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Effects of age on volumes of cortex, white matter and subcortical structures.

The effect of age was investigated in and compared across 16 automatically segmented brain measures: cortical gray matter, cerebral white matter, hippocampus, amygdala, thalamus, the accumbens area, caudate, putamen, pallidum, brainstem, cerebellar cortex, cerebellar white matter, the lateral ventricle, the inferior lateral ventricle, and the 3rd and 4th ventricle. Significant age effects were found for all volumes except pallidum and the 4th ventricle. Heterogeneous age responses were seen in that age relationships for cortex, amygdala, thalamus, the accumbens area, and caudate were linear, while cerebral white matter, hippocampus, brainstem, cerebellar white, and gray matter, as well as volume of the lateral, inferior lateral, and 3rd ventricles showed curvilinear relationships with age. In general, the findings point to global and large effects of age across brain volumes.

Adult↗

Longitudinal changes in white matter following ischemic stroke: a three-year follow-up study.

Information on longitudinal changes in white matter after stroke is limited. The aim of the present study was to quantitatively investigate longitudinal changes in the microstructural integrity of non-lesioned white matter at 1-3 years following ischemic stroke. In a sample of 80 ischemic stroke patients, we obtained diffusion tensor imaging (DTI) measures of fractional anisotropy (FA), an apparent measure of white matter integrity, in radiologically normal-appearing white matter at baseline and 3 years of follow-up. Mixed model regression analysis results showed a significant improvement in FA from baseline during the first 2 years of follow-up that stabilized by the third year of follow-up. These results demonstrate a long-term improvement in apparent white matter integrity following ischemic stroke that continues, at least, into the second year following the insult.

Aged↗

Aging in the CNS: comparison of gray/white matter volume and diffusion tensor data.

This study investigated the global and regional effects of aging on brain volume, mean diffusivity (MD), and fractional anisotropy (FA) in 73 normal female subjects using voxel-based analysis. On a global scale, gray matter volume and FA were negatively correlated, whereas MD was positively correlated with age. Voxel-wise analyses showed brain volume and FA were negatively correlated predominantly in anterior structures, whereas MD was positively correlated in the cortical gray matter and periventricular white matter. Volume preservation was observed in the cingulate gyrus and subjacent white matter. FA increase was observed in the putamen. Voxel-based direct comparisons of volume and diffusion properties showed FA was more strongly negatively correlated in the fronto-temporal white matter, compared with volume and MD. Stronger positive correlation of MD was observed in the thalamus, caudate nucleus, and midbrain and stronger negative correlation of brain volume was observed in the frontal lobe and basal ganglia, compared with the other. These results indicate that diffusion properties and brain volume are complementary markers to the effects of aging.

Adult↗

The topography of white matter hyperintensities on brain MRI in healthy 60- to 64-year-old individuals.

We report the topography of brain white matter hyperintensities (WMHs) on T2-weighted fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging in 477 healthy subjects aged 60-64 years selected randomly from the community. WMHs were delineated by using a computer algorithm. We found that all subjects had periventricular WMHs and 96.6% subjects also had deep WMHs. The mean volume of WMHs was 4.9 ml, comprising 0.83% of the white matter, of which 1.2 ml was severe in intensity. The deep WMHs were distributed throughout the cerebral hemispheres, with the occipital and frontal white matter bearing the greatest burden. The territory of the lenticulostriate arteries had the greatest WMHs. A white matter region of 4 mm adjacent to the cortex was not affected by hyperintensities. The mean (SD) number of discrete WMHs was 19.6 (7.1) per subject, of which 6.1 (4.4) were severe in intensity. Nearly half (48.6%) of the subjects had at least one large WMH (>12 mm diameter) and one eighth (12.5%) of the subjects had at least one large WMH that appeared to be severe in MRI. The overall load of WMHs was similar in men and women, but the latter had a higher proportion of their white matter so affected. This study provides the first detailed topographic analysis of WMHs in a large representative middle-aged sample, emphasizes their high prevalence in mid-adult life and raises issues about their etiology and significance.

Aging↗

Structural white matter deficits in high-functioning individuals with autistic spectrum disorder: a voxel-based investigation.

A number of imaging and neuropathological studies have reported structural abnormalities in white matter areas such as the corpus callosum in autism spectrum disorder (ASD). Differences in both global brain volume and the size of specific neural structures have been reported. In order to expand these previously reported findings and to describe more precisely the nature of such structural changes, we performed a voxel-based morphometric whole brain analysis, using a group-specific template, in male adolescents with ASD. Fifteen individuals with normal intelligence and ASD, and a group of 16 controls, matched for age, sex, and IQ, were investigated. High-resolution T1-weighted 3D data sets were acquired and analysed. Local white matter volume deficits were found in the corpus callosum, particularly in the anterior splenium and isthmus, and right hemisphere. White matter volume deficits were also found in the left middle temporal, right middle frontal, and left superior frontal gyri. No significant areas of increased white matter volume were found. Our findings support the hypothesis that reduced white matter volume in the corpus callosum and right hemisphere may play a role in the pathophysiology of ASD.

Adolescent↗

Bootstrap white matter tractography (BOOT-TRAC).

White matter tractography is a noninvasive method for estimating and visualizing the white matter connectivity patterns in the human brain using diffusion tensor imaging (DTI) data. Sources of experimental noise may induce errors in the measured fiber directions, which will reduce the accuracy of the estimated white matter trajectories. In this study, a statistical nonparametric bootstrap method is described for estimating the dispersion and other errors in white matter tractography results. Prior studies have derived models of tractography error using the signal-to-noise ratio (SNR) and diffusion anisotropy of the DTI data. Tractography errors measured using bootstrap methods were generally consistent with an analytic model of tractography error except in areas where branching was evident. White matter tractography with bootstrap resampling is also applied to estimate the probabilities of connection between brain regions. The approach was used to generate probabilistic connectivity maps between the cerebral peduncles and specific cortical regions.

Brain↗

Pediatric diffusion tensor imaging: normal database and observation of the white matter maturation in early childhood.

Recent advances in diffusion tensor imaging (DTI) have made it possible to reveal white matter anatomy and to detect neurological abnormalities in children. However, the clinical use of this technique is hampered by the lack of a normal standard of reference. The goal of this study was to initiate the establishment of a database of DTI images in children, which can be used as a normal standard of reference for diagnosis of pediatric neurological abnormalities. Seven pediatric volunteers and 23 pediatric patients (age range: 0-54 months) referred for clinical MR examinations, but whose brains were shown to be normal, underwent anatomical and DTI acquisitions on a 1.5 T MR scanner. The white matter maturation, as observed on DTI color maps, was described and illustrated. Changes in diffusion fractional anisotropy (FA), average apparent diffusion constant (ADC(ave)), and T2-weighted (T2W) signal intensity were quantified in 12 locations to characterize the anatomical variability of the maturation process. Almost all prominent white matter tracts could be identified from birth, although their anisotropy was often low. The evolution of FA, shape, and size of the white matter tracts comprised generally three phases: rapid changes during the first 12 months; slow modifications during the second year; and relative stability after 24 months. The time courses of FA, ADC(ave), and T2W signal intensity confirmed our visual observations that maturation of the white matter and the normality of its architecture can be assessed with DTI in young children. The database is available online and is expected to foster the use of this promising technique in the diagnosis of pediatric pathologies.

Brain↗

Higher blood pressure predicts lower regional grey matter volume: Consequences on short-term information processing.

Hypertension is a risk factor for diffuse brain atrophy. Yet, there is little evidence that higher blood pressure predicts focal brain atrophy, as indicated by a lower volume of regional brain tissue. This voxel-based morphometry study tested (a) whether higher blood pressure predicts lower regional grey or white matter volume and (b) whether a blood-pressure-related reduction in regional brain tissue volume predicts poorer neuropsychological test performance. Participants were 76 men (M age = 61.33, SD = 4.95 years) and 58 women (M age = 59.86, SD = 5.10 years) without a cardiovascular, cerebrovascular, or neuropsychiatric disease. Results showed that among men, higher resting systolic blood pressure predicted lower grey matter volume in the supplementary motor area and adjacent superior frontal gyrus, the anterior cingulate cortex, and middle temporal gyrus. Among men, lower grey matter volume in the supplementary motor area also predicted a slower time to complete the Trail Making Part B Test of executive control and a poorer recall of items from the Four-word Short-term Memory Test of working memory. These relationships were independent of age, total brain tissue volume, educational history, severity of carotid atherosclerosis, and the extent of periventricular and subcortical white matter lesions. Among women, no statistically significant relationships were found between blood pressure, regional brain tissue volume, and cognitive function. These findings suggest a functional relationship among men between higher blood pressure, lower regional grey matter volume, and poorer cognitive function that is independent of other risk factors and confounding medical conditions.

Aged↗

Mapping an intrinsic MR property of gray matter in auditory cortex of living humans: a possible marker for primary cortex and hemispheric differences.

Recently, magnetic resonance properties of cerebral gray matter have been spatially mapped--in vivo--over the cortical surface. In one of the first neuroscientific applications of this approach, this study explores what can be learned about auditory cortex in living humans by mapping longitudinal relaxation rate (R1), a property related to myelin content. Gray matter R1 (and thickness) showed repeatable trends, including the following: (1) Regions of high R1 were always found overlapping posteromedial Heschl's gyrus. They also sometimes occurred in planum temporale and never in other parts of the superior temporal lobe. We hypothesize that the high R1 overlapping Heschl's gyrus (which likely indicates dense gray matter myelination) reflects auditory koniocortex (i.e., primary cortex), a heavily myelinated area that shows comparable overlap with the gyrus. High R1 overlapping Heschl's gyrus was identified in every instance suggesting that R1 may ultimately provide a marker for koniocortex in individuals. Such a marker would be significant for auditory neuroimaging, which has no standard means (anatomic or physiologic) for localizing cortical areas in individual subjects. (2) Inter-hemispheric comparisons revealed greater R1 on the left on Heschl's gyrus, planum temporale, superior temporal gyrus and superior temporal sulcus. This asymmetry suggests greater gray matter myelination in left auditory cortex, which may be a substrate for the left hemisphere's specialized processing of speech, language, and rapid acoustic changes. These results indicate that in vivo R1 mapping can provide new insights into the structure of human cortical gray matter and its relation to function.

Adult↗

Gray matter atrophy associated with duration of temporal lobe epilepsy.

Hippocampal sclerosis is the most common abnormality associated with medial temporal lobe epilepsy (MTLE). Converging evidence supports that hippocampal sclerosis progresses with time. However, it is unclear whether extrahippocampal atrophy in patients with MTLE, similarly to hippocampal sclerosis, is an unremitting progressive process. In this article, we investigate the relationship between duration of epilepsy and gray matter concentration reduction in patients with MTLE within and outside the hippocampus. We employed a voxel-based morphometry study of MRI of the entire brain of 36 patients with drug refractory MTLE and 49 neurologically healthy age-matched controls. We performed a voxel-based parametric and nonparametric investigation of the association between gray matter concentration, age and duration of epilepsy. We complemented the investigation by extracting the gray matter concentration of regions of interest (ROIs) within the limbic system, and we investigated the association between the gray matter concentration on the ROIs and duration of epilepsy. Patients with MTLE exhibited gray matter concentration reduction that is negatively correlated with the duration of epilepsy within the ipsilateral hippocampus, temporal lobes as well as extratemporal limbic structures that are closely connected with the hippocampus. In conclusion, longer duration of refractory epilepsy was associated with a more intense hippocampal and extrahippocampal atrophy in patients with MTLE. The mechanism of progressive neuronal damage in MTLE may be related to active seizure activity within a limbic network, and early seizure control may prevent further brain atrophy in patients with refractory MTLE.

Adolescent↗

Left lateralized white matter microstructure accounts for individual differences in reading ability and disability.

Diffusion tensor imaging (DTI) was used to investigate the association between variation in white matter microstructure and individual differences in reading skill within children. Unlike previous DTI studies of reading, our sample examined children in both the average reading range as well as several children in the performance range of reading disability (RD). Results replicate previous findings of a strong correlation between fractional anisotropy (FA) values in a left temporo-parietal white matter region and standardized reading scores of typically developing children. Furthermore, FA values in this same region accounted for differences between children scoring in the average range and children scoring in the RD range, suggesting that the role of white matter tract microstructure is best characterized as an extreme range on a continuum of typical variation. Furthermore, significant correlations between working memory and frontal white matter tract regions were present in this same population, yet were demonstrated to be independent of the relationships found between reading and more posterior regions. Results form a "correlational double dissociation" that demonstrates domain specificity in the influence of white matter tract structures to individual differences in cognitive performance.

Adolescent↗

Gray matter volume reduction in obsessive-compulsive disorder with schizotypal personality trait.

OBJECTIVES: Obsessive-compulsive disorder (OCD) with schizotypal personality trait (SPT) and OCD without SPT demonstrated differences in cognitive dysfunction and treatment response. This study aimed to investigate whether brain volume differs between OCD with SPT and OCD without SPT. METHODS: OCD with SPT (n=20), OCD without SPT (n=47), healthy comparison subjects (n=83) and schizophrenic patients (n=59) participated in this study. We assessed brain volume such as gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF) using magnetic resonance imaging. The imaging data sets were filtered using anisotropic diffusion methods to improve the signal to noise ratio. The semi-automated region-growing method was used to remove images of tissues exterior to the brain. The fuzzy C-means algorithm was used to segment the extracted brain images into gray matter, white matter and cerebrospinal fluid. RESULTS: OCD with SPT (p=0.048) and Schizophrenic patients (p<0.001) demonstrated a significant GM volume reduction compared to healthy controls. OCD without SPT revealed no significant GM volume reduction compared to healthy controls (p=0.504). CONCLUSION: This study suggests that OCD with SPT could be distinguished as a distinct subtype of OCD, based on observations of gray matter volume.

Adult↗

Biophysical changes in normal-appearing white matter and subcortical nuclei in late-life major depression detected using magnetization transfer.

Neuroanatomical changes have been identified in patients diagnosed with late-life major depressive disorder (MDD) compared with controls. These primarily comprise a decrease in focal brain volumes and an increase in MRI-determined high intensity lesions that are largely confined to the white matter. The physiological status of normal-appearing white matter in patients with MDD remains unknown. Magnetization transfer (MT) is a relatively new neuroimaging technique that permits us to examine the biophysical characteristics of specific brain regions. Using MT, we studied eight patients with late-life MDD and eight non-depressed controls. MT ratios (MTR), which reflect the integrity of the macromolecular protein pool, were ascertained in normal-appearing white matter and subcortical nuclei. Patients had significantly lower MTRs in the genu and splenium of the corpus callosum, the right caudate nucleus and putamen, and the occipital white matter compared with controls. The findings indicate that the structure of the macromolecular protein matrix may be compromised in normal-appearing white matter and critical subcortical nuclei in patients with late-life major depression. These changes may provide important substrates to mood disorders and have implications for neuronal connectivity and its role in the pathophysiology of late-life depression.

Aged↗

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

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

Adolescent↗

Influence of algal and bacterial particulate organic matter on benzo[a]pyrene bioaccumulation in Daphnia magna.

In order to better asses the influence of organic matter on the bioavailability of hydrophobic organic contaminants, the effect of algae and POM of bacterial origin on the bioaccumulation of benzo[a]pyrene in Daphnia magna was evaluated. The bioaccumulation was monitored with increasing concentrations of particulate organic matter (POM) and dissolved organic matter (DOM). In all experiments, the presence of POM greatly reduced the bioaccumulation of benzo[a]pyrene. The reduction was more pronounced in the presence of algae, for which we observed a 99%-reduction effect in the presence of 6 x10 (5) cell/mL (equivalent to 5.3 mg C/L). The bioaccumulation of benzo[a]pyrene was decreased by 49% by organic matter of bacterial origin at 4.7 mg C/L. Assuming that benzo[a]pyrene was partitioned between water, DOM and POM and supposing that D. magna accumulated free benzo[a]pyrene via respiration and POM-bond benzo[a]pyrene via ingestion, bioaccumulation data allowed to estimate the dietary uptake rate of benzo[a]pyrene as well as partitioning coefficients K(POC) and K(DOC). Despite the ingestion of contaminated particles, we could not observe any dietary uptake of benzo[a]pyrene in daphnids. We verified, as usually supposed, that the bioaccumulation of benzo[a]pyrene to D. magna occurs mainly via direct contact. Very high partitioning coefficients (log K(POC) between 5.2 and 6.2) were estimated. This study pointed out the great influence of biogenic organic matter on the fate and the bioavailability of benzo[a]pyrene in aquatic ecosystems.

Animals↗

Surgical treatment of temporal lobe epilepsy associated with subcortical ectopic gray matter under the guidance of intraoperative electrocorticography.

We describe a dual pathology presenting as intractable temporal lobe epilepsy associated with subcortical ectopic gray matter. The patient was a 28-year-old male with a 12-year history of refractory temporal lobe epilepsy. Preoperative diagnostic imaging revealed right hippocampal sclerosis, in addition to subcortical ectopic gray matter extending from the posterior end of the inferior horn of the right lateral ventricle to the cerebral parenchyma in the temporoparietal lobe. As surgical therapy for epilepsy, right anterior temporal lobectomy with amygdalohippocampectomy was initially performed. Intraoperative electrocorticography (ECoG) was extremely useful at this point in determining the range of excision of ectopic gray matter after resection of mesial temporal lobe structures. Based on ECoG findings, about 50% of the ectopic gray matter was excised. As of 2 years postoperatively, the patient has remained seizure free with no medication. In cases concomitantly manifesting hippocampal sclerosis and subcortical ectopic gray matter, epilepsy may be associated with dual pathology. This case report raises the potentially important issue of the possible presence of areas of structural abnormality that are non-epileptogenic.

Adult↗

Influence of dissolved organic carbon content on modelling natural organic matter acid-base properties.

Natural organic matter (NOM) behaviour towards proton is an important parameter to understand NOM fate in the environment. Moreover, it is necessary to determine NOM acid-base properties before investigating trace metals complexation by natural organic matter. This work focuses on the possibility to determine these acid-base properties by accurate and simple titrations, even at low organic matter concentrations. So, the experiments were conducted on concentrated and diluted solutions of extracted humic and fulvic acid from Laurentian River, on concentrated and diluted model solutions of well-known simple molecules (acetic and phenolic acids), and on natural samples from the Seine river (France) which are not pre-concentrated. Titration experiments were modelled by a 6 acidic-sites discrete model, except for the model solutions. The modelling software used, called PROSECE (Programme d'Optimisation et de SpEciation Chimique dans l'Environnement), has been developed in our laboratory, is based on the mass balance equilibrium resolution. The results obtained on extracted organic matter and model solutions point out a threshold value for a confident determination of the studied organic matter acid-base properties. They also show an aberrant decreasing carboxylic/phenolic ratio with increasing sample dilution. This shift is neither due to any conformational effect, since it is also observed on model solutions, nor to ionic strength variations which is controlled during all experiments. On the other hand, it could be the result of an electrode troubleshooting occurring at basic pH values, which effect is amplified at low total concentration of acidic sites. So, in our conditions, the limit for a correct modelling of NOM acid-base properties is defined as 0.04 meq of total analysed acidic sites concentration. As for the analysed natural samples, due to their high acidic sites content, it is possible to model their behaviour despite the low organic carbon concentration.

Carbon↗

White matter involvement in mitochondrial diseases.

White matter involvement is recently being realized as a common finding in mitochondrial disorders. It is considered an inherent part of the classical mitochondrial syndromes which are usually associated with alterations in the mitochondrial DNA such as: Leigh disease, Kearns-Sayre syndrome, mitochondrial encephalomyopathy lactic acidosis, and stroke like episodes, mitochondrial neuro-gastro-intestinal encephalomyopathy and Leber's hereditary optic neuropathy. White matter involvement is also described in mitochondrial disorders due to mutations in the nuclear DNA which are transmitted in an autosomal pattern. MRI findings suggestive of a mitochondrial disease are: small cyst-like lesions in abnormal white matter, involvement of both cerebral and cerebellar white matter, and a combination of a leukoencephalopathy with bilateral basal ganglia lesions. The clinical manifestations may be disproportionate to the extent of white matter involvement. Other organs may frequently be involved. The onset is often in infancy with a neurodegenerative course. The finding of a leukoencephalopathy in a patient with a complex neurologic picture and multisystem involvement should prompt a thorough mitochondrial evaluation.

Brain Diseases↗