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Arthur W Toga

Publications and source records attributed to Arthur W Toga.

At least 19 recordsLinked to original sources
PubMed2024

Sex and APOE ε4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer's disease.

INTRODUCTION: The effects of sex and apolipoprotein E (APOE)-Alzheimer's disease (AD) risk factors-on white matter microstructure are not well characterized. METHODS: Diffusion magnetic resonance imaging data from nine well-established longitudinal cohorts of aging were free water (FW)-corrected and harmonized. This dataset included 4741 participants (age = 73.06 ± 9.75) with 9671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FAFWcorr) were used to assess differences in white matter microstructure by sex and APOE ε4 carrier status. RESULTS: Sex differences in FAFWcorr in projection tracts and APOE ε4 differences in FW limbic and occipital transcallosal tracts were most pronounced. DISCUSSION: There are prominent differences in white matter microstructure by sex and APOE ε4 carrier status. This work adds to our understanding of disparities in AD. Additional work to understand the etiology of these differences is warranted. HIGHLIGHTS: Sex and apolipoprotein E (APOE) ε4 carrier status relate to white matter microstructural integrity. Females generally have lower free water-corrected fractional anisotropy compared to males. APOE ε4 carriers tended to have higher free water than non-carriers.

Humans↗
PubMed2003

Dynamics of gray matter loss in Alzheimer's disease.

We detected and mapped a dynamically spreading wave of gray matter loss in the brains of patients with Alzheimer's disease (AD). The loss pattern was visualized in four dimensions as it spread over time from temporal and limbic cortices into frontal and occipital brain regions, sparing sensorimotor cortices. The shifting deficits were asymmetric (left hemisphere > right hemisphere) and correlated with progressively declining cognitive status (p < 0.0006). Novel brain mapping methods allowed us to visualize dynamic patterns of atrophy in 52 high-resolution magnetic resonance image scans of 12 patients with AD (age 68.4 +/- 1.9 years) and 14 elderly matched controls (age 71.4 +/- 0.9 years) scanned longitudinally (two scans; interscan interval 2.1 +/- 0.4 years). A cortical pattern matching technique encoded changes in brain shape and tissue distribution across subjects and time. Cortical atrophy occurred in a well defined sequence as the disease progressed, mirroring the sequence of neurofibrillary tangle accumulation observed in cross sections at autopsy. Advancing deficits were visualized as dynamic maps that change over time. Frontal regions, spared early in the disease, showed pervasive deficits later (>15% loss). The maps distinguished different phases of AD and differentiated AD from normal aging. Local gray matter loss rates (5.3 +/- 2.3% per year in AD v 0.9 +/- 0.9% per year in controls) were faster in the left hemisphere (p < 0.029) than the right. Transient barriers to disease progression appeared at limbic/frontal boundaries. This degenerative sequence, observed in vivo as it developed, provides the first quantitative, dynamic visualization of cortical atrophic rates in normal elderly populations and in those with dementia.

Aged↗
PubMed2003

Asymmetry of the brain surface from deformation field analysis.

The detection of asymmetry of exposed brain surfaces is examined, and a new method, deformation-based asymmetry (DBA), is introduced. DBA is based on analysis of two high-resolution magnetic resonance brain images, each with features representative of the subject group from which they were derived. Warping of individual brain images to their group representative image using octree spatial normalization provides sets of displacement vectors that are used in estimating deformation variance. For DBA group-representative left and right hemisphere images are compared. Representative hemisphere images are warped to each other and asymmetry analyzed using standardized d-values calculated as the ratio of displacement vector magnitude to the estimated component of variance in the direction of the displacement vector for each surface voxel. D-values were calculated within hemispheres by dividing subjects into two equal groups and comparing left-to-left and right-to-right. D-values from this ipsilateral hemisphere grouping were pooled. D-values from contralateral hemispheres were compared with the pooled ipsilateral hemisphere data. The proportion of d-values above a fixed level was used to test for difference between the two groups. High-resolution magnetic resonance (MR) images from 20 young, right-handed males were studied using DBA. No significant differences were seen between sub-grouped ipsilateral d-values (P > 0.10). Highly significant asymmetries (P < 0.0001) were found between hemispheres, and in each lobe. Common right frontal and left occipital petalias were seen. The DBA method can theoretically be applied to any two groups of globally similar structures where analysis of dissimilarity of regional features is sought.

Adult↗
PubMed2003

Shedding light on brain mapping: advances in human optical imaging.

Several functional brain imaging techniques have been used to study human cortical organization. Optical imaging of intrinsic signals (OIS) offers perhaps the best combination of spatial coverage, resolution and speed for mapping the functional topography of human cortex. In this review, we discuss recent advances in optical imaging technology and methodology that have made human OIS easier to implement and more accessible, including improvements in detector characteristics and the development of sophisticated algorithms for reducing motion artifact. Moreover, we discuss how these advances have helped enhance our understanding of the functional organization of the human brain. We also review newly developed analyses for interpreting and validating optical signals, including refined signal analysis techniques and multimodality comparisons. Combined, these advances have enabled the study of not only primary sensory and motor cortices, but also higher cognitive processes such as language production and comprehension. Continued improvement and implementation of this technique promises to shed new light on the functional organization of human cortex.

Algorithms↗
PubMed2003

Evaluation of coupling between optical intrinsic signals and neuronal activity in rat somatosensory cortex.

We investigated the coupling between perfusion-related brain imaging signals and evoked neuronal activity using optical imaging of intrinsic signals (OIS) at 570 and 610 nm. OIS at 570 nm reflects changes in cerebral blood volume (CBV), and the 610 nm response is related to hemoglobin oxygenation changes. We assessed the degree to which these components of the hemodynamic response were coupled to neuronal activity in rat barrel, hindpaw, and forepaw somatosensory cortex by simultaneously recording extracellular evoked field potentials (EPs) and OIS while varying stimulation frequency. In all stimulation paradigms, 10 Hz stimulation evoked the largest optical and electrophysiological responses. Across all animals, the 610 late phase and 570 responses correlated linearly with sigmaEP (P < 0.05) during both whisker deflection and electrical hindpaw stimulation, but the 610 early phase did not (whisker P = 0.27, hindpaw P = 0.28). The signal-to-noise ratio (SNR) of the 610 early phase (whisker 3.1, hindpaw 5.3) was much less than that for the late phase (whisker 14, hindpaw 51) and 570 response (whisker 11, hindpaw 46). During forepaw stimulation, however, the 610 early phase had a SNR (17) higher than that during hindpaw stimulation and correlated well with neuronal activity (P < 0.05). We conclude that the early deoxygenation change does not correlate consistently with neuronal activity, possibly because of its low SNR. The robust CBV-related response, however, has a high SNR and correlates well with evoked cortical activity.

Animals↗
PubMed2003

The LONI Pipeline Processing Environment.

The analysis of raw data in neuroimaging has become a computationally entrenched process with many intricate steps run on increasingly larger datasets. Many software packages exist that provide either complete analyses or specific steps in an analysis. These packages often possess diverse input and output requirements, utilize different file formats, run in particular environments, and have limited abilities with certain types of data. The combination of these packages to achieve more sensitive and accurate results has become a common tactic in brain mapping studies but requires much work to ensure valid interoperation between programs. The handling, organization, and storage of intermediate data can prove difficult as well. The LONI Pipeline Processing Environment is a simple, efficient, and distributed computing solution to these problems enabling software inclusion from different laboratories in different environments. It is used here to derive a T1-weighted MRI atlas of the human brain from 452 normal young adult subjects with fully automated processing. The LONI Pipeline Processing Environment's parallel processing efficiency using an integrated client/server dataflow model was 80.9% when running the atlas generation pipeline from a PC client (Acer TravelMate 340T) on 48 dedicated server processors (Silicon Graphics Inc. Origin 3000). The environment was 97.5% efficient when the same analysis was run on eight dedicated processors.

Brain Mapping↗
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

Cortical sulcal maps in autism.

This study presents the first three-dimensional mapping of cortical sulcal patterns in autism, a pervasive developmental disorder, the underlying neurobiology of which remains unknown. High-resolution T(1)-weighted MRI scans were acquired in 21 autistic (age 10.7 +/- 3.1 years) and 20 normal control (age 11.3 +/- 2.9) children and adolescents. Using parametric mesh-based analytic techniques, we created three-dimensional models of the cerebral cortex and detailed maps of 22 major sulci in stereotaxic space. These average maps revealed anatomic shifting of major sulci primarily in frontal and temporal areas. Specifically, we found anterior and superior shifting of the superior frontal sulci bilaterally (P < or = 0.0003), anterior shifting of the right Sylvian fissure (P = 0.0002), the superior temporal sulcus (P = 0.0006 right, P = 0.02 left) and the left inferior frontal sulcus (P < or = 0.002) in the autistic group relative to the normal group. Less significant sulcal shifts occurred in the intraparietal and collateral sulci. These findings may indicate delayed maturation in autistic subjects in these brain regions involved in functions including working memory, emotion processing, language and eye gaze.

Autistic Disorder↗
PubMed2003

Category-specific naming deficit identified by intraoperative stimulation mapping and postoperative neuropsychological testing. Case report.

Category-specific naming deficits and differential brain activation patterns have been reported in patients naming living as opposed to nonliving objects. The authors report on a case in which they used preoperative functional magnetic resonance (fMR) imaging, intraoperative electrocortical stimulation mapping (ESM), and postoperative neuropsychological testing to map language function. Using the latter two modalities, the authors identified a specific locus for category-specific naming in the posterior inferior temporal lobe, presumably a part of the basal temporal language area. Preoperative fMR imaging findings revealed the presence of a language area in the inferior temporal lobe; intraoperative ESM results indicated that this cortical area may be category specific for living objects; and after resection of the area, the results of postoperative neuropsychological testing confirmed that the patient made significantly more errors while naming living objects compared with nonliving ones (p < 0.001), independent of the effects of word frequency and with an intact system of object recognition and comprehension. These authors are the first to identify a specific and well-localized area of category-specific naming in the inferior temporal lobe and to demonstrate congruence of intraoperative and postoperative category-specific naming deficits. They also emphasize the roles of preoperative and intraoperative testing in predicting clinical outcomes.

Adult↗
PubMed2002

Genetic contributions to altered callosal morphology in schizophrenia.

Patients with schizophrenia exhibit abnormalities in midsagittal corpus callosum area, shape, and/or displacement. Our goal was to confirm these findings and to establish the genetic and nongenetic contributions to altered callosal morphology in schizophrenia. Relationships between ventricular enlargements potentially contributing to callosal displacements were assessed as a secondary goal. High-resolution magnetic resonance images were obtained from co-twins of monozygotic and dizygotic pairs discordant for schizophrenia and healthy control twins (N = 40 pairs). Investigators blind to group status segmented the corpus callosum and ventricles in native brain volumes aligned using a rigid-body transformation with no scaling. Total and parcellated midsagittal callosal areas and measures indexing vertical displacements of the corpus callosum were used in statistical tests to identify schizophrenia and sex effects and to dissociate genetic and nongenetic influences on morphology. Anatomical mesh modeling methods provided group average and surface variability maps of the callosum. Callosal areas did not differ between groups defined by sex or biological risk. Vertical displacements of the callosum, pronounced in male patients, were confirmed in schizophrenia and observed between dizygotic, but not monozygotic co-twins discordant for schizophrenia. Like their affected twins, however, unaffected monozygotic co-twins of the schizophrenia probands exhibited significant callosal displacements. Lateral and third ventricle enlargements were related to callosal displacements. Results clearly support that genetic rather than disease-specific or shared environmental influences contribute to altered callosal morphology in schizophrenia. An upward bowing of the callosum may thus provide an easily identifiable neuroanatomic marker to screen individuals possessing a biological vulnerability for schizophrenia.

Brain Mapping↗
PubMed2002

Cortex mapping reveals regionally specific patterns of genetic and disease-specific gray-matter deficits in twins discordant for schizophrenia.

The symptoms of schizophrenia imply disruption to brain systems supporting higher-order cognitive activity, but whether these systems are impacted differentially against a background of diffuse cortical gray-matter deficit remains ambiguous. Some unaffected first-degree relatives of schizophrenics also manifest cortical gray-matter deficits, but it is unclear whether these changes are isomorphic with those in patients, and the answer is critical to understanding the neurobiological conditions necessary for disease expression given a predisposing genotype. Here we report three-dimensional cortical surface maps (probabilistic atlases matching subjects' anatomy point by point throughout cortex) in monozygotic (MZ) and dizygotic (DZ) twins discordant for chronic schizophrenia along with demographically matched control twins. A map encoding the average differences between schizophrenia patients and their unaffected MZ co-twins revealed deficits primarily in dorsolateral prefrontal cortex, superior temporal gyrus, and superior parietal lobule. A map encoding variation associated with genetic proximity to a patient (MZ co-twins > DZ co-twins > control twins) isolated deficits primarily in polar and dorsolateral prefrontal cortex. In each case, the statistical significance was confirmed through analysis of 10,000 Monte Carlo permutations, and the remaining cortex was shown to be significantly less affected by contrast analysis. The disease-related deficits in gray matter were correlated with measures of symptom severity and cognitive dysfunction but not with duration of illness or antipsychotic drug treatment. Genetic and disease-specific influences thus affect gray matter in partially nonoverlapping areas of predominantly heteromodal association cortex, changes that may act synergistically in producing overt behavioral features of the disorder.

Brain Mapping↗
PubMed2002

Spatial/temporal correlation of BOLD and optical intrinsic signals in humans.

Comparing the BOLD signal with electrophysiological maps and other perfusion-dependent signals, such as the optical intrinsic signal (OIS), within subjects should provide insight into the etiology of the BOLD signal. Tongue activations were compared in five human subjects using BOLD fMRI, 610-nm OIS, and the electrocortical stimulation map (ESM). Robust fMRI activations centered on the lateral inferior aspect of the central sulcus and extended into pre- and post-central gyri, adjacent to ESM tongue loci. OIS and fMRI maps colocalized, although optical responses were spatially larger (P <.001 across multiple thresholds) and contained more gyral components. The timecourses of the fMRI and OIS signals were similar, appearing within 2.5 s and peaking 6-8 s after task onset. Although many processes contribute to increased 610-nm reflectance, optical spectroscopy and fluorescent dye imaging suggest that a significant part of this signal is due to a concomitant decrease in deoxyhemoglobin and increase in oxyhemoglobin concentrations. The spatial/temporal correlation of BOLD and the positive 610-nm response within subjects suggests that the two signals may share similar etiologies. The OIS/fMRI inconsistencies may be due to cell swelling and light-scattering contributions to OIS and fMRI sensitivity. This study also demonstrates that fMRI maps do not precisely colocalize with ESM, rather they emphasize changes in adjacent venous/sulcal structures.

Brain↗
PubMed2002

A twin study of genetic contributions to hippocampal morphology in schizophrenia.

Our goal was to establish whether altered hippocampal morphology represents a trait marker for genetic vulnerability in schizophrenia. We outlined the hippocampi on high-resolution MR images obtained from matched samples of control and discordant monozygotic and dizygotic co-twins (N = 40 pairs). Hippocampal measures were used in statistical tests specifically designed to identify disease-associated genetic and nongenetic influences on morphology. 3D surface average maps of the hippocampus were additionally compared in biological risk groups. Smaller hippocampal volumes were confirmed in schizophrenia. Dizygotic affected co-twins showed smaller left hippocampi compared to their healthy siblings. Disease-associated effects were not present between monozygotic discordant co-twins. Monozygotic, but not dizygotic, unaffected co-twins exhibited smaller left hippocampi compared to control twins, supporting genetic influences. Surface areas and posterior volumes similarly revealed schizophrenia and genetic liability effects. Results suggest that hippocampal volume reduction may be a trait marker for identifying individuals possessing a genetic predisposition for 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

Mapping genetic influences on human brain structure.

Recent advances in brain imaging and genetics have empowered the mapping of genetic and environmental influences on the human brain. These techniques shed light on the 'nature/nurture' debate, revealing how genes determine individual differences in intelligence quotient (IQ) or risk for disease. They visualize which aspects of brain structure and function are heritable, and to what degree, linking these features with behavioral or cognitive traits or disease phenotypes. In genetically transmitted disorders such as schizophrenia, patterns of brain structure can be associated with increased disease liability, and sites can be mapped where non-genetic triggers may initiate disease. We recently developed a large-scale computational brain atlas, including data components from the Finnish Twin registry, to store information on individual variations in brain structure and their heritability. Algorithms from random field theory, anatomical modeling, and population genetics were combined to detect a genetic continuum in which brain structure is heavily genetically determined in some areas but not others. These algorithmic advances motivate studies of disease in which the normative atlas acts as a quantitative reference for the heritability of structural differences and deficits in patient populations. The resulting genetic brain maps isolate biological markers for inherited traits and disease susceptibility, which may serve as targets for genetic linkage and association studies. Computational methods from brain imaging and genetics can be fruitfully merged, to shed light on the inheritance of personality differences and behavioral traits, and the genetic transmission of diseases that affect the human brain.

Algorithms↗
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↗