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. Here we analyzed 4. Tesla DTI scans from 374 healthy adults, including 60 monozygotic twin pairs, 45 same-sex dizygotic pairs, and 164 mixed-sex DZ twins and their siblings; mean age: 24.4 years ± 1.9 SD). All DTI scans were nonlinearly aligned to a geometrically-symmetric, population-based image template. We computed voxel-wise maps of significant asymmetries (left/right differences) for common diffusion measures that reflect fiber integrity (fractional and geodesic anisotropy; FA, GA and mean diffusivity, MD). In quantitative genetic models computed from all same-sex twin pairs (N=210 subjects), genetic factors accounted for 33% of the variance in asymmetry for the inferior fronto-occipital fasciculus, 37% for the anterior thalamic radiation, and 20% for the forceps major and uncinate fasciculus (all L > R). Shared environmental factors accounted for around 15% of the variance in asymmetry for the cortico-spinal tract (R > L) and about 10% for the forceps minor (L > R). Sex differences in asymmetry (men > women) were significant, and were greatest in regions with prominent FA asymmetries. These maps identify heritable DTI-derived features, and may empower genome-wide searches for genetic polymorphisms that influence brain asymmetry.

Reducing structural variation to determine the genetics of white matter integrity across hemispheres - a dti study of 100 twins

Studies of cerebral asymmetry can open doors to understanding the functional specialization of each brain hemisphere, and how this is altered in disease. Here we examined hemispheric asymmetries in fiber architecture using diffusion tensor imaging (DTI) in 100 subjects, using high-dimensional fluid warping to disentangle shape differences from measures sensitive to myelination. Confounding effects of purely structural asymmetries were reduced by using co-registered structural images to fluidly warp 3D maps of fiber characteristics (fractional and geodesic anisotropy) to a structurally symmetric minimal deformation template (MDT). We performed a quantitative genetic analysis on 100 subjects to determine whether the sources of the remaining signal asymmetries were primarily genetic or environmental. A twin design was used to identify the heritable features of fiber asymmetry in various regions of interest, to further assist in the discovery of genes influencing brain micro-architecture and brain lateralization. Genetic influences and left/right asymmetries were detected in the fiber architecture of the frontal lobes, with minor differences depending on the choice of registration template.

Genetics of anisotropy asymmetry: Registration and sample size effects

Brain asymmetry has been a topic of interest for neuroscientists for many years. The advent of diffusion tensor imaging (DTI) allows researchers to extend the study of asymmetry to a microscopic scale by examining fiber integrity differences across hemispheres rather than the macroscopic differences in shape or structure volumes. Even so, the power to detect these microarchitectural differences depends on the sample size and how the brain images are registered and how many subjects are studied. We fluidly registered 4 Tesla DTI scans from 180 healthy adult twins (45 identical and fraternal pairs) to a geometrically-centered population mean template. We computed voxelwise maps of significant asymmetries (left/right hemisphere differences) for common fiber anisotropy indices (FA, GA). Quantitative genetic models revealed that 47-62% of the variance in asymmetry was due to genetic differences in the population. We studied how these heritability estimates varied with the type of registration target (T1- or T2-weighted) and with sample size. All methods consistently found that genetic factors strongly determined the lateralization of fiber anisotropy, facilitating the quest for specific genes that might influence brain asymmetry and fiber integrity.

Mapping cortical change in Alzheimer's disease, brain development, and schizophrenia

This paper describes algorithms that can identify patterns of brain structure and function associated with Alzheimer's disease, schizophrenia, normal aging, and abnormal brain development based on imaging data collected in large human populations. Extraordinary information can be discovered with these techniques: dynamic brain maps reveal how the brain grows in childhood, how it changes in disease, and how it responds to medication. Genetic brain maps can reveal genetic influences on brain structure, shedding light on the nature-nurture debate, and the mechanisms underlying inherited neurobehavioral disorders. Recently, we created time-lapse movies of brain structure for a variety of diseases. These identify complex, shifting patterns of brain structural deficits, revealing where, and at what rate, the path of brain deterioration in illness deviates from normal. Statistical criteria can then identify situations in which these changes are abnormally accelerated, or when medication or other interventions slow them. In this paper, we focus on describing our approaches to map structural changes in the cortex. These methods have already been used to reveal the profile of brain anomalies in studies of dementia, epilepsy, depression, childhood- and adult-onset schizophrenia, bipolar disorder, attention-deficit/hyperactivity disorder, fetal alcohol syndrome, Tourette syndrome, Williams syndrome, and in methamphetamine abusers. Specifically, we describe an image analysis pipeline known as cortical pattern matching that helps compare and pool cortical data over time and across subjects. Statistics are then defined to identify brain structural differences between groups, including localized alterations in cortical thickness, gray matter density (GMD), and asymmetries in cortical organization. Subtle features, not seen in individual brain scans, often emerge when population-based brain data are averaged in this way. Illustrative examples are presented to show the profound effects of development and various diseases on the human cortex. Dynamically spreading waves of gray matter loss are tracked in dementia and schizophrenia, and these sequences are related to normally occurring changes in healthy subjects of various ages.

Investigating the concept of potential quality: An exploratory study in the real estate industry

Purpose The purpose of this research is to examine the concept of “potential quality” – that is, a company's tangible search qualities (such as the physical servicescape and virtual servicescape) – within the context of the real‐estate industry in the USA. Design/methodology/approach This qualitative study collects data by conducting personal in‐depth interviews with 34 respondents who had been recent buyers or renters of property. The data are then coded and themed to identify quality dimensions relevant to this industry. Findings The results indicate that a buyer's perception of the overall service quality of real‐estate service consists of two components: the interaction with a realtor (process quality); and the virtual servicescape, especially the firm's website design and content (potential quality). The study concludes that existing scales (such as SERVQUAL and RESERV) fail to capture the tangible component of service quality sufficiently in the real‐estate industry. Research limitations/implications The study uses data from only one industry (real estate) and from only one demographic segment (professionals in higher education). Practical implications Service providers of intangible, high‐contact services must appreciate the importance of the virtual servicescape as a surrogate quality indicator that can help to reduce information asymmetries and consumers' uncertainty with regard to initiating a business relationship. Real estate firms need to pay attention to the training of agents and the design and content of their e‐service systems. Originality/value This study integrates potential quality, process quality, and outcome quality in a comprehensive proposed model. In particular, the study identifies “potential quality” as a combination of the attributes of the virtual service environment and the physical service environment.

Development of a method to assess the quality of ankle joint reduction in 3D

This project developed a quantitative method for determining the quality of the surgical alignment of the bone fragments after an ankle fracture. The research examined the feasibility of utilising MRI-based bone models versus the gold standard CT-based bone models in order to reduce the amount of ionising radiation the patient is exposed to. In doing so, the thesis reports that there is potential for MRI to be used instead of CT depending on the scanning parameters used to obtain the medical images, the distance of the implant relative to the joint surface, and the implant material.

Muscle morphometry of the individual hamstring muscles in semi-elite AFL Players: Preliminary findings from a longitudinal study

Hamstring strains in the Australian Football League (AFL) have a high incidence (15%) and recurrence rate (34%) with lateral hamstring injuries most common (83%). Retrospective studies have found significant muscle volume asymmetries ≤23 months post hamstring injury; however examination of the association between hamstring strains and muscle asymmetry has not been investigated prospectively. This study presents baseline data from a longitudinal study focusing on individual hamstring morphometry in uninjured and injured semi-elite AFL players.

Morphometric analyses of the hamstring muscles using MRI: What is the best way?

Associations between injury and muscle asymmetries, as determined with magnetic resonance (MR) imaging, have been investigated in a number of sports medicine-based studies. For interventional or prospective studies into musculoskeletal injuries, it is important to determine the repeatability of the morphometric procedures used for quantifying muscle asymmetries. This study examines the intra-observer repeatability of manual segmentation for determining bilateral volumes of the individual hamstring muscles.