Biomedical subjects

Paul M Thompson

Publications and source records attributed to Paul M Thompson.

At least 37 records · Page 2Linked to original sources

PubMed2006

3D comparison of hippocampal atrophy in amnestic mild cognitive impairment and Alzheimer's disease.

Alzheimer's disease is the most common neurodegenerative disorder in the elderly. Amnestic mild cognitive impairment (MCI) is a relatively newly defined clinical entity that requires memory decline while activities of daily living remain intact. Most amnestic MCI patients develop Alzheimer's disease. Using an innovative surface-based hippocampal analytic technique we analysed the structural magnetic resonance hippocampal data of 31 amnestic MCI and 34 Alzheimer's disease subjects. We tested the hypothesis that Alzheimer's disease subjects have greater atrophy of the CA1, CA2 and CA3 hippocampal subfields relative to amnestic MCI subjects. 3D hippocampal maps localized the main group differences to the CA1 region bilaterally and the CA2 and CA3 region on the left [corrected] (right [corrected] P = 0.0024, left [corrected] P = 0.0002, both corrected for multiple comparisons). Age, race, gender, education and Mini-Mental State Examination were significant predictors of hippocampal volume. Hippocampal volume was a significant predictor of clinical diagnosis. Our study suggests that as Alzheimer's disease progresses, subregional hippocampal atrophy spreads in a pattern that follows the known trajectory of neurofibrillary tangle dissemination. Novel hippocampal analytic techniques that can track the spread of hippocampal pathology in 3D with such precision are a promising research tool.

Aged↗

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

Increased local gyrification mapped in Williams syndrome.

Applying a recently developed method to analyze gyrification with excellent spatial resolution across thousands of points across the lateral and medial cortical surface, we mapped differences in cortical surface anatomy between subjects with Williams syndrome (WS; n=42) and an age-matched sample of healthy subjects (n=40). WS subjects showed increased gyrification bilaterally in occipital regions and over the cuneus. Differences were more pronounced in the left hemisphere than in the right, with additional regions of increased gyrification in WS in the left precuneus, posterior and anterior cingulate, paracentral and mesial frontal lobe. No cortical area was significantly more convoluted in healthy subjects relative to the WS subjects. On the lateral surfaces, the direction and pattern of gyrification asymmetries were similar in WS subjects and controls; posterior brain regions had greater gyrification in the left hemisphere, while anterior brain regions showed greater gyrification in the right hemisphere. On the medial surfaces, control subjects and WS individuals differed considerably with respect to the degree but also direction of gyrification asymmetry. Our findings confirm and extend previous studies measuring cortical complexity at the global whole-brain or hemispheric levels. The observed gyrification abnormalities in individuals with WS might be related to dysfunctions in neuronal circuits and consequently contribute to the distinct cognitive and behavioral profile accompanying the disorder.

Adolescent↗

PubMed2006

Gender effects on callosal thickness in scaled and unscaled space.

Some empirical data suggest that sexual dimorphisms in callosal morphology exist, but findings are not consistently replicated across laboratories. We applied novel computational surface-based methods to encode callosal thickness at high spatial resolution. We further examined whether callosal thickness and related gender effects are influenced by brain size adjustments achieved through data scaling. Significant gender differences were absent in scaled data, and women showed no regional thickness increases compared with men (in either scaled or unscaled data). In unscaled data, men exhibited significantly greater callosal thickness in a number of regions that may be attributable to larger brain dimensions in men. Alternatively, given their regional specificity, the observed differences in unscaled callosal thickness may contribute to gender-specific cognition and behavior.

Corpus Callosum↗

PubMed2006

Ventricular volume and dementia progression in the Cardiovascular Health Study.

Elevated cerebral ventricular volume may be associated with dementia risk and progression. A fully-automated technique that agreed highly with radiological readings was used to estimate lateral ventricle volume on MR scans done at baseline in 1997-99 of 377 subjects in the Cardiovascular Health Study (CHS) from the Pittsburgh Center. 327 subjects were normal or diagnosed with mild cognitive impairment (MCI) at baseline and were evaluated 4 years later. Baseline ventricular volume was analyzed in multivariate models with age, gender, education level, presence and incidence of cerebral infarcts, and dementia category (normal, MCI, or dementia) at baseline and follow-up as fixed effects. Ventricular volume at baseline was significantly higher among subjects normal at baseline and demented 4 years later. Age, gender, education level, and dementia progression were significant factors affecting ventricular volume. Ventricular volume was higher in dementia compared to MCI, higher in MCI compared to controls, and higher in Possible-Alzheimer's-disease (AD) dementia compared to Probable-AD. Larger ventricles in healthy subjects may indicate susceptibility to, or progression of, dementia-related pathology.

Aged↗

PubMed2006

Longitudinal stability of MRI for mapping brain change using tensor-based morphometry.

Measures of brain change can be computed from sequential MRI scans, providing valuable information on disease progression, e.g., for patient monitoring and drug trials. Tensor-based morphometry (TBM) creates maps of these brain changes, visualizing the 3D profile and rates of tissue growth or atrophy, but its sensitivity depends on the contrast and geometric stability of the images. As part of the Alzheimer's Disease Neuroimaging Initiative (ADNI), 17 normal elderly subjects were scanned twice (at a 2-week interval) with several 3D 1.5 T MRI pulse sequences: high and low flip angle SPGR/FLASH (from which Synthetic T1 images were generated), MP-RAGE, IR-SPGR (N = 10) and MEDIC (N = 7) scans. For each subject and scan type, a 3D deformation map aligned baseline and follow-up scans, computed with a nonlinear, inverse-consistent elastic registration algorithm. Voxelwise statistics, in ICBM stereotaxic space, visualized the profile of mean absolute change and its cross-subject variance; these maps were then compared using permutation testing. Image stability depended on: (1) the pulse sequence; (2) the transmit/receive coil type (birdcage versus phased array); (3) spatial distortion corrections (using MEDIC sequence information); (4) B1-field intensity inhomogeneity correction (using N3). SPGR/FLASH images acquired using a birdcage coil had least overall deviation. N3 correction reduced coil type and pulse sequence differences and improved scan reproducibility, except for Synthetic T1 images (which were intrinsically corrected for B1-inhomogeneity). No strong evidence favored B0 correction. Although SPGR/FLASH images showed least deviation here, pulse sequence selection for the ADNI project was based on multiple additional image analyses, to be reported elsewhere.

Aged↗

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

Functional and aggregative responses of harbour seals to changes in salmonid abundance.

There is intense debate over the potential impact of seal predation on declining salmon stocks in both the Pacific and Atlantic oceans. However, efforts to model such interactions have been constrained by a lack of data on the functional and numerical responses of these predators. Based upon theory, and data from small-scale terrestrial and freshwater systems, a type 3 functional response is expected to best describe predation by generalist pinnipeds. Similarly, theory also predicts that seal numbers should increase with salmon density in rivers following an aggregative response of predator to prey. We tested these predictions by studying the diet and local density of harbour seals in relation to seasonal variations in the abundance of salmonid in a Scottish river system. As predicted, the abundance of seals in the river was directly related to the abundance of returning salmon, and dietary data supported the type 3 functional response to changes in salmonid abundance. These studies provide empirical support for the use of type 3 response in modelling studies.

Animals↗

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

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

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

Quantifying the influence of sociality on population structure in bottlenose dolphins.

1. The social structure of a population plays a key role in many aspects of its ecology and biology. It influences its genetic make-up, the way diseases spread through it and the way animals exploit their environment. However, the description of social structure in nonprimate animals is receiving little attention because of the difficulty in abstracting social structure from the description of association patterns between individuals. 2. Here we focus on recently developed analytical techniques that facilitate inference about social structure from association patterns. We apply them to the population of bottlenose dolphins residing along the Scottish east coast, to detect the presence of communities within this population and infer its social structure from the temporal variation in association patterns between individuals. 3. Using network analytical techniques, we show that the population is composed of two social units with restricted interactions. These two units seem to be related to known differences in the ranging pattern of individuals. By examining social structuring at different spatial scales, we confirm that the identification of these two units is the result of genuine social affiliation and is not an artefact of their spatial distribution. 4. We also show that the structure of this fission-fusion society relies principally on short-term casual acquaintances lasting a few days with a smaller proportion of associations lasting several years. These findings highlight how network analyses can be used to detect and understand the forces driving social organization of bottlenose dolphins and other social species.

Animals↗

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↗