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Biomedical subjects

Elizabeth R Sowell

Publications and source records attributed to Elizabeth R Sowell.

18 recordsLinked to original sources
PubMed2006

Sex differences in cortical thickness mapped in 176 healthy individuals between 7 and 87 years of age.

Findings from previous magnetic resonance imaging studies of sex differences in gray matter have been inconsistent, with some showing proportionally increased gray matter in women and some showing no differences between the sexes. Regional sex differences in gray matter thickness have not yet been mapped over the entire cortical surface in a large sample of subjects spanning the age range from early childhood to old age. We applied algorithms for cortical pattern matching and techniques for measuring cortical thickness to the structural magnetic resonance images of 176 healthy individuals between the ages of 7 and 87 years. We also mapped localized differences in brain size. Maps of sex differences in cortical thickness revealed thicker cortices in women in right inferior parietal and posterior temporal regions even without correcting for total brain volume. In these regions, the cortical mantle is up to 0.45 mm thicker, on average, in women than in men. Analysis of a subset of 18 female and 18 male subjects matched for age and brain volume confirmed the significance of thicker gray matter in temporal and parietal cortices in females, independent of brain size differences. Further analyses were conducted in the adult subjects where gender differences were evaluated using height as a covariate, and similar sex differences were observed even when body size differences between the sexes were controlled. Together, these results suggest that greater cortical thickness in posterior temporal inferior parietal regions in females relative to males are independent of differences in brain or body size. Age-by-sex interactions were not significant in the temporoparietal region, suggesting that sex differences in these regions are present from at least late childhood and then are maintained throughout life. Male brains were larger than female brains in all locations, though male enlargement was most prominent in the frontal and occipital poles, bilaterally. Given the large sample and the large range of ages studied, these results help to address controversies in the study of central nervous system sexual dimorphisms.

Adolescent↗
PubMed2006

Mapping brain maturation.

Human brain maturation is a complex, lifelong process that can now be examined in detail using neuroimaging techniques. Ongoing projects scan subjects longitudinally with structural magnetic resonance imaging (MRI), enabling the time-course and anatomical sequence of development to be reconstructed. Here, we review recent progress on imaging studies of development. We focus on cortical and subcortical changes observed in healthy children, and contrast them with abnormal developmental changes in early-onset schizophrenia, fetal alcohol syndrome, attention-deficit-hyperactivity disorder (ADHD) and Williams syndrome. We relate these structural changes to the cellular processes that underlie them, and to cognitive and behavioral changes occurring throughout childhood and adolescence.

Adolescent↗
PubMed2005

Mapping cerebellar vermal morphology and cognitive correlates in prenatal alcohol exposure.

Prenatal exposure to alcohol can result in neuroanatomical and neurocognitive deficits. High-resolution magnetic resonance imaging, surface-based image analytic methods, and neuropsychological measures were used to characterize the cerebellar vermis and to evaluate potential cognitive correlates of vermal morphology in 21 children and adolescents with prenatal alcohol exposure and 21 normally developing individuals. Alcohol-exposed individuals showed statistically significant reductions in the midline sagittal areas of the anterior vermis and posterior-inferior vermis, and significant displacement of the anterior and posterior-inferior vermal regions. Anterior vermal dysmorphology was negatively correlated with verbal learning and memory performance within the alcohol-exposed group. These observations expand on previous reports of cerebellar abnormalities in prenatal alcohol exposure, in that they localize the specific pattern of cerebellar vermal dysmorphology.

Adolescent↗
PubMed2004

Longitudinal mapping of cortical thickness and brain growth in normal children.

Recent advances in magnetic resonance imaging (MRI) technology now allow the tracing of developmental changes in the brains of children. We applied computer-matching algorithms and new techniques for measuring cortical thickness (in millimeters) to the structural MRI images of 45 children scanned twice (2 yr apart) between the ages 5 and 11. Changes in brain size were also assessed, showing local brain growth progressing at a rate of approximately 0.4-1.5 mm per year, most prominently in frontal and occipital regions. Estimated cortical thickness ranged from 1.5 mm in occipital regions to 5.5 mm in dorsomedial frontal cortex. Gray matter thinning coupled with cortical expansion was highly significant in right frontal and bilateral parieto-occipital regions. Significant thickening was restricted to left inferior frontal (Broca's area) and bilateral posterior perisylvian (Wernicke's area on the left) regions. In the left hemisphere, gray matter thickness was correlated with changing cognitive abilities. For the first time, developmental changes in gray matter thickness, brain size, and structure-function relationships have been traced within the same individuals studied longitudinally during a time of rapid cognitive development.

Adult↗
PubMed2004

Teratogenic effects of alcohol: a decade of brain imaging.

Heavy alcohol exposure can have serious and long-lasting effects on the developing fetal brain. In the last decade, researchers have utilized quantitative structural magnetic resonance imaging (MRI) to examine the brains of living children and adults with histories of heavy prenatal alcohol exposure. In addition to microcephaly, these studies indicated structural abnormalities in various regions of the brain, including the cerebellum, corpus callosum, and the basal ganglia. Most recently, we have utilized novel imaging and analytic techniques to study the brain as a whole in an effort to elucidate more subtle differences than was possible with earlier techniques. Results indicated displacements in the corpus callosum, increased gray matter densities in both hemispheres in the perisylvian regions, and altered gray matter asymmetry in portions of the temporal lobes in the brains of alcohol-exposed subjects. In addition, prominent shape abnormalities were observed in the brains of these subjects, with narrowing in the temporal region and reduced brain growth in portions of the frontal lobe. These results imply that brain growth continues to be adversely affected long after the prenatal insult and that the brain regions most affected may be consistent with the neurocognitive deficits characteristic of individuals prenatally exposed to alcohol.

Alcohol Drinking↗
PubMed2004

Mapping brain size and cortical gray matter changes in elderly depression.

BACKGROUND: In elderly depression, volumetric brain imaging findings suggest abnormalities of the frontal lobe, particularly the orbitofrontal cortex, and the hippocampus. No studies to date have mapped cortical abnormalities over the entire brain surface in major depression. Here, we conducted detailed spatial analyses of brain size and gray matter within the cortical mantle in elderly patients with major depression. METHODS: High-resolution, three-dimensional, structural magnetic resonance imaging data and cortical pattern matching methods were used in 24 depressed elderly patients and 19 group-matched controls to measure local brain size and proportions of gray matter at thousands of homologous cortical surface locations. RESULTS: Prominent brain size reductions were observed in the depressed subjects in the orbitofrontal cortex bilaterally. Cortical gray matter measurements revealed significant gray matter increases in the orbitofrontal cortex, adjacent to focal trend level significant decreases of gray matter in the same region. Depressed patients also exhibited significant gray matter increases in parietal cortices, as well as the left temporal cortex. CONCLUSIONS: Complex cortical changes may contribute to the brain size reduction of the orbitofrontal cortex and to the gray matter abnormalities detected in orbitofrontal cortex and temporoparietal cortices, thereby providing a potentially new window into the pathophysiology of elderly depression.

Aged↗
PubMed2004

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.

Algorithms↗
PubMed2004

Anterior cingulate, gyrus rectus, and orbitofrontal abnormalities in elderly depressed patients: an MRI-based parcellation of the prefrontal cortex.

OBJECTIVE: To examine structural abnormalities in subregions of the prefrontal cortex in elderly patients with depression, the authors explored differences in gray matter, white matter, and CSF volumes by applying a parcellation method based on magnetic resonance imaging (MRI). METHOD: Twenty-four elderly patients with major depression and 19 group-matched comparison subjects were studied with high-resolution MRI. Cortical surface extraction, tissue segmentation, and cortical parcellation methods were applied to obtain volume measures of gray matter, white matter, and CSF in seven prefrontal subregions: the anterior cingulate, gyrus rectus, orbitofrontal cortex, precentral gyrus, superior frontal cortex, middle frontal cortex, and inferior frontal cortex. RESULTS: Highly significant bilateral volume reductions in gray matter were observed in the anterior cingulate, the gyrus rectus, and the orbitofrontal cortex. Depressed patients also exhibited significant bilateral white matter volume reductions and significant CSF volume increases in the anterior cingulate and the gyrus rectus. Finally, the depressed group showed significant CSF volume reductions in the orbitofrontal cortex relative to the comparison subjects. None of the other regions examined revealed significant structural abnormalities. CONCLUSIONS: The prominent bilateral gray matter deficits in the anterior cingulate and the gyrus rectus as well as the orbitofrontal cortex may reflect disease-specific modifications of elderly depression. The differential pattern of abnormalities detected in the white matter and CSF compartments imply that distinct etiopathological mechanisms might underlie the structural cortical changes in these regions.

Aged↗
PubMed2004

Mapping changes in the human cortex throughout the span of life.

In this review, the authors summarize the literature on brain morphological changes that occur throughout the human life span from childhood into old age. They examine changes observed postmortem and in vivo where various brain MRI analytic methods have been applied. They evaluate brain changes observed with volumetric image analytic methods and voxel-based morphometric methods that may be used to better localize where changes occur. The primary focus of the review is on recent studies using state-of-the-art cortical pattern-matching techniques to assess age-related changes in cortical asymmetries, gray matter distribution, and brain growth across various age spans. The authors attempt to integrate findings from the in vivo studies with results from postmortem studies and analyze the complicated question of when brain maturation stops and brain aging begins. Analyzing the regional patterns of change initiated at various ages may help elucidate relationships between changing brain morphology and changing cognitive functions that occur throughout life. Long-range longitudinal studies, correlations between imaging and postmortem data, and more advanced image acquisition and analysis technologies will be needed to fully interpret brain morphological changes observed in vivo in relation to development and aging.

Adolescent↗
PubMed2003

Cortical abnormalities in children and adolescents with attention-deficit hyperactivity disorder.

BACKGROUND: Results of structural brain imaging studies of patients with attention-deficit hyperactivity disorder have shown subtle reductions in total brain volume and in volumes of the right frontal lobe and caudate nucleus. Although various conventional volumetric and voxel-based methods of image analysis have been used in these studies, regional brain size and grey-matter abnormalities have not yet been mapped over the entire cortical surface in patients with this disorder. We aimed to map these features in patients with attention-deficit hyperactivity disorder. METHODS: We used high-resolution MRI and surface-based, computational image analytic techniques to map regional brain size and grey-matter abnormalities at the cortical surface in a group of 27 children and adolescents with attention-deficit hyperactivity disorder and 46 controls, who were group-matched by age and sex. FINDINGS: Abnormal morphology was noted in the frontal cortices of patients with attention-deficit hyperactivity disorder, with reduced regional brain size localised mainly to inferior portions of dorsal prefrontal cortices bilaterally. Brain size was also reduced in anterior temporal cortices bilaterally. Prominent increases in grey matter were recorded in large portions of the posterior temporal and inferior parietal cortices bilaterally. INTERPRETATION: The frontal, temporal, and parietal regions are heteromodal association cortices that constitute a distributed neural system, which subserves attention and behavioural inhibition. We have identified region-specific anatomical abnormalities in cortical components of attentional systems, which may help better account for the symptoms of attention-deficit hyperactivity disorder.

Adolescent↗
PubMed2003

Mapping cortical change across the human life span.

We used magnetic resonance imaging and cortical matching algorithms to map gray matter density (GMD) in 176 normal individuals ranging in age from 7 to 87 years. We found a significant, nonlinear decline in GMD with age, which was most rapid between 7 and about 60 years, over dorsal frontal and parietal association cortices on both the lateral and interhemispheric surfaces. Age effects were inverted in the left posterior temporal region, where GMD gain continued up to age 30 and then rapidly declined. The trajectory of maturational and aging effects varied considerably over the cortex. Visual, auditory and limbic cortices, which are known to myelinate early, showed a more linear pattern of aging than the frontal and parietal neocortices, which continue myelination into adulthood. Our findings also indicate that the posterior temporal cortices, primarily in the left hemisphere, which typically support language functions, have a more protracted course of maturation than any other cortical region.

Adolescent↗
PubMed2003

Increases in regional subarachnoid CSF without apparent cortical gray matter deficits in schizophrenia: modulating effects of sex and age.

OBJECTIVE: The authors investigated the modulating effects of biological sex and age on regional decreases in cortical gray matter and increases in subarachnoid CSF in 25 patients with chronic schizophrenia and 28 group-matched healthy comparison subjects. METHOD: Computational cortical pattern-matching methods were employed to measure the local proportions of gray matter and subarachnoid CSF at thousands of homologous cortical surface locations in each subject using high-resolution magnetic resonance images. Principal-component analysis reduced tissue proportion values obtained at each cortical surface point into component scores for each subject. Principal-component analysis scores were used as dependent variables in statistical analyses that included diagnosis, age, and sex as predictor variables. To reveal more regional changes in tissue proportions, statistical differences in gray matter and CSF were compared at each cortical surface location and mapped in three dimensions. RESULTS: Principal-component analyses revealed main effects of diagnosis, sex, and age for the CSF increases seen in the schizophrenia patients, in male subjects, and in association with age. Significant diagnosis-by-age, diagnosis-by-sex, and diagnosis-by-sex-by-age interactions were also observed, revealing CSF increases in male patients at younger ages. Statistical maps showed regional increases in subarachnoid CSF in association with the above effects. For cortical gray matter measurements, only main effects of age were observed. CONCLUSIONS: Regionally specific increases in sulcal and subarachnoid CSF occur during adulthood and appear prematurely in male schizophrenia patients. Cortical gray matter reductions show aging effects but are below the threshold of significance in schizophrenia.

Adult↗
PubMed2002

Mapping cortical gray matter asymmetry patterns in adolescents with heavy prenatal alcohol exposure.

Here we report on detailed three-dimensional quantitative maps of brain surface and gray matter density asymmetry patterns during normal adolescent development and show how these anatomical features of the brain are disrupted as a result of prenatal exposure to large quantities of alcohol. We studied two independent samples of normally developing children, adolescents, and young adults, totaling 83 subjects from two different research groups, and compared them to 21 individuals with heavy prenatal alcohol exposure. Surface-based image analysis techniques allowed us to match cortical anatomy across subjects and between hemispheres based on manually delineated sulcal landmarks. Quantitative maps of brain surface asymmetry reveal prominent peri-Sylvian hemispheric differences in which the superior temporal and inferior parietal cortices are shifted backward in the left relative to the right hemisphere in both normal and alcohol-exposed subjects. Cortical surface gray matter asymmetry, mapped here in adolescent populations, is most prominent in the posterior inferior temporal lobes (right greater than left), and this effect does not differ between groups of normally developing children, adolescents, or young adults. Alcohol-exposed individuals show a significant reduction in this asymmetry, whether studied with surface-based or more traditional volumetric region of interest analyses. This region of cortex, near the junction of Brodmann's areas 21, 22, and 37, primarily subserves language functions that are known to be impaired on average in the alcohol-exposed subjects. Our findings elucidate regional patterns of brain surface and gray matter asymmetry during normal development and may contribute to a more comprehensive understanding of the neural substrates of cognitive dysfunction after heavy prenatal alcohol exposure.

Adolescent↗
PubMed2002

Development of cortical and subcortical brain structures in childhood and adolescence: a structural MRI study.

The purpose of the present study was to describe in greater anatomical detail the changes in brain structure that occur during maturation between childhood and adolescence. High-resolution MRI, tissue classification, and anatomical segmentation of cortical and subcortical regions were used in a sample of 35 normally developing children and adolescents between 7 and 16 years of age (mean age 11 years; 20 males, 15 females). Each cortical and subcortical measure was examined for age and sex effects on raw volumes and on the measures as proportions of total supratentorial cranial volume. Results indicate age-related increases in total supratentorial cranial volume and raw and proportional increases in total cerebral white matter. Gray-matter volume reductions were only observed once variance in total brain size was proportionally controlled. The change in total cerebral white-matter proportion was significantly greater than the change in total cerebral gray-matter proportion over this age range, suggesting that the relative gray-matter reduction is probably due to significant increases in white matter. Total raw cerebral CSF volume increases were also observed. Within the cerebrum, regional patterns varied depending on the tissue (or CSF) assessed. Only frontal and parietal cortices showed changes in gray matter, white matter, and CSF measures. Once the approximately 7% larger brain volume in males was controlled, only mesial temporal cortex, caudate, thalamus, and basomesial diencephalic structures showed sex effects with the females having greater relative volumes in these regions than the males. Overall, these results are consistent with earlier reports and describe in greater detail the regional pattern of age-related differences in gray and white matter in normally developing children and adolescents.

Adolescent↗
PubMed2002

Mapping sulcal pattern asymmetry and local cortical surface gray matter distribution in vivo: maturation in perisylvian cortices.

Previous in vivo morphometric studies of human brain maturation between childhood and young adulthood have revealed a spatial and temporal pattern of progressive brain changes that is consistent with the post mortem cytoarchitectonic and cognitive developmental literatures. In this study, we mapped age differences in structural asymmetries at the cortical surface in groups of normally developing children (7-11 years), adolescents (12-16 years) and young adults (23-30 years) using novel surface-based mesh modeling image analytic methods. We also assessed relationships between cortical surface sulcal asymmetry and the local density of the underlying cortical gray matter. Results from this study reveal that perisylvian sulcal asymmetries are much more prominent in the adults than in the children studied. The superior posterior extent of the Sylvian fissure in the right hemisphere is approximately 7 mm more superior in the average adult than in the average child studied, whereas little difference is observed during this age range in the location of this anatomical structure in the left hemisphere. Age-related differences in Sylvian fissure asymmetry were significant (P = 0.0129, permutation test), showing increased asymmetry with increasing age. We also show age-related increases in local gray matter proportion bilaterally in the temporo-parietal cortices that are anatomically and temporally related to the sulcal asymmetries. Results from this cross-sectional study imply that asymmetries in the Sylvian fissure are dynamically changing into young adulthood and show that variability in brain tissue density is related to asymmetry in this region. These morphological differences may be related to changing cognitive abilities and are relevant in interpreting results from studies of abnormal brain development where perisylvian brain regions are implicated.

Adolescent↗
PubMed2002

Regional brain shape abnormalities persist into adolescence after heavy prenatal alcohol exposure.

We assessed regional brain shape abnormalities and spatial relationships between brain shape and abnormalities observed in the underlying tissue in children and adolescents prenatally exposed to large quantities of alcohol. We used high resolution, 3-D, structural magnetic resonance imaging data and novel, whole-brain, surface-based image analysis procedures to study 21 subjects with heavy prenatal alcohol exposure (8-22 years, mean age 12.6 years) and 21 normally developing control subjects (8-25 years, mean age 13.5 years). Significant brain size and shape abnormalities were observed in the alcohol-exposed subjects in inferior parietal/ perisylvian regions bilaterally, where their brains appeared to be narrower than those of the controls in the same general location where they also had increased gray matter density. Highly significant decreased brain surface extent or reduced brain growth was also observed in the ventral aspects of the frontal lobes most prominent in the left hemisphere. For the first time in this report we have mapped brain morphologic abnormalities to the cortical surface in subjects with prenatal alcohol exposure and have shown that the size and shape of the brain is altered in these individuals. The results imply that brain growth continues to be adversely affected long after the prenatal insult of alcohol exposure to the developing brain and the brain regions most implicated, frontal and inferior parietal/ perisylvian, may be consistent with behavioral deficits characteristic of individuals prenatally exposed to alcohol.

Adolescent↗