Clinical significance of cloned expansion and CD5 down-regulation in Epstein-Barr Virus (EBV)-infected CD8+ T lymphocytes in EBV-associated hemophagocytic lymphohistiocytosis.

Epstein-Barr virus (EBV) is the pathogen that most commonly triggers infection-associated hemophagocytic lymphohistiocytosis (HLH) and ectopically infects CD8(+) T cells in EBV-associated HLH (EBV-HLH). We recently described an EBV-HLH patient who had a clonally expanded population of EBV-infected CD8(+) T cells with CD5 down-regulation. To determine whether this finding could serve as a useful marker for EBV-HLH, we investigated 5 additional patients.

Genetic influences on brain asymmetry: a DTI study of 374 twins and siblings.

Brain asymmetry, or the structural and functional specialization of each brain hemisphere, has fascinated neuroscientists for over a century. Even so, genetic and environmental factors that influence brain asymmetry are largely unknown. Diffusion tensor imaging (DTI) now allows asymmetry to be studied at a microscopic scale by examining differences in fiber characteristics across hemispheres rather than differences in structure shapes and volumes.

A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly.

A recently identified variant within the fat mass and obesity-associated (FTO) gene is carried by 46% of Western Europeans and is associated with an approximately 1.2 kg higher weight, on average, in adults and an approximately 1 cm greater waist circumference. With >1 billion overweight and 300 million obese persons worldwide, it is crucial to understand the implications of carrying this very common allele for the health of our aging population.

When more is less: associations between corpus callosum size and handedness lateralization.

Although not consistently replicated, a substantial number of studies suggest that left-handers have larger callosal regions than right-handers. We challenge this notion and propose that callosal size is not linked to left-handedness or right-handedness per se but to the degree of handedness lateralization. To test this hypothesis, we investigated the thickness of the corpus callosum in a large data set (n=361).

Subregional hippocampal deformations in major depressive disorder.

Background: Hippocampal atrophy is a well reported feature of major depressive disorder, although the evidence has been mixed. The present study sought to examine hippocampal volume and subregional morphology in patients with major depressive disorder, who were all medication-free and in an acute depressive episode of moderate severity.

Methods: Structural magnetic resonance imaging scans were acquired in 37 patients (mean age 42 years) and 37 age, gender and IQ-matched healthy individuals.

A GENETIC ANALYSIS OF CORTICAL THICKNESS IN 372 TWINS.

Imaging genetics is a new field of neuroscience that blends methods from computational anatomy and quantitative genetics to identify genetic influences on brain structure and function. Here we analyzed brain MRI data from 372 young adult twins to identify cortical regions in which gray matter volume is influenced by genetic differences across subjects. Thickness maps, reconstructed from surface models of the cortical gray/white and gray/CSF interfaces, were smoothed with a 25 mm FWHM kernel and automatically parcellated into 34 regions of interest per hemisphere.

VENTRICULAR MAPS IN 804 SUBJECTS CORRELATE WITH COGNITIVE DECLINE, CSF PATHOLOGY, AND IMMINENT ALZHEIMER'S DISEASE.

There is an urgent need for neuroimaging biomarkers of Alzheimer's disease (AD) that correlate with cognitive decline, and with accepted measures of pathology detectable in cerebrospinal fluid (CSF). Ideal biomarkers should also be able to predict future decline, and should be computable automatically from hundreds to thousands of images without user intervention. Here we used our multi-atlas fluid image alignment method (MAFIA [1]), to automatically segment parametric 3D surface models of the lateral ventricles in brain MRI scans from 184 AD, 391 MCI, and 229 healthy elderly controls.

Biphasic direct current shift, haemoglobin desaturation and neurovascular uncoupling in cortical spreading depression.

Cortical spreading depression is a propagating wave of depolarization that plays important roles in migraine, stroke, subarachnoid haemorrhage and brain injury. Cortical spreading depression is associated with profound vascular changes that may be a significant factor in the clinical response to cortical spreading depression events. We used a combination of optical intrinsic signal imaging, electro-physiology, potassium sensitive electrodes and spectroscopy to investigate neurovascular changes associated with cortical spreading depression in the mouse.

Reduced hippocampal and parahippocampal volumes in murderers with schizophrenia.

Evidence has accumulated to suggest that individuals with schizophrenia are at increased risk for violent offending. Furthermore, converging evidence suggests that abnormalities in the fronto-limbic system, including the prefrontal cortex, the hippocampus, and the parahippocampal gyrus, may contribute towards both neuropsychological disturbances in schizophrenia and violent behavior. Since the behavioral and clinical consequences of disturbed fronto-limbic circuitry appear to differ in schizophrenia and violence, it may be argued that patients with schizophrenia who exhibit violent behavior would demonstrate different structural abnormalities compared to their non-violent counterparts.

Mesh-based spherical deconvolution: a flexible approach to reconstruction of non-negative fiber orientation distributions.

Diffusion-weighted MRI has enabled the imaging of white matter architecture in vivo. Fiber orientations have classically been assumed to lie along the major eigenvector of the diffusion tensor, but this approach has well-characterized shortcomings in voxels containing multiple fiber populations. Recently proposed methods for recovery of fiber orientation via spherical deconvolution utilize a spherical harmonics framework and are susceptible to noise, yielding physically-invalid results even when additional measures are taken to minimize such artifacts.

LONI MiND: metadata in NIfTI for DWI.

A wide range of computational methods have been developed for reconstructing white matter geometry from a set of diffusion-weighted images (DWIs), and many clinical studies rely on publicly-available implementations of these methods for analyzing DWI datasets. Unfortunately, the poor interoperability between DWI analysis tools often effectively restricts users to the algorithms provided by a single software suite, which may be suboptimal relative to those in other packages, or outdated given recent developments in the field. A major barrier to data portability and the interoperability between DWI analysis tools is the lack of a standard format for representing and communicating essential DWI-related metadata at various stages of post-processing.

Genome-wide analysis reveals novel genes influencing temporal lobe structure with relevance to neurodegeneration in Alzheimer's disease.

In a genome-wide association study of structural brain degeneration, we mapped the 3D profile of temporal lobe volume differences in 742 brain MRI scans of Alzheimer's disease patients, mildly impaired, and healthy elderly subjects. After searching 546,314 genomic markers, 2 single nucleotide polymorphisms (SNPs) were associated with bilateral temporal lobe volume (P<5 x 10(-7)). One SNP, rs10845840, is located in the GRIN2B gene which encodes the N-methyl-d-aspartate (NMDA) glutamate receptor NR2B subunit.

Voxelwise genome-wide association study (vGWAS).

The structure of the human brain is highly heritable, and is thought to be influenced by many common genetic variants, many of which are currently unknown. Recent advances in neuroimaging and genetics have allowed collection of both highly detailed structural brain scans and genome-wide genotype information. This wealth of information presents a new opportunity to find the genes influencing brain structure.

Neuroanatomical Correlates of Intelligence.

With the advancement of image acquisition and analysis methods in recent decades, unique opportunities have emerged to study the neuroanatomical correlates of intelligence. Traditional approaches examining global measures have been complemented by insights from more regional analyses based on pre-defined areas. Newer state-of-the-art approaches have further enhanced our ability to localize the presence of correlations between cerebral characteristics and intelligence with high anatomic precision.

The construction of a Chinese MRI brain atlas: a morphometric comparison study between Chinese and Caucasian cohorts.

We developed a novel brain atlas template to facilitate computational brain studies of Chinese subjects and populations using high quality magnetic resonance imaging (MRI) and well-validated image analysis techniques. To explore the ethnicity-based structural brain differences, we used the MRI scans of 35 Chinese male subjects (24.03+/-2.

3D comparison of low, intermediate, and advanced hippocampal atrophy in MCI.

We applied the hippocampal radial atrophy mapping technique to the baseline and follow-up magnetic resonance image data of 169 amnestic mild cognitive impairment (MCI) participants in the imaging arm of the Alzheimer's Disease Cooperative Study MCI Donepezil/Vitamin E trial. Sixty percent of the subjects with none to mild hippocampal atrophy rated with the visual medial temporal atrophy rating scale (MTA score < 2) and 33.8% of the subjects with moderate to severe (MTA > or = 2) hippocampal atrophy converted to Alzheimer's disease (AD) during 3-year follow-up.

Mapping Alzheimer's disease progression in 1309 MRI scans: power estimates for different inter-scan intervals.

Neuroimaging centers and pharmaceutical companies are working together to evaluate treatments that might slow the progression of Alzheimer's disease (AD), a common but devastating late-life neuropathology. Recently, automated brain mapping methods, such as tensor-based morphometry (TBM) of structural MRI, have outperformed cognitive measures in their precision and power to track disease progression, greatly reducing sample size estimates for drug trials. In the largest TBM study to date, we studied how sample size estimates for tracking structural brain changes depend on the time interval between the scans (6-24 months).

Brain MRI tissue classification based on local Markov random fields.

A new method for tissue classification of brain magnetic resonance images (MRI) of the brain is proposed. The method is based on local image models where each models the image content in a subset of the image domain. With this local modeling approach, the assumption that tissue types have the same characteristics over the brain needs not to be evoked.

Automated 3D mapping of baseline and 12-month associations between three verbal memory measures and hippocampal atrophy in 490 ADNI subjects.

We used a previously validated automated machine learning algorithm based on adaptive boosting to segment the hippocampi in baseline and 12-month follow-up 3D T1-weighted brain MRIs of 150 cognitively normal elderly (NC), 245 mild cognitive impairment (MCI) and 97 Dementia of the Alzheimer's type (DAT) ADNI subjects. Using the radial distance mapping technique, we examined the hippocampal correlates of delayed recall performance on three well-established verbal memory tests--ADAScog delayed recall (ADAScog-DR), the Rey Auditory Verbal Learning Test -DR (AVLT-DR) and Wechsler Logical Memory II-DR (LM II-DR). We observed no significant correlations between delayed recall performance and hippocampal radial distance on any of the three verbal memory measures in NC.

Sulcal set optimization for cortical surface registration.

Flat mapping based cortical surface registration constrained by manually traced sulcal curves has been widely used for inter subject comparisons of neuroanatomical data. Even for an experienced neuroanatomist, manual sulcal tracing can be quite time consuming, with the cost increasing with the number of sulcal curves used for registration. We present a method for estimation of an optimal subset of size N(C) from N possible candidate sulcal curves that minimizes a mean squared error metric over all combinations of N(C) curves.

Alzheimer's Disease Neuroimaging Initiative (ADNI): clinical characterization.

Background: Neuroimaging measures and chemical biomarkers may be important indices of clinical progression in normal aging and mild cognitive impairment (MCI) and need to be evaluated longitudinally.

Objective: To characterize cross-sectionally and longitudinally clinical measures in normal controls, subjects with MCI, and subjects with mild Alzheimer disease (AD) to enable the assessment of the utility of neuroimaging and chemical biomarker measures.

Methods: A total of 819 subjects (229 cognitively normal, 398 with MCI, and 192 with AD) were enrolled at baseline and followed for 12 months using standard cognitive and functional measures typical of clinical trials.

Three-dimensional surface maps link local atrophy and fast ripples in human epileptic hippocampus.

Objectives: There is compelling evidence that pathological high-frequency oscillations (HFOs), called fast ripples (FR, 150-500Hz), reflect abnormal synchronous neuronal discharges in areas responsible for seizure genesis in patients with mesial temporal lobe epilepsy (MTLE). It is hypothesized that morphological changes associated with hippocampal atrophy (HA) contribute to the generation of FR, yet there is limited evidence that hippocampal FR-generating sites correspond with local areas of atrophy.

Methods: Interictal HFOs were recorded from hippocampal microelectrodes in 10 patients with MTLE.

Sex differences in orbitofrontal gray as a partial explanation for sex differences in antisocial personality.

Attention is increasingly being given to understanding sex difference in psychopathology to better understand the etiology of disorders. This study tests the hypothesis that sex differences in ventral and middle frontal gray volume contribute to sex differences in antisocial personality disorder (APD) and crime. Participants were recruited from temporary employment agencies, consisting of normal controls, substance/alcohol-dependent controls, axis I/II psychiatric controls and individuals with APD.

Meeting the Challenges of Neuroimaging Genetics.

As research encompassing neuroimaging and genetics gains momentum, extraordinary information will be uncovered on the genetic architecture of the human brain. However, there are significant challenges to be addressed first. Not the least of these challenges is to accomplish the sample size necessary to detect subtle genetic influences on the morphometry and function of the healthy brain.

3D mapping of brain differences in native signing congenitally and prelingually deaf subjects.

In the prelingual and congenital deaf, functional reorganization is known to occur throughout brain regions normally associated with hearing. However, the anatomical correlates of these changes are not yet well understood. Here, we perform the first tensor-based morphometric analysis of voxel-wise volumetric differences in native signing prelingual and congenitally deaf subjects when compared with hearing controls.