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At least 1,639 records · Page 91Linked to original sources
PubMed2005

Particulate matter in polluted air may increase biomarkers of inflammation in mouse brain.

The etiology of neurodegenerative disorders is at present unknown. However, many of these disorders are associated with an increase in oxidative and inflammatory events. Although a small percentage of these disorders are familial cases linked to specific genetic defects, most are idiopathic. Thus, environmental factors are thought to play an important role in the onset and progression of such disorders. We have demonstrated that exposure (4 h, 5 days per week for 2 weeks) to concentrated airborne particulate matter increases inflammatory indices in brain of ovalbumin-sensitized BALB/c mice. Animals were divided into three exposure groups: filtered air (control), ultrafine particles, or fine and ultrafine particles. The levels of proinflammatory cytokines interleukin-1 alpha (IL-1alpha) and tumor necrosis factor alpha (TNF-alpha) were increased in brain tissue of mice exposed to particulate matter compared to that of control animals. Levels of the immune-related transcription factor NF-kappaB were also found to be substantially elevated in the brain of exposed groups compared with the control group. These data indicate that components of inhaled particulate matter may trigger a proinflammatory response in nervous tissue that could contribute to the pathophysiology of neurodegenerative diseases.

Air Pollutants↗
PubMed2005

White matter changes in mild cognitive impairment and AD: A diffusion tensor imaging study.

Diffusion tensor imaging (DTI) can detect, in vivo, the directionality of molecular diffusion and estimate the microstructural integrity of white matter (WM) tracts. In this study, we examined WM changes in patients with Alzheimer's disease (AD) and in subjects with amnestic mild cognitive impairment (MCI) who are at greater risk for developing AD. A DTI index of WM integrity, fractional anisotropy (FA), was calculated in 14 patients with probable mild AD, 14 participants with MCI and 21 elderly healthy controls (NC). Voxel-by-voxel comparisons showed significant regional reductions of FA in participants with MCI and AD compared to controls in multiple posterior white matter regions. Moreover, there was substantial overlap of locations of regional decrease in FA in the MCI and AD groups. These data demonstrate that white matter changes occur in MCI, prior to the development of dementia.

Aged↗
PubMed2006

Glucocorticoid receptor variant and risk of dementia and white matter lesions.

OBJECTIVE: Elevated glucocorticoid levels are associated with dementia. A glucocorticoid receptor gene variant (ER22/23EK) is related to relative glucocorticoid resistance. We investigated whether the ER22/23EK allele is associated with dementia and structural brain abnormalities. METHODS: This study was performed in two prospective population-based cohort studies among elderly. The first study included 6034 participants who were screened for dementia (mean follow-up 5.8 years). The second study included 1011 elderly subjects with an MRI at baseline and follow-up. The ER22/23EK allele was assessed for association with dementia, cognitive function and white matter lesions. RESULTS: The ER22/23EK allele was associated with a decreased risk of dementia. Among non-demented participants, ER22/23EK-carriers had a better performance on psychomotor speed tests than non-carriers. No differences were found in memory function between genotypes. In addition, both presence and progression of white matter lesions was lower in ER22/23EK-carriers. No association was found with brain atrophy on MRI. CONCLUSIONS: Our findings suggest a protective effect of the ER22/23EK allele on the risk of dementia and white matter lesions.

Aged↗
PubMed2004

Confocal imaging of changes in glial calcium dynamics and homeostasis after mechanical injury in rat spinal cord white matter.

Periaxonal glia play an important role in maintaining axonal function in white matter. However, little is known about the changes that occur in glial cells in situ immediately after traumatic injury. We used fluo-3 and confocal microscopy to examine the effects of localized (<0.5 mm) mechanical trauma on intracellular calcium (Ca(i)(2+)) levels in glial cells in a mature rat spinal cord white matter preparation in vitro. At the injury site, the glial Ca(i)(2+) signal increased by 300-400% within 5 min and then irreversibly declined indicating cell lysis and death. In glial cells at sites adjacent to the injury (1.5-2 mm from epicenter), Ca(i)(2+) levels peaked at 10-15 min, and thereafter declined but remained significantly above rest levels. At distal sites (6-9 mm), Ca(i)(2+) levels rose and declined even slower, peaking at 80-90 min. Injury in zero calcium dampened Ca(i)(2+) responses, indicating a role for calcium influx in the generation and propagation of the injury-induced Ca(i)(2+) signal. By 50-80 min post-injury, surviving glial cells demonstrated an enhanced ability to withstand supraphysiological Ca(i)(2+) loads induced by the calcium ionophore A-23187. Glial fibrillary acidic protein (GFAP) and CNPase immunolabeling determined that the glial cells imaged with fluo-3 included both astrocytes and oligodendrocytes. These data provide the first direct evidence that the effects of localized mechanical trauma include a glial calcium signal that can spread along white matter tracts for up to 9 mm within less than 3 h. The results further show that trauma can enhance calcium regulation in surviving glial cells in the acute post-injury period.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed2004

Diffusion tensor imaging of adult age differences in cerebral white matter: relation to response time.

Diffusion tensor imaging (DTI) measures the displacement of water molecules across tissue components, thus providing information regarding the microstructure of cerebral white matter. Fractional anisotropy (FA), the degree to which diffusion is directionally dependent, is typically higher for compact, homogeneous fiber bundles such as the corpus callosum. Previous DTI studies in adults have demonstrated an age-related decline in white matter FA, but whether the relation between FA and behavioral performance varies as a function of age has not been determined. We investigated adult age differences in FA, and age-related changes in the relation between FA and response time (RT), in a visual target-detection task. The results confirmed that, independently of age, FA is higher in the corpus callosum than in other brain regions. We also observed an age-related decline in FA that did not vary significantly across the brain regions. For both age groups, a lower level of integrity of the cerebral white matter (as indexed by FA), in specific brain regions, was associated with slower responses in the visual task. An age-related change in this relation was evident, however, in that the best predictor of RT for younger adults was FA in the splenium of the corpus callosum, whereas for older adults the best predictor was FA in the anterior limb of the internal capsule. This pattern is consistent with measures of the task-related cortical activation obtained from these same individuals and suggests an age-related increase in the attentional control of responses mediated by corticostriatal or corticothalamic circuits.

Adult↗
PubMed2004

Singularities in diffusion tensor fields and their relevance in white matter fiber tractography.

The technique of diffusion tensor tractography utilizes directions of maximum diffusion to reconstruct pathways of white matter structures in the brain. Critically, successful tracking of these white matter pathways depends on well-defined maximal diffusion directional information. By examination of diffusion tensor field properties in the human brain, we demonstrate that the geometry of tracked pathways is influenced by points in the field where the maximum diffusion direction is poorly defined. In common with tensor fields describing other mathematical and physical phenomena, such as 3D surface differential geometry and gravitational fields, we refer to these points as singularities. Here we describe an automated procedure for detecting singularities and demonstrate that these occur where there is (i) fiber crossing, (ii) pathways passing close to one another within a voxel (partial volume effect), and (iii) noise propagation into low anisotropy regions. In order to highlight the relevance of singularities in tracking white matter structures, we determined their effect on computation of the cortico-spinal pathway.

Algorithms↗
PubMed2004

Cross-relaxation imaging reveals detailed anatomy of white matter fiber tracts in the human brain.

Cross-relaxation imaging is a new quantitative MRI modality, which allows mapping of fundamental parameters determining the magnetization transfer (MT) effect in tissues, cross-relaxation rate constant (k) and bound pool fraction (f). This study introduces a new time-efficient technique for cross-relaxation imaging, which obtains three-dimensional (3D) whole-brain k and f maps with scan time of <30 min and isotropic spatial resolution of 1.4 mm. The technical principle of the method is based on four-point fit of a matrix model of pulsed MT to imaging data obtained with variable offset frequency saturation while using a complimentary R1 (=1 / T1) map. Anatomical correlations of in vivo cross-relaxation parametric maps were evaluated in three healthy subjects. The f maps revealed correspondence of areas with highly elevated f = 12-15% to major fiber tracts such as corpus callosum, anterior commissure, optic radiations, and major brain fasciculi. The rest of white matter (WM) demonstrated lower f = 9-11%, resulting in clear visual contrast of fiber tracts. Even lower f = 6.5-8.5% were found in gray matter (GM) with the highest f = 8.5% in the anterior thalamus. Distribution of k was relatively uniform in WM and produced sharp contrast between GM and WM (k = 1.6 and 3.3 s(-1), respectively). The most marked feature of k maps was their ability to visualize the corticospinal tract, which had elevated k = 3.4-3.8 s(-1) but appeared invisible on f maps. The observed patterns on f maps can be explained by variations in the density of myelinated fibers, while the trends of k may reflect regional differences in axonal organization. Cross-relaxation imaging can be used in various clinical studies focused on brain development and white matter diseases.

Analysis of Variance↗
PubMed2004

Short-term accrual of gray matter pathology in patients with progressive multiple sclerosis: an in vivo study using diffusion tensor MRI.

The mechanisms underlying the progressive course of multiple sclerosis (MS) are not fully understood yet. Since diffusion tensor (DT) MRI can provide quantitative estimates of both MRI-visible and MRI-occult brain damage related to MS, the present study investigated the value of DT MRI-derived measures for the assessment of the short-term accumulation of white and gray matter (GM) pathology in patients with primary progressive (PP) and secondary progressive (SP) MS. Fifty-four patients with PPMS and 22 with SPMS were studied at baseline and after a mean follow-up of 15 months. Dual-echo, T1-weighted, and DT MRI scans of the brain were acquired on both occasions. Total lesion volumes (TLV) and percentage brain volume changes (PBVC) were computed. Mean diffusivity (MD) and fractional anisotropy (FA) maps of the normal-appearing white (NAWM) and gray matter (NAGM) were produced, and histogram analysis was performed. In both patient groups, a significant increase of average lesion MD (P = 0.01) and of average NAGM MD (P = 0.007) was found at follow-up. No significant differences between PPMS and SPMS patient groups were found for the on-study changes of any MRI-derived measure. No significant correlations were found between the percentage changes of DT MRI-derived measures and those of TLV and PBVC. No significant changes of DT MRI-derived measures were observed in age-matched healthy controls over the same study period. Over a 1-year period of follow-up, DT MRI can detect tissue changes beyond the resolution of conventional MRI in the NAGM of patients with progressive MS. The accumulation of DT MRI-detectable gray matter damage does not seem to merely depend upon the concomitant increase of T2-visible lesion load and the reduction of brain volume. These observations suggest that progressive NAGM damage might yet be an additional factor leading to the accumulation of disability in progressive MS.

Adult↗
PubMed2004

Bilateral thalamic gray matter changes in patients with restless legs syndrome.

Restless legs syndrome (RLS) is a common neurological disorder of a primary unpleasant sensation with an urge to move the legs occurring at rest. The etiology of idiopathic RLS is unknown and structural cerebral abnormalities have so far not been detected. We studied 51 right-handed patients with an idiopathic restless legs syndrome in two independent samples (Regensburg RLS-group: n = 28, Munich RLS-group: n = 23) and compared them to 51 sex- and age-matched healthy volunteers. High-resolution T1-weighted magnetic resonance imaging (MRI) of each subject was obtained and analyzed using voxel-based morphometry (VBM) to detect regionally specific differences in gray matter between patients and controls. Conjunction analysis was used to combine results from both centers. In patients with idiopathic RLS, both study centers observed independently a bilateral gray matter increase in the pulvinar. In the conjunction analysis including all patients and controls from both study centers, a significant gray matter increase in the pulvinar bilaterally (right: x = 16, y = -21, z = 12, Z = 4.57; left: x = -16, y = -24, z = 12, Z = 4.10) was present. This is the first demonstration of structural changes in the brain of patients with idiopathic RLS. These changes in thalamic structures are either involved in the pathogenesis of RLS or may reflect a consequence of chronic increase in afferent input of behaviorally relevant information.

Adult↗
PubMed2005

The neuroanatomy of general intelligence: sex matters.

We examined the relationship between structural brain variation and general intelligence using voxel-based morphometric analysis of MRI data in men and women with equivalent IQ scores. Compared to men, women show more white matter and fewer gray matter areas related to intelligence. In men IQ/gray matter correlations are strongest in frontal and parietal lobes (BA 8, 9, 39, 40), whereas the strongest correlations in women are in the frontal lobe (BA10) along with Broca's area. Men and women apparently achieve similar IQ results with different brain regions, suggesting that there is no singular underlying neuroanatomical structure to general intelligence and that different types of brain designs may manifest equivalent intellectual performance.

Adolescent↗
PubMed2005

Extra-hippocampal grey matter density abnormalities in paediatric mesial temporal sclerosis.

The aim of this study was to identify grey matter density abnormalities in children with temporal lobe epilepsy and mesial temporal sclerosis. Magnetic resonance T1 weighted 3D datasets were obtained in children with temporal lobe epilepsy (20 left and 10 right sided, mean age 11.9 years, range 6.6-17.5) and compared to scans obtained from age-matched controls (n = 22, mean age 12.8 years, range 7.1-17.5) using voxel-based morphometry. This method detected reduced grey matter ipsilateral to the seizure focus not only in the hippocampus, but also in the lateral temporal lobe and in extra-temporal regions including the thalamus, posterior cingulate cortex and cerebellum. Bilateral differences were present in the frontal and parietal opercular cortices and lateral temporal regions. These grey matter density reductions broadly reflect the pattern of hippocampal connections and may be caused by the disruption of cortical development by the recurrent seizures, as well as by loss of functional input from the sclerotic hippocampus.

Adolescent↗
PubMed2005

Application of Brodmann's area templates for ROI selection in white matter tractography studies.

Brodmann's areas are part of the common vernacular used by neuroscientists to indicate specific location of brain activity in functional brain imaging studies. Here, we have employed a template based on the Brodmann's areas as a means of compartmentalizing underlying white matter pathways. White matter tractography was performed on the diffusion tensor data of sixteen subjects using a streamline tracking technique with Runge-Kutta integration. After co-registration, the Brodmann template was utilized for ROI selection. Tracts were segmented based on their termination in a particular area of the template. Binary masks were generated based on the tractography segmentation for a given Brodmann's area in each individual subject. Following registration to a normalized coordinate space, the binary masks were averaged, generating a map that estimates the probability of tractography connectivity for particular white matter pathways to a specific Brodmann's area. The probability maps were color-coded and overlaid on anatomical images to provide perspective. In this study, particular attention was given to the areas of the frontal cortex. A composite map of these areas was generated by assigning each voxel to the Brodmann's area with the highest probability of connectivity, based on the average results. The average maps generated with this method reveal consistent patterns of connectivity across subjects. The use of a normalized template for ROI selection automates the process of segmenting tractography data, making it particularly useful for multi-subject studies. In the future, this method could be used to help elucidate relationships between function and anatomical structure.

Adult↗
PubMed2006

Mapping radiation dose distribution on the fractional anisotropy map: applications in the assessment of treatment-induced white matter injury.

We describe a method to map whole brain radiation dose distribution on to diffusion tensor MR (DT-MR) fractional anisotropy (FA) images and illustrate its applications for studying dose-effect relationships and regional susceptibility in two childhood medulloblastoma survivors. To determine the FA changes voxel-by-voxel in white matter, the post-treatment follow-up FA maps were coregistered to baseline pre-treatment FA maps and automatic segmentation for white matter was carried out. DeltaFA maps representing relative FA change in white matter were hence generated for visual inspection and quantitative analysis. The radiation dose distribution, calculated from radiotherapy plan and exported as images, was coregistered to baseline FA images. DT-MR imaging and processing noise was small with root mean square value of 1.49% for mean DeltaFA. We evaluated the mean DeltaFA changes of regions-of-interest according to radiation dose regions to provide an estimate of the dose-response and found increasing reduction in mean DeltaFA with increasing radiation dose up to 45 Gy after which there was a reversal in the mean FA trend and mean FA approached baseline value. We also found more severe mean FA reduction in the frontal lobes compared to the parietal lobes despite the same radiation dose, suggesting regional susceptibility in the frontal lobe, and mean FA increase in the brainstem after radiation in both patients. We conclude that the method described may be useful in estimating dose-effect relationships and studying regional susceptibility of the brain to radiation in medulloblastoma survivors.

Anisotropy↗
PubMed2006

Decrease of thalamic gray matter following limb amputation.

Modern neuroscience has elucidated general mechanisms underlying the functional plasticity of the adult mammalian brain after limb deafferentation. However, little is known about possible structural alterations following amputation and chronic loss of afferent input in humans. Using voxel-based morphometry (VBM), based on high-resolution magnetic resonance images, we investigated the brain structure of 28 volunteers with unilateral limb amputation and compared them to healthy controls. Subjects with limb amputation exhibited a decrease in gray matter of the posterolateral thalamus contralateral to the side of the amputation. The thalamic gray matter differences were positively correlated with the time span after the amputation but not with the frequency or magnitude of coexisting phantom pain. Phantom limb pain was unrelated to thalamic structural variations, but was positively correlated to a decrease in brain areas related to the processing of pain. No gray matter increase was detected. The unilateral thalamic differences may reflect a structural correlate of the loss of afferent input as a secondary change following deafferentation.

Adolescent↗
PubMed2006

MRI detects white matter reorganization after neural progenitor cell treatment of stroke.

We evaluated the effects of neural progenitor cell treatment of stroke on white matter reorganization using MRI. Male Wistar rats (n = 26) were subjected to 3 h of middle cerebral artery occlusion and were treated with neural progenitor cells (n = 17) or without treatment (n = 9) and were sacrificed at 5-7 weeks thereafter. MRI measurements revealed that grafted neural progenitor cells selectively migrated towards the ischemic boundary regions. White matter reorganization, confirmed histologically, was coincident with increases of fractional anisotropy (FA, P < 0.01) after stroke in the ischemic recovery regions compared to that in the ischemic core region in both treated and control groups. Immunoreactive staining showed axonal projections emanating from neurons and extruding from the corpus callosum into the ipsilateral striatum bounding the lesion areas after stroke. Fiber tracking (FT) maps derived from diffusion tensor imaging revealed similar orientation patterns to the immunohistological results. Complementary measurements in stroke patients indicated that FT maps exhibit an overall orientation parallel to the lesion boundary. Our data demonstrate that FA and FT identify and characterize cerebral tissue undergoing white matter reorganization after stroke and treatment with neural progenitor cells.

Algorithms↗
PubMed2006

Extensive heterogeneity in white matter intensity in high-resolution T2*-weighted MRI of the human brain at 7.0 T.

MRI at high magnetic field strength potentially allows for an increase in resolution and image contrast. The gains are particularly dramatic for T(2)(*)-weighted imaging, which is sensitive to susceptibility effects caused by a variety of sources, including deoxyhemoglobin, iron concentration, and tissue microstructure. On the other hand, the acquisition of high quality whole brain MRI at high field is hampered by the increased inhomogeneity in B(o) and B(1) fields. In this report, high-resolution gradient echo MRI was performed using an 8-channel detector to obtain T(2)(*)-weighted images over large brain areas. The high SNR achieved with the multi-channel array enabled T(2)(*)-weighted images of the brain with an unprecedented spatial resolution of up to 0.2 x 0.2 x 0.5 mm(3). This high resolution greatly facilitated the detection of microscopic susceptibility effects. In addition to the expected contrast between gray, white matter, cerebral spinal fluid, and veins, a large degree of heterogeneity in contrast was observed throughout the white matter of normal brain. The measured T(2)(*) values in white matter varied as much as 30% with some of the variation apparently correlating with the presence of large fiber bundles.

Adult↗
PubMed2006

Distribution of grey matter atrophy in Huntington's disease patients: a combined ROI-based and voxel-based morphometric study.

The striatum, a subcortical structure, is the principal target of the neurodegenerative process in Huntington's disease (HD). The measurement of striatal atrophy using the bicaudate ratio on CT scanner images has therefore been used for years to assess disease progression, but this measure only takes into account unidimensional changes in the head of the caudate nucleus. Recently, voxel-based morphometry (VBM), which permits automated statistical comparisons of whole-brain MRI images, has been proposed to quantify striatal atrophy. However, VBM was not originally designed to study subcortical structures, and severe deep brain deformations that occur in HD may hamper the automatic processing of VBM. Here, we validate the use of the optimised protocol of VBM to quantify subcortical atrophy in HD by comparing results obtained with this method to those provided by manual segmentation of subcortical structures. We studied 20 patients with early HD and 12 controls matched for age, sex and handedness using an improved T1-weighted sequence that eased grey matter segmentation. Both manual and automated methods evidenced the dorso-ventral gradient of striatal atrophy, a loss of grey matter in the globus pallidus and the thalamus, and similar correlations between clinical scores and subcortical atrophy. Furthermore, we were able to detect with VBM grey matter loss in the substantia nigra, the hypothalamus, the amygdala, the insular cortex and the premotor and sensorimotor cortices. Finally, VBM provided results consistent with previous post mortem results and proved to be a sensitive biomarker capable of correctly managing subcortical distortions throughout HD patients' brains.

Adult↗
PubMed2005

Organization of electrically and chemically evoked defensive behaviors within the deeper collicular layers as compared to the periaqueductal gray matter of the rat.

Stimulation of the periaqueductal gray matter (PAG) and the deeper layers of superior colliculus (SC) produces both freezing (tense immobility) and flight (trotting, galloping and jumping) behaviors along with exophthalmus (fully opened bulging eyes) and, less often, micturition and defecation. The topography of these behaviors within the distinct layers of SC remains unclear. Therefore, this study compared the defensive repertoire of intermediate (ILSC) and deep (DLSC) layers of SC to those of dorsolateral periaqueductal gray matter (DLPAG) and lateral periaqueductal gray matter (LPAG) [Neuroscience 125 (2004) 71]. Electrical stimulation was carried out through intensity- (0-70 microA) and frequency-varying (0-130 Hz) pulses. Chemical stimulation employed a slow microinfusion of N-methyl-d-aspartic acid (NMDA, 0-2.3 nmol, 0.5 nmol/min). Probability curves of intensity-, frequency- and NMDA-evoked behaviors, as well as the unbiased estimates of median stimuli, were obtained by threshold logistic analysis. Compared with the PAG, the most important differences were the lack of frequency-evoked jumping in both layers of SC and the lack of NMDA-evoked galloping in the ILSC. Moreover, although galloping and jumping were also elicited by NMDA stimulation of DLSC, effective doses were about three times higher than those of DLPAG, suggesting the spreading of the injectate to the latter structure. In contrast, exophthalmus, immobility and trotting were evoked throughout the tectum structures. However, whatever the response and kind of stimulus, the lowest thresholds were always found in the DLPAG and the highest ones in the ILSC. Besides, neither the appetitive, nor the offensive, muricide or male reproductive behaviors were produced by any kind of stimulus in the presence of appropriate targets. Accordingly, the present data suggest that the deeper layers of SC are most likely involved in the increased attentiveness (exophthalmus, immobility) or restlessness (trotting) behaviors that herald a full-blown flight reaction (galloping, jumping) mediated in the PAG.

Aggression↗