Biomedical subjects

Arthur W Toga

Publications and source records attributed to Arthur W Toga.

At least 37 records · Page 2Linked to original sources

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↗

PubMed2006

Mapping corpus callosum deficits in autism: an index of aberrant cortical connectivity.

BACKGROUND: Volumetric studies have reported reductions in the size of the corpus callosum (CC) in autism, but the callosal regions contributing to this deficit have differed among studies. In this study, a computational method was used to detect and map the spatial pattern of CC abnormalities in male patients with autism. METHODS: Twenty-four boys with autism (aged 10.0 +/- 3.3 years) and 26 control boys (aged 11.0 +/- 2.5 years) underwent a magnetic resonance imaging (MRI) scan at 3 Tesla. Total and regional areas of the CC were determined using traditional morphometric methods. Three-dimensional (3D) surface models of the CC were also created from the MRI scans. Statistical maps were created to visualize morphologic variability of the CC and to localize regions of callosal thinning in autism. RESULTS: Traditional morphometric methods detected a significant reduction in the total callosal area and in the anterior third of the CC in patients with autism; however, 3D maps revealed significant reductions in both the splenium and genu of the CC in patients. CONCLUSIONS: Statistical maps of the CC revealed callosal deficits in autism with greater precision than traditional morphometric methods. These abnormalities suggest aberrant connections between cortical regions, which is consistent with the hypothesis of abnormal cortical connectivity in autism.

Adolescent↗

PubMed2006

3D mapping of ventricular and corpus callosum abnormalities in HIV/AIDS.

OBJECTIVE: 40 million people worldwide are now infected with HIV/AIDS, an illness that often leads to rapidly progressing dementia and death. Even so, little is known about how AIDS affects the brain. Using computational anatomy techniques, we mapped how AIDS impacts the corpus callosum (CC) and ventricular system, two systems that show prominent changes on MRI. We (1) identified regions with greatest differences between AIDS patients and healthy controls and (2) correlated specific 3D patterns of structural differences with measures of immune system deterioration and cognitive decline. METHODS: 51 3D brain MRI scans from 30 non-demented AIDS patients (age: 43.4 years +/- 7.6 SD) and 21 HIV-seronegative controls (age: 39.5 years +/- 12.2) were aligned to ICBM standard space. 3D surface mesh reconstructions of the lateral ventricles and CC were spatially averaged and compared across diagnostic groups. Structural alterations were correlated with viral load, T cell counts, and cognitive impairment. RESULTS: Statistical maps revealed the 3D profile of ventricular expansion and callosal thinning in AIDS. Specific 3D ventricular changes were linked with immune system decline (CD4+ T cell counts; P < 0.001) and cognitive impairment (P < 0.009), but not viral load. Frontal horn maps distinguished AIDS patients from controls better than occipital and temporal horn measures. T cell decline linked with callosal thinning in anterior regions connecting frontal areas with greatest cortical atrophy. CONCLUSION: These maps (1) reveal how brain changes in HIV/AIDS relate to immune decline and impaired cognition, and, after further validation and testing, (2) may offer possible neuroimaging markers for anti-viral drug trials, which gauge how well treatments oppose disease progression in the brain.

AIDS Dementia Complex↗

PubMed2006

Three-dimensional patterns of hippocampal atrophy in mild cognitive impairment.

OBJECTIVE: To measure hippocampal volumes in patients diagnosed as having subtypes of mild cognitive impairment (MCI) relative to those of elderly control subjects and those of patients with Alzheimer disease (AD) using 3-dimensional mesh reconstructions. DESIGN: A magnetic resonance imaging volumetric study of MCI subgroups (MCI, amnesic subtype [MCI-A]; and MCI, multiple cognitive domain subtype) using 3-dimensional mesh reconstructions of the structure. SETTING: Referral dementia clinic. SUBJECTS: Twenty-six subjects with MCI (MCI-A, n = 6; and MCI, multiple cognitive domain subtype, n = 20), 20 subjects with AD, and 20 controls who were equivalent in age, education, and sex distributions. MAIN OUTCOME MEASURES: Three-dimensional parametric mesh models of the hippocampus and total hippocampal volumes. RESULTS: The hippocampi of the patients with AD were significantly atrophic relative to those of the healthy controls. The MCI, multiple cognitive domain subtype, group did not differ from the controls, yet was significantly different from the MCI-A and the AD groups. The MCI-A patients had significant hippocampal atrophy compared with the controls, and did not differ significantly from the patients with AD. CONCLUSION: These data add to the growing evidence that there are multiple forms of MCI, that they have distinct neuropathological correlates, and that MCI, multiple cognitive domain subtype, is not a more advanced form of the MCI-A subtype.

Aged↗

PubMed2006

Conversion of mild cognitive impairment to Alzheimer disease predicted by hippocampal atrophy maps.

BACKGROUND: While most patients with mild cognitive impairment (MCI) transition to Alzheimer disease (AD), others develop non-AD dementia, remain in the MCI state, or improve. OBJECTIVE: To test the following hypotheses: smaller hippocampal volumes predict conversion of MCI to AD, whereas larger hippocampal volumes predict cognitive stability and/or improvement; and patients with MCI who convert to AD have greater atrophy in the CA1 hippocampal subfield and subiculum. DESIGN: Prospective longitudinal cohort study. SETTING: University of California-Los Angeles Alzheimer's Disease Research Center. PATIENTS: We followed up 20 MCI subjects clinically and neuropsychologically for 3 years. MAIN OUTCOME MEASURE: Baseline regional hippocampal atrophy was analyzed with region-of-interest and 3-dimensional hippocampal mapping techniques. RESULTS: During the 3-year study, 6 patients developed AD (MCI-c), 7 remained stable (MCI-nc), and 7 improved (MCI-i). Patients with MCI-c had 9% smaller left and 13% smaller right mean hippocampal volumes compared with MCI-nc patients. Radial atrophy maps showed greater atrophy of the CA1 subregion in MCI-c. Patients with MCI-c had significantly smaller hippocampi than MCI-i patients (left, 24%; right, 27%). Volumetric analyses showed a trend for greater hippocampal atrophy in MCI-nc relative to MCI-i patients (eg, 16% volume loss). After permutation tests corrected for multiple comparison, the atrophy maps showed a significant difference on the right. Subicular differences were seen between MCI-c and MCI-i patients, and MCI-nc and MCI-i patients. Multiple linear regression analysis confirmed the group effect to be highly significant and independent of age, hemisphere, and Mini-Mental State Examination scores at baseline. CONCLUSIONS: Smaller hippocampi and specifically CA1 and subicular involvement are associated with increased risk for conversion from MCI to AD. Patients with MCI-i tend to have larger hippocampal volumes and relative preservation of both the subiculum and CA1.

Aged↗

PubMed2006

Dynamically spreading frontal and cingulate deficits mapped in adolescents with schizophrenia.

CONTEXT: We previously detected a dynamic wave of gray matter loss in childhood-onset schizophrenia that started in parietal association cortices and proceeded frontally to envelop dorsolateral prefrontal and temporal cortices, including superior temporal gyri. OBJECTIVE: To map gray matter loss rates across the medial hemispheric surface, including the cingulate and medial frontal cortex, in the same cohort studied previously. DESIGN: Five-year longitudinal study. SETTING: National Institute of Mental Health, Bethesda, Md. Subjects Twelve subjects with childhood-onset schizophrenia, 12 healthy controls, and 9 medication- and IQ-matched subjects with psychosis not otherwise specified. INTERVENTIONS: Three-dimensional magnetic resonance imaging at baseline and follow-up. MAIN OUTCOME MEASURES: Gyral pattern and shape variations encoded by means of high-dimensional elastic deformation mappings driving each subject's cortical anatomy onto a group average; changes in cortical gray matter mapped by computing warping fields that matched sulcal patterns across hemispheres, subjects, and time. RESULTS: Selective, severe frontal gray matter loss occurred bilaterally in a dorsal-to-ventral pattern across the medial hemispheric surfaces in the schizophrenic subjects. A sharp boundary in the pattern of gray matter loss separated frontal regions and cingulate-limbic areas. CONCLUSION: Frontal and limbic regions may not be equally vulnerable to gray matter attrition, which is consistent with the cognitive, metabolic, and functional vulnerability of the frontal cortices in schizophrenia.

Adolescent↗

PubMed2006

Quantitative evaluation of automated skull-stripping methods applied to contemporary and legacy images: effects of diagnosis, bias correction, and slice location.

Performance of automated methods to isolate brain from nonbrain tissues in magnetic resonance (MR) structural images may be influenced by MR signal inhomogeneities, type of MR image set, regional anatomy, and age and diagnosis of subjects studied. The present study compared the performance of four methods: Brain Extraction Tool (BET; Smith [2002]: Hum Brain Mapp 17:143-155); 3dIntracranial (Ward [1999] Milwaukee: Biophysics Research Institute, Medical College of Wisconsin; in AFNI); a Hybrid Watershed algorithm (HWA, Segonne et al. [2004] Neuroimage 22:1060-1075; in FreeSurfer); and Brain Surface Extractor (BSE, Sandor and Leahy [1997] IEEE Trans Med Imag 16:41-54; Shattuck et al. [2001] Neuroimage 13:856-876) to manually stripped images. The methods were applied to uncorrected and bias-corrected datasets; Legacy and Contemporary T1-weighted image sets; and four diagnostic groups (depressed, Alzheimer's, young and elderly control). To provide a criterion for outcome assessment, two experts manually stripped six sagittal sections for each dataset in locations where brain and nonbrain tissue are difficult to distinguish. Methods were compared on Jaccard similarity coefficients, Hausdorff distances, and an Expectation-Maximization algorithm. Methods tended to perform better on contemporary datasets; bias correction did not significantly improve method performance. Mesial sections were most difficult for all methods. Although AD image sets were most difficult to strip, HWA and BSE were more robust across diagnostic groups compared with 3dIntracranial and BET. With respect to specificity, BSE tended to perform best across all groups, whereas HWA was more sensitive than other methods. The results of this study may direct users towards a method appropriate to their T1-weighted datasets and improve the efficiency of processing for large, multisite neuroimaging studies.

Adult↗

PubMed2006

Dynamic mapping of normal human hippocampal development.

The hippocampus, which plays an important role in memory functions and emotional responses, has distinct subregions subserving different functions. Because the volume and shape of the hippocampus are altered in many neuropsychiatric disorders, it is important to understand the trajectory of normal hippocampal development. We present the first dynamic maps to reveal the anatomical sequence of normal human hippocampal development. A novel hippocampal mapping technique was applied to a database of prospectively obtained brain magnetic resonance imaging (MRI) scans (100 scans in 31 children and adolescents), scanned every 2 yr for 6-10 yr between ages 4 and 25. Our results establish that the structural development of the human hippocampus is remarkably heterogeneous, with significant differences between posterior (increase over time) and anterior (loss over time) subregions. These distinct developmental trajectories of hippocampal subregions may parallel differences in their functional development.

Adolescent↗

PubMed2006

LONI visualization environment.

Over the past decade, the use of informatics to solve complex neuroscientific problems has increased dramatically. Many of these research endeavors involve examining large amounts of imaging, behavioral, genetic, neurobiological, and neuropsychiatric data. Superimposing, processing, visualizing, or interpreting such a complex cohort of datasets frequently becomes a challenge. We developed a new software environment that allows investigators to integrate multimodal imaging data, hierarchical brain ontology systems, on-line genetic and phylogenic databases, and 3D virtual data reconstruction models. The Laboratory of Neuro Imaging visualization environment (LONI Viz) consists of the following components: a sectional viewer for imaging data, an interactive 3D display for surface and volume rendering of imaging data, a brain ontology viewer, and an external database query system. The synchronization of all components according to stereotaxic coordinates, region name, hierarchical ontology, and genetic labels is achieved via a comprehensive BrainMapper functionality, which directly maps between position, structure name, database, and functional connectivity information. This environment is freely available, portable, and extensible, and may prove very useful for neurobiologists, neurogenetisists, brain mappers, and for other clinical, pedagogical, and research endeavors.

Brain Mapping↗

PubMed2006

Towards multimodal atlases of the human brain.

Atlases of the human brain have an important impact on neuroscience. The emergence of ever more sophisticated imaging techniques, brain mapping methods and analytical strategies has the potential to revolutionize the concept of the brain atlas. Atlases can now combine data describing multiple aspects of brain structure or function at different scales from different subjects, yielding a truly integrative and comprehensive description of this organ. These integrative approaches have provided significant impetus for the human brain mapping initiatives, and have important applications in health and disease.

Anatomy, Artistic↗

PubMed2006

Adaptive reproducing kernel particle method for extraction of the cortical surface.

We propose a novel adaptive approach based on the Reproducing Kernel Particle Method (RKPM) to extract the cortical surfaces of the brain from three-dimensional (3-D) magnetic resonance images (MRIs). To formulate the discrete equations of the deformable model, a flexible particle shape function is employed in the Galerkin approximation of the weak form of the equilibrium equations. The proposed support generation method ensures that support of all particles cover the entire computational domains. The deformable model is adaptively adjusted by dilating the shape function and by inserting or merging particles in the high curvature regions or regions stopped by the target boundary. The shape function of the particle with a dilation parameter is adaptively constructed in response to particle insertion or merging. The proposed method offers flexibility in representing highly convolved structures and in refining the deformable models. Self-intersection of the surface, during evolution, is prevented by tracing backward along gradient descent direction from the crest interface of the distance field, which is computed by fast marching. These operations involve a significant computational cost. The initial model for the deformable surface is simple and requires no prior knowledge of the segmented structure. No specific template is required, e.g., an average cortical surface obtained from many subjects. The extracted cortical surface efficiently localizes the depths of the cerebral sulci, unlike some other active surface approaches that penalize regions of high curvature. Comparisons with manually segmented landmark data are provided to demonstrate the high accuracy of the proposed method. We also compare the proposed method to the finite element method, and to a commonly used cortical surface extraction approach, the CRUISE method. We also show that the independence of the shape functions of the RKPM from the underlying mesh enhances the convergence speed of the deformable model.

Algorithms↗

PubMed2006

Mapping heritability and molecular genetic associations with cortical features using probabilistic brain atlases: methods and applications to schizophrenia.

There is an urgent need to decipher the complex nature of genotype-phenotype relationships within the multiple dimensions of brain structure and function that are compromised in neuropsychiatric syndromes such as schizophrenia. Doing so requires sophisticated methodologies to represent population variability in neural traits and to probe their heritable and molecular genetic bases. We have recently developed and applied computational algorithms to map the heritability of, as well as genetic linkage and association to, neural features encoded using brain imaging in the context of three-dimensional (3D), populationbased, statistical brain atlases. One set of algorithms builds on our prior work using classical twin study methods to estimate heritability by fitting biometrical models for additive genetic, unique, and common environmental influences. Another set of algorithms performs regression-based (Haseman-Elston) identical-bydescent linkage analysis and genetic association analysis of DNA polymorphisms in relation to neural traits of interest in the same 3D population-based brain atlas format. We demonstrate these approaches using samples of healthy monozygotic (MZ) and dizygotic (DZ) twin pairs, as well as MZ and DZ twin pairs discordant for schizophrenia, but the methods can be generalized to other classes of relatives and to other diseases. The results confirm prior evidence of genetic influences on gray matter density in frontal brain regions. They also provide converging evidence that the chromosome 1q42 region is relevant to schizophrenia by demonstrating linkage and association of markers of the Transelin-Associated-Factor-X and Disrupted-In- Schizophrenia-1 genes with prefrontal cortical gray matter deficits in twins discordant for schizophrenia.

Algorithms↗

PubMed2005

Regional specificity of cerebrospinal fluid abnormalities in first episode schizophrenia.

The timing and regional specificity of cerebrospinal fluid (CSF) enlargements have not been well described in schizophrenia. High-resolution magnetic resonance images and computational image analysis methods were used to localize cross-sectional changes in lateral ventricle and sulcal and subarachnoid CSF in first episode schizophrenia patients (51 males/21 females) and healthy subjects (37 males/41 females). Volumes were obtained for each lateral ventricle horn and regional differences identified by comparing the distances from the ventricular surfaces to the central core at anatomically matched locations. Extra-cortical CSF differences were compared by measuring the proportion of CSF voxels sampled from spatially homologous cortical surface points. Significant extra-cortical CSF enlargements were observed in first episode patients, where regional differences surrounded the temporal, anterior frontal and parietal cortices. Volume and ventricular surface analyses failed to show significant effects of diagnosis. However, interactions indicated dorsal superior horn expansions in female patients compared with same-sex controls. Since ventricular enlargements are widely reported in chronic patients, our observations at first episode suggest ventricular enlargement may progress after disease onset with early changes occurring around the dorsal superior horn. In contrast, sulcal and subarachnoid CSF increases may be manifest near or before the first episode but after brain development is complete, reflecting pronounced reductions in proximal brain tissue.

Adult↗

PubMed2005

Lobar distribution of lesion volumes in late-life depression: the Biomedical Informatics Research Network (BIRN).

White matter hyperintense lesions on T2-weighted images are associated with late-life depression. Little work has been carried out examining differences in lesion location between elderly individuals with and without depression. In contrast to previous studies examining total brain white matter lesion volume, this study examined lobar differences in white matter lesion volumes derived from brain magnetic resonance imaging. This study examined 49 subjects with a DSM-IV diagnosis of major depression and 50 comparison subjects without depression. All participants were age 60 years or older. White matter lesion volumes were measured in each hemisphere using a semiautomated segmentation process and localized to lobar regions using a lobar atlas created for this sample using the imaging tools provided by the Biomedical Informatics Research Network (BIRN). The lobar lesion volumes were compared against depression status. After controlling for age and hypertension, subjects with depression exhibited significantly greater total white matter lesion volume in both hemispheres and in both frontal lobes than did control subjects. Although a similar trend was observed in the parietal lobes, the difference did not reach a level of statistical significance. Models of the temporal and occipital lobes were not statistically significant. Older individuals with depression have greater white matter disease than healthy controls, predominantly in the frontal lobes. These changes are thought to disrupt neural circuits involved in mood regulation, thus increasing the risk of developing depression.

Aged↗

PubMed2005

Standard atlas space for C57BL/6J neonatal mouse brain.

A standard atlas space with stereotaxic co-ordinates for the postnatal day 0 (P0) C57BL/6J mouse brain was constructed from the average of eight individual co-registered MR image volumes. Accuracy of registration and morphometric variations in structures between subjects were analyzed statistically. We also applied this atlas coordinate system to data acquired using different imaging protocols as well as to a high-resolution histological atlas obtained from separate animals. Mapping accuracy in the atlas space was examined to determine the applicability of this atlas framework. The results show that the atlas space defined here provides a stable framework for image registration for P0 normal mouse brains. With an appropriate feature-based co-registration strategy, the probability atlas can also provide an accurate anatomical map for images acquired using invasive imaging methods. The atlas templates and the probability map of the anatomical labels are available at http://www.loni.ucla.edu/MAP/ .

Anatomy, Artistic↗

PubMed2005

Thinning of the cerebral cortex visualized in HIV/AIDS reflects CD4+ T lymphocyte decline.

HIV/AIDS infection is the fourth leading cause of death worldwide, and one in every 100 adults aged 15-49 years is HIV-infected. Forty percent of AIDS patients suffer from neurological symptoms, but the selective profile of damage caused by HIV in the brain is not well understood. Here, we report 3D maps revealing how AIDS affects the human cerebral cortex, identifying the most vulnerable regions and where deficits link with cognitive decline and immune-system suppression. With high-resolution brain MRI scans, we created composite maps of cortical gray-matter thickness in 26 AIDS patients and 14 healthy controls to establish the selective pattern of brain deficits in AIDS. In AIDS, primary sensory, motor, and premotor cortices were 15% thinner. Thinner frontopolar and language cortex correlated with immune system deterioration measured through blood levels of CD4+ T lymphocytes. Prefrontal and parietal tissue loss correlated with cognitive/motor deficits. T cell depletion and cognitive impairment are, therefore, associated with specific 3D brain-deficit patterns visualized with MRI. These quantitative MRI-based maps reveal that HIV selectively damages the cortex. They provide an approach to gauge the impact of AIDS on the living brain and show that the brain is still vulnerable to infection even when patients are receiving antiretroviral therapy.

Acquired Immunodeficiency Syndrome↗

PubMed2005

Impact of acquisition protocols and processing streams on tissue segmentation of T1 weighted MR images.

The segmentation of T1-weighted images into gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) is a fundamental processing step in neuroimaging, the results of which affect many other structural imaging analyses. Variability in the segmentation process can decrease the power of a study to detect anatomical differences, and minimizing such variability can lead to more robust results. This paper outlines a straightforward strategy that can be used (1) to select more optimal data acquisition and processing protocols and (2) to quantify the impact of such optimization. Using this approach with multiple scans of a single subject, we found that the choice of a segmentation algorithm had the largest impact on variability, while the choice of a pulse sequence had the second largest impact. The data indicate that the classification of GM is the most variable, and that the optimal protocol may differ across tissue types. Therefore, the intended use of segmentation data should play a role in optimization. Examples are provided to demonstrate that the minimization of variability is not sufficient for optimization; the overall accuracy of the approach must also be considered. Simple volumetric computations are included to illustrate the potential gain of optimization; these results show that volume estimates from optimal pathways were on average three times less variable than estimates from suboptimal pathways. Therefore, the simple strategy illustrated here can be applied to many studies to optimize tissue segmentation, which should lead to a net increase in the power of structural neuroimaging studies.

Adult↗

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↗