those with milder injury compared to the earlier cohort. The discrepancy may be explained by a change in the patient recruitment pool circa 2007 associated with an increase in public awareness of concussion. PMID:26903842

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

    PubMed

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

    2014-10-01

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

  16. Abnormal bone marrow distribution following unsuccessful hip replacement: a potential confusion on white cell scanning.

    PubMed

    Cunningham, D A

    1991-01-01

    A case is presented in which a grossly abnormal distribution of bone marrow following failed hip replacement would have led to the false diagnosis of osteomyelitis. The value of combining bone marrow scanning with indium white cell scanning in possible osteomyelitis is emphasised. PMID:2019282

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

    PubMed

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

    2014-10-01

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

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

    PubMed

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

    2010-11-01

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

  19. Snake-based brain white matter fiber reconstruction.

    PubMed

    Lu, Meng; Di, Jia

    2014-01-01

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

  20. Histological and ultrastructural analysis of white matter damage after naturally-occurring spinal cord injury.

    PubMed

    Smith, Peter M; Jeffery, Nick D

    2006-04-01

    Detailed analysis of the structural changes that follow human clinical spinal cord injury is limited by difficulties in achieving adequate tissue fixation. This study bypasses this obstacle by examining the spinal cord from paraplegic domestic animals, enabling us to document the ultrastructural changes at different times following injury. In all but one case, injury resulted from a combination of contusion and compression. There was infarction and hemorrhage, followed by gray matter destruction and the rapid development of a variety of white matter changes including axon swelling and myelin degeneration. Axons greater than 5 microm in diameter were more susceptible to degenerative changes, whereas smaller axons, particularly those in the subpial region, were relatively well preserved. Demyelinated axons were seen within 2 weeks after injury and, at later time points, both Schwann cell and oligodendrocyte remyelination was common. More subtle white matter abnormalities were identified by examining sagittal sections, including focal accumulation of organelles in the axoplasm and partial and paranodal myelin abnormalities. These observations serve to validate observations from experimental models of spinal contusion but also highlight the complexity of naturally occurring (ie, clinical) spinal injury. They also raise the possibility that focal abnormalities such as paranodal demyelination may contribute to early axonal dysfunction and possibly to progressive tissue damage. PMID:16768749

  1. White Matter Tauopathy with Globular Glial Inclusions: A Distinct Sporadic Frontotemporal Lobar Degeneration

    PubMed Central

    Kovacs, Gabor G.; Majtenyi, Katalin; Spina, Salvatore; Murrell, Jill R.; Gelpi, Ellen; Hoftberger, Romana; Fraser, Graham; Crowther, R. Anthony; Goedert, Michel; Budka, Herbert; Ghetti, Bernardino

    2009-01-01

    Frontotemporal lobar degenerations are a group of disorders characterized by circumscribed degeneration of the frontal and temporal lobes and diverse histopathological features. We report clinical, neuropathological, ultrastructural, biochemical and genetic data on seven individuals with a four-repeat (4R) tauopathy characterized by the presence of globular glial inclusions (GGIs) in brain white matter. Clinical manifestations were compatible with the behavioral variant of frontotemporal dementia (FTD) and included motor neuron symptoms; there was prominent neuronal loss in the frontal and temporal cortex, subiculum and amygdala. The surrounding white matter showed abundant GGIs composed of abnormal filaments present mostly in oligodendrocytes. The severity of white matter tau abnormalities correlated with a reduction in myelin and axons and with microglial activation. Western blotting of sarkosyl-insoluble tau demonstrated the presence of two major tau bands of 64 and 68 kDa. No mutations in the microtubule-associated protein tau (MAPT) gene were detected in two affected individuals. We propose that 4R tau-immunoreactive GGIs are the neuropathologic hallmark of a distinct sporadic tauopathy with variable clinical presentations that include FTD and occasionally upper motor neuron disease. This type of tauopathy with GGIs expands the group of neurodegenerative disorders in which oligodendroglial pathology predominates, beyond the synucleinopathy multiple system atrophy disorders. PMID:18800011

  2. 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

  3. Mechanisms of white matter change induced by meditation training

    PubMed Central

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

    2014-01-01

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

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

    SciTech Connect

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

    1994-02-01

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

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

    PubMed

    Uchihara, Toshiki; Shishido-Hara, Yukiko

    2015-04-01

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

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

    PubMed

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

    2016-01-15

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

  7. Specific white matter tissue microstructure changes associated with obesity

    PubMed Central

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

    2016-01-01

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

  8. Tissue plasminogen activator prevents white matter damage following stroke

    PubMed Central

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

    2011-01-01

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

  9. Occipital deep white matter hyperintensity as seen by MRI: 1. Clinical significance.

    PubMed

    Miyazaki, M; Hashimoto, T; Tayama, M; Kuroda, Y

    1992-05-01

    Magnetic resonance imaging was performed in 270 patients with various neurologic complaints (1-15Y) with a 0.5 tesla superconducting imaging system using a field echo T1-weighted sequence and spin echo T2-weighted and PD-weighted sequences. Twenty-seven of them had deep white matter hyperintensity (DWMH) in the occipital lobe on T2-weighted images. The frequency of mild DWMH differed in different age groups, suggesting that mild DWMH may result from delayed myelination in the central nervous system. However, the frequency of severe DWMH, which was revealed as isointense relative to cerebrospinal fluid, did not differ in different age groups and it was significantly more common in severely retarded patients. Classification of DWMH based on the signal intensity is valuable to distinguish white matter abnormalities in the occipital lobe from delayed myelination in the same site. PMID:1514653

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

    PubMed Central

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

    2014-01-01

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

  11. 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. PMID:26825902

  12. Age and Sex Effects on White Matter Tracts in Psychosis from Adolescence through Middle Adulthood.

    PubMed

    Schwehm, Andrew; Robinson, Delbert G; Gallego, Juan A; Karlsgodt, Katherine H; Ikuta, Toshikazu; Peters, Bart D; Malhotra, Anil K; Szeszko, Philip R

    2016-09-01

    There is controversy regarding specificity of white matter abnormalities in psychosis, their deviation from healthy aging, and the influence of sex on these measures. We used diffusion tensor imaging to characterize putative white matter microstructure in 224 patients with psychosis and healthy volunteers across the age range of 15-64 years. Sixty-five younger (age <30 years; 47M/18F) patients with psychosis (all experiencing a first episode of illness) and 48 older (age ⩾30 years; 30M/18F) patients were age-matched to younger and older healthy volunteer groups (N=63 (40M/23F) and N=48 (29M/19F), respectively). The trajectories of two inter-hemispheric (splenium and genu), two projection (cortico-pontine and anterior thalamic), and five bilateral association (inferior fronto-occipital, inferior longitudinal, superior longitudinal, cingulum, and uncinate) tracts were quantified using tractography to derive measures of fractional anisotropy and mean, axial, and radial diffusivity. Fractional anisotropy was significantly lower in the inferior longitudinal fasciculus and superior longitudinal fasciculus in all patients compared with all healthy volunteers, with comparable effect sizes observed in both the younger and older patients compared with their respective healthy volunteer groups. Moreover, age-associated differences in fractional anisotropy within these tracts were comparable between groups across the age span. In addition, female patients had significantly lower fractional anisotropy across all tracts compared with female controls regardless of age. Our findings demonstrate comparable putative white matter abnormalities in two independent samples of patients with psychosis and argue against their progression in patients. These data further highlight the novel and potentially underappreciated role of sex in understanding white matter dysfunction in the neurobiology of psychosis. PMID:27067129

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-06-01

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

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

    PubMed Central

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

    2016-01-01

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

  16. Genetics Home Reference: leukoencephalopathy with vanishing white matter

    MedlinePlus

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

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2016-07-01

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

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

    PubMed Central

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

    2013-01-01

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

  2. 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,…

  3. Maternal adiposity negatively influences infant brain white matter development

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

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

    2014-11-01

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

  5. 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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-01-01

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

  8. White Matter Integrity Reductions in Intermittent Explosive Disorder.

    PubMed

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

    2016-10-01

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

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

    PubMed Central

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

    2014-01-01

    The normal myelination of neuronal axons is essential to neurodevelopment, allowing fast inter-neuronal communication. The most dynamic period of myelination occurs in the first few years of life, in concert with a dramatic increase in cognitive abilities. How these processes relate, however, is still unclear. Here we aimed to use a data-driven technique to parcellate developing white matter into regions with consistent white matter growth trajectories and investigate how these regions related to cognitive development. In a large sample of 183 children aged 3 months to 4 years, we calculated whole brain myelin volume fraction (VFM) maps using quantitative multicomponent relaxometry. We used spatial independent component analysis (ICA) to blindly segment these quantitative VFM images into anatomically meaningful parcels with distinct developmental trajectories. We further investigated the relationship of these trajectories with standardized cognitive scores in the same children. The resulting components represented a mix of unilateral and bilateral white matter regions (e.g., cortico-spinal tract, genu and splenium of the corpus callosum, white matter underlying the inferior frontal gyrus) as well as structured noise (misregistration, image artifact). The trajectories of these regions were associated with individual differences in cognitive abilities. Specifically, components in white matter underlying frontal and temporal cortices showed significant relationships to expressive and receptive language abilities. Many of these relationships had a significant interaction with age, with VFM becoming more strongly associated with language skills with age. These data provide evidence for a changing coupling between developing myelin and cognitive development. Hum Brain Mapp 35:4475–4487, 2014. PMID:24578096

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

    PubMed

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

    2002-11-01

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

  11. 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

  12. Brain white matter changes during treatment of a child for acute lymphoblastic leukemia.

    PubMed

    Maeda, Miho; Hayakawa, Jun; Ueda, Takahiro; Migita, Makoto; Asano, Takeshi; Fukunaga, Yoshitaka; Amano, Yasuo

    2005-10-01

    A 13-year old boy with acute lymphoblastic leukemia had bilateral paresis of the upper extremities and aphasia 1 week after high dose methotrexate and triple intrathecal therapy (methotrexate, cytarabin, hydrocortisone). The stroke-like neurological symptoms disappeared on the third day. T2-weighted magnetic resonance imaging showed hyperintensities of white matter on the second day. Despite resolution of the neurological symptoms, magnetic resonance images were still abnormal 3 years after the attack. Methotrexate has been considered to be responsible for ischemic damage to oligodendroglial cells, resulting in demyelination. The changes are occasionally prolonged without persistent neurologic symptoms. PMID:16247223

  13. Primary Sjögren's Syndrome White Matter Changes and Cognitive Dysfunction.

    PubMed

    Dess, Mary; Heidenreich, Wayne F

    2016-01-01

    This case report describes a 52-year-old, female applicant for long term-care insurance with a history of an autoimmune connective tissue disease initially diagnosed as systemic lupus erythematosus (SLE). Over several years, the signs and symptoms evolved into a clear diagnosis of primary Sjögren's syndrome (PSS). The specific criteria for this diagnosis are reviewed including the symptoms, antinuclear antibodies (ANA), extractable nuclear antigen antibodies (ENA), abnormal salivary scintigraphy and positive Schirmer test. Symptoms of neuropathy and the possibility of a cognitive dysfunction are discussed as part of PSS. The association of white matter lesions (WML) with PSS is significant for underwriting consideration. PMID:27562110

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-04-01

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

  16. Cerebral white matter integrity during primary HIV infection

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  18. 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

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  20. Automated segmentation and measurement of global white matter lesion volume in patients with multiple sclerosis.

    PubMed

    Alfano, B; Brunetti, A; Larobina, M; Quarantelli, M; Tedeschi, E; Ciarmiello, A; Covelli, E M; Salvatore, M

    2000-12-01

    A fully automated magnetic resonance (MR) segmentation method for identification and volume measurement of demyelinated white matter has been developed. Spin-echo MR brain scans were performed in 38 patients with multiple sclerosis (MS) and in 46 healthy subjects. Segmentation of normal tissues and white matter lesions (WML) was obtained, based on their relaxation rates and proton density maps. For WML identification, additional criteria included three-dimensional (3D) lesion shape and surrounding tissue composition. Segmented images were generated, and normal brain tissues and WML volumes were obtained. Sensitivity, specificity, and reproducibility of the method were calculated, using the WML identified by two neuroradiologists as the gold standard. The average volume of "abnormal" white matter in normal subjects (false positive) was 0.11 ml (range 0-0.59 ml). In MS patients the average WML volume was 31.0 ml (range 1.1-132.5 ml), with a sensitivity of 87.3%. In the reproducibility study, the mean SD of WML volumes was 2.9 ml. The procedure appears suitable for monitoring disease changes over time. J. Magn. Reson. Imaging 2000;12:799-807. PMID:11105017

  1. SOX2+ Cell Population from Normal Human Brain White Matter Is Able to Generate Mature Oligodendrocytes

    PubMed Central

    Oliver-De La Cruz, Jorge; Carrión-Navarro, Josefa; García-Romero, Noemí; Gutiérrez-Martín, Antonio; Lázaro-Ibáñez, Elisa; Escobedo-Lucea, Carmen; Perona, Rosario; Belda-Iniesta, Cristobal; Ayuso-Sacido, Angel

    2014-01-01

    Objectives A number of neurodegenerative diseases progress with a loss of myelin, which makes them candidate diseases for the development of cell-replacement therapies based on mobilisation or isolation of the endogenous neural/glial progenitor cells, in vitro expansion, and further implantation. Cells expressing A2B5 or PDGFRA/CNP have been isolated within the pool of glial progenitor cells in the subcortical white matter of the normal adult human brain, all of which demonstrate glial progenitor features. However, the heterogeneity and differentiation potential of this pool of cells is not yet well established. Methods We used diffusion tensor images, histopathology, and immunostaining analysis to demonstrate normal cytoarchitecture and the absence of abnormalities in human temporal lobe samples from patients with mesial temporal sclerosis. These samples were used to isolate and enrich glial progenitor cells in vitro, and later to detect such cells in vivo. Results We have identified a subpopulation of SOX2+ cells, most of them co-localising with OLIG2, in the white matter of the normal adult human brain in vivo. These cells can be isolated and enriched in vitro, where they proliferate and generate immature (O4+) and mature (MBP+) oligodendrocytes and, to a lesser extent, astrocytes (GFAP+). Conclusion Our results demonstrate the existence of a new glial progenitor cell subpopulation that expresses SOX2 in the white matter of the normal adult human brain. These cells might be of use for tissue regeneration procedures. PMID:24901457

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

    PubMed Central

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

    2013-01-01

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

  3. Serum cholesterol and variant in cholesterol-related gene CETP predict white matter microstructure.

    PubMed

    Warstadt, Nicholus M; Dennis, Emily L; Jahanshad, Neda; Kohannim, Omid; Nir, Talia M; McMahon, Katie L; de Zubicaray, Greig I; Montgomery, Grant W; Henders, Anjali K; Martin, Nicholas G; Whitfield, John B; Jack, Clifford R; Bernstein, Matt A; Weiner, Michael W; Toga, Arthur W; Wright, Margaret J; Thompson, Paul M

    2014-11-01

    Several common genetic variants influence cholesterol levels, which play a key role in overall health. Myelin synthesis and maintenance are highly sensitive to cholesterol concentrations, and abnormal cholesterol levels increase the risk for various brain diseases, including Alzheimer's disease. We report significant associations between higher serum cholesterol (CHOL) and high-density lipoprotein levels and higher fractional anisotropy in 403 young adults (23.8 ± 2.4 years) scanned with diffusion imaging and anatomic magnetic resonance imaging at 4 Tesla. By fitting a multi-locus genetic model within white matter areas associated with CHOL, we found that a set of 18 cholesterol-related, single-nucleotide polymorphisms implicated in Alzheimer's disease risk predicted fractional anisotropy. We focused on the single-nucleotide polymorphism with the largest individual effects, CETP (rs5882), and found that increased G-allele dosage was associated with higher fractional anisotropy and lower radial and mean diffusivities in voxel-wise analyses of the whole brain. A follow-up analysis detected white matter associations with rs5882 in the opposite direction in 78 older individuals (74.3 ± 7.3 years). Cholesterol levels may influence white matter integrity, and cholesterol-related genes may exert age-dependent effects on the brain. PMID:24997672

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

    PubMed

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

    2010-05-01

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

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

    PubMed Central

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

    2016-01-01

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

  6. White matter stimulation for the treatment of epilepsy.

    PubMed

    Girgis, Fady; Miller, Jonathan P

    2016-04-01

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

  7. MR imaging correlates of white-matter pathology in a preterm baboon model

    PubMed Central

    Griffith, Jennifer L; Shimony, Joshua S; Cousins, Stephanie A; Rees, Sandra E; McCurnin, Donald C; Inder, Terrie E; Neil, Jeffrey J

    2013-01-01

    Introduction Cerebral white matter (WM) abnormalities on magnetic resonance imaging (MRI) correlate with neurodevelopmental disability in infants born prematurely. Methods We assessed the histopathological correlates of MRI abnormalities in a baboon model of premature birth. Baboons were delivered at 125 days gestation (dg, term ~ 185 dg) and maintained in an animal intensive care unit for 14 (n = 26) or 28 days (n = 17). Gestational control animals were delivered at 140 dg (n = 9) or 153 dg (n = 4). Cerebral WM in fixed brains was evaluated using MRI, diffusion tensor imaging (DTI), and histopathology. Results Quantitative histological measures of WM and ventricular volumes correlated with qualitative MRI scores of WM volume loss and ventriculomegaly. Diffuse astrocytosis was associated with signal abnormality on T2-weighted imaging and higher apparent diffusion coefficient in WM. Loss of oligodendrocytes was associated with lower relative anisotropy characterized by higher radial diffusivity values. The relationship between histopathology and MRI abnormalities was more pronounced in animals in the 28 d model, equivalent to the term human infant. Discussion MRI reflects microstructural and anatomical abnormalities that are characteristic of WM injury in the preterm brain, and these changes are more evident on MRI at term equivalent postmenstrual age. PMID:22258130

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

    PubMed

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

    2015-05-01

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

  9. 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. PMID:24788877

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

    PubMed

    Becker, Mary P; Collins, Paul F; Lim, Kelvin O; Muetzel, R L; Luciana, M

    2015-12-01

    Diffusion tensor imaging (DTI) studies of cannabis users report alterations in brain white matter microstructure, primarily based on cross-sectional research, and etiology of the alterations remains unclear. We report findings from longitudinal voxelwise analyses of DTI data collected at baseline and at a 2-year follow-up on 23 young adult (18-20 years old at baseline) regular cannabis users and 23 age-, sex-, and IQ-matched non-using controls with limited substance use histories. Onset of cannabis use was prior to age 17. Cannabis users displayed reduced longitudinal growth in fractional anisotropy in the central and parietal regions of the right and left superior longitudinal fasciculus, in white matter adjacent to the left superior frontal gyrus, in the left corticospinal tract, and in the right anterior thalamic radiation lateral to the genu of the corpus callosum, along with less longitudinal reduction of radial diffusion in the right central/posterior superior longitudinal fasciculus, corticospinal tract, and posterior cingulum. Greater amounts of cannabis use were correlated with reduced longitudinal growth in FA as was relatively impaired performance on a measure of verbal learning. These findings suggest that continued heavy cannabis use during adolescence and young adulthood alters ongoing development of white matter microstructure, contributing to functional impairment. PMID:26602958

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

    PubMed

    Brickman, Adam M

    2013-12-01

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

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

    PubMed

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

    2015-02-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-11-01

    The purpose of this study was to explore white matter microstructural alterations in the patients with generalized anxiety disorder (GAD) using diffusion tensor imaging (DTI) technique, and to assess neural associations with the symptom severity. Twenty-eight first-episode, treatment-naive GAD patients without co-morbidities and 28 matched healthy controls underwent DTI acquisition and clinical symptom assessments. Tract-based spatial statistics (TBSS) was used to analyze white matter microstructural abnormalities in patients with GAD, as well as their associations with clinical symptom scores in a voxel-wise manner. Compared to controls, patients showed decreased fractional anisotropy (FA) values in 7 clusters of white matter in bilateral uncinate fasciculus, body of corpus callosum, left middle cingulum (cingulate gyrus), bilateral anterior thalamic radiation and corona radiate, right anterior limb of internal capsule, bilateral inferior frontal-occipital fasciculus, bilateral superior and inferior longitudinal fasciculus, and increased mean diffusivity and radial diffusivity in widespread white matter regions. Reduced FA values in right uncinate fasciculus, left cingulum bundle showed significantly negative correlations with clinical symptom severity for Hamilton anxiety Rating Scale scores. Our findings suggest microstructural abnormalities in uncinate fasciculus and cingulum bundle play key roles in the underlying neural basis of GAD. PMID:27515289

  15. A Comparative White Matter Study with Parkinson's disease, Parkinson's Disease with Dementia and Alzheimer's Disease

    PubMed Central

    Perea, Rodrigo D; Rada, Rebecca C; Wilson, Jessica; Vidoni, Eric D; Morris, Jill K; Lyons, Kelly E; Pahwa, Rajesh; Burns, Jeffrey M; Honea, Robyn A

    2014-01-01

    Alzheimer's disease (AD) and Parkinson's disease (PD) are among the most common neurodegenerative disorders affecting older populations. AD is characterized by impaired memory and cognitive decline while the primary symptoms of PD include resting tremor, bradykinesia and rigidity. In PD, mild cognitive changes are frequently present, which could progress to dementia (PD dementia (PDD)). PDD and AD dementias are different in pathology although the difference in microstructural changes remains unknown. To further understand these diseases, it is essential to understand the distinct mechanism of their microstructural changes. We used diffusion tensor imaging (DTI) to investigate white matter tract differences between early stage individuals with AD (n=14), PD (n=12), PDD (n=9), and healthy non-demented controls (CON) (n=13). We used whole brain tract based spatial statistics (TBSS) and a region of interest (ROI) analysis focused on the substantia nigra (SN). We found that individuals with PDD had more widespread white matter degeneration compared to PD, AD, and CON. Individuals with AD had few regional abnormalities in the anterior and posterior projections of the corpus callosum while PD and CON did not appear to have significant white matter degeneration when compared to other groups. ROI analyses showed that PDD had the highest diffusivity in the SN and were significantly different from CON. There were no significant ROI differences between CON, PD, or AD. In conclusion, global white matter microstructural deterioration is evident in individuals with PDD, and DTI may provide a means with which to tease out pathological differences between AD and PD dementias. PMID:24724042

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

    PubMed

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

    2014-12-10

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

  17. Focal white matter changes in spasmodic dysphonia: a combined DTI and neuropathological study

    PubMed Central

    Simonyan, Kristina; Tovar-Moll, Fernanda; Ostuni, John; Hallett, Mark; Kalasinsky, Victor F.; Lewin-Smith, Michael R.; Rushing, Elisabeth J.; Vortmeyer, Alexander O.; Ludlow, Christy L.

    2008-01-01

    Spasmodic dysphonia (SD) is a neurological disorder characterized by involuntary spasms in the laryngeal muscles during speech production. Although clinical symptoms of SD are well characterized, the pathophysiology of this voice disorder is unknown. We describe here, for the first time to our knowledge, disorder-specific brain abnormalities in SD patients as determined by a combined approach of diffusion tensor imaging (DTI) and postmortem histopathology. We used DTI to identify brain changes in SD and to target those brain regions for neuropathological examination. DTI showed rightsided decrease of fractional anisotropy in the genu of the internal capsule and bilateral increase of overall water diffusivity in the white matter along the corticobulbar/corticospinal tract in 20 SD patients compared to 20 healthy subjects. In addition, water diffusivity was bilaterally increased in the lentiform nucleus, ventral thalamus, and cerebellar white and gray matter in SD patients. These brain changes were substantiated with focal histopathological abnormalities presented as a loss of axonal density and myelin content in the right genu of the internal capsule and clusters of mineral depositions containing calcium, phosphorus and iron in the parenchyma and vessel walls of the posterior limb of the internal capsule, putamen, globus pallidus, and cerebellum in the postmortem brain tissue from one SD patient compared to three controls. The specificity of these brain abnormalities is confirmed by their localization limited only to the corticobulbar/corticospinal tract and its main input/output structures. We also found positive correlation between the diffusivity changes and clinical symptoms of SD (r = 0.509, p = 0.037). These brain abnormalities may alter the central control of voluntary voice production and, therefore, may underlie the pathophysiology of SD. PMID:18083751

  18. Repeated mild traumatic brain injury results in long-term white-matter disruption

    PubMed Central

    Donovan, Virginia; Kim, Claudia; Anugerah, Ariana K; Coats, Jacqueline S; Oyoyo, Udochuwku; Pardo, Andrea C; Obenaus, Andre

    2014-01-01

    Mild traumatic brain injury (mTBI) is an increasing public health concern as repetitive injuries can exacerbate existing neuropathology and result in increased neurologic deficits. In contrast to other models of repeated mTBI (rmTBI), our study focused on long-term white-matter abnormalities after bilateral mTBIs induced 7 days apart. A controlled cortical impact (CCI) was used to induce an initial mTBI to the right cortex of Single and rmTBI Sprague Dawley rats, followed by a second injury to the left cortex of rmTBI animals. Shams received only a craniectomy. Ex vivo diffusion tensor imaging (DTI), transmission electron microscopy (TEM), and histology were performed on the anterior corpus callosum at 60 days after injury. The rmTBI animals showed a significant bilateral increase in radial diffusivity (myelin), while only modest changes in axial diffusivity (axonal) were seen between the groups. Further, the rmTBI group showed an increased g-ratio and axon caliber in addition to myelin sheath abnormalities using TEM. Our DTI results indicate ongoing myelin changes, while the TEM data show continuing axonal changes at 60 days after rmTBI. These data suggest that bilateral rmTBI induced 7 days apart leads to progressive alterations in white matter that are not observed after a single mTBI. PMID:24473478

  19. Subcortical Gray Matter Volume Abnormalities in Healthy Bipolar Offspring: Potential Neuroanatomical Risk Marker for Bipolar Disorder?

    ERIC Educational Resources Information Center

    Ladouceur, Cecile D.; Almeida, Jorge R. C.; Birmaher, Boris; Axelson, David A.; Nau, Sharon; Kalas, Catherine; Monk, Kelly; Kupfer, David J.; Phillips, Mary L.

    2008-01-01

    A study is conducted to examine the extent to which bipolar disorder (BD) is associated with gray matter volume abnormalities in brain regions in healthy bipolar offspring relative to age-matched controls. Results show increased gray matter volume in the parahippocampus/hippocampus in healthy offspring at genetic risk for BD.

  20. Segmentation of MRI brain scans into gray matter, white matter, and CSF

    NASA Astrophysics Data System (ADS)

    Sandor, Tamas; Ong, Hoo-Tee; Valtchinov, Vladimir I.; Albert, Marilyn; Jolesz, Ferenc A.

    1997-04-01

    An algorithm is described that can separate gray matter, white matter and CSF in brain scans taken with 3DFFT T1- weighted gradient echo magnetic resonance imaging. Although the algorithm is fully automated, it requires brain contours as input that utilize user-defined features. The inter- and intra-operator errors stemming from the variability of the contour definition and affecting the segmentation were assessed by using coronal brain scans of 19 subjects. The inter-operator errors were (1.61 plus or minus 2.38)% (P equals 0.01) for gray matter, (0.31 plus or minus 2.06)% (P equals 0.53) for white matter and (0.28 plus or minus 3.84)% (P equals 0.76) for cerebrospinal fluid (CSF). the intra- operator error was (0.28 plus or minus 0.55)% (P greater than 0.04) for gray matter, (0.40 plus or minus 0.37)% (P equals 0.0002) for white matter and (0.26 plus or minus 1.31)% (P equals 0.39) for CSF.

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

    PubMed

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

    2005-01-01

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

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

    PubMed Central

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

    2015-01-01

    Frontoparietal white matter supports information transfer between brain areas involved in complex haptic tasks such as somatosensory discrimination. The purpose of this study was to gain an understanding of the relationship between microstructural integrity of frontoparietal network white matter and haptic performance in persons with chronic stroke and to compare frontoparietal network integrity in participants with stroke and age matched control participants. Nineteen individuals with stroke and 16 controls participated. Haptic performance was quantified using the Hand Active Sensation Test (HASTe), an 18-item match-to-sample test of weight and texture discrimination. Three tesla MRI was used to obtain diffusion-weighted and high-resolution anatomical images of the whole brain. Probabilistic tractography was used to define 10 frontoparietal tracts total; Four intrahemispheric tracts measured bilaterally 1) thalamus to primary somatosensory cortex (T–S1), 2) thalamus to primary motor cortex (T–M1), 3) primary to secondary somatosensory cortex (S1 to SII) and 4) primary somatosensory cortex to middle frontal gyrus (S1 to MFG) and, 2 interhemispheric tracts; S1–S1 and precuneus interhemispheric. A control tract outside the network, the cuneus interhemispheric tract, was also examined. The diffusion metrics fractional anisotropy (FA), mean diffusivity (MD), axial (AD) and radial diffusivity (RD) were quantified for each tract. Diminished FA and elevated MD values are associated with poorer white matter integrity in chronic stroke. Nine of 10 tracts quantified in the frontoparietal network had diminished structural integrity poststroke compared to the controls. The precuneus interhemispheric tract was not significantly different between groups. Principle component analysis across all frontoparietal white matter tract MD values indicated a single factor explained 47% and 57% of the variance in tract mean diffusivity in stroke and control groups respectively. Age

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

    PubMed

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

    2016-01-01

    Frontoparietal white matter supports information transfer between brain areas involved in complex haptic tasks such as somatosensory discrimination. The purpose of this study was to gain an understanding of the relationship between microstructural integrity of frontoparietal network white matter and haptic performance in persons with chronic stroke and to compare frontoparietal network integrity in participants with stroke and age matched control participants. Nineteen individuals with stroke and 16 controls participated. Haptic performance was quantified using the Hand Active Sensation Test (HASTe), an 18-item match-to-sample test of weight and texture discrimination. Three tesla MRI was used to obtain diffusion-weighted and high-resolution anatomical images of the whole brain. Probabilistic tractography was used to define 10 frontoparietal tracts total; Four intrahemispheric tracts measured bilaterally 1) thalamus to primary somatosensory cortex (T-S1), 2) thalamus to primary motor cortex (T-M1), 3) primary to secondary somatosensory cortex (S1 to SII) and 4) primary somatosensory cortex to middle frontal gyrus (S1 to MFG) and, 2 interhemispheric tracts; S1-S1 and precuneus interhemispheric. A control tract outside the network, the cuneus interhemispheric tract, was also examined. The diffusion metrics fractional anisotropy (FA), mean diffusivity (MD), axial (AD) and radial diffusivity (RD) were quantified for each tract. Diminished FA and elevated MD values are associated with poorer white matter integrity in chronic stroke. Nine of 10 tracts quantified in the frontoparietal network had diminished structural integrity poststroke compared to the controls. The precuneus interhemispheric tract was not significantly different between groups. Principle component analysis across all frontoparietal white matter tract MD values indicated a single factor explained 47% and 57% of the variance in tract mean diffusivity in stroke and control groups respectively. Age

  4. Cocaine-induced loss of white matter proteins in the adult mouse nucleus accumbens is attenuated by administration of a β-lactam antibiotic during cocaine withdrawal.

    PubMed

    Kovalevich, Jane; Corley, Gladys; Yen, William; Rawls, Scott M; Langford, Dianne

    2012-12-01

    We report significantly decreased white matter protein levels in the nucleus accumbens in an adult mouse model of chronic cocaine abuse. Previous studies from human cocaine abuse patients show disruption of white matter and myelin loss, thus supporting our observations. Understanding the neuropathological mechanisms for white matter disruption in cocaine abuse patients is complicated by polydrug use and other comorbid factors, hindering the development of effective therapeutic strategies to ameliorate damage or compliment rehabilitation programs. In this context, our data further demonstrate that cocaine-induced loss of white matter proteins is absent in mice treated with the β-lactam antibiotic, ceftriaxone, during cocaine withdrawal. Other studies report that ceftriaxone, a glutamate transporter subtype-1 activator, is neuroprotective in murine models of multiple sclerosis, thereby demonstrating potential therapeutic properties for diseases with white matter loss. Cocaine-induced white matter abnormalities likely contribute to the cognitive, motor, and psychological deficits commonly afflicting cocaine abusers, yet the underlying mechanisms responsible for these changes remain unknown. Our observations describe an adult animal model for the study of cocaine-induced myelin loss for the first time, and highlight a potential pharmacological intervention to ameliorate cocaine-induced white matter loss. PMID:23031254

  5. Cocaine-Induced Loss of White Matter Proteins in the Adult Mouse Nucleus Accumbens Is Attenuated by Administration of a β-Lactam Antibiotic during Cocaine Withdrawal

    PubMed Central

    Kovalevich, Jane; Corley, Gladys; Yen, William; Rawls, Scott M.; Langford, Dianne

    2013-01-01

    We report significantly decreased white matter protein levels in the nucleus accumbens in an adult mouse model of chronic cocaine abuse. Previous studies from human cocaine abuse patients show disruption of white matter and myelin loss, thus supporting our observations. Understanding the neuropathological mechanisms for white matter disruption in cocaine abuse patients is complicated by polydrug use and other comorbid factors, hindering the development of effective therapeutic strategies to ameliorate damage or compliment rehabilitation programs. In this context, our data further demonstrate that cocaine-induced loss of white matter proteins is absent in mice treated with the β-lactam antibiotic, ceftriaxone, during cocaine withdrawal. Other studies report that ceftriaxone, a glutamate transporter subtype-1 activator, is neuroprotective in murine models of multiple sclerosis, thereby demonstrating potential therapeutic properties for diseases with white matter loss. Cocaine-induced white matter abnormalities likely contribute to the cognitive, motor, and psychological deficits commonly afflicting cocaine abusers, yet the underlying mechanisms responsible for these changes remain unknown. Our observations describe an adult animal model for the study of cocaine-induced myelin loss for the first time, and highlight a potential pharmacological intervention to ameliorate cocaine-induced white matter loss. PMID:23031254

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

    PubMed

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

    2016-02-15

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

  7. Neuropathologic basis of white matter hyperintensity accumulation with advanced age

    PubMed Central

    Woltjer, Randall; Kaye, Jeffrey; Mattek, Nora; Dodge, Hiroko H.; Green, Sarah; Tran, Huong; Howieson, Diane B.; Wild, Katherine; Silbert, Lisa C.

    2013-01-01

    Objective: To determine which vascular pathology measure most strongly correlates with white matter hyperintensity (WMH) accumulation over time, and whether Alzheimer disease (AD) neuropathology correlates with WMH accumulation. Methods: Sixty-six older persons longitudinally followed as part of an aging study were included for having an autopsy and >1 MRI scan, with last MRI scan within 36 months of death. Mixed-effects models were used to examine the associations between longitudinal WMH accumulation and the following neuropathologic measures: myelin pallor, arteriolosclerosis, microvascular disease, microinfarcts, lacunar infarcts, large-vessel infarcts, atherosclerosis, neurofibrillary tangle rating, and neuritic plaque score. Each measure was included one at a time in the model, adjusted for duration of follow-up and age at death. A final model included measures showing an association with p < 0.1. Results: Mean age at death was 94.5 years (5.5 SD). In the final mixed-effects models, arteriolosclerosis, myelin pallor, and Braak score remained significantly associated with increased WMH accumulation over time. In post hoc analysis, we found that those with Braak score 5 or 6 were more likely to also have high atherosclerosis present compared with those with Braak score 1 or 2 (p = 0.003). Conclusion: Accumulating white matter changes in advanced age are likely driven by small-vessel ischemic disease. Additionally, these results suggest a link between AD pathology and white matter integrity disruption. This may be due to wallerian degeneration secondary to neurodegenerative changes. Alternatively, a shared mechanism, for example ischemia, may lead to both vascular brain injury and neurodegenerative changes of AD. The observed correlation between atherosclerosis and AD pathology supports the latter. PMID:23935177

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2014-06-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-06-01

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

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

    PubMed Central

    Salat, David H.

    2014-01-01

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

  15. Age Differences in Periventricular and Deep White Matter Lesions

    PubMed Central

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

    2015-01-01

    Deep white matter hyperintensity (DWMH) and periventricular white matter lesion volumes (PV) are associated with age and subsequent stroke. We studied age differences in these volumes accounting for collinearity and risk factors. Subjects were 563 healthy family members of early-onset coronary artery disease (CAD) patients. Using 3T MRI, lesions were classified as DWMH or PV. Age association with lesion classification was analyzed using random effects Tobit regression, adjusting for intracranial volume (ICV), and risk factors. Subjects were 60% women, 36% African-American, mean age 51 ± 11 years. In multivariable analysis adjusted for PV and ICV, DWMH was associated with age (p<0.001), and female sex (p = 0.003) . PV, adjusted for DWMH and ICV, was age associated (p<0.001). For each age decade, DWMH showed 0.07 log units/decade greater volume (95% CI = 0.04-0.11); PV was 0.18 log units/decade greater (95% CI 0.14 – 0.23); slope differences (p < 0.001). In people with a family history of CAD, PV and DWMH are independently and differentially associated with age controlling for traditional risk factors. PMID:25659858

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

    PubMed Central

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

    2015-01-01

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

  17. Lifespan maturation and degeneration of human brain white matter.

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2012-08-21

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

  20. White Matter Integrity is Reduced in Bulimia Nervosa

    PubMed Central

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

    2013-01-01

    Objective To investigate brain white matter (WM) functionality in bulimia nervosa (BN) in relation to anxiety. Method Twenty-one control (CW, mean age 27±7 years) and 20 BN women (mean age 25±5 years) underwent brain diffusion tensor imaging (DTI) to measure fractional anisotropy (FA; an indication of WM axon integrity) and the apparent diffusion coefficient (ADC; reflecting WM cell damage). Results FA was decreased in BN in the bilateral corona radiata extending into the posterior limb of the internal capsule, the corpus callosum, the right sub-insular white matter and right fornix. In CW but not BN trait anxiety correlated negatively with fornix, corpus callosum and left corona radiata FA. ADC was increased in BN compared to CW in the bilateral corona radiata, corpus callosum, inferior fronto-occipital and uncinate fasciculus. Alterations in BN WM functionality were not due to structural brain alterations. Discussion WM integrity is disturbed in BN, especially in the corona radiate, which has been associated with taste and brain reward processing. Whether this is a premorbid condition or an effect from the illness is yet uncertain. The relationships between WM FA and trait anxiety in CW but not BN may suggest that altered WM functionality contributes to high anxious traits in BN. PMID:23354827

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

    PubMed

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

    2015-09-01

    Diverse aspects of physical, affective and cognitive health relate to social integration, reflecting engagement in social activities and identification with diverse roles within a social network. However, the mechanisms by which social integration interacts with the brain are unclear. In healthy adults (N = 155), we tested the links between social integration and measures of white matter microstructure using diffusion tensor imaging. Across the brain, there was a predominantly positive association between a measure of white matter integrity, fractional anisotropy (FA), and social network diversity. This association was particularly strong in a region near the anterior corpus callosum and driven by a negative association with the radial component of the diffusion signal. This callosal region contained projections between bilateral prefrontal cortices, as well as cingulum and corticostriatal pathways. FA within this region was weakly associated with circulating levels of the inflammatory cytokine interleukin-6 (IL-6), but IL-6 did not mediate the social network and FA relationship. Finally, variation in FA indirectly mediated the relationship between social network diversity and intrinsic functional connectivity of medial corticostriatal pathways. These findings suggest that social integration relates to myelin integrity in humans, which may help explain the diverse aspects of health affected by social networks. PMID:25605966

  2. Vanishing White Matter Disease in a Spanish Population

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    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

    2012-01-01

    Youths with conduct disorder or oppositional defiant disorder and psychopathic traits (CD/ODD+PT) are at high risk of adult anti-social behaviour 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 MRI 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. PMID:22819939

  4. Age at onset and seizure frequency affect white matter diffusion coefficient in patients with mesial temporal lobe epilepsy.

    PubMed

    Nagy, Szilvia A; Horváth, Réka; Perlaki, Gábor; Orsi, Gergely; Barsi, Péter; John, Flóra; Horváth, Andrea; Kovács, Norbert; Bogner, Péter; Ábrahám, Hajnalka; Bóné, Beáta; Gyimesi, Csilla; Dóczi, Tamás; Janszky, József

    2016-08-01

    In mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), structural abnormalities are present not only in the hippocampus but also in the white matter with ipsilateral predominance. Although the timing of epilepsy onset is commonly associated with clinical and semiological dissimilarities, limited data exist regarding white matter diffusion changes with respect to age at epilepsy onset. The aim of this study was to investigate diffusion changes in the white matter of patients with unilateral MTLE-HS with respect to clinical parameters and to compare them with an age- and sex-matched healthy control group. Apparent diffusion coefficients (ADCs) were derived using monoexponential approaches from 22 (11 early and 11 late age at onset) patients with unilateral MTLE-HS and 22 age- and sex-matched control subjects after acquiring diffusion-weighted images on a 3T MRI system. Data were analyzed using two-tailed t-tests and multiple linear regression models. In the group with early onset MTLE-HS, ADC was significantly elevated in the ipsilateral hemispheric (p=0.04) and temporal lobe white matter (p=0.01) compared with that in controls. These differences were not detectable in late onset MTLE-HS patients. Apparent diffusion coefficient of the group with early onset MTLE-HS was negatively related to age at epilepsy onset in the ipsilateral hemispheric white matter (p=0.03) and the uncinate fasciculus (p=0.03), while in patients with late onset MTLE-HS, ADC was no longer dependent on age at epilepsy onset itself but rather on the seizure frequency in the ipsilateral uncinate fasciculus (p=0.03). Such diffusivity pattern has been associated with chronic white matter degeneration, reflecting myelin loss and higher extracellular volume which are more pronounced in the frontotemporal regions and also depend on clinical features. In the group with early onset MTLE-HS, the timing of epilepsy seems to be the major cause of white matter abnormalities while in late

  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

    2015-12-01

    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. PMID:25956761

  6. Genetic markers of white matter integrity in schizophrenia revealed by parallel ICA

    PubMed Central

    Gupta, Cota Navin; Chen, Jiayu; Liu, Jingyu; Damaraju, Eswar; Wright, Carrie; Perrone-Bizzozero, Nora I.; Pearlson, Godfrey; Luo, Li; Michael, Andrew M.; Turner, Jessica A.; Calhoun, Vince D.

    2015-01-01

    It is becoming a consensus that white matter integrity is compromised in schizophrenia (SZ), however the underlying genetics remains elusive. Evidence suggests a polygenic basis of the disorder, which involves various genetic variants with modest individual effect sizes. In this work, we used a multivariate approach, parallel independent component analysis (P-ICA), to explore the genetic underpinnings of white matter abnormalities in SZ. A pre-filtering step was first applied to locate 6527 single nucleotide polymorphisms (SNPs) discriminating patients from controls with a nominal uncorrected p-value of 0.01. These potential susceptibility loci were then investigated for associations with fractional anisotropy (FA) images in a cohort consisting of 73 SZ patients and 87 healthy controls (HC). A significant correlation (r = −0.37, p = 1.25 × 10−6) was identified between one genetic factor and one FA component after controlling for scanning site, ethnicity, age, and sex. The identified FA-SNP association remained stable in a 10-fold validation. A 5000-run permutation test yielded a p-value of 2.00 × 10−4. The FA component reflected decreased white matter integrity in the forceps major for SZ patients. The SNP component was overrepresented in genes whose products are involved in corpus callosum morphology (e.g., CNTNAP2, NPAS3, and NFIB) as well as canonical pathways of synaptic long term depression and protein kinase A signaling. Taken together, our finding delineates a part of genetic architecture underlying SZ-related FA reduction, emphasizing the important role of genetic variants involved in neural development. PMID:25784871

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    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. PMID:26937382

  9. 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. PMID:26315603

  10. Longitudinal in vivo MRI in a Huntington's disease mouse model: Global atrophy in the absence of white matter microstructural damage.

    PubMed

    Steventon, Jessica J; Trueman, Rebecca C; Ma, Da; Yhnell, Emma; Bayram-Weston, Zubeyde; Modat, Marc; Cardoso, Jorge; Ourselin, Sebastian; Lythgoe, Mark; Stewart, Andrew; Rosser, Anne E; Jones, Derek K

    2016-01-01

    Huntington's disease (HD) is a genetically-determined neurodegenerative disease. Characterising neuropathology in mouse models of HD is commonly restricted to cross-sectional ex vivo analyses, beset by tissue fixation issues. In vivo longitudinal magnetic resonance imaging (MRI) allows for disease progression to be probed non-invasively. In the HdhQ150 mouse model of HD, in vivo MRI was employed at two time points, before and after the onset of motor signs, to assess brain macrostructure and white matter microstructure. Ex vivo MRI, immunohistochemistry, transmission electron microscopy and behavioural testing were also conducted. Global brain atrophy was found in HdhQ150 mice at both time points, with no neuropathological progression across time and a selective sparing of the cerebellum. In contrast, no white matter abnormalities were detected from the MRI images or electron microscopy images alike. The relationship between motor function and MR-based structural measurements was different for the HdhQ150 and wild-type mice, although there was no relationship between motor deficits and histopathology. Widespread neuropathology prior to symptom onset is consistent with patient studies, whereas the absence of white matter abnormalities conflicts with patient data. The myriad reasons for this inconsistency require further attention to improve the translatability from mouse models of disease. PMID:27581950

  11. Macro- and micro-structural white matter differences correlate with cognitive performance in healthy aging.

    PubMed

    Marques, Paulo César Gonçalves; Soares, José Miguel Montenegro; Magalhães, Ricardo José da Silva; Santos, Nadine Correia; Sousa, Nuno Jorge Carvalho

    2016-03-01

    Studies have shown that white matter (WM) volumetric reductions and overall degradation occur with aging. Nonetheless little is known about the WM alterations that may underlie different cognitive status in older individuals. The main goal of the present work was to identify and characterize possible macro and microstructural WM alterations that could distinguish between older healthy individuals with contrasting cognitive profiles (i.e., "poor" vs "good" cognitive performers). Structural and diffusion magnetic resonance imaging was performed in order to quantify local WM volumes, white matter signal abnormalities (WMSA) volume (a measure of lesion burden) and diffusion tensor imaging scalar maps known to probe WM microstructure. A battery of neurocognitive/psychological tests was administered to assess the cognitive performance. Poor performers showed a higher slope for the positive association between WMSA volume and age compared to good performers. Even when controlling for WMSA volume, poor performers also evidenced lower fractional anisotropy, as well as positive associations with age with higher slopes of regression parameters in radial and axial diffusivity. Altogether results suggest that cognitive performance is related to differences in WM, with poor cognitive performers displaying signs of faster aging in WM. PMID:25824621

  12. Ionotropic glutamate receptor expression in human white matter.

    PubMed

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

    2016-09-01

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

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

    PubMed

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

    2015-08-01

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

  14. Military blast exposure, ageing and white matter integrity

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-06-01

    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, whether age-related changes differed between ASD and control groups, and the relation between DTI measures and ASD symptomatology. Reduced fractional anisotropy and axial diffusivity were observed in ASD in numerous WM tracts, including the corpus callosum and thalamocortical fibres-tracts crucial for interhemispheric connectivity and higher order information processing. Widespread WM compromise in ASD is consistent with the view that ASD is a disorder of generalized complex information processing. PMID:26899725

  16. Identification of Infants at Risk for Autism Using Multi-parameter Hierarchical White Matter Connectomes

    PubMed Central

    Wee, Chong-Yaw; Shi, Feng; Thung, Kim-Han; Yap, Pew-Thian; Shen, Dinggang

    2016-01-01

    Autism spectrum disorder (ASD) is a variety of developmental disorders that cause life-long communication and social deficits. However, ASD could only be diagnosed at children as early as 2 years of age, while early signs may emerge within the first year. White matter (WM) connectivity abnormalities have been documented in the first year of lives of ASD subjects. We introduce a novel multi-kernel support vector machine (SVM) framework to identify infants at high-risk for ASD at 6 months old, by utilizing the diffusion parameters derived from a hierarchical set of WM connectomes. Experiments show that the proposed method achieves an accuracy of 76%, in comparison to 70% with the best single connectome. The complementary information extracted from hierarchical networks enhances the classification performance, with the top discriminative connections consistent with other studies. Our framework provides essential imaging connectomic markers and contributes to the evaluation of ASD risks as early as 6 months. PMID:26900607

  17. Delayed white matter growth trajectory in young nonpsychotic siblings of patients with childhood-onset schizophrenia.

    PubMed

    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

    2012-09-01

    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 nonpsychotic 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

  18. Ischemic Preconditioning in White Matter: Magnitude and Mechanism

    PubMed Central

    Hamner, Margaret A.; Ye, Zucheng; Lee, Richard V.; Colman, Jamie R.; Le, Thu; Gong, Davin C.; Weinstein, Jonathan R.

    2015-01-01

    Ischemic preconditioning (IPC) is a robust neuroprotective phenomenon whereby brief ischemic exposure confers tolerance to a subsequent ischemic challenge. IPC has not been studied selectively in CNS white matter (WM), although stroke frequently involves WM. We determined whether IPC is present in WM and, if so, its mechanism. We delivered a brief in vivo preconditioning ischemic insult (unilateral common carotid artery ligation) to 12- to 14-week-old mice and determined WM ischemic vulnerability [oxygen–glucose deprivation (OGD)] 72 h later, using acutely isolated optic nerves (CNS WM tracts) from the preconditioned (ipsilateral) and control (contralateral) hemispheres. Functional and structural recovery was assessed by quantitative measurement of compound action potentials (CAPs) and immunofluorescent microscopy. Preconditioned mouse optic nerves (MONs) showed better functional recovery after OGD than the non-preconditioned MONs (31 ± 3 vs 17 ± 3% normalized CAP area, p < 0.01). Preconditioned MONs also showed improved axon integrity and reduced oligodendrocyte injury compared with non-preconditioned MONs. Toll-like receptor-4 (TLR4) and type 1 interferon receptor (IFNAR1), key receptors in innate immune response, are implicated in gray matter preconditioning. Strikingly, IPC-mediated WM protection was abolished in both TLR4−/− and IFNAR1−/− mice. In addition, IPC-mediated protection in WM was also abolished in IFNAR1fl/fl LysMcre, but not in IFNAR1fl/fl control, mice. These findings demonstrated for the first time that IPC was robust in WM, the phenomenon being intrinsic to WM itself. Furthermore, WM IPC was dependent on innate immune cell signaling pathways. Finally, these data demonstrated that microglial-specific expression of IFNAR1 plays an indispensable role in WM IPC. SIGNIFICANCE STATEMENT Ischemic preconditioning (IPC) has been studied predominantly in gray matter, but stroke in humans frequently involves white matter (WM) as well. Here we

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

    PubMed Central

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

    2014-01-01

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

  20. Regional gray matter abnormalities in patients with schizophrenia determined with optimized voxel-based morphometry

    NASA Astrophysics Data System (ADS)

    Guo, XiaoJuan; Yao, Li; Jin, Zhen; Chen, Kewei

    2006-03-01

    This study examined regional gray matter abnormalities across the whole brain in 19 patients with schizophrenia (12 males and 7 females), comparing with 11 normal volunteers (7 males and 4 females). The customized brain templates were created in order to improve spatial normalization and segmentation. Then automated preprocessing of magnetic resonance imaging (MRI) data was conducted using optimized voxel-based morphometry (VBM). The statistical voxel based analysis was implemented in terms of two-sample t-test model. Compared with normal controls, regional gray matter concentration in patients with schizophrenia was significantly reduced in the bilateral superior temporal gyrus, bilateral middle frontal and inferior frontal gyrus, right insula, precentral and parahippocampal areas, left thalamus and hypothalamus as well as, however, significant increases in gray matter concentration were not observed across the whole brain in the patients. This study confirms and extends some earlier findings on gray matter abnormalities in schizophrenic patients. Previous behavior and fMRI researches on schizophrenia have suggested that cognitive capacity decreased and self-conscious weakened in schizophrenic patients. These regional gray matter abnormalities determined through structural MRI with optimized VBM may be potential anatomic underpinnings of schizophrenia.

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

    PubMed Central

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

    2012-01-01

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

  2. Multi-parametric evaluation of the white matter maturation.

    PubMed

    Kulikova, S; Hertz-Pannier, L; Dehaene-Lambertz, G; Buzmakov, A; Poupon, C; Dubois, J

    2015-11-01

    In vivo evaluation of the brain white matter maturation is still a challenging task with no existing gold standards. In this article we propose an original approach to evaluate the early maturation of the white matter bundles, which is based on comparison of infant and adult groups using the Mahalanobis distance computed from four complementary MRI parameters: quantitative qT1 and qT2 relaxation times, longitudinal λ║ and transverse λ⊥ diffusivities from diffusion tensor imaging. Such multi-parametric approach is expected to better describe maturational asynchrony than conventional univariate approaches because it takes into account complementary dependencies of the parameters on different maturational processes, notably the decrease in water content and the myelination. Our approach was tested on 17 healthy infants (aged 3- to 21-week old) for 18 different bundles. It finely confirmed maturational asynchrony across the bundles: the spino-thalamic tract, the optic radiations, the cortico-spinal tract and the fornix have the most advanced maturation, while the superior longitudinal and arcuate fasciculi, the anterior limb of the internal capsule and the external capsule have the most delayed maturation. Furthermore, this approach was more reliable than univariate approaches as it revealed more maturational relationships between the bundles and did not violate a priori assumptions on the temporal order of the bundle maturation. Mahalanobis distances decreased exponentially with age in all bundles, with the only difference between them explained by different onsets of maturation. Estimation of these relative delays confirmed that the most dramatic changes occur during the first post-natal year. PMID:25183543

  3. Relationship Between White Matter Hyperintensities Penumbra and Cavity Formation

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Yoshii, F; Duara, R

    1989-04-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-12-10

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

  8. 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

  9. Mild White Matter Changes in Un-medicated Obsessive-Compulsive Disorder Patients and Their Unaffected Siblings

    PubMed Central

    Fan, Siyan; van den Heuvel, Odile A.; Cath, Danielle C.; van der Werf, Ysbrand D.; de Wit, Stella J.; de Vries, Froukje E.; Veltman, Dick J.; Pouwels, Petra J. W.

    2016-01-01

    Objective: Obsessive-compulsive disorder (OCD) is a common neuropsychiatric disorder with moderate genetic influences and white matter abnormalities in frontal-striatal and limbic regions. Inconsistencies in reported white matter results from diffusion tensor imaging (DTI) studies can be explained, at least partly, by medication use and between-group differences in disease profile and stage. We used a family design aiming to establish whether white matter abnormalities, if present in un-medicated OCD patients, also exist in their unaffected siblings. Method: Forty-four OCD patients, un-medicated for at least the past 4 weeks, 15 of their unaffected siblings, and 37 healthy controls (HC) underwent DTI using a 3-Tesla MRI-scanner. Data analysis was done using tract-based spatial statistics (TBSS). Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) values were compared within seven skeletonised regions of interest (ROIs), i.e., corpus callosum, bilateral cingulum bundle, bilateral inferior longitudinal fasciculus/frontal-occipital fasciculus (ILF/FOF) and bilateral superior longitudinal fasciculus (SLF). Results: Un-medicated OCD patients, compared with HC, had significantly lower FA in the left cingulum bundle. FA was trend-significantly lower in all other ROIs, except for the corpus callosum. Significant three-group differences in FA (and in RD at trend-significant level) were observed in the left cingulum bundle, with the unaffected siblings representing an intermediate group between OCD patients and HC. Conclusions: OCD patients showed lower FA in the left cingulum bundle, partly driven by trend-significantly higher values in RD. Since the unaffected siblings were found to be an intermediate group between OCD patients and HC, this white matter alteration may be considered an endophenotype for OCD. PMID:26793045

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

    PubMed

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

    2015-08-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-12-01

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

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

    PubMed

    Dohn, Anders; Garza-Villarreal, Eduardo A; Chakravarty, M Mallar; Hansen, Mads; Lerch, Jason P; Vuust, Peter

    2015-05-01

    Absolute pitch (AP), the ability to identify a musical pitch without a reference, has been examined behaviorally in numerous studies for more than a century, yet only a few studies have examined the neuroanatomical correlates of AP. Here, we used MRI and diffusion tensor imaging to investigate structural differences in brains of musicians with and without AP, by means of whole-brain vertex-wise cortical thickness (CT) analysis and tract-based spatial statistics (TBSS) analysis. APs displayed increased CT in a number of areas including the bilateral superior temporal gyrus (STG), the left inferior frontal gyrus, and the right supramarginal gyrus. Furthermore, we found higher fractional anisotropy in APs within the path of the inferior fronto-occipital fasciculus, the uncinate fasciculus, and the inferior longitudinal fasciculus. The findings in gray matter support previous studies indicating an increased left lateralized posterior STG in APs, yet they differ from previous findings of thinner cortex for a number of areas in APs. Finally, we found a relation between the white-matter results and the CT in the right parahippocampal gyrus. In this study, we present novel findings in AP research that may have implications for the understanding of the neuroanatomical underpinnings of AP ability. PMID:24304583

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

    ERIC Educational Resources Information Center

    Back, Stephen A.

    2006-01-01

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

  15. 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…

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  17. 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…

  18. 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…

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

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

    PubMed

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

    2016-05-01

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

  3. 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

  4. HDAC inhibition prevents white matter injury by modulating microglia/macrophage polarization through the GSK3β/PTEN/Akt axis.

    PubMed

    Wang, Guohua; Shi, Yejie; Jiang, Xiaoyan; Leak, Rehana K; Hu, Xiaoming; Wu, Yun; Pu, Hongjian; Li, Wei-Wei; Tang, Bo; Wang, Yun; Gao, Yanqin; Zheng, Ping; Bennett, Michael V L; Chen, Jun

    2015-03-01

    Severe traumatic brain injury (TBI) elicits destruction of both gray and white matter, which is exacerbated by secondary proinflammatory responses. Although white matter injury (WMI) is strongly correlated with poor neurological status, the maintenance of white matter integrity is poorly understood, and no current therapies protect both gray and white matter. One candidate approach that may fulfill this role is inhibition of class I/II histone deacetylases (HDACs). Here we demonstrate that the HDAC inhibitor Scriptaid protects white matter up to 35 d after TBI, as shown by reductions in abnormally dephosphorylated neurofilament protein, increases in myelin basic protein, anatomic preservation of myelinated axons, and improved nerve conduction. Furthermore, Scriptaid shifted microglia/macrophage polarization toward the protective M2 phenotype and mitigated inflammation. In primary cocultures of microglia and oligodendrocytes, Scriptaid increased expression of microglial glycogen synthase kinase 3 beta (GSK3β), which phosphorylated and inactivated phosphatase and tensin homologue (PTEN), thereby enhancing phosphatidylinositide 3-kinases (PI3K)/Akt signaling and polarizing microglia toward M2. The increase in GSK3β in microglia and their phenotypic switch to M2 was associated with increased preservation of neighboring oligodendrocytes. These findings are consistent with recent findings that microglial phenotypic switching modulates white matter repair and axonal remyelination and highlight a previously unexplored role for HDAC activity in this process. Furthermore, the functions of GSK3β may be more subtle than previously thought, in that GSK3β can modulate microglial functions via the PTEN/PI3K/Akt signaling pathway and preserve white matter homeostasis. Thus, inhibition of HDACs in microglia is a potential future therapy in TBI and other neurological conditions with white matter destruction. PMID:25691750

  5. [A suspected case of Wegener granulomatosis accompanied with pachymeningitis and white matter lesions].

    PubMed

    Yokoyama, Tomohisa; Abe, Tetsuya; Kurakawa, Eri; Kasuga, Ikuma; Park, Jinho; Akata, Souichi; Aoshima, Masahiro; Ohyashiki, Kazuma

    2005-03-01

    A 53-year-old woman was admitted to our hospital because of high fever and abnormal chest radiograph shadows. Chest X-ray on admission showed a nodular shadow in the right upper lung field and a mass shadow with a cavity in the left middle lung field. Laboratory data indicated leukocytosis and elevation of C-reactive protein. Pulmonary suppuration was suspected, panipenem/betamipron was prescribed, but a mass and consolidation developed, and the medication was changed to ciprofloxacin. Convulsive seizures with loss of consciousness appeared after the change to ciprofloxacin. Lumbar puncture revealed pleocytosis with a predominance of mononuclear cells (198/3) and elevated protein(83 mg/dl). Brain CT showed no abnormal image, and acute aseptic meningitis was diagnosed and was treated with cefotaxime, clindamycin, fluconazole, acicrovir and sulfamethoxazole/trimethoprim. However, the treatment did not result in symptomatic improvement, and brain MRI showed intracranial disorders. Serum PR3-ANCA was elevated to 15 U/ml. Taken together with chest X-ray, sinusitis and clinical course, a generalized form of Wegener's granulomatosis was diagnosed. She was given 60 mg/day of prednisolone, 100 mg/day of cyclophosphamide and 9 g/day of sulfamethoxazole-trimethoprim and progressively improved. In this process, enhanced MR images showed thickened dural enhancement of the falx and bilateral anterior regions, which showed improvement on brain MRI at 8 months after starting treatment. We report a rare case of Wegener's granulomatosis accompanied with pachymeningitis and white matter lesions. PMID:15912757

  6. A Whole-Brain Investigation of White Matter Microstructure in Adolescents with Conduct Disorder

    PubMed Central

    Sarkar, Sagari; Dell’Acqua, Flavio; Froudist Walsh, Seán; Blackwood, Nigel; Scott, Stephen; Craig, Michael C.

    2016-01-01

    Background The biological basis of severe antisocial behaviour in adolescents is poorly understood. We recently reported that adolescents with conduct disorder (CD) have significantly increased fractional anisotropy (FA) of the uncinate fasciculus (a white matter (WM) tract that connects the amygdala to the frontal lobe) compared to their non-CD peers. However, the extent of WM abnormality in other brain regions is currently unclear. Methods We used tract-based spatial statistics to investigate whole brain WM microstructural organisation in 27 adolescent males with CD, and 21 non-CD controls. We also examined relationships between FA and behavioural measures. Groups did not differ significantly in age, ethnicity, or substance use history. Results The CD group, compared to controls, had clusters of significantly greater FA in 7 brain regions corresponding to: 1) the bilateral inferior and superior cerebellar peduncles, corticopontocerebellar tract, posterior limb of internal capsule, and corticospinal tract; 2) right superior longitudinal fasciculus; and 3) left cerebellar WM. Severity of antisocial behavior and callous-unemotional symptoms were significantly correlated with FA in several of these regions across the total sample, but not in the CD or control groups alone. Conclusions Adolescents with CD have significantly greater FA than controls in WM regions corresponding predominantly to the fronto-cerebellar circuit. There is preliminary evidence that variation in WM microstructure may be dimensionally related to behaviour problems in youngsters. These findings are consistent with the hypothesis that antisocial behaviour in some young people is associated with abnormalities in WM ‘connectivity’. PMID:27271503

  7. Myelination-related genes are associated with decreased white matter integrity in schizophrenia.

    PubMed

    Chavarria-Siles, Ivan; White, Tonya; de Leeuw, Christiaan; Goudriaan, Andrea; Lips, Esther; Ehrlich, Stefan; Turner, Jessica A; Calhoun, Vince D; Gollub, Randy L; Magnotta, Vincent A; Ho, Beng-Choon; Smit, August B; Verheijen, Mark H G; Posthuma, Danielle

    2016-03-01

    Disruptions in white matter (WM) tract structures have been implicated consistently in the pathophysiology of schizophrenia. Global WM integrity--as measured by fractional anisotropy (FA)--is highly heritable and may provide a good endophenotype for genetic studies of schizophrenia. WM abnormalities in schizophrenia are not localized to one specific brain region but instead reflect global low-level decreases in FA coupled with focal abnormalities. In this study, we sought to investigate whether functional gene sets associated with schizophrenia are also associated with WM integrity. We analyzed FA and genetic data from the Mind Research Network Clinical Imaging Consortium to study the effect of multiple oligodendrocyte gene sets on schizophrenia and WM integrity using a functional gene set analysis in 77 subjects with schizophrenia and 104 healthy controls. We found that a gene set involved in myelination was significantly associated with schizophrenia and FA. This gene set includes 17 genes that are expressed in oligodendrocytes and one neuronal gene (NRG1) that is known to regulate myelination. None of the genes within the gene set were associated with schizophrenia or FA individually, suggesting that no single gene was driving the association of the gene set. Our findings support the hypothesis that multiple genetic variants in myelination-related genes contribute to the observed correlation between schizophrenia and decreased WM integrity as measured by FA. PMID:26014434

  8. Tract-based spatial statistics analysis of white matter changes in children with anisometropic amblyopia.

    PubMed

    Li, Qian; Zhai, Liying; Jiang, Qinying; Qin, Wen; Li, Qingji; Yin, Xiaohui; Guo, Mingxia

    2015-06-15

    Amblyopia is a neurological disorder of vision that follows abnormal binocular interaction or visual deprivation during early life. Previous studies have reported multiple functional or structural cortical alterations. Although white matter was also studied, it still cannot be clarified clearly which fasciculus was affected by amblyopia. In the present study, tract-based spatial statistics analysis was applied to diffusion tensor imaging (DTI) to investigate potential diffusion changes of neural tracts in anisometropic amblyopia. Fractional anisotropy (FA) value was calculated and compared between 20 amblyopic children and 18 healthy age-matched controls. In contrast to the controls, significant decreases in FA values were found in right optic radiation (OR), left inferior longitudinal fasciculus/inferior fronto-occipital fasciculus (ILF/IFO) and right superior longitudinal fasciculus (SLF) in the amblyopia. Furthermore, FA values of these identified tracts showed positive correlation with visual acuity. It can be inferred that abnormal visual input not only hinders OR from well developed, but also impairs fasciculi associated with dorsal and ventral visual pathways, which may be responsible for the amblyopic deficiency in object discrimination and stereopsis. Increased FA was detected in right posterior part of corpus callosum (CC) with a medium effect size, which may be due to compensation effect. DTI with subsequent measurement of FA is a useful tool for investigating neuronal tract involvement in amblyopia. PMID:25899779

  9. Quantification of white matter and gray matter volumes from T1 parametric images using fuzzy classifiers.

    PubMed

    Herndon, R C; Lancaster, J L; Toga, A W; Fox, P T

    1996-01-01

    White matter (WM) and gray matter (GM) were accurately measured using a technique based on a single standardized fuzzy classifier (FC) for each tissue. Fuzzy classifier development was based on experts' visual assessments of WM and GM boundaries from a set of T1 parametric MR images. The fuzzy classifier method's accuracy was validated and optimized by a set of T1 phantom images that were based on hand-detailed human brain cryosection images. Nine sets of axial T1 images of varying thickness equally distributed throughout the brain were simulated. All T1 data sets were mapped to the standardized FCs and rapidly segmented into WM and GM voxel fraction images. Resulting volumes revealed that, in most cases, the difference between measured and actual volumes was less than 5%. This was consistent throughout most of the brain, and as expected, the accuracy improved to generally less than 2% for the 1-mm simulated brain slices. PMID:8724407

  10. DTI Study of Cerebral Normal-Appearing White Matter in Hereditary Neuropathy With Liability to Pressure Palsies (HNPP).

    PubMed

    Wang, Wei-Wei; Song, Chun-Li; Huang, Liang; Song, Qing-Wei; Liang, Zhan-Hua; Wei, Qiang; Hu, Jia-Ni; Miao, Yan-Wei; Wu, Bing; Xie, Lizhi

    2015-10-01

    The majority of previous studies on hereditary neuropathy with liability to pressure palsies (HNPP) were focused on peripheral nerves, whereas cerebral alterations in HNPP have been less attended to. In this work, Diffusion tensor imaging (DTI) was used to detect the changes in WM, especially in the normal-appearing white matter (NAWM) in HNPP patients for its sensitivity in probing the microstructure of WM, the sensitive metric was searched for probing cerebral alterations and the regional distribution of cerebral abnormalities was identified. Twelve HNPP patients and 12 age- and gender-matched healthy controls underwent the conventional MRI, DTI scan, and electrophysiological examination. The conventional MRI images were first analyzed to identify abnormal intense regions and the NAWM regions. NAWM refers to the white matter regions that do not include the lesions on conventional MRI. The apparent diffusion coefficient and fractional anisotropy (FA) values of the NAWM were then measured and compared between patient and control groups. The sensitivity and specificity of 3 methods and the cerebral regional distribution of MR signal abnormalities were further analyzed. Hyperintense foci were observed on T2 weighted image and fluid attenuated inversion recovery images in 6 patients. Compared to the controls, FA values of the patients were significantly lower in bilateral frontal, orbitofrontal, and temporal NAWMs; whereas the electrophysiological examination results of patients and controls exhibited no statistically significant difference. The sensitivity of FA value was higher than that of electrophysiological examination and conventional MRI. The majority of abnormal signals on conventional MRI images and abnormal FA values were located in the frontal and temporal lobes. The results of our study show cerebral WM changes in HNPP patients. FA value in DTI has been shown to be sensitive to the cerebral microstructural changes in HNPP. The frontal lobe is the

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

    PubMed

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

    2010-01-01

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

  12. White matter microstructural changes in psychogenic erectile dysfunction patients.

    PubMed

    Zhang, P; Liu, J; Li, G; Pan, J; Li, Z; Liu, Q; Qin, W; Dong, M; Sun, J; Huang, X; Wu, T; Chang, D

    2014-05-01

    Brain dysfunction in erectile dysfunction (ED) has been identified by multiple neuroimaging studies. A recent MRI study indicated grey matter alterations in ED patients. This study aims to investigate the microstructural changes of cerebral white matter (WM) in psychological ED patients and their possible correlations with clinical variables. Twenty-seven psychological ED patients and 27 healthy subjects (HS) were included and underwent a magnetic resonance (MR) diffusion tensor imaging (DTI) scan. The tract-based spatial statistics were employed to identify the WM structure alterations in psychological ED patients. The multiple DTI-derived indices' [fractional anisotropy (FA), axial diffusivity (AD) and mean diffusivity (MD)] correlations with the symptoms and their durations, respectively, were analysed. The IIEF-5, quality of erection questionnaire (QEQ) and the self-esteem and relationship (SEAR) questionnaire were used to assess the symptoms of psychological ED patients. Compared with HS, the psychological ED patients showed increased FA values, reduced MD values and reduced AD values in multiple WM tracts including the corpus callosum (genu, body and splenium), corticospinal tract, internal capsule, corona radiata, external capsule and superior longitudinal fasciculus (p < 0.05, threshold-free cluster enhancement corrected). Both of the IIEF scores and QEQ scores of ED patients showed a significantly negative correlation with the average FA values, and positive correlation with average AD values and MD values in the splenium of the corpus callosum (p < 0.05). The results provided preliminary evidence of WM microstructural changes in patients with psychological ED. The morphological alterations in the splenium of the corpus callosum were related to the symptom severity. PMID:24711250

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Schmidt, Martin J; Laubner, Steffi; Kolecka, Malgorzata; Failing, Klaus; Moritz, Andreas; Kramer, Martin; Ondreka, Nele

    2015-01-01

    Large cerebral ventricles are a frequent finding in brains of dogs with brachycephalic skull conformation, in comparison with mesaticephalic dogs. It remains unclear whether oversized ventricles represent a normal variant or a pathological condition in brachycephalic dogs. There is a distinct relationship between white matter and grey matter in the cerebrum of all eutherian mammals. The aim of this study was to determine if this physiological proportion between white matter and grey matter of the forebrain still exists in brachycephalic dogs with oversized ventricles. The relative cerebral grey matter, white matter and cerebrospinal fluid volume in dogs were determined based on magnetic-resonance-imaging datasets using graphical software. In an analysis of covariance (ANCOVA) using body mass as the covariate, the adjusted means of the brain tissue volumes of two groups of dogs were compared. Group 1 included 37 mesaticephalic dogs of different sizes with no apparent changes in brain morphology, and subjectively normal ventricle size. Group 2 included 35 brachycephalic dogs in which subjectively enlarged cerebral ventricles were noted as an incidental finding in their magnetic-resonance-imaging examination. Whereas no significant different adjusted means of the grey matter could be determined, the group of brachycephalic dogs had significantly larger adjusted means of lateral cerebral ventricles and significantly less adjusted means of relative white matter volume. This indicates that brachycephalic dogs with subjective ventriculomegaly have less white matter, as expected based on their body weight and cerebral volume. Our study suggests that ventriculomegaly in brachycephalic dogs is not a normal variant of ventricular volume. Based on the changes in the relative proportion of WM and CSF volume, and the unchanged GM proportions in dogs with ventriculomegaly, we rather suggest that distension of the lateral ventricles might be the underlying cause of pressure

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

    PubMed Central

    Schmidt, Martin J.; Laubner, Steffi; Kolecka, Malgorzata; Failing, Klaus; Moritz, Andreas; Kramer, Martin; Ondreka, Nele

    2015-01-01

    Large cerebral ventricles are a frequent finding in brains of dogs with brachycephalic skull conformation, in comparison with mesaticephalic dogs. It remains unclear whether oversized ventricles represent a normal variant or a pathological condition in brachycephalic dogs. There is a distinct relationship between white matter and grey matter in the cerebrum of all eutherian mammals. The aim of this study was to determine if this physiological proportion between white matter and grey matter of the forebrain still exists in brachycephalic dogs with oversized ventricles. The relative cerebral grey matter, white matter and cerebrospinal fluid volume in dogs were determined based on magnetic-resonance-imaging datasets using graphical software. In an analysis of covariance (ANCOVA) using body mass as the covariate, the adjusted means of the brain tissue volumes of two groups of dogs were compared. Group 1 included 37 mesaticephalic dogs of different sizes with no apparent changes in brain morphology, and subjectively normal ventricle size. Group 2 included 35 brachycephalic dogs in which subjectively enlarged cerebral ventricles were noted as an incidental finding in their magnetic-resonance-imaging examination. Whereas no significant different adjusted means of the grey matter could be determined, the group of brachycephalic dogs had significantly larger adjusted means of lateral cerebral ventricles and significantly less adjusted means of relative white matter volume. This indicates that brachycephalic dogs with subjective ventriculomegaly have less white matter, as expected based on their body weight and cerebral volume. Our study suggests that ventriculomegaly in brachycephalic dogs is not a normal variant of ventricular volume. Based on the changes in the relative proportion of WM and CSF volume, and the unchanged GM proportions in dogs with ventriculomegaly, we rather suggest that distension of the lateral ventricles might be the underlying cause of pressure

  16. White matter structures associated with loneliness in young adults

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2010-03-01

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

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

    PubMed Central

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

    2015-01-01

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

  20. Automated localization of periventricular and subcortical white matter lesions

    NASA Astrophysics Data System (ADS)

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

    2007-03-01

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

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

    PubMed

    Connell, Sean; Ouyang, Hui; Shi, Riyi

    2011-10-01

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

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

    PubMed

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

    2015-01-01

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

  3. Brain asymmetry in the white matter making and globularity

    PubMed Central

    Theofanopoulou, Constantina

    2015-01-01

    Recent studies from the field of language genetics and evolutionary anthropology have put forward the hypothesis that the emergence of our species-specific brain is to be understood not in terms of size, but in light of developmental changes that gave rise to a more globular braincase configuration after the split from Neanderthals-Denisovans. On the grounds that (i) white matter myelination is delayed relative to other brain structures and, in humans, is protracted compared with other primates and that (ii) neural connectivity is linked genetically to our brain/skull morphology and language-ready brain, I argue that one significant evolutionary change in Homo sapiens’ lineage is the interhemispheric connectivity mediated by the Corpus Callosum. The size, myelination and fiber caliber of the Corpus Callosum present an anterior-to-posterior increase, in a way that inter-hemispheric connectivity is more prominent in the sensory motor areas, whereas “high- order” areas are more intra-hemispherically connected. Building on evidence from language-processing studies that account for this asymmetry (‘lateralization’) in terms of brain rhythms, I present an evo-devo hypothesis according to which the myelination of the Corpus Callosum, Brain Asymmetry, and Globularity are conjectured to make up the angles of a co-evolutionary triangle that gave rise to our language-ready brain. PMID:26441731

  4. White matter hyperintensities characterize monogenic frontotemporal dementia with granulin mutations.

    PubMed

    Paternicò, Donata; Premi, Enrico; Gazzina, Stefano; Cosseddu, Maura; Alberici, Antonella; Archetti, Silvana; Cotelli, Maria S; Micheli, Anna; Turla, Marinella; Gasparotti, Roberto; Padovani, Alessandro; Borroni, Barbara

    2016-02-01

    No study but one has suggested the presence of white matter hyperintensities (WMHs) in frontotemporal dementia (FTD), limited to 4 cases carrying pathogenic Granulin (GRN) gene mutations. We investigated the presence of WMHs in a cohort of 14 FTD patients with pathogenic GRN mutations (GRN+), 28 patients without GRN mutations (GRN-) and 18 healthy controls (HC). We further considered 11 asymptomatic GRN+ subjects and 11 young age-matched healthy controls (yHC). The WMH burden was automatically computed and a voxelwise-based analysis was carried out to explore the differences in WMH brain spatial distribution. FTD-GRN+ patients had increased total WMH burden than both HC (p < 0.001) and FTD-GRN-(p = 0.01) groups. WMHs were mainly localized in the right middle frontal and superior temporal gyri, in the left superior frontal in the left parietal gyri. No significant differences of WMH burden between asymptomatic GRN+ and yHC were observed. The presence of WMHs in cases of FTD may suggest a novel mechanism of GRN disease-related neurodegeneration, may be of help in the differential diagnosis, and in guiding genetic screening. PMID:26827655

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Theofanopoulou, Constantina

    2015-01-01

    Recent studies from the field of language genetics and evolutionary anthropology have put forward the hypothesis that the emergence of our species-specific brain is to be understood not in terms of size, but in light of developmental changes that gave rise to a more globular braincase configuration after the split from Neanderthals-Denisovans. On the grounds that (i) white matter myelination is delayed relative to other brain structures and, in humans, is protracted compared with other primates and that (ii) neural connectivity is linked genetically to our brain/skull morphology and language-ready brain, I argue that one significant evolutionary change in Homo sapiens' lineage is the interhemispheric connectivity mediated by the Corpus Callosum. The size, myelination and fiber caliber of the Corpus Callosum present an anterior-to-posterior increase, in a way that inter-hemispheric connectivity is more prominent in the sensory motor areas, whereas "high- order" areas are more intra-hemispherically connected. Building on evidence from language-processing studies that account for this asymmetry ('lateralization') in terms of brain rhythms, I present an evo-devo hypothesis according to which the myelination of the Corpus Callosum, Brain Asymmetry, and Globularity are conjectured to make up the angles of a co-evolutionary triangle that gave rise to our language-ready brain. PMID:26441731

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

    PubMed Central

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

    2015-01-01

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

  8. Anaerobic function of CNS white matter declines with age.

    PubMed

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

    2011-04-01

    The mammalian central nervous system (CNS) is generally believed to be completely dependent on the presence of oxygen (O(2)) to maintain energy levels necessary for excitability. However, previous studies on CNS white matter (WM) have shown that a large subset of CNS-myelinated axons of mice aged 4 to 6 weeks remains excitable in the absence of O(2). We investigated whether this surprising WM tolerance to anoxia varied with age. Acutely isolated mouse optic nerve (MON), a purely myelinated WM tract, was studied electrophysiologically. Excitability in the MONs from 1-month-, 4-month-, and 8-month-old mice was assessed quantitatively as the area under the supramaximal compound action potential (CAP). Anoxia-resistant WM function declined with age. After 60  minutes of anoxia, ∼23% of the CAP remained in 1-month-old mice, 8% in 4-month-old mice, and ∼0 in the 8-month-old group. Our results indicated that although some CNS axons function anaerobically in young adult animals, they lose this ability in later adulthood. This finding may help explain the clinical impression that favorable outcome after stroke and other brain injuries declines with age. PMID:21179073

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

    PubMed

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

    2016-05-15

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

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

    PubMed

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

    2015-07-01

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

  11. Altered white matter architecture in BDNF met carriers.

    PubMed

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

    2013-01-01

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

  12. Sexual dimorphism in the white matter of rodents

    PubMed Central

    Cerghet, Mirela; Skoff, Robert P.; Swamydas, Muthulekha; Bessert, Denise

    2009-01-01

    Sexual dimorphism of astrocytes and neurons is well documented in many brain and spinal cord structures. Sexual dimorphism of oligodendrocytes (Olgs) and myelin has received less attention. We recently showed that density of Olgs in corpus callosum, fornix, and spinal cord of wild-type male rodents are more densely packed than in females; myelin proteins and myelin gene expression is likewise greater in males than in female rodents. However, glial cell proliferation and cell death were two times greater in female corpus callosum. Endogenous sex hormones, specifically lack of androgens, produce an Olg female phenotype in castrated male mouse. In vitro studies using Olgs culture also showed differences between males and females Olg survival and signaling pathways in response to sexual hormones. Sexual dimorphism of white matter tracts and glia in rodents indicates the necessity for controlling gender in experimental studies of neurodegenerative disorders. Most importantly, our studies suggest that hormones may contribute to sexual dimorphism observed in certain human diseases including multiple sclerosis. PMID:19625027

  13. 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

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

    PubMed Central

    Ryan, Lee; Walther, Katrin

    2015-01-01

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

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

    PubMed

    Bennett, I J; Madden, D J

    2014-09-12

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

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

    PubMed

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

    2016-02-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2016-06-01

    White matter microstructure forms a complex and dynamical system that is critical for efficient and synchronized brain function. Neuroimaging findings in children with autism spectrum disorder (ASD) suggest this condition is associated with altered white matter microstructure, which may lead to atypical macroscale brain connectivity. In this study, we used diffusion tensor imaging measures to examine the extent that white matter tracts are interrelated within ASD and typical development. We assessed the strength of inter-regional white matter correlations between typically developing and ASD diagnosed individuals. Using hierarchical clustering analysis, clustering patterns of the pairwise white matter correlations were constructed and revealed to be different between the two groups. Additionally, we explored the use of graph theory analysis to examine the characteristics of the patterns formed by inter-regional white matter correlations and compared these properties between ASD and typical development. We demonstrate that the ASD sample has significantly less coherence in white matter microstructure across the brain compared to that in the typical development sample. The ASD group also presented altered topological characteristics, which may implicate less efficient brain networking in ASD. These findings highlight the potential of graph theory based network characteristics to describe the underlying networks as measured by diffusion magnetic resonance imaging and furthermore indicates that ASD may be associated with altered brain network characteristics. Our findings are consistent with those of a growing number of studies and hypotheses that have suggested disrupted brain connectivity in ASD. PMID:27021440

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

    PubMed

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

    2016-04-15

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

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

    PubMed

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

    2016-03-01

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

  1. 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

  2. Cognitive correlates of gray matter abnormalities in adolescent siblings of patients with childhood-onset schizophrenia

    PubMed Central

    Wagshal, Dana; Knowlton, Barbara Jean; Cohen, Jessica Rachel; Bookheimer, Susan Yost; Bilder, Robert Martin; Fernandez, Vindia Gisela; Asarnow, Robert Franklin

    2015-01-01

    Patients with childhood onset schizophrenia (COS) display widespread gray matter (GM) structural brain abnormalities. Healthy siblings of COS patients share some of these structural abnormalities, suggesting that GM abnormalities are endophenotypes for schizophrenia. Another possible endophenotype for schizophrenia that has been relatively unexplored is corticostriatal dysfunction. The corticostriatal system plays an important role in skill learning. Our previous studies have demonstrated corticostriatal dysfunction in COS siblings with a profound skill learning deficit and abnormal pattern of brain activation during skill learning. This study investigated whether structural abnormalities measured using volumetric brain morphometry (VBM) were present in siblings of COS patients and whether these were related to deficits in cognitive skill learning. Results revealed smaller GM volume in COS siblings relative to controls in a number of regions, including occipital, parietal, and subcortical regions including the striatum, and greater GM volume relative to controls in several subcortical regions. Volume in the right superior frontal gyrus and cerebellum were related to performance differences between groups on the weather prediction task, a measure of cognitive skill learning. Our results support the idea that corticostriatal and cerebellar impairment in unaffected siblings of COS patients are behaviorally relevant and may reflect genetic risk for schizophrenia. PMID:25541139

  3. White matter correlates of episodic memory encoding and retrieval in schizophrenia.

    PubMed

    Green, Amity E; Croft, Rodney J; Maller, Jerome J; Fitzgerald, Paul B

    2016-08-30

    Episodic memory (EM) impairments in schizophrenia (SZ) are predictive of functional outcome and are a potential endophenotype of the disorder. The current study investigated the neuroanatomical correlates of EM encoding and retrieval in SZ with structural magnetic resonance and diffusion tensor imaging (DTI) measures in 22 patients with SZ and 22 age- and gender-matched healthy controls. Tract-based Spatial Statistics (TBSS) was used to investigate microstructural alterations in white matter (WM), while FreeSurfer surface-based analysis was used to determine abnormalities in grey matter (GM) and WM volumetrics and cortical thickness. Compared to controls, patients demonstrated GM deficits in temporal and parietal regions and lower fractional anisotropy (FA) of WM in diffuse brain regions. Patients also demonstrated reduced functioning in both encoding and retention of auditory-verbal EM. Among patients but not controls, EM encoding correlated with WM volume in the orbitofrontal cortex and increased radial diffusivity in the fornix, whereas EM retrieval correlated with WM volume in posterior parietal cortex. These findings suggest a differential role for frontal and parietal WM in EM encoding and retrieval processes, while myelin integrity of the fornix may play a specific role in mediating EM encoding processes in SZ. PMID:27479923

  4. Global association between cortical thinning and white matter integrity reduction in schizophrenia.

    PubMed

    Sasamoto, Akihiko; Miyata, Jun; Kubota, Manabu; Hirao, Kazuyuki; Kawada, Ryosaku; Fujimoto, Shinsuke; Tanaka, Yusuke; Hazama, Masaaki; Sugihara, Genichi; Sawamoto, Nobukatsu; Fukuyama, Hidenao; Takahashi, Hidehiko; Murai, Toshiya

    2014-03-01

    Previous neuroimaging studies have revealed that both gray matter (GM) and white matter (WM) are altered in several morphological aspects in schizophrenia patients. Although several studies reported associations between GM and WM alterations in restricted regions, the existence of a global association between GM and WM pathologies is unknown. Considering the wide distribution of GM morphological changes and the profound genetic background of WM abnormalities, it would be natural to postulate a global association between pathologies of GM and WM in schizophrenia. In this investigation, we studied 35 schizophrenia patients and 35 healthy control subjects using T1-weighted magnetic resonance imaging and diffusion tensor imaging (DTI) and investigated the association between GM thickness and WM fractional anisotropy (FA) as a proxy of pathology in each tissue. To investigate cortical thickness, surface-based analysis was used. The mean cortical thickness for the whole brain was computed for each hemisphere, and group comparisons were performed. For DTI data, mean FA for the whole brain was calculated, and group comparisons were performed. Subsequently, the correlation between mean cortical thickness and mean FA was investigated. Results showed that the mean cortical thickness was significantly thinner, and the mean FA was significantly lower in schizophrenia patients. Only in the patient group the mean cortical thickness and mean FA showed significant positive correlations in both hemispheres. This correlation remained significant even after controlling for demographic and clinical variables. Thus, our results indicate that the GM and WM pathologies of schizophrenia are intertwined at the global level. PMID:23461997

  5. Associations of white matter integrity and cortical thickness in patients with schizophrenia and healthy controls.

    PubMed

    Ehrlich, Stefan; Geisler, Daniel; Yendiki, Anastasia; Panneck, Patricia; Roessner, Veit; Calhoun, Vince D; Magnotta, Vincent A; Gollub, Randy L; White, Tonya

    2014-05-01

    Typical brain development includes coordinated changes in both white matter (WM) integrity and cortical thickness (CT). These processes have been shown to be disrupted in schizophrenia, which is characterized by abnormalities in WM microstructure and by reduced CT. The aim of this study was to identify patterns of association between WM markers and cortex-wide CT in healthy controls (HCs) and patients with schizophrenia (SCZ). Using diffusion tensor imaging and structural magnetic resonance imaging data of the Mind Clinical Imaging Consortium study (130 HC and 111 SCZ), we tested for associations between (a) fractional anisotropy in selected manually labeled WM pathways (corpus callosum, anterior thalamic radiation, and superior longitudinal fasciculus) and CT, and (b) the number of lesion-like WM regions ("potholes") and CT. In HC, but not SCZ, we found highly significant negative associations between WM integrity and CT in several pathways, including frontal, temporal, and occipital brain regions. Conversely, in SCZ the number of WM potholes correlated with reduced CT in the left lateral temporal gyrus, left fusiform, and left lateral occipital brain area. Taken together, we found differential patterns of association between WM integrity and CT in HC and SCZ. Although the pattern in HC can be explained from a developmental perspective, the reduced gray matter CT in SCZ patients might be the result of focal but spatially heterogeneous disruptions of WM integrity. PMID:23661633

  6. Associations of White Matter Integrity and Cortical Thickness in Patients With Schizophrenia and Healthy Controls

    PubMed Central

    Ehrlich, Stefan

    2014-01-01

    Typical brain development includes coordinated changes in both white matter (WM) integrity and cortical thickness (CT). These processes have been shown to be disrupted in schizophrenia, which is characterized by abnormalities in WM microstructure and by reduced CT. The aim of this study was to identify patterns of association between WM markers and cortex-wide CT in healthy controls (HCs) and patients with schizophrenia (SCZ). Using diffusion tensor imaging and structural magnetic resonance imaging data of the Mind Clinical Imaging Consortium study (130 HC and 111 SCZ), we tested for associations between (a) fractional anisotropy in selected manually labeled WM pathways (corpus callosum, anterior thalamic radiation, and superior longitudinal fasciculus) and CT, and (b) the number of lesion-like WM regions (“potholes”) and CT. In HC, but not SCZ, we found highly significant negative associations between WM integrity and CT in several pathways, including frontal, temporal, and occipital brain regions. Conversely, in SCZ the number of WM potholes correlated with reduced CT in the left lateral temporal gyrus, left fusiform, and left lateral occipital brain area. Taken together, we found differential patterns of association between WM integrity and CT in HC and SCZ. Although the pattern in HC can be explained from a developmental perspective, the reduced gray matter CT in SCZ patients might be the result of focal but spatially heterogeneous disruptions of WM integrity. PMID:23661633

  7. Neuromarkers of the common angiotensinogen polymorphism in healthy older adults: A comprehensive assessment of white matter integrity and cognition.

    PubMed

    Salminen, Lauren E; Schofield, Peter R; Pierce, Kerrie D; Zhao, Yi; Luo, Xi; Wang, Youdan; Laidlaw, David H; Cabeen, Ryan P; Conturo, Thomas E; Tate, David F; Akbudak, Erbil; Lane, Elizabeth M; Heaps, Jodi M; Bolzenius, Jacob D; Baker, Laurie M; Cagle, Lee M; Paul, Robert H

    2016-01-01

    The common angiotensinogen (AGT) M268T polymorphism (rs699; historically referred to as M235T) has been identified as a significant risk factor for cerebrovascular pathologies, yet it is unclear if healthy older adults carrying the threonine amino acid variant have a greater risk for white matter damage in specific fiber tracts. Further, the impact of the threonine variant on cognitive function remains unknown. The present study utilized multiple indices of diffusion tensor imaging (DTI) and neuropsychological assessment to examine the integrity of specific white matter tracts and cognition between individuals with homozygous genotypes of M268T (MetMet n=27, ThrThr n=27). Differences in subcortical hyperintensity (SH) volume were also examined between groups. Results indicated that the threonine variant was associated with significantly reduced integrity in the superior longitudinal fasciculus (SLF) and the cingulate gyrus segment of the cingulum bundle (cingulum CG) compared to those with the methionine variant, and poorer cognitive performance on tests of attention/processing speed and language. Despite these associations, integrity of these tracts did not significantly mediate relationships between cognition and genetic status, and SH did not differ significantly between groups. Collectively our results suggest that the threonine variant of M268T is a significant risk factor for abnormalities in specific white matter tracts and cognitive domains in healthy older adults, independent of SH burden. PMID:26318936

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

    PubMed Central

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

    2014-01-01

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

  9. Supervised novelty detection in brain tissue classification with an application to white matter hyperintensities

    NASA Astrophysics Data System (ADS)

    Kuijf, Hugo J.; Moeskops, Pim; de Vos, Bob D.; Bouvy, Willem H.; de Bresser, Jeroen; Biessels, Geert Jan; Viergever, Max A.; Vincken, Koen L.

    2016-03-01

    Novelty detection is concerned with identifying test data that differs from the training data of a classifier. In the case of brain MR images, pathology or imaging artefacts are examples of untrained data. In this proof-of-principle study, we measure the behaviour of a classifier during the classification of trained labels (i.e. normal brain tissue). Next, we devise a measure that distinguishes normal classifier behaviour from abnormal behavior that occurs in the case of a novelty. This will be evaluated by training a kNN classifier on normal brain tissue, applying it to images with an untrained pathology (white matter hyperintensities (WMH)), and determine if our measure is able to identify abnormal classifier behaviour at WMH locations. For our kNN classifier, behaviour is modelled as the mean, median, or q1 distance to the k nearest points. Healthy tissue was trained on 15 images; classifier behaviour was trained/tested on 5 images with leave-one-out cross-validation. For each trained class, we measure the distribution of mean/median/q1 distances to the k nearest point. Next, for each test voxel, we compute its Z-score with respect to the measured distribution of its predicted label. We consider a Z-score >=4 abnormal behaviour of the classifier, having a probability due to chance of 0.000032. Our measure identified >90% of WMH volume and also highlighted other non-trained findings. The latter being predominantly vessels, cerebral falx, brain mask errors, choroid plexus. This measure is generalizable to other classifiers and might help in detecting unexpected findings or novelties by measuring classifier behaviour.

  10. Altered interhemispheric and temporal lobe white matter microstructural organization in severe chronic schizophrenia.

    PubMed

    Holleran, Laurena; Ahmed, Mohamed; Anderson-Schmidt, Heike; McFarland, John; Emsell, Louise; Leemans, Alexander; Scanlon, Cathy; Dockery, Peter; McCarthy, Peter; Barker, Gareth J; McDonald, Colm; Cannon, Dara M

    2014-03-01

    Diffusion MRI investigations in schizophrenia provide evidence of abnormal white matter (WM) microstructural organization as indicated by reduced fractional anisotropy (FA) primarily in interhemispheric, left frontal and temporal WM. Using tract-based spatial statistics (TBSS), we examined diffusion parameters in a sample of patients with severe chronic schizophrenia. Diffusion MRI data were acquired on 19 patients with chronic severe schizophrenia and 19 age- and gender-matched healthy controls using a 64 gradient direction sequence, (b=1300 s/mm(2)) collected on a Siemens 1.5T MRI scanner. Diagnosis of schizophrenia was determined by Diagnostic and Statistical Manual for Mental Disorders 4th Edition (DSM-IV) Structured Clinical Interview for DSM disorder (SCID). Patients were treatment resistance, having failed to respond to at least two antipsychotic medications, and had prolonged periods of moderate to severe positive or negative symptoms. Analysis of diffusion parameters was carried out using TBSS. Individuals with chronic severe schizophrenia had significantly reduced FA with corresponding increased radial diffusivity in the genu, body, and splenium of the corpus callosum, the right posterior limb of the internal capsule, right external capsule, and the right temporal inferior longitudinal fasciculus. There were no voxels of significantly increased FA in patients compared with controls. A decrease in splenium FA was shown to be related to a longer illness duration. We detected widespread abnormal diffusivity properties in the callosal and temporal lobe WM regions in individuals with severe chronic schizophrenia who have not previously been exposed to clozapine. These deficits can be driven by a number of factors that are indistinguishable using in vivo diffusion-weighted imaging, but may be related to reduced axonal number or packing density, abnormal glial cell arrangement or function, and reduced myelin. PMID:24150571

  11. Electrophysiological white matter dysfunction and association with neurobehavioral deficits following low-level primary blast trauma.

    PubMed

    Park, Eugene; Eisen, Rebecca; Kinio, Anna; Baker, Andrew J

    2013-04-01

    animals as indicated by the increased frequency of fecal droppings (p=0.029) and reduced exploratory activity (p=0.036) in the open-field test. Blast rats had fewer transitions and time spent in lit sections of the light/dark box. Electrophysiological recordings from the corpus callosum indicated greater deficits in unmyelinated fibers of the corpus callosum relative to myelinated fibers characterized by reduced CAP amplitude response at 14 days post-injury. Analysis of the relationship between stimulation distance to evoked response indicated an underlying abnormality in N1 myelinated fibers at close stimulation distances. Collectively, our results indicate that subclinical blast exposure can result in persistent neurological changes in cerebral white matter occurring in parallel with detectable neurobehavioral deficits. PMID:23238347

  12. Fingolimod protects against neonatal white matter damage and long-term cognitive deficits caused by hyperoxia.

    PubMed

    Serdar, Meray; Herz, Josephine; Kempe, Karina; Lumpe, Katharina; Reinboth, Barbara S; Sizonenko, Stéphane V; Hou, Xinlin; Herrmann, Ralf; Hadamitzky, Martin; Heumann, Rolf; Hansen, Wiebke; Sifringer, Marco; van de Looij, Yohan; Felderhoff-Müser, Ursula; Bendix, Ivo

    2016-02-01

    Cerebral white matter injury is a leading cause of adverse neurodevelopmental outcome in prematurely born infants involving cognitive deficits in later life. Despite increasing knowledge about the pathophysiology of perinatal brain injury, therapeutic options are limited. In the adult demyelinating disease multiple sclerosis the sphingosine-1-phosphate (S1P) receptor modulating substance fingolimod (FTY720) has beneficial effects. Herein, we evaluated the neuroprotective potential of FTY720 in a neonatal model of oxygen-toxicity, which is associated with hypomyelination and impaired neuro-cognitive outcome. A single dose of FTY720 (1mg/kg) at the onset of neonatal hyperoxia (24h 80% oxygen on postnatal day 6) resulted in improvement of neuro-cognitive development persisting into adulthood. This was associated with reduced microstructural white matter abnormalities 4 months after the insult. In search of the underlying mechanisms potential non-classical (i.e. lymphocyte-independent) pathways were analysed shortly after the insult, comprising modulation of oxidative stress and local inflammatory responses as well as myelination, oligodendrocyte degeneration and maturation. Treatment with FTY720 reduced hyperoxia-induced oxidative stress, microglia activation and associated pro-inflammatory cytokine expression. In vivo and in vitro analyses further revealed that oxygen-induced hypomyelination is restored to control levels, which was accompanied by reduced oligodendrocyte degeneration and enhanced maturation. Furthermore, hyperoxia-induced elevation of S1P receptor 1 (S1P1) protein expression on in vitro cultured oligodendrocyte precursor cells was reduced by activated FTY720 and protection from degeneration is abrogated after selective S1P1 blockade. Finally, FTY720s' classical mode of action (i.e. retention of immune cells within peripheral lymphoid organs) was analysed demonstrating that FTY720 diminished circulating lymphocyte counts independent from hyperoxia

  13. Omega-3 polyunsaturated fatty acid supplementation and white matter changes in major depression.

    PubMed

    Chhetry, Binod Thapa; Hezghia, Adrienne; Miller, Jeffrey M; Lee, Seonjoo; Rubin-Falcone, Harry; Cooper, Thomas B; Oquendo, Maria A; Mann, J John; Sublette, M Elizabeth

    2016-04-01

    White matter abnormalities are implicated in major depressive disorder (MDD). As omega-3 polyunsaturated fatty acids (PUFAs) are low in MDD and affect myelination, we hypothesized that PUFA supplementation may alleviate depression through improving white matter integrity. Acutely depressed MDD patients (n = 16) and healthy volunteers (HV, n = 12) had 25-direction diffusion tensor imaging before and after 6 weeks of fish oil supplementation. Plasma phospholipid omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and omega-6 PUFA arachidonic acid (AA) levels were determined before and after supplementation using high-throughput extraction and gas chromatography and expressed as a percentage of total phospholipids (PUFA%). Fractional anisotropy (FA) was computed using a least-squares-fit diffusion tensor with non-linear optimization. Regression analyses were performed with changes in PUFA levels or Hamilton Depression Rating Scale scores as predictors, voxel-wise difference maps of FA as outcome, covariates age and sex, with family-wise correction for multiple comparisons. Increases in plasma phospholipid DHA% (but not EPA% or AA%) after fish oil predicted increases in FA in MDD but not HV, in a cluster including genu and body of the corpus callosum, and anterior corona radiata and cingulum (cluster-level p < 0.001, peak t-score = 8.10, p = 0.002). There was a trend for greater change in FA in MDD responders over nonresponders (t = -1.874, df = 13.56, p = 0.08). Decreased depression severity predicted increased FA in left corticospinal tract and superior longitudinal fasciculus (cluster-level p < 0.001, peak t-score = 5.04, p = 0.0001). Increased FA correlated with increased DHA% and decreased depression severity after fish oil supplementation suggests therapeutic effects of omega-3 PUFAs may be related to improvements in white matter integrity. PMID:26802812

  14. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-07-01

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

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

    PubMed

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

    2010-05-15

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

  18. Age-related decline in the microstructural integrity of white matter in children with early- and continuously-treated PKU: A DTI study of the corpus callosum☆

    PubMed Central

    White, Desiree A.; Connor, Lisa Tabor; Nardos, Binyam; Shimony, Joshua S.; Archer, Rebecca; Snyder, Abraham Z.; Moinuddin, Asif; Grange, Dorothy K.; Steiner, Robert D.; McKinstry, Robert C.

    2013-01-01

    Structural, volumetric, and microstructural abnormalities have been reported in the white matter of the brain in individuals with phenylketonuria (PKU). Very little research, however, has been conducted to investigate the development of white matter in children with PKU, and the developmental trajectory of their white matter microstructure is unknown. In the current study, diffusion tensor imaging (DTI) was used to examine the development of the microstructural integrity of white matter across six regions of the corpus callosum in 34 children (7–18 years of age) with early- and continuously-treated PKU. Comparison was made with 61 demographically-matched healthy control children. Two DTI variables were examined: mean diffusivity (MD) and relative anisotropy (RA). RA was comparable to that of controls across all six regions of the corpus callosum. In contrast, MD was restricted for children with PKU in anterior (i.e., genu, rostral body, anterior midbody) but not posterior (posterior midbody, isthmus, splenium) regions of the corpus callosum. In addition, MD restriction became more pronounced with increasing age in children with PKU in the two most anterior regions of the corpus callosum (i.e., genu, rostral body). These findings point to an age-related decrement in the microstructural integrity of the anterior white matter of the corpus callosum in children with PKU. PMID:20123469

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

    PubMed

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

    2013-11-15

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

  20. Probing dark matter crests with white dwarfs and IMBHs

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

    White dwarfs (WDs) are the most promising captors of dark matter (DM) particles in the crests that are expected to build up in the cores of dense stellar clusters. The DM particles could reach sufficient densities in WD cores to liberate energy through self-annihilation. The extinction associated with our Galactic Centre makes it impossible to detect the potential-associated luminosities, contrary to smaller stellar systems which are close enough to us and not heavily extincted, such as -Cen. We investigate the prospects of detection of DM-burning WDs in a stellar cluster harbouring an intermediate-mass black hole (IMBH), which leads to higher densities of DM at the centre. We calculate the capture rate and estimate the luminosity that a WD would emit depending on its distance to the centre of the cluster. Direct-summation N-body simulations of -Cen yield a non-negligible number of WDs in the range of radii of interest. We apply our assumption to published Hubble Space Telescope/Advanced Camera for Surveys observations of stars in the centre of -Cen and, although we are not able to identify any evident candidate, we proof that their bunching up at high luminosities would be unique. We predict that DM burning will lead to a truncation of the cooling sequence at the faint end. The detection of DM burning in future observations of dense stellar clusters could allow us to probe different models of DM distributions and characteristics. On the other hand, if DM-burning WDs really exist, their number and properties could give hints to the existence of IMBHs.

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Norcross, Jason; Sherman, Paul; McGuire, Steve; Kochunov, Peter

    2016-01-01

    Introduction: Previous literature has described the increase in white matter hyperintensity (WMH) burden associated with hypobaric exposure in the U-2 and altitude chamber operating personnel. Although astronauts have similar hypobaric exposure pressures to the U2 pilot population, astronauts have far fewer exposures and each exposure would be associated with a much lower level of decompression stress due to rigorous countermeasures to prevent decompression sickness. Therefore, we postulated that the WMH burden in the astronaut population would be less than in U2 pilots. Methods: Twenty-one post-flight de-identified astronaut MRIs (5 mm slice thickness FLAIR sequences) were evaluated for WMH count and volume. The only additional data provided was an age range of the astronauts (43-57) and if they had ever performed an EVA (13 yes, 8 no). Results: WMH count in these 21 astronaut MRI was 21.0 +/- 24.8 (mean+/- SD) and volume was 0.382 +/- 0.602 ml, which was significantly higher than previously published results for the U2 pilots. No significant differences between EVA and no EVA groups existed. Age range of astronaut population is not directly comparable to the U2 population. Discussion: With significantly less frequent (sometimes none) and less stressful hypobaric exposures, yet a much higher incidence of increased WMH, this indicates the possibility of additional mechanisms beyond hypobaric exposure. This increase unlikely to be attributable just to the differences in age between astronauts and U2 pilots. Forward work includes continuing review of post-flight MRI and evaluation of pre to post flight MRI changes if available. Data mining for potential WMH risk factors includes collection of age, sex, spaceflight experience, EVA hours, other hypobaric exposures, hyperoxic exposures, radiation, high performance aircraft experience and past medical history. Finally, neurocognitive and vision/eye results will be evaluated for any evidence of impairment linked to

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

    PubMed

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

    2016-09-01

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

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

    PubMed

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

    2015-10-01

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

  5. Reduced white matter integrity is related to cognitive instability.

    PubMed

    Fjell, Anders M; Westlye, Lars T; Amlien, Inge K; Walhovd, Kristine B

    2011-12-01

    Increased performance variability has been demonstrated in several groups and conditions, including aging and cognitive decline. Structural brain characteristics underlying this phenomenon have so far been elusive. However, there is reason to expect that disconnectivity in associative pathways, whether caused by immature or degraded white matter (WM) tracts, will increase performance variability by neural noise. The aim of this study was to test whether the quality of WM, measured by diffusion tensor imaging, is related to performance variability in healthy adults. Intraindividual standard deviation of the reaction time (sdRT) across trials and median reaction time (mRT) from 270 participants were obtained from a speeded continuous performance task (Eriksen flanker task) with two conditions (congruent, incongruent). Tract-based spatial statistics was used to test the relationship with diffusion characteristics [fractional anisotropy (FA), mean diffusion (MD), radial diffusion (RD), axial diffusion (AD)]. Robust relationships between sdRT and all diffusion measures were found in most WM areas, independently of mRT, age, and sex. The effects were anatomically more widespread in the congruent than the incongruent condition, covering almost 50% of the voxels for RD and MD, and >25% of the voxels for FA and AD. Partial betas were in the range 0.45-0.55, and the strength of the relationships increased significantly with age. For mRT, the effects were smaller and unstable across condition. We concluded that performance variability is a likely consequence of individual differences in WM integrity, and that it is a promising behavioral correlate of individual differences in WM microstructure. PMID:22159119

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

    PubMed Central

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

    2015-01-01

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

  7. Voxel-based morphometry (VBM) studies in schizophrenia—can white matter changes be reliably detected with VBM?

    PubMed Central

    Melonakos, Eric; Shenton, Martha; Rathi, Yogesh; Terry, Doug; Bouix, Sylvain; Kubicki, Marek

    2012-01-01

    Voxel-Based Morphometry (VBM) is a hypothesis-free, whole-brain, voxel-by-voxel analytic method that attempts to compare imaging data between populations. Schizophrenia studies have utilized this method to localize differences in Diffusion Tensor Imaging (DTI) derived Fractional Anisotropy (FA), a measure of white matter integrity, between patients and healthy controls. The number of publications has grown, although it is unclear how reliable and reproducible this method is, given the subtle white matter abnormalities expected in schizophrenia. Here we analyze and combine results from 23 studies published to date that use VBM to study schizophrenia in order to evaluate the reproducibility of this method in DTI analysis. Coordinates of each region reported in DTI VBM studies published thus far in schizophrenia were plotted onto a Montreal Neurological Institute atlas, and their anatomical locations were recorded. Results indicated that the reductions of FA in patients with schizophrenia were scattered across the brain. Moreover, even the most consistently reported regions were reported independently in less than 35% of the papers studied. Other instances of reduced FA were replicated at an even lower rate. Our findings demonstrate striking inconsistency, with none of the regions reported in much more than a third of the published papers. Poor replication rate suggests that the application of VBM to DTI data may not be the optimal way for studying the subtle microstructural abnormalities that are being hypothesized in schizophrenia. PMID:21684124

  8. Cocaine addiction: diffusion tensor imaging study of the inferior frontal and anterior cingulate white matter.

    PubMed

    Romero, Maria J; Asensio, Samuel; Palau, Carmina; Sanchez, Amparo; Romero, Francisco J

    2010-01-30

    Inferior frontal and anterior cingulate white matter integrity in 32 cocaine-dependent subjects was compared with that in 33 age-matched healthy control subjects. Diffusion tensor imaging data were acquired with a 1.5-T magnetic resonance imaging system. Cocaine-dependent subjects presented significantly lower fractional anisotropy values in inferior frontal white matter at the anterior-posterior commissure plane and higher anterior cingulate white matter values than control subjects. White matter integrity was also associated with impulsivity and motivation to change (Readiness to Change Questionnaire). These findings support the hypothesis that cocaine dependence involves a disruption of orbitofrontal connectivity and suggest that the anterior cingulate brain area might play a role in the motivation to change. PMID:19959341

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

    PubMed

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

    2010-07-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2016-06-01

    Type 2 diabetes mellitus (T2DM) is characterized by obesity, hyperglycemia and insulin resistance. Both T2DM and obesity are associated with cerebral complications, including an increased risk of cognitive impairment and dementia, however the underlying mechanisms are largely unknown. In the current study, we aimed to determine the relative contributions of obesity and the presence of T2DM to altered white matter structure. We used diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) to measure white matter integrity and volume in obese T2DM patients without micro- or macrovascular complications, age- gender- and BMI-matched normoglycemic obese subjects and age- and gender-matched normoglycemic lean subjects. We found that obese T2DM patients compared with lean subjects had lower axial diffusivity (in the right corticospinal tract, right inferior fronto-occipital tract, right superior longitudinal fasciculus and right forceps major) and reduced white matter volume (in the right inferior parietal lobe and the left external capsule region). In normoglycemic obese compared with lean subjects axial diffusivity as well as white matter volume tended to be reduced, whereas there were no significant differences between normoglycemic obese subjects and T2DM patients. Decreased white matter integrity and volume were univariately related to higher age, being male, higher BMI, HbA1C and fasting glucose and insulin levels. However, multivariate analyses demonstrated that only BMI was independently related to white matter integrity, and age, gender and BMI to white matter volume loss. Our data indicate that obese T2DM patients have reduced white matter integrity and volume, but that this is largely explained by BMI, rather than T2DM per se. PMID:26815786

  13. Genetic Underpinnings of White Matter ‘Connectivity’: Heritability, Risk, and Heterogeneity in Schizophrenia

    PubMed Central

    Voineskos, Aristotle N.

    2014-01-01

    Schizophrenia is a highly heritable disorder. Thus, the combination of genetics and brain imaging may be a useful strategy to investigate the effects of risk genes on anatomical connectivity, and for gene discovery, i.e. discovering the genetic correlates of white matter phenotypes. Following a database search, I review evidence for heritability of white matter phenotypes. I also review candidate gene investigations, examining association of putative risk variants with white matter phenotypes, as well as the recent flurry of research exploring relationships of genome-wide significant risk loci with white matter phenotypes. Finally, I review multivariate and polygene approaches, which constitute a new wave of imaging-genetics research, including large collaborative initiatives aiming to discover new genes that may predict aspects of white matter microstructure. The literature supports the heritability of white matter phenotypes. Loci in genes intimately implicated in oligodendrocyte and myelin development, growth and maintenance, and neurotrophic systems are associated with white matter microstructure. GWAS variants have not yet sufficiently been explored using DTI-based evaluation of white matter to draw conclusions, although micro-RNA 137 is promising due to its potential regulation of other GWAS schizophrenia genes. Many imaging-genetic studies only include healthy participants, which, while helping control for certain confounds, cannot address questions related to disease heterogeneity or symptom expression, and thus more studies should include participants with schizophrenia. With sufficiently large sample sizes, the future of this field lies in polygene strategies aimed at risk prediction and heterogeneity dissection of schizophrenia that can translate to personalized interventions. PMID:24893906

  14. Assessing the effects of age on long white matter tracts using diffusion tensor tractography

    PubMed Central

    Davis, Simon W.; Dennis, Nancy A.; Buchler, Norbou G.; White, Leonard E.; Madden, David J.; Cabeza, Roberto

    2009-01-01

    Aging is associated with significant white matter deterioration and this deterioration is assumed to be at least partly a consequence of myelin degeneration. The present study investigated specific predictions of the myelodegeneration hypothesis using diffusion tensor tractography. This technique has several advantages over other methods of assessing white matter architecture, including the possibility of isolating individual white matter tracts and measuring effects along the whole extent of each tract. The study yielded three main findings. First, age-related white matter deficits increased gradually from posterior to anterior segments within specific fiber tracts traversing frontal and parietal, but not temporal cortex. This pattern inverts the sequence of myelination during childhood and early development observed in previous studies and lends support to a “last-in-first-out” theory of the white matter health across the lifespan. Second, both the effects aging on white matter and their impact on cognitive performance were stronger for radial diffusivity (RD) than for axial diffusivity (AD). Given that RD has previously been shown to be more sensitive to myelin integrity than AD, this second finding is also consistent with the myelodegeneration hypothesis. Finally, the effects of aging on select white matter tracts were associated with age difference in specific cognitive functions. Specifically, FA in anterior tracts was shown to be primarily associated with executive tasks and FA in posterior tracts mainly associated with visual memory tasks. Furthermore, these correlations were mirrored in RD, but not AD, suggesting that RD is more sensitive to age-related changes in cognition. Taken together, the results help to clarify how age-related white matter decline impairs cognitive performance. PMID:19385018

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

    PubMed Central

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

    2015-01-01

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

  16. Regional Abnormality of Grey Matter in Schizophrenia: Effect from the Illness or Treatment?

    PubMed

    Yue, Ying; Kong, Li; Wang, Jijun; Li, Chunbo; Tan, Ling; Su, Hui; Xu, Yifeng

    2016-01-01

    Both schizophrenia and antipsychotic treatment are known to modulate brain morphology. However, it is difficult to establish whether observed structural brain abnormalities are due to disease or the effects of treatment. The aim of this study was to investigate the effects of illness and antipsychotic treatment on brain structures in antipsychotic-naïve first-episode schizophrenia based on a longitudinal short-term design. Twenty antipsychotic-naïve subjects with first-episode schizophrenia and twenty-four age- and sex-matched healthy controls underwent 3T MRI scans. Voxel-based morphometry (VBM) was used to examine the brain structural abnormality in patients compared to healthy controls. Nine patients were included in the follow-up examination after 8 weeks of treatment. Tensor-based morphometry (TBM) was used to identify longitudinal brain structural changes. We observed significantly reduced grey matter volume in the right superior temporal gyrus in antipsychotic-naïve patients with schizophrenia compared with healthy controls. After 8 weeks of treatment, patients showed significantly increased grey matter volume primarily in the bilateral prefrontal cortex, insula, right thalamus, left superior occipital cortex and the bilateral cerebellum. In addition, a greater enlargement of the prefrontal cortex is associated with the improvement in negative symptoms, and a more enlarged thalamus is associated with greater improvement in positive symptoms. Our results suggest the following: (1) the abnormality in the right superior temporal gyrus is present in the early stages of schizophrenia, possibly representing the core region related to schizophrenia; and (2) atypical antipsychotics could modulate brain morphology involving the thalamus, cortical grey matter and cerebellum. In addition, examination of the prefrontal cortex and thalamus might facilitate an efficient response to atypical antipsychotics in terms of symptom improvement. PMID:26789520

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

    PubMed

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

    2014-10-22

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

  18. 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. PMID:26277436

  19. Effects of White Matter Injury on Resting State fMRI Measures in Prematurely Born Infants

    PubMed Central

    Smyser, Christopher D.; Snyder, Abraham Z.; Shimony, Joshua S.; Blazey, Tyler M.; Inder, Terrie E.; Neil, Jeffrey J.

    2013-01-01

    The cerebral white matter is vulnerable to injury in very preterm infants (born prior to 30 weeks gestation), resulting in a spectrum of lesions. These range from severe forms, including cystic periventricular leukomalacia and periventricular hemorrhagic infarction, to minor focal punctate lesions. Moderate to severe white matter injury in preterm infants has been shown to predict later neurodevelopmental disability, although outcomes can vary widely in infants with qualitatively comparable lesions. Resting state functional connectivity magnetic resonance imaging has been increasingly utilized in neurodevelopmental investigations and may provide complementary information regarding the impact of white matter injury on the developing brain. We performed resting state functional connectivity magnetic resonance imaging at term equivalent postmenstrual age in fourteen preterm infants with moderate to severe white matter injury secondary to periventricular hemorrhagic infarction. In these subjects, resting state networks were identifiable throughout the brain. Patterns of aberrant functional connectivity were observed and depended upon injury severity. Comparisons were performed against data obtained from prematurely-born infants with mild white matter injury and healthy, term-born infants and demonstrated group differences. These results reveal structural-functional correlates of preterm white matter injury and carry implications for future investigations of neurodevelopmental disability. PMID:23874510

  20. Altered White Matter Integrity in the Congenital and Late Blind People

    PubMed Central

    Wang, Dawei; Qin, Wen; Liu, Yong; Zhang, Yunting; Jiang, Tianzi; Yu, Chunshui

    2013-01-01

    The blind subjects have experienced a series of brain structural and functional alterations due to the visual deprivation. It remains unclear as to whether white matter changes differ between blind subjects with visual deprivation before and after a critical developmental period. The present study offered a direct comparison in changes of white matter fractional anisotropy (FA) between congenital blind (CB) and late blind (LB) individuals. Twenty CB, 21 LB (blindness onset after 18 years old), and 40 sight control (SC) subjects were recruited. Both the tract-based spatial statistics (TBSS) and voxel-based analysis (VBA) showed lower FA in the bilateral optic radiations in both blind groups, suggesting that the loss of white matter integrity was the prominent hallmark in the blind people. The LB group showed more extensive white matter impairment than the CB group, indicating the mechanisms of white matter FA changes are different between the CB and LB groups. Using a loose threshold, a trend of an increased FA was found in the bilateral corticospinal tracts in the LB but with a smaller spatial extent relative to the CB. These results suggest that white matter FA changes in the blind subjects are the reflection of multiple mechanisms, including the axonal degeneration, deafferentation, and plasticity. PMID:23710371

  1. Pathological and biochemical studies on a case of Pick disease with severe white matter atrophy.

    PubMed

    Yamakawa, Kazuo; Takanashi, Masashi; Watanabe, Masao; Nakamura, Noriyuki; Kobayashi, Tomonori; Hasegawa, Masato; Mizuno, Yoshikuni; Tanaka, Shigeki; Mori, Hideo

    2006-12-01

    We report on a male patient with Pick disease who had shown severe white matter atrophy and dilatation of the lateral ventricle in the frontal lobe from an early stage. Upon admission to our hospital 2 years after disease onset, the patient showed apathy, and MRI revealed severe atrophy of the cortex and white matter of the frontal lobe. He died at age 74, 11 years after disease onset. Autopsy revealed severe atrophy of the frontal and temporal lobes, severe loss of white matter in the frontal lobe, dilatation of the lateral ventricles, and cortical thinning. Histopathological examination showed severe loss of myelinated fibers in the frontal white matter and severe neuronal loss with gliosis in the frontal and temporal cortices. Many Pick bodies were seen. Our patient had a rare case of Pick disease predominantly affecting the frontal lobe with severe involvement of the white matter from an early stage. This case suggests that myelinated fibers in the white matter as well as cerebral neurons are primarily affected in Pick disease. PMID:17203597

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

    PubMed

    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

  3. 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

  4. Magnified effects of the COMT gene on white-matter microstructure in very old age.

    PubMed

    Papenberg, Goran; Lövdén, Martin; Laukka, Erika J; Kalpouzos, Grégoria; Keller, Lina; Graff, Caroline; Köhncke, Ylva; Li, Tie-Qiang; Fratiglioni, Laura; Bäckman, Lars

    2015-09-01

    Genetic factors may partly account for between-person differences in brain integrity in old age. Evidence from human and animal studies suggests that the dopaminergic system is implicated in the modulation of white-matter integrity. We investigated whether a genetic variation in the Catechol-O-Methyltransferase (COMT) Val158Met polymorphism, which influences dopamine availability in prefrontal cortex, contributes to interindividual differences in white-matter microstructure, as measured with diffusion-tensor imaging. In a sample of older adults from a population-based study (60-87 years; n = 238), we found that the COMT polymorphism affects white-matter microstructure, indexed by fractional anisotropy and mean diffusivity, of several white-matter tracts in the oldest age group (81-87 years), although there were no reliable associations between COMT and white-matter microstructure in the two younger age groups (60-66 and 72-78 years). These findings extend previous observations of magnified genetic effects on cognition in old age to white-matter integrity. PMID:25056932

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

    PubMed

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

    2013-02-01

    Mathematical skills are of critical importance, both academically and in everyday life. Neuroimaging research has primarily focused on the relationship between mathematical skills and functional brain activity. Comparatively few studies have examined which white matter regions support mathematical abilities. The current study uses diffusion tensor imaging (DTI) to test whether individual differences in white matter predict performance on the math subtest of the Preliminary Scholastic Aptitude Test (PSAT). Grades 10 and 11 PSAT scores were obtained from 30 young adults (ages 17-18) with wide-ranging math achievement levels. Tract based spatial statistics was used to examine the correlation between PSAT math scores, fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD). FA in left parietal white matter was positively correlated with math PSAT scores (specifically in the left superior longitudinal fasciculus, left superior corona radiata, and left corticospinal tract) after controlling for chronological age and same grade PSAT critical reading scores. Furthermore, RD, but not AD, was correlated with PSAT math scores in these white matter microstructures. The negative correlation with RD further suggests that participants with higher PSAT math scores have greater white matter integrity in this region. Individual differences in FA and RD may reflect variability in experience dependent plasticity over the course of learning and development. These results are the first to demonstrate that individual differences in white matter are associated with mathematical abilities on a nationally administered scholastic aptitude measure. PMID:23108272

  6. A tract-specific framework for white matter morphometry combining macroscopic and microscopic tract features

    PubMed Central

    Zhang, Hui; Awatea, Suyash P; Das, Sandhitsu R; Woo, John H; Melhem, Elias R; Gee, James C; Yushkevich, Paul A

    2010-01-01

    Diffusion tensor imaging plays a key role in our understanding of white matter both in normal populations and in populations with brain disorders. Existing techniques focus primarily on using diffusivity-based quantities derived from diffusion tensor as surrogate measures of microstructural tissue properties of white matter. In this paper, we describe a novel tract-specific framework that enables the examination of white matter morphometry at both the macroscopic and microscopic scales. The framework leverages the skeleton-based modeling of sheet-like white matter fasciculi using the continuous medial representation, which gives a natural definition of thickness and supports its comparison across subjects. The thickness measure provides a macroscopic characterization of white matter fasciculi that complements existing analysis of microstructural features. The utility of the framework is demonstrated in quantifying white matter atrophy in Amyotrophic Lateral Sclerosis, a severe neurodegenerative disease of motor neurons. We show that, compared to using microscopic features alone, combining the macroscopic and microscopic features gives a more complete characterization of the disease. PMID:20547469

  7. Prestroke statins, progression of white matter hyperintensities, and cognitive decline in stroke patients with confluent white matter hyperintensities.

    PubMed

    Xiong, Yunyun; Wong, Adrian; Cavalieri, Margherita; Schmidt, Reinhold; Chu, Winnie W C; Liu, Xinfeng; Wong, Ka Sing; Mok, Vincent

    2014-07-01

    Cerebral white matter hyperintensities (WMH) are a consequence of cerebral small vessel disease. Statins have been shown to reduce recurrent stroke among patients with various stroke subtypes, including lacunar stroke, which also arises from small vessel disease. In this study, we investigated the hypothesis that prestroke statin use would reduce the progression of WMH and/or cognitive decline among stroke patients with confluent WMH. Patients (n = 100) were participants of the VITAmins To Prevent Stroke magnetic resonance imaging substudy. All patients had confluent WMH on magnetic resonance imaging at baseline. Eighty-one patients completed the 2-year follow-up. We assessed general cognition and executive function using the mini-mental state examination and Mattis dementia rating scale-initiation/perseveration subscale, respectively. We compared the change in volume of WMH and cognition between prestroke statin use and prestroke nonstatin use groups. We also evaluated the effects of prestroke statin use on incident lacunes and microbleeds. The prestroke statin use group (n = 51) had less WMH volume progression (1.54 ± 4.52 cm(3) vs 5.01 ± 6.00 cm(3), p = 0.02) compared with the prestroke nonstatin use group (n = 30). Multivariate linear regression modeling identified prestroke statin use as an independent predictor of WMH progression (β = -0.31, p = 0.008). Prestroke statin use was also associated with less decline (Mattis dementia rating scale-initiation/perseveration subscale; β = 0.47, p = 0.001). No association was observed with changes in mini-mental state examination scores. There were no between group differences on incident lacunes or incident microbleeds. Prestroke statin use may reduce WMH progression and decline in executive function in stroke patients with confluent WMH. PMID:24692001

  8. High-affinity choline uptake and acetylcholine-metabolizing enzymes in CNS white matter. A quantitative study.

    PubMed

    Hassel, Bjørnar; Solyga, Volker; Lossius, Andreas

    2008-12-01

    The presence of nicotinic and muscarinic receptors suggests the occurrence of cholinergic neurotransmission in white matter; however no quantitative information exists on acetylcholine formation and breakdown in white matter. We compared white structures of pig brain (fimbria, corpus callosum, pyramidal tracts, and occipital white matter) to gray structures (temporal, parietal and cerebellar cortices, hippocampus, and caudate) and found that sodium-dependent, high-affinity choline uptake in white structures was 25-31% of that in hippocampus. White matter choline acetyltransferase activity was 10-50% of the hippocampal value; the highest activity was found in fimbria. Acetylcholine esterase activity in white structures was 20-25% of that in hippocampus. The caudate, which is rich in cholinergic interneurons, gave values for all three parameters that were 2.8-4 times higher than in hippocampus. The results suggest a certain capacity for cholinergic neurotransmission in central nervous white matter. The white matter activity of pyruvate dehydrogenase, which provides acetyl-CoA for acetylcholine synthesis, ranged between 33 and 50% of the hippocampal activity; the activity in the caudate was similar to that in hippocampus and the other gray structures, which was true also for other enzymes of glucose metabolism: hexokinase, phosphoglucomutase, and glucose-6-phosphate dehydrogenase. Acetylcholine esterase activity in white matter was inhibited by the nerve agent soman, which may help explain the reported deleterious effect of soman on white matter. Further, this finding suggests that acetylcholine esterase inhibitors used in Alzheimer's disease may have an effect in white matter. PMID:18674580

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

    PubMed

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

    2016-04-01

    White matter hyperintensities are associated with increased risk of dementia and cognitive decline. The current study investigates the relationship between white matter hyperintensities burden and patterns of brain atrophy associated with brain ageing and Alzheimer's disease in a large populatison-based sample (n = 2367) encompassing a wide age range (20-90 years), from the Study of Health in Pomerania. We quantified white matter hyperintensities using automated segmentation and summarized atrophy patterns using machine learning methods resulting in two indices: the SPARE-BA index (capturing age-related brain atrophy), and the SPARE-AD index (previously developed to capture patterns of atrophy found in patients with Alzheimer's disease). A characteristic pattern of age-related accumulation of white matter hyperintensities in both periventricular and deep white matter areas was found. Individuals with high white matter hyperintensities burden showed significantly (P < 0.0001) lower SPARE-BA and higher SPARE-AD values compared to those with low white matter hyperintensities burden, indicating that the former had more patterns of atrophy in brain regions typically affected by ageing and Alzheimer's disease dementia. To investigate a possibly causal role of white matter hyperintensities, structural equation modelling was used to quantify the effect of Framingham cardiovascular disease risk score and white matter hyperintensities burden on SPARE-BA, revealing a statistically significant (P < 0.0001) causal relationship between them. Structural equation modelling showed that the age effect on SPARE-BA was mediated by white matter hyperintensities and cardiovascular risk score each explaining 10.4% and 21.6% of the variance, respectively. The direct age effect explained 70.2% of the SPARE-BA variance. Only white matter hyperintensities significantly mediated the age effect on SPARE-AD explaining 32.8% of the variance. The direct age effect explained 66.0% of the SPARE

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

    Current neuroimaging investigation of the white matter typically focuses on measurements derived from diffusion tensor imaging, such as fractional anisotropy (FA). In contrast, imaging studies of the gray matter oftentimes focus on morphological features such as cortical thickness, folding and surface curvature. As a result, it is not clear how to combine findings from these two types of approaches in order to obtain a consistent picture of morphological changes in both gray and white matter. In this paper, we propose a joint investigation of gray and white matter morphology by combining geometrical information from white and the gray matter. To achieve this, we first introduce a novel method for computing multi-scale white matter tract geometry. Its formulation is based on the differential geometry of curve sets and is easily incorporated into a continuous scale-space framework. We then incorporate this method into a novel framework for “fusing” white and gray matter geometrical information. Given a set of fiber tracts originating in a particular cortical region, the key idea is to compute two scalar fields that represent geometrical characteristics of the white matter and of the surface of the cortical region. A quantitative marker is created by combining the distributions of these scalar values using Mutual Information. This marker can be then used in the study of normal and pathological brain structure and development. We apply this framework to a study on autism spectrum disorder in children. Our preliminary results support the view that autism may be characterized by early brain overgrowth, followed by reduced or arrested growth [7]. PMID:25066750

  12. The abnormally weighting energy hypothesis: the missing link between dark matter and dark energy

    SciTech Connect

    Alimi, J-M; Fuezfa, A E-mail: andre.fuzfa@fundp.ac.be

    2008-09-15

    We generalize tensor-scalar theories of gravitation by the introduction of an 'abnormally weighting' type of energy. This theory of tensor-scalar anomalous gravity is based on a relaxation of the weak equivalence principle that is currently restricted to ordinary visible matter only. As a consequence, the mechanism of convergence toward general relativity is modified and produces cosmic acceleration naturally as an inescapable gravitational feedback induced by the mass variation of some invisible sector. The cosmological implications of this new theoretical framework are studied. From the Hubble diagram cosmological test alone, this theory provides estimates of the amount of baryons and dark matter in the Universe that are consistent with the independent cosmological tests of the cosmic microwave background and big bang nucleosynthesis. Cosmic coincidence is naturally achieved from an equally natural assumption on the amplitude of the scalar coupling strength. Finally, from the adequacy for supernovae data, we derive a new intriguing relation between the space-time dependences of the gravitational coupling and the dark matter mass, providing an example of a crucial constraint on microphysics from cosmology. This provides glimpses of an enticing new symmetry between the visible and invisible sectors, namely that the scalar charges of visible and invisible matter are exactly opposite.

  13. White matter connectivity in children with autism spectrum disorders: a tract-based spatial statistics study

    PubMed Central

    2012-01-01

    Background Autism spectrum disorders (ASD) are associated with widespread alterations in white matter (WM) integrity. However, while a growing body of studies is shedding light on microstructural WM alterations in high-functioning adolescents and adults with ASD, literature is still lacking in information about whole brain structural connectivity in children and low-functioning patients with ASD. This research aims to investigate WM connectivity in ASD children with and without mental retardation compared to typically developing controls (TD). Methods Diffusion tensor imaging (DTI) was performed in 22 young children with ASD (mean age: 5.54 years) and 10 controls (mean age: 5.25 years). Data were analysed both using the tract-based spatial statistics (TBSS) and the tractography. Correlations were investigated between the WM microstructure in the identified altered regions and the productive language level. Results The TBSS analysis revealed widespread increase of fractional anisotropy (FA) in major WM pathways. The tractographic approach showed an increased fiber length and FA in the cingulum and in the corpus callosum and an increased mean diffusivity in the indirect segments of the right arcuate and the left cingulum. Mean diffusivity was also correlated with expressive language functioning in the left indirect segments of the arcuate fasciculus. Conclusions Our study confirmed the presence of several structural connectivity abnormalities in young ASD children. In particular, the TBSS profile of increased FA that characterized the ASD patients extends to children a finding previously detected in ASD toddlers only. The WM integrity abnormalities detected may be relevant to the pathophysiology of ASD, since the structures involved participate in some core atypical characteristics of the disorder. PMID:23194030

  14. Unique white matter microstructural patterns in ADHD presentations-a diffusion tensor imaging study.

    PubMed

    Svatkova, Alena; Nestrasil, Igor; Rudser, Kyle; Goldenring Fine, Jodene; Bledsoe, Jesse; Semrud-Clikeman, Margaret

    2016-09-01

    Attention-deficit/hyperactivity disorder predominantly inattentive (ADHD-PI) and combined (ADHD-C) presentations are likely distinct disorders that differ neuroanatomically, neurochemically, and neuropsychologically. However, to date, little is known about specific white matter (WM) regions differentiating ADHD presentations. This study examined differences in WM microstructure using diffusion tensor imaging (DTI) data from 20 ADHD-PI, 18 ADHD-C, and 27 typically developed children. Voxel-wise analysis of DTI measurements in major fiber bundles was carried out using tract-based spatial statistics (TBSS). Clusters showing diffusivity abnormalities were used as regions of interest for regression analysis between fractional anisotropy (FA) and neuropsychological outcomes. Compared to neurotypicals, ADHD-PI children showed higher FA in the anterior thalamic radiations (ATR), bilateral inferior longitudinal fasciculus (ILF), and in the left corticospinal tract (CST). In contrast, the ADHD-C group exhibited higher FA in the bilateral cingulum bundle (CB). In the ADHD-PI group, differences in FA in the left ILF and ATR were accompanied by axial diffusivity (AD) abnormalities. In addition, the ADHD-PI group exhibited atypical mean diffusivity in the forceps minor (FMi) and left ATR and AD differences in right CB compared to healthy subjects. Direct comparison between ADHD presentations demonstrated radial diffusivity differences in FMi. WM clusters with FA irregularities in ADHD were associated with neurobehavioral performance across groups. In conclusion, differences in WM microstructure in ADHD presentations strengthen the theory that ADHD-PI and ADHD-C are two distinct disorders. Regions with WM irregularity seen in both ADHD presentations might serve as predictors of executive and behavioral functioning across groups. Hum Brain Mapp 37:3323-3336, 2016. © 2016 Wiley Periodicals, Inc. PMID:27159198

  15. Thalamic fractional anisotropy predicts accrual of cerebral white matter damage in older subjects with small-vessel disease

    PubMed Central

    Cavallari, Michele; Moscufo, Nicola; Meier, Dominik; Skudlarski, Pawel; Pearlson, Godfrey D; White, William B; Wolfson, Leslie; Guttmann, Charles RG

    2014-01-01

    White matter hyperintensities (WMHs) and lacunes are magnetic resonance imaging hallmarks of cerebral small-vessel disease, which increase the risk of stroke, cognitive, and mobility impairment. Although most studies of cerebral small-vessel disease have focused on white matter abnormalities, the gray matter (GM) is also affected, as evidenced by frequently observed lacunes in subcortical GM. Diffusion tensor imaging (DTI) is sensitive to subtle neurodegenerative changes in deep GM structures. We explored the relationship between baseline DTI characteristics of the thalamus, caudate, and putamen, and the volume and subsequent accrual of WMHs over a 4-year period in 56 community-dwelling older (⩾75 years) individuals. Baseline thalamic fractional anisotropy (FA) was an independent predictor of WMH accrual. WMH accrual also correlated with baseline lacune count and baseline WMH volume, the latter showing the strongest predictive power, explaining 27.3% of the variance. The addition of baseline thalamic FA in multivariate modeling increased this value by 70%, which explains 46.5% of the variance in WMH accrual rate. Thalamic FA might serve as a novel predictor of cerebral small-vessel disease progression in clinical settings and trials. Furthermore, our findings point to the possibility of a causal relationship between thalamic damage and the accrual of WMHs. PMID:24824915

  16. Left ventricular geometry and white matter lesions in ischemic stroke patients.

    PubMed

    Butenaerts, Demian; Chrzanowska-Wasko, Joanna; Slowik, Agnieszka; Dziedzic, Tomasz

    2016-06-01

    Abnormal left ventricular (LV) geometry is associated with extracardiac organ damage in patients with hypertension. The aim of this study was to determine the relationship between LV geometry and white matter lesions (WMLs) in ischemic stroke patients. We retrospectively analyzed data from 155 patients (median age 62; 49.8% male) with mild ischemic stroke (median National Institutes of Health Stroke Scale score 4) who underwent brain magnetic resonance imaging and echocardiography. Patients were categorized into four groups: normal LV geometry, concentric remodeling, eccentric left ventricular hypertrophy (LVH) and concentric LVH. WMLs were graded using the Fazekas scale on fluid-attenuated inversion recovery images. Extensive WMLs were defined as a Fazekas score > 2. Extensive WMLs were more prevalent in patients with concentric LVH, eccentric LVH and concentric remodeling than in those with normal LV geometry. After adjusting for hypertension, age, diabetes mellitus, hypercholesterolemia, glomerular filtration rate and ischemic heart disease, patients with concentric remodeling [odds ratio (OR) 3.94, 95% confidence interval (CI) 1.26-12.31, p = 0.02] and those with concentric LVH (OR 3.69, 95% CI 1.24-10.95, p = 0.02), but not patients with eccentric LVH (OR 2.44, 95% CI 0.72-8.29, p = 0.15), had higher risk of extensive WMLs than patients with normal LV geometry. PMID:26581453

  17. Interpersonal competence in young adulthood and right laterality in white matter.

    PubMed

    De Pisapia, Nicola; Serra, Mauro; Rigo, Paola; Jager, Justin; Papinutto, Nico; Esposito, Gianluca; Venuti, Paola; Bornstein, Marc H

    2014-06-01

    The right hemisphere of the human brain is known to be involved in processes underlying emotion and social cognition. Clinical neuropsychology investigations and brain lesion studies have linked a number of personality and social disorders to abnormal white matter (WM) integrity in the right hemisphere. Here, we tested the hypothesis that interpersonal competencies are associated with integrity of WM tracts in the right hemisphere of healthy young adults. Thirty-one participants underwent diffusion tensor imaging scanning. Fractional anisotropy was used to quantify water diffusion. After the scanning session, participants completed the Adolescent Interpersonal Competence Questionnaire. Fractional anisotropy was subsequently correlated with Adolescent Interpersonal Competence Questionnaire scores using tract-based spatial statistics. Higher interpersonal competencies are related to higher WM integrity in several major tracts of the right hemisphere, in specific the uncinate fasciculus, the cingulum, the forceps minor, the infero-fronto occipital fasciculus, the inferior longitudinal fasciculus, and the superior longitudinal fasciculus. These results provide the first direct analysis of the neuroanatomical basis of interpersonal competencies and young adult self-reported skills in social contexts. PMID:24345175

  18. White matter alterations in anorexia nervosa: A systematic review of diffusion tensor imaging studies

    PubMed Central

    Martin Monzon, Beatriz; Hay, Phillipa; Foroughi, Nasim; Touyz, Stephen

    2016-01-01

    AIM: To identify findings concerning white matter (WM) fibre microstructural alterations in anorexia nervosa (AN). METHODS: A systematic electronic search was undertaken in several databases up to April 2015. The search strategy aimed to locate all studies published in English or Spanish that included participants with AN and which investigated WM using diffusion tensor imaging (DTI). Trials were assessed for quality assessment according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses checklist and a published quality index guideline. RESULTS: A total of 6 studies met the inclusion criteria, four of people in the acute state of the illness, one included both recovered and unwell participants, and one included people who had recovered. Participants were female with ages ranging from 14 to 29 years. All studies but one measured a range of psychopathological features. Fractional anisotropy and mean diffusivity were the main DTI correlates reported. Alterations were reported in a range of WM structures of the limbic system, most often of the fornix and cingulum as well as the fronto-occipital fibre tracts, i.e., regions associated with anxiety, body image and cognitive function. Subtle abnormalities also appeared to persist after recovery. CONCLUSION: This diversity likely reflects the symptom complexity of AN. However, there were few studies, they applied different methodologies, and all were cross-sectional. PMID:27014606

  19. White matter microstructure alterations in primary dysmenorrhea assessed by diffusion tensor imaging.

    PubMed

    Liu, Peng; Wang, Geliang; Liu, Yanfei; Yu, Qingbao; Yang, Fan; Jin, Lingmin; Sun, Jinbo; Yang, Xuejuan; Qin, Wei; Calhoun, Vince D

    2016-01-01

    Primary dysmenorrhea (PDM), a significant public health problem for adolescents and young women, is characterized by painful menstrual cramps. Recent neuroimaging studies have revealed that brain functional and structural abnormalities are related to the pathomechanism of PDM. However, it is not clear whether there are white matter (WM) alterations in PDM. We analyzed diffusion tensor imaging data from 35 patients and 35 healthy controls (HCs) matched for age and handedness. Tract-based spatial statistics and probabilistic tractography were used to measure integrity of WM microstructure. Compared to HCs, patients had increased fractional anisotropy (FA) along with decreased mean diffusivity (MD) and radial diffusivity (RD) in the corpus callosum (CC), superior longitudinal fasciculus (LF), corona radiata (CR), internal capsule (IC) and external capsule (EC). The FA of the splenium CC and right IC positively correlated with PDM duration while FA of the right anterior CR positively correlated with PDM severity in patient group. These WM tracts were found to show connections to other brain regions implicated in sensoimotor, affective, cognitive and pain processing functions through tractography. These findings provide preliminary evidence for WM microstructure alterations in PDM, which is potentially valuable for understanding pathomechanism of PDM. PMID:27161845

  20. Integrity of white matter microstructure in alcoholics with and without Korsakoff's syndrome.

    PubMed

    Segobin, Shailendra; Ritz, Ludivine; Lannuzel, Coralie; Boudehent, Céline; Vabret, François; Eustache, Francis; Beaunieux, Hélène; Pitel, Anne-Lise

    2015-07-01

    Alcohol dependence results in two different clinical forms: "uncomplicated" alcoholism (UA) and Korsakoff's syndrome (KS). Certain brain networks are especially affected in UA and KS: the frontocerebellar circuit (FCC) and the Papez circuit (PC). Our aims were (1) to describe the profile of white matter (WM) microstructure in FCC and PC in the two clinical forms, (2) to identify those UA patients at risk of developing KS using their WM microstructural integrity as a biomarker. Tract-based spatial statistics and nonparametric voxel-based permutation tests were used to compare diffusion tensor imaging (DTI) data in 7 KS, 20 UA, and 14 healthy controls. The two patient groups were also pooled together and compared to controls. k-means classifications were then performed on mean fractional anisotropy values of significant clusters across all subjects for two fiber tracts from the FCC (the middle cerebellar peduncle and superior cerebellar peduncle) and two tracts from the PC (fornix and cingulum). We found graded effects of WM microstructural abnormalities in the PC of UA and KS. UA patients classified at risk of developing KS using fiber tracts of the PC from DTI data also had the lowest scores of episodic memory. That finding suggests that WM microstructure could be used as a biomarker for early detection of UA patients at risk of developing KS. PMID:25873017

  1. Serum Cholesterol and Variant in Cholesterol-Related Gene CETP Predict White Matter Microstructure

    PubMed Central

    Warstadt, Nicholus M.; Dennis, Emily L.; Jahanshad, Neda; Kohannim, Omid; Nir, Talia M.; McMahon, Katie L.; de Zubicaray, Greig I.; Montgomery, Grant W.; Henders, Anjali K.; Martin, Nicholas G.; Whitfield, John B.; Jack, Clifford R.; Bernstein, Matt A.; Weiner, Michael W.; Toga, Arthur W.; Wright, Margaret J.; Thompson, Paul M.

    2014-01-01

    Several common genetic variants influence cholesterol levels, which play a key role in overall health. Myelin synthesis and maintenance are highly sensitive to cholesterol concentrations, and abnormal cholesterol levels increase the risk for various brain diseases, including Alzheimer's disease (AD). We report significant associations between higher serum cholesterol (CHOL) levels and high-density lipoproteins (HDL) and higher fractional anisotropy in 403 young adults (23.8±2.4 years) scanned with diffusion imaging and anatomical MRI at 4 Tesla. By fitting a multi-locus genetic model within white matter areas associated with CHOL, we found that a set of 18 cholesterol-related SNPs implicated in AD risk predicted FA. We focused on the SNP with the largest individual effects - CETP (rs5882) – and found that increased G-allele dosage was associated with higher FA and lower radial and mean diffusivities in voxel-wise analyses of the whole brain. A follow-up analysis detected WM associations with rs5882 in the opposite direction in 78 older individuals (74.3±7.3 years). Cholesterol levels may influence WM integrity, and cholesterol-related genes may exert age-dependent effects. PMID:24997672

  2. Cognitive Control and White Matter Callosal Microstructure in Methamphetamine Dependent Subjects: A DTI Study

    PubMed Central

    Salo, Ruth; Nordahl, Thomas E; Buonocore, Michael H; Natsuaki, Yutaka; Waters, Christy; Moore, Charles D; Galloway, Gantt P; Leamon, Martin H

    2009-01-01

    Background Methamphetamine (MA) abuse causes damage to structures within the human cerebrum, with particular susceptibility to white matter (WM). Abnormalities have been reported in anterior regions with less evidence of changes in posterior regions. MA abusers have also shown deficits on attention tests that measure response conflict and cognitive control. Methods We examined cognitive control using a computerized measure of the Stroop selective attention task and indices of WM microstructure obtained from diffusion tensor imaging (DTI) in the callosal genu and splenium of 37 currently abstinent MA abusers and 17 non-substance abusing controls. Measurements of Fractional Anisotropy (FA), apparent diffusion coefficient (ADC) of callosal fibers and diffusion tensor eigenvalues were obtained in all subjects. Results The MA abusers exhibited greater Stroop reaction time interference (i.e., reduced cognitive control) [p=.04] compared to controls. After correcting for multiple comparisons, FA within the genu correlated significantly with measures of cognitive control in the MA abusers [p=.04, bonferroni corrected] but not in controls [p=.26]. Group differences in genu, but not splenium, FA were trend significant [p=.09]. Conclusions MA abuse appears to alter anterior callosal WM microstructure with less evidence of change within posterior callosal WM microstructure. DTI indices within the genu, but not splenium, correlated with measures of cognitive control in chronic MA abusers. PMID:18814867

  3. White Matter MS-Lesion Segmentation Using a Geometric Brain Model.

    PubMed

    Strumia, Maddalena; Schmidt, Frank R; Anastasopoulos, Constantinos; Granziera, Cristina; Krueger, Gunnar; Brox, Thomas

    2016-07-01

    Brain magnetic resonance imaging (MRI) in patients with Multiple Sclerosis (MS) shows regions of signal abnormalities, named plaques or lesions. The spatial lesion distribution plays a major role for MS diagnosis. In this paper we present a 3D MS-lesion segmentation method based on an adaptive geometric brain model. We model the topological properties of the lesions and brain tissues in order to constrain the lesion segmentation to the white matter. As a result, the method is independent of an MRI atlas. We tested our method on the MICCAI MS grand challenge proposed in 2008 and achieved competitive results. In addition, we used an in-house dataset of 15 MS patients, for which we achieved best results in most distances in comparison to atlas based methods. Besides classical segmentation distances, we motivate and formulate a new distance to evaluate the quality of the lesion segmentation, while being robust with respect to minor inconsistencies at the boundary level of the ground truth annotation. PMID:26829786

  4. White matter microstructure alterations in primary dysmenorrhea assessed by diffusion tensor imaging

    PubMed Central

    Liu, Peng; Wang, Geliang; Liu, Yanfei; Yu, Qingbao; Yang, Fan; Jin, Lingmin; Sun, Jinbo; Yang, Xuejuan; Qin, Wei; Calhoun, Vince D.

    2016-01-01

    Primary dysmenorrhea (PDM), a significant public health problem for adolescents and young women, is characterized by painful menstrual cramps. Recent neuroimaging studies have revealed that brain functional and structural abnormalities are related to the pathomechanism of PDM. However, it is not clear whether there are white matter (WM) alterations in PDM. We analyzed diffusion tensor imaging data from 35 patients and 35 healthy controls (HCs) matched for age and handedness. Tract-based spatial statistics and probabilistic tractography were used to measure integrity of WM microstructure. Compared to HCs, patients had increased fractional anisotropy (FA) along with decreased mean diffusivity (MD) and radial diffusivity (RD) in the corpus callosum (CC), superior longitudinal fasciculus (LF), corona radiata (CR), internal capsule (IC) and external capsule (EC). The FA of the splenium CC and right IC positively correlated with PDM duration while FA of the right anterior CR positively correlated with PDM severity in patient group. These WM tracts were found to show connections to other brain regions implicated in sensoimotor, affective, cognitive and pain processing functions through tractography. These findings provide preliminary evidence for WM microstructure alterations in PDM, which is potentially valuable for understanding pathomechanism of PDM. PMID:27161845

  5. Aging and large-scale functional networks: white matter integrity, gray matter volume, and functional connectivity in the resting state.

    PubMed

    Marstaller, L; Williams, M; Rich, A; Savage, G; Burianová, H

    2015-04-01

    Healthy aging is accompanied by neurobiological changes that affect the brain's functional organization and the individual's cognitive abilities. The aim of this study was to investigate the effect of global age-related differences in the cortical white and gray matter on neural activity in three key large-scale networks. We used functional-structural covariance network analysis to assess resting state activity in the default mode network (DMN), the fronto-parietal network (FPN), and the salience network (SN) of young and older adults. We further related this functional activity to measures of cortical thickness and v