Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.

Brain Sciences Center (BSC)

Diffusion Magnetic Resonance Imaging (dMRI)

The input for tractography algorithms used for the reconstruction of the complex axonal fiber architecture so as to infer 'structural connectivity' between gray matter regions. In dMRI, a critically important goal is to estimate the orientation of white matter fiber bundles as accurately as possible, especially in regions where multiple fiber bundles intersect one another at various angles or where a fiber bundle bends or fans out and splits into multiple trajectories. Improving signal-to-noise ratio (SNR) by minimizing T2 decay during the diffusion encoding period, and accelerating the data acquisition rate without significantly impacting SNR (i.e. increasing SNR per unit time of data acquisition) are key to obtaining more informative dMRI data for tractography analysis.

Deoxyribonucleic Acid (DNA)

a molecule that carries most of the genetic instructions used in the development, functioning and reproduction of all known living organisms and many viruses. DNA (along with RNA) is a nucleic acid; alongside proteins and carbohydrates, nucleic acids compose the three major macromolecules essential for all known forms of life. Most DNA molecules consist of two biopolymer strands coiled around each other to form a double helix. The two DNA strands are known as polynucleotides since they are composed of simpler units called nucleotides.[2] Each nucleotide is composed of a nitrogen-containing nucleobase^aEUR"either cytosine (C), guanine (G), adenine (A), or thymine (T)^aEUR"as well as a monosaccharide sugar called deoxyribose and a phosphate group. The nucleotides are joined to one another in a chain by covalent bonds between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone.

Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)

The 2013 update to the American Psychiatric Association's (APA) classification and diagnostic tool. In the United States the DSM serves as a universal authority for psychiatric diagnosis. Treatment recommendations, as well as payment by health care providers, are often determined by DSM classifications, so the appearance of a new version has significant practical importance.

Diffusion Tensor Imaging (DTI)

Used to assess the integrity of the white matter and to visualize major tracts for rough anatomical connectivity. Each voxel is assigned a fractional anisotropy (FA) value. Typically, low fractional anisotropy values indicate damage to the white matter.

Functional Magnetic Resonance Imaging (fMRI)

A functional neuroimaging procedure using MRI technology that measures brain activity by detecting changes associated with blood flow. This technique relies on the fact that cerebral blood flow and neuronal activation are coupled. When an area of the brain is in use, blood flow to that region also increases.[citation needed] The primary form of fMRI uses the blood-oxygen-level dependent (BOLD) contrast, discovered by Seiji Ogawa. This is a type of specialized brain and body scan used to map neural activity in the brain or spinal cord of humans or other animals by imaging the change in blood flow (hemodynamic response) related to energy use by brain cells. Since the early 1990s, fMRI has come to dominate brain mapping research because it does not require people to undergo shots, surgery, or to ingest substances, or be exposed to ionising radiation, etc.

Gulf War Illness (GWI)

Shortly after the Gulf War (1990-91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.

Magnetoencephalography (MEG)

A noninvasive technique that detects magnetic fields above the surface of the head produced by postsynaptic potentials in the brain.

Montreal Cognitive Assessment (MoCA)

Cognitive function assessment. It consists of 30 questions that test visuospatial/ executive functioning, ability to name objects, memory, attention, general language skills (fluency), abstraction, delayed recall, and orientation.

Magnetic Resonance Spectroscopy (MRS)

Used to roughly assess neuron health. Typically, we consider the ratios of N-acetyl aspartate, glutamine+glutamate, and choline over creatine.

Operation Enduring Freedom - Afghanistan (OEF)

The U.S. government used the term "Operation Enduring Freedom - Afghanistan" (OEF) to officially describe the War in Afghanistan, from the period between October 2001 and December 2014. ... Continued operations in Afghanistan by the United States' military forces, both non-combat and combat, now occur under the name "Operation Freedom's Sentinel".

Operation Iraqi Freedom (OIF)

The period of the Iraq war lasting from 2003 to 2010 was referred to as Operation Iraqi Freedom (OIF) by the United States military. The conflict is also known as the War in Iraq, the Occupation of Iraq, the Second Gulf War, Gulf War II, and Gulf War 2.

Post-traumatic Stress Disorder (PTSD)

A complex psychiatric syndrome that develops in response to trauma exposure. Individuals with PTSD experience intrusive recollections or reexperiencing of the traumatic event, avoidance of trauma reminders, emotional numbing, and hyperarousal. In addition, PTSD is associated with high rates of concomitant physical and mental health problems, increased health care use, and impairment in social and occupational functioning. Almost 7% of the general population and up to 30% of veterans meet lifetime criteria for PTSD. Indeed, PTSD is one of the most common psychiatric disorders, representing a significant and costly public health concern.

Structural Magnetic Resonance Imaging (sMRI)

Performed to assess gray-matter volume. The data are acquired using a Philips 3T Achieva XL magnet with a SENSE 8 channel head coil. Approximately 500,000 voxels per brain are analyzed. In the first analysis, the volume of about 100 separate brain regions is calculated using FreeSurfer software (www.surfer.nmr.mgh.harvard. edu). This provides a coarse-grain, volumetric analysis of areas of the brain. In the second analysis, called voxel-based morphometry, the density of each voxel is assessed for a fine-grain analysis of each area.5 Typically, gray-matter volume decreases with age but at rates that are different for different people, for different areas of the brain, and for men and women. In that sense, one can talk about "gray-matter age" versus chronological age. A person may be 68 years old but have the gray-matter volume of a 50-year-old. Defining brain age based on measurements (as contrasted with chronological age) is a pervasive theme in this project.

Synchronous Neural Interactions (SNI)

Zero-lag partial correlations in pairs of MEG time series and denote the strength and polarity (positive or negative) of neuronal interactions. Anomalies in SNIs as assessed by MEG differentiate psychiatric disorders from healthy brain functioning and can discriminate among various brain diseases. From this research, a highly distinctive, unique PTSD SNI signature characterized by miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas has emerged. These findings, in addition to the growing research applying MEG to other psychiatric disorders, highlight the utility of MEG in identifying biomarkers of disease and underscore the potential for broader clinical applications of MEG.

VA Medical Center (VAMC)