Brain White Matter Microstructure Research Articles

Effects of androgenization on the white matter microstructure of female-to-male transsexuals. A diffusion tensor imaging study

Diffusion tensor imaging (DTI) can sensitively detect white matter sex differences and the effects of pharmacological treatments. Before cross-sex hormone treatment, the white matter microstructure of several brain bundles in female-to-male transsexuals (FtMs) differs from those in females but not from that in males. The purpose of this study was to investigate whether cross-sex hormone treatment (androgenization) affects the brain white matter microstructure. Using a Siemens 3 T Trio Tim Magneton, DTI was performed twice, before and during cross-sex hormonal treatment with testosterone in 15 FtMs scanned. Fractional anisotropy (FA) was analyzed on white matter of the whole brain, and the latter was spatially analyzed using Tract-Based Spatial Statistics. Before each scan the subjects were assessed for serum testosterone, sex hormone binding globulin level (SHBG), and their free testosterone index. After at least seven months of cross-gender hormonal treatment, FA values increased in the right superior longitudinal fasciculus (SLF) and the right corticospinal tract (CST) in FtMs compared to their pre-treatment values. Hierarchical regression analyses showed that the increments in the FA values in the SLF and CST are predicted by the free testosterone index before hormonal treatment. All these observations suggest that testosterone treatment changes white matter microstructure in FtMs.

Broad Disruption of Brain White Matter Microstructure and Relationship with Neuropsychological Performance in Male Patients with Severe Alcohol Dependence

In the last years, refined magnetic resonance diffusion tensor imaging (DTI) methods have become available to study microstructural alterations in the human brain. We investigated to what extent white matter tissue abnormalities are present in male patients after chronic, excessive alcohol consumption and if these alterations are correlated with measures of alcohol consumption and neuropsychological performance. Twenty-four detoxified adult male patients with severe alcohol dependence and 23 healthy male control subjects were included in the study. Neuropsychological tests were assessed for executive function, attention, memory and visuospatial function. DTI was acquired and preprocessing of the data was performed using tract-based spatial statistics. Group differences of fractional anisotropy (FA) as well as correlation analyses with neuropsychological measures and drinking history were calculated. Performance in alcoholic patients was significantly poorer in tests of non-verbal reasoning and attention. In detoxified alcoholic patients, lower FA was primarily found in the body of the corpus callosum, but these findings did not correlate directly with behavioral measures. However, executive and psychomotor performance (Trail-Making Test) correlated significantly with FA in right anterior cingulate and left motor areas. These findings provide further evidence for reduced integrity of interhemispheric connections in male patients with severe alcohol dependence, and neurocognitive performance was in part correlated with FA.

The effects of the serotonin transporter polymorphism and age on frontal white matter integrity in healthy adult women

Studies of populations at genetic risk have the potential to explore the underlying structural and functional mechanisms in the development of psychological disorders. The polymorphic region (5-HTTLPR) in the serotonin transporter gene (SLC6A4) has been associated with major depression (MDD) (Caspi et al., 2003). In healthy women, variation in the human brain white matter microstructure integrity in the uncinate fascicule (UF) has been suggested as an endophenotypes in the development of MDD. Pacheco et al. (2009) found a unique effect of age and 5-HTTLPR within the left frontal UF. The present study examined whether these associations persist along the adult life span. Thirty-seven right-handed healthy women between 21 and 61 years of age were invited for a diffusion MRI study. The functional polymorphism 5-HTTLPR located in the promoter region of the SLC6A4 gene was genotyped using polymerase chain reaction (PCR). Fractional anisotropy (FA) was generated for the UF based on Tract-Based Spatial Statistics (TBSS). Models of emotion regulation circuitry suggest that working memory is important in conscious emotion regulation (Price and Drevets, 2010). To explore if 5-HTTLPR is related to this aspects of emotion processing, a working memory pathway, the superior longitudinal fascicule (SLF) was included. The results demonstrate that age may explain the hypothesized association between 5-HTTLPR and frontal UF white matter integrity in healthy adult women. Both white matter changes associated with the aging process and those associated with growth and development may explain why the earlier reported unique effects of genotype in frontal UF FA do not persist into adulthood.

Linking an Anxiety-Related Personality Trait to Brain White Matter Microstructure

Emotional, cognitive, and behavioral response patterns underlying temperament and personality are established early and remain stable from childhood. Anxiety-related traits are associated with psychiatric disease and represent predisposing factors for various affective disorders, including depression and anxiety. Emotional processing relies on the structural and functional integrity of distributed neuronal circuits. Therefore, anxiety-related personality traits and associated increased risk of psychiatric disease might be rooted in structural variability in large-scale neuronal networks. To test the hypothesis that individuals with high scores on the harm avoidance (HA) subscale of the Temperament and Character Inventory show reduced white matter (WM) structural integrity in distributed brain areas, including corticolimbic pathways involved in emotional processing and reappraisal. Healthy participants completed the Temperament and Character Inventory and underwent diffusion tensor imaging. Tract-based spatial statistics were used to examine the associations between HA and WM integrity across the brain. Center for the Study of Human Cognition, Department of Psychology, University of Oslo, Oslo, Norway. A total of 263 healthy adults aged 20 to 85 years recruited through newspaper advertisements. Neuroimaging diffusivity indexes of brain WM microstructure, including fractional anisotropy, mean and radial diffusivity, and their associations with HA. In line with our hypothesis, increased HA was associated with decreased fractional anisotropy and increased mean and radial diffusivity in major WM tracts, including pathways connecting critical hubs in a corticolimbic circuit. There was no evidence of modulating effects of sex, degree of subclinical depression, alcohol consumption, general intellectual abilities, or years of education. Increased HA is associated with decreased WM microstructure, implying that structural connectivity modulates anxiety-related aspects of personality. Decreased WM integrity reflects increased susceptibility to psychiatric disease and represents a promising biomarker that might ultimately facilitate targeted pharmacological and psychological interventions and treatment of disease.

Experience-dependent plasticity of white-matter microstructure extends into old age

Experience-dependent alterations in the human brain's white-matter microstructure occur in early adulthood, but it is unknown whether such plasticity extends throughout life. We used cognitive training, diffusion-tensor imaging (DTI), and structural MRI to investigate plasticity of the white-matter tracts that connect the left and right hemisphere of the frontal lobes. Over a period of about 180 days, 20 younger adults and 12 older adults trained for a total of one hundred and one 1-h sessions on a set of three working memory, three episodic memory, and six perceptual speed tasks. Control groups were assessed at pre- and post-test. Training affected several DTI metrics and increased the area of the anterior part of the corpus callosum. These alterations were of similar magnitude in younger and older adults. The findings indicate that experience-dependent plasticity of white-matter microstructure extends into old age and that disruptions of structural interhemispheric connectivity in old age, which are pronounced in aging, are modifiable by experience and amenable to treatment.

Selective effects of aging on brain white matter microstructure: A diffusion tensor imaging tractography study

We examined age-related changes in the cerebral white matter. Structural magnetic resonance images (MRIs) and diffusion tensor images (DTIs) were acquired from 69 healthy subjects aged 22–84years. Quantitative DTI tractography was performed for nine different white matter tracts to determine tract volume, fractional anisotropy (FA), mean diffusivity (MD), axial, and radial diffusivities. We used automated and manual segmentation to determine volumes of gray matter (GM), white mater (WM), cerebrospinal fluid (CSF), and intracranial space. The results showed significant effects of aging on WM, GM, CSF volumes, and selective effects of aging on structural integrity of different white matter tracts. WM of the prefrontal region was the most vulnerable to aging, while temporal lobe connections, cingulum, and parieto-occipital commissural connections showed relative preservation with age. This study was cross-sectional, and therefore, additional longitudinal studies are needed to confirm our findings.

Disruption of brain white matter microstructure in primary Sjogren's syndrome: evidence from diffusion tensor imaging

The relationship between cognitive symptoms and underlying neuropathology in primary SS (PSS) is poorly understood. We used high-resolution quantitative brain MRI to identify potential structural correlates of cognitive symptoms. Subjects completed a comprehensive neuropsychometric evaluation. Imaging was performed on a 3 T MRI scanner with T(1) and proton density-weighted, fluid-attenuated inversion recovery (FLAIR) and diffusion tensor imaging (DTI) sequences. We compared MRI group metrics (impaired PSS, not-impaired PSS and controls) and tested for correlations between DTI results and neuropsychological measurements (significance threshold P = 0.05). Nineteen PSS patients (who met American-European Consensus Group 2002 criteria) and 17 healthy controls completed the cognitive evaluation. MRI scans were performed in six impaired PSS, seven not-impaired PSS and seven controls. No differences were found in regional volumetrics, nor was there a difference in T(2) lesion load between groups. Fractional anisotropy (FA) in the inferior frontal white matter (WM) was lower (P = 0.021) and mean diffusivity higher (P = 0.003) in the impaired PSS relative to the control group. Inferior frontal FA was correlated with cognitive symptoms (P = 0.0064) and with verbal memory (P = 0.0125). In this exploratory study, frontal region WM microstructure alterations accompanied cognitive symptoms and were associated with mild cognitive impairment in PSS. While additional study is warranted to assess the specificity and stability of these results, DTI could provide novel insight into the pathological processes accompanying the subtle cognitive dysfunction commonly experienced by PSS patients.

Diffusion Tensor Imaging of Mild to Moderate Blast-Related Traumatic Brain Injury and Its Sequelae

To evaluate the effects of mild to moderate blast-related traumatic brain injury (TBI) on the microstructure of brain white matter (WM) and neurobehavioral outcomes, we studied 37 veterans and service members (mean age 31.5 years, SD = 7.2; post-injury interval 871.5 days; SD = 343.1), whose report of acute neurological status was consistent with sustaining mild to moderate TBI due to blast while serving in Iraq or Afghanistan. Fifteen veterans without a history of TBI or exposure to blast (mean age 31.4 years, SD = 5.4) served as a comparison group, including seven subjects with extracranial injury (post-injury interval 919.5 days, SD = 455.1), and eight who were uninjured. Magnetic resonance imaging disclosed focal lesions in five TBI participants. Post-concussion symptoms (Neurobehavioral Symptom Inventory), post-traumatic stress disorder (PTSD) symptoms (PTSD Checklist-Civilian), and global distress and depression (Brief Symptom Inventory) were worse in the TBI participants than the comparison group, but no group differences were found in perceived physical or mental functioning (SF-12). Verbal memory (Selective Reminding) was less efficient in the TBI group, but there were no group differences in nonverbal memory (Selective Reminding) or decision making (Iowa Gambling Task). Verbal memory in the TBI group was unrelated to PTSD severity. Diffusion tensor imaging (DTI) using tractography, standard single-slice region-of-interest measurement, and voxel-based analysis disclosed no group differences in fractional anisotropy (FA) and apparent diffusion coefficient (ADC). However, FA of the left and right posterior internal capsule and left corticospinal tract was positively correlated with total words consistently recalled, whereas ADC for the left and right uncinate fasciculi and left posterior internal capsule was negatively correlated with this measure of verbal memory. Correlations of DTI variables with symptom measures were non-significant and inconsistent. Our data do not show WM injury in mild to moderate blast-related TBI in veterans despite their residual symptoms and difficulty in verbal memory. Limitations of the study and implications for future research are also discussed.

Relationships of brain white matter microstructure with clinical and MR measures in relapsing‐remitting multiple sclerosis

To assess the relationships of microstructural damage in the cerebral white matter (WM), as measured by diffusion tensor imaging (DTI), with clinical parameters and magnetic resonance imaging (MRI) measures of focal tissue damage in patients with multiple sclerosis (MS). Forty-five relapsing-remitting (RR) MS patients (12 male, 33 female; median age = 29 years, Expanded Disability Status Scale (EDSS) = 1.5, disease duration = 3 years) were studied. T2-lesion masks were created and voxelwise DTI analyses performed with Tract-Based Spatial Statistics (TBSS). T2-lesion volume (T2-LV) was significantly (P < 0.05, corrected) correlated with fractional anisotropy (FA) in both lesions and normal-appearing WM (NAWM). Relationships (P = 0.08, corrected) between increasing EDSS score and decreasing FA were found in the splenium of the corpus callosum (sCC) and along the pyramidal tract (PY). All FA associations were driven by changes in the perpendicular (to primary tract direction) diffusivity. No significant global and voxelwise FA changes were found over a 2-year follow-up. FA changes related to clinical disability in RR-MS patients with minor clinical disability are localized to specific WM tracts such as the sCC and PY and are driven by changes in perpendicular diffusivity both within lesions and NAWM. Longitudinal DTI measurements do not seem able to chart the early disease course in the WM of MS patients.

Corpus Callosal Microstructural Integrity Influences Interhemispheric Processing: A Diffusion Tensor Imaging Study

Normal aging and chronic alcoholism result in disruption of brain white matter microstructure that does not typically cause complete lesions but may underlie degradation of functions requiring interhemispheric information transfer. We examined whether the microstructural integrity of the corpus callosum assessed with diffusion tensor imaging (DTI) would relate to interhemispheric processing speed. DTI yields estimates of fractional anisotropy (FA), a measure of orientation and intravoxel coherence of water diffusion usually in white matter fibers, and diffusivity (<D>), a measure of the amount of intracellular and extracellular fluid diffusion. We tested the hypothesis that FA and <D> would be correlated with (i) the crossed-uncrossed difference (CUD), testing visuomotor interhemispheric transfer; and (ii) the redundant targets effect (RTE), testing parallel processing of visual information presented to each cerebral hemisphere. FA was lower and <D> higher in alcoholics than in controls. In controls but not alcoholics, large CUDs correlated with low FA and high <D> in total corpus callosum and regionally in the genu and splenium. In alcoholics but not controls, small RTEs, elicited with equiluminant stimuli, correlated with low FA in genu and splenium and high <D> in the callosal body. The results provide in vivo evidence for disruption of corpus callosum microstructure in normal aging and alcoholism that has functional ramifications for efficiency in interhemispheric processing.

Disruption of Brain White Matter Microstructure by Excessive Intracellular and Extracellular Fluid in Alcoholism: Evidence from Diffusion Tensor Imaging

Magnetic resonance diffusion tensor imaging (DTI) has revealed the disruption of brain white matter microstructure in normal aging and alcoholism undetectable with conventional structural MR imaging. The metrics of DTI can be useful in establishing the nature of the observed microstructural aberrations. Abnormally low fractional anisotropy (FA), a measure of diffusion orientation and coherence, may result from increased intracellular or extracellular fluid, which would be reflected in complementary high apparent diffusion coefficients (bulk mean diffusivity) and low FA, or from disorganization of fiber structure, which would be reflected in low FA but with a lack of the inverse FA and diffusivity relationship. To test these competing possibilities, we examined 15 alcoholic men and 31 control men with DTI to quantify diffusivity in the genu and splenium of the corpus callosum and centrum semiovale. In addition to the previously observed FA deficits in all the three brain regions, the alcoholics had abnormally high white matter diffusivity values in the genu and centrum. Further, inverse correlations between FA and diffusivity were significant in the genu (r=-0.52, p<0.05) and centrum (r=-0.92, p=0.0001). Multiple regression analyses examining diffusivity and age as predictors of FA identified diffusivity as a significant unique contributor to FA in both regions. These results suggest that decreased orientational coherence of brain white matter in alcoholism is attributable, at least in part, to the accumulation of intracellular and extracellular fluid in excess of that occurring in aging, and that the differential influence of these fluid compartments can vary across brain regions.

Genetic regulation of regional microstructure of the corpus callosum in late life.

In order to identify brain structural phenotypes that remain under significant genetic control in late adulthood, we examined the heritability of corpus callosum macrostructure (i.e. size) using MRI and microstructure (e.g. myelin) using diffusion tensor imaging in 15 monozygotic and 18 dizygotic twin pairs of elderly men. The relative proportion of genetic to environmental influences varied considerably by region and structural type and was 5:1 for callosal macrostructure, 3:1 for splenium microstructure, and 1:1 for genu microstructure. This is the first in vivo identification of quantifiable phenotypes of brain white matter microstructure and demonstrates significant and differential genetic regulation in old age, with anterior interhemispheric connecting pathways more susceptible than posterior pathways to environmental influences.

Equivalent disruption of regional white matter microstructure in ageing healthy men and women.

Diffusion tensor imaging was used to measure regional differences in brain white matter microstructure (intravoxel coherence) and macrostructure (intervoxel coherence) and age-related differences between men and women. Neuropsychiatrically healthy men and women, spanning the adult age range, showed the same pattern of variation in regional white matter coherence. The greatest coherence measured was in corpus callosum, where commissural fibers have one primary orientation, lower in the centrum semiovale, where fibers cross from multiple axes, and lowest in pericallosal areas, where fibers weave and interstitial fluid commonly pools. Age-related declines in intravoxel coherence was equally strong and strikingly similar in men and women, with evidence for greater age-dependent deterioration in frontal than parietal regions. Degree of regional white matter coherence correlated with gait, balance, and interhemispheric transfer test scores.

In Vivo Detection and Functional Correlates of White Matter Microstructural Disruption in Chronic Alcoholism

Postmortem studies report degradation of brain white matter microstructure in chronic alcoholism, but until recently, in vivo neuroimaging could provide measurement only at a macrostructural level. The development of magnetic resonance diffusion tensor imaging (DTI) for clinical use offers a method for depicting and quantifying the diffusion properties of white matter expressed as intravoxel and intervoxel coherence of tracts and fibers. This study used DTI to examine the intravoxel coherence measured as fractional anisotropy (FA) and intervoxel coherence (C) of white matter tracts of the genu and splenium of the corpus callosum and of the centrum semiovale in 15 detoxified alcoholic men and 31 nonalcoholic control subjects. Exploratory correlational analyses examined the relationships between regional DTI measures and tests of attention and working memory in the alcoholic patients. The alcoholic group had lower regional FA than the control group. C was lower in the alcoholics than controls in the splenium only. Working memory correlated positively with splenium FA, whereas attention correlated positively with genu C. These results provide in vivo evidence for disruption of white matter microstructure in alcoholism and suggest that interruption of white matter fiber coherence contributes to disturbance in attention and working memory in chronic alcoholism.