Diffusion tensor imaging of cerebral white matter integrity in cognitive aging

In this article we review recent research on diffusion tensor imaging (DTI) of white matter (WM) integrity and the implications for age-related differences in cognition. Neurobiological mechanisms defined from DTI analyses suggest that a primary dimension of age-related decline in WM is a decline in the structural integrity of myelin, particularly in brain regions that myelinate later developmentally. Research integrating behavioral measures with DTI indicates that WM integrity supports the communication among cortical networks, particularly those involving executive function, perceptual speed, and memory (i.e., fluid cognition). In the absence of significant disease, age shares a substantial portion of the variance associated with the relation between WM integrity and fluid cognition. Current data are consistent with one model in which age-related decline in WM integrity contributes to a decreased efficiency of communication among networks for fluid cognitive abilities. Neurocognitive disorders for which older adults are at risk, such as depression, further modulate the relation between WM and cognition, in ways that are not as yet entirely clear. Developments in DTI technology are providing a new insight into both the neurobiological mechanisms of aging WM and the potential contribution of DTI to understanding functional measures of brain activity. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.     

Q-ball imaging of macaque white matter architecture

Diffusion-weighted magnetic resonance imaging holds substantial promise as a technique for non-invasive imaging of white matter (WM) axonal projections. For diffusion imaging to be capable of providing new insight into the connectional neuroanatomy of the human brain, it will be necessary to histologically validate the technique against established tracer methods such as horseradish peroxidase and biocytin histochemistry. The macaque monkey provides an ideal model for histological validation of the diffusion imaging method due to the phylogenetic proximity between humans and macaques, the gyrencephalic structure of the macaque cortex, the large body of knowledge on the neuroanatomic connectivity of the macaque brain and the ability to use comparable magnetic resonance acquisition protocols in both species. Recently, it has been shown that high angular resolution diffusion imaging (HARDI) can resolve multiple axon orientations within an individual imaging voxel in human WM. This capability promises to boost the accuracy of tract reconstructions from diffusion imaging. If the macaque is to serve as a model for histological validation of the diffusion tractography method, it will be necessary to show that HARDI can also resolve intravoxel architecture in macaque WM. The present study therefore sought to test whether the technique can resolve intravoxel structure in macaque WM. Using a HARDI method called q-ball imaging (QBI) it was possible to resolve composite intravoxel architecture in a number of anatomic regions. QBI resolved intravoxel structure in, for example, the dorsolateral convexity, the pontine decussation, the pulvinar and temporal subcortical WM. The paper concludes by reviewing remaining challenges for the diffusion tractography project.     

脑白质疏松症患者P300研究

目的探讨脑梗死伴脑白质疏松症(LA)患者P300潜伏期与认知功能的关系。方法将150例脑梗死患者根据典型影像学改变分为LA组87例和非LA组63例,分别记录患者P300潜伏期和MMSE评分,检测患者P300潜伏期,观察LA组与非LA组之间潜伏期差异。结果 LA组P300潜伏期较非LA组显著延长(P0.05),MMSE分值降低(P0.05),P300潜伏期与MMSE评分呈负相关。结论 LA组患者P300潜伏期与认知功能存在因果关系。     

Defective translation initiation causes vanishing of cerebral white matter

Leukoencephalopathy with vanishing white matter (VWM) is one of the most prevalent inherited white-matter disorders, especially in Caucasian populations. VWM is unusual because of its sensitivity to febrile infections and minor head trauma. The basic defect of this enigmatic brain disease resides in the regulation of initiation of protein synthesis. Recently, undue activation of the unfolded-protein response has emerged as an important factor in the pathophysiology of VWM. Here, we discuss the mechanisms that might be responsible for the selective involvement of the brain white matter in VWM. At present, VWM research is in need of an animal model to study disease mechanisms and therapeutic interventions.     

Childhood influences on youth obesity

We develop a model to estimate the influence of child and parental characteristics on the likelihood that a child will become an obese or overweight youth. We use this model to test whether it is possible to forecast obesity and overweight among youth. Comparing Receiver Operating Characteristic (ROC) scores from these forecasts, we find that a model using childhood covariates does as well in forecasting youth obesity and overweight as a model using the covariate values contemporaneous with the youth obesity and overweight outcomes. The datasets used in this paper, the National Longitudinal Survey of Youth (NLSY79) and the NLSY79 Children and Young Adults, provide data from 1986 to 2002, allowing for the study of a child's transition to and from obesity or overweight over a long period. Explanatory variables that significantly influence the likelihood of youth obesity or overweight outcomes include the mother's obesity status and education, the youth's mental health, and certain demographic features including race, sex, and family size. These factors provide potential targets for policies that could be implemented early in life among children most likely to become obese or overweight.     

Lipid composition of human cerebral white matter and myelin in phenylketonuria

Abstract— White matter and purified myelin from cerebral tissue obtained at autopsy from four phenylketonuric and five non-phenylketonuric mentally-retarded patients were analysed for lipids, DNA and protein. The lipid composition of the white matter and myelin was compared with that of a representative non-myelin component of white matter, the crude mitochondrial fraction. The total lipid content was significantly lower and the ratio of cholesterol to galactolipid was significantly higher in the white matter from the PKU patients than in that from the non-PKU patients. The lipid compositions of the myelin and ‘mitochondrial’ fraction, although differing from each other, did not exhibit appreciable differences between the PKU and non-PKU brain samples. However, the amount of myelin recovered from the brains of the PKU patients was, on the average, 40 percent lower than that recovered from non-PKU brains. The abnormal cholesterol: galactolipid ratio of PKU white matter could be accounted for by the altered proportion of myelin to non-myelin lipid components. The finding in PKU brains of a normal composition of lipids in the purified myelin and the absence of cholesterol esters in the white matter suggest that the deficiency in myelin may reflect an early arrest of myelination.     

Increased risk of cerebral white matter lesions in obstructive sleep apnea syndrome

Sleep and Biological Rhythms - The aim of this study was to investigate the relation between obstructive sleep apnea syndrome (OSAS) and cerebral white matter lesions (CWML) on brain magnetic...     

Oxidation of lipids and membranes II: Effects of oxidants on cerebral white matter homogenates

Bovine cerebral white matter homogenates were oxidized by various oxidizing solutions of equal molarity and subsequently extracted with water. Most of the oxidants tested (K-dichromate, FeCl₃, H₂O₂, O₂, and chloroperbenzoic, ascorbic, performic, and periodic acids) rendered the various myelin constituents less extractable than the constituents of unoxidized control homogenates. KMnO₄, and to a lesser degree hemoglobin, rendered myelin constituents more extractable with water than those of the control homogenates. The findings indicate that most of the oxidants produced stabilization of the lamellar pattern, probably through cross-linking and polymerization. KMnO₄ and hemoglobin caused labilization and breakdown of the membranous structure. Proof that stabilization of membranes is caused by some oxidants and that fragmentation occurs by the action of KMnO₄ and hemoglobin was obtained by the light-scattering technique and by electron microscopy of the oxidized homogenates. Evidence obtained indicated that formation of hydrophobic end groups during oxidation favors polymerization, while prevalence of hydrophilic groups is associated with fragmentation.     

Association between carotid plaque characteristics and cerebral white matter lesions: one-year follow-up study by MRI

Objective

To prospectively assess the relation between carotid plaque characteristics and the development of new cerebral white matter lesions (WMLs) at MRI.

Methods

Fifty TIA/stroke patients with ipsilateral 30–69% carotid stenosis underwent MRI of the plaque at baseline. Total plaque volume and markers of vulnerability to thromboembolism (lipid-rich necrotic core [LRNC] volume, fibrous cap [FC] status, and presence of intraplaque hemorrhage [IPH]) were assessed. All patients also underwent brain MRI at baseline and after one year. Ipsilateral cerebral WMLs were quantified with a semiautomatic method.

Results

Mean WML volume significantly increased over a one-year period (6.52 vs. 6.97 mm³, P = 0.005). WML volume at baseline and WML progression did not significantly differ (P>0.05) between patients with 30–49% and patients with 50–69% stenosis. There was a significant correlation between total plaque volume and baseline ipsilateral WML volume (Spearman ρ = 0.393, P = 0.005). There was no significant correlation between total plaque volume and ipsilateral WML progression. There were no significant associations between LRNC volume and WML volume at baseline and WML progression. WML volume at baseline and WML progression did not significantly differ between patients with a thick and intact FC and patients with a thin and/or ruptured FC. WML volume at baseline and WML progression also did not significantly differ between patients with and without IPH.

Conclusion

The results of this study indicate that carotid plaque burden is significantly associated with WML severity, but that there is no causal relationship between carotid plaque vulnerability and the occurrence of WMLs.     

Unconfined compression of white matter

The porous properties of brain tissue are important for understanding normal and abnormal cerebrospinal fluid flow in the brain. In this study, a poroviscoelastic model was fitted to the stress relaxation response of white matter in unconfined compression performed under a range of low strain rates. A set of experiments was also performed on the tissue samples using a no-slip boundary condition. Results from these experiments demonstrated that the rheological response of the white matter is primarily governed by the intrinsic viscoelastic properties of the solid phase. The permeability of white matter was found to be of the order of 10(-12) m4/Ns.     

Time use and food pattern influences on obesity

The rise of obesity in the United States over the past 25 years has resulted in an increase in the number of research studies published related to the causes, consequences, and possible solutions to the problem. Most would agree that obesity is a multi-dimensional problem that requires a range of solutions related to individual diet and activity, food and built environment, and public policy. Examination of complex relationships between food choice, time use patterns, sociodemographic characteristics and obesity has been limited by data availability and disciplinary focus. Using the theory of the production of health capital, this paper links empirical data from the Consumer Expenditure, Current Population, and American Time Use Surveys to provide estimates of the impacts of food expenditure and time use patterns on obesity in single female headed households of 31-50 years of age.     

Descending influences of periaqueductal gray matter and somatosensory cerebral cortex on neurones in trigeminal brain stem nuclei.

Single relay (to thalamus) and nonrelay neurones that responded to innocuous and/or noxious oral-facial stimuli were located in trigeminal brain stem nuclei oralis and caudalis. The responses of the cells and the digastric muscle to these stimuli were tested with conditioning stimulation of the periaqueductal gray matter (PGM) and somatosensory cerebral cortex in cats. A greater suppression of nociceptive responses with PGM stimulation was noted, and this effect may contribute to the profound analgesic action that has been reported to occur with PGM stimulation.     

In vivo gene transfer to cerebral white matter lesions with a recombinant adenovirus vector

Ischemic white matter lesions have been reported in rats after bilateral common carotid ligation (BCAL). Previously, comparing normotensive rats (WKY) with spontaneously hypertensive rats (SHR), we too found that sustained moderate ischemia with spontaneous hypertension accelerated the formation of ischemic white matter lesions. In this study, we explored the feasibility of gene therapy for lesioned white matter by means of an adenovirus vector expressing a reporter gene, LacZ. Using sham-operated and hypoperfused SHR as well as sham-operated and hypoperfused WKY, we demonstrated that (i) adenovirus vectors could deliver a foreign gene into oligodendrocytes and astrocytes in the cerebral white matter; (ii) the transduction efficiency was most effective in SHR after BCAL; and (iii) the level of alpha(V)-integrin was significantly correlated with adenoviral transduction efficiency.     

Effect of antibodies to rat and human cerebral cortex and white matter on heterologous T- and B-cells]

A study was made of the cytotoxic and complement-fixation activity of the antisera to the cortex and white matter of the rat and human brain upon the mouse and rat thymus and bone marrow cells. The cytotoxicity test proved to be more sensitive and precise. Cytotoxins to rodent thymocytes were revealed on ly in the antisera against the human brain cortex; at the same time they were revealed both in the antisera against the cortex and against the white matter of the rat brain (much more was found in the former). The sera against the rat brain cortex lost their cytotoxicity after the exhaustion with the same antigen, but retained it when the exhaustion was carried out by the white matter.