Biomedical subjects

Paul M Thompson

Publications and source records attributed to Paul M Thompson.

At least 19 recordsLinked to original sources

PubMed2026

Mapping Focal and Generalized Effects of Common Genetic Variants on Human Brain Structure.

Genome-wide association studies (GWAS) have advanced the quest to understand how specific genetic variants influence human brain structure and function. Recent work has identified hundreds of common variants associated with subcortical brain volumes, sparking interest in how these genetic markers overlap across brain networks. While this can be estimated by hierarchical clustering of the genetic correlation matrix to identify modular patterns of shared architecture, no brain-wide maps of these effects are available. To address this, we computed polygenic scores (PGS) from loci associated with ten brain volume regions of interest (ROIs): nine major subcortical structures and intracranial volume, with each locus weighted by its association with regional volume. In an independent sample from the discovery GWAS, we performed large-scale segmentation of 3D volumetric T1-weighted MRI scans using voxel-based morphometry (VBM) to map 3D profile of regions where gray matter volume (GMV) was associated with each PGS. We found statistically significant, localized effects for PGS defined for the amygdala, thalamus, and basal ganglia, but PGS for brainstem volume was associated with widespread differences throughout the brain. These brain-wide maps reveal patterns consistent with both localized and distributed genetic influences, offering a novel approach to interpret the genomic architecture of brain structure.

GWAS↗

PubMed2026

Genetic modifiers of APOE-ε4-associated cognitive decline.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease. However, APOE-ε4 is not deterministic, highlighting the need to identify additional genetic and environmental factors. APOE-ε4 has been linked to accelerated cognitive decline, so we sought to investigate genetic factors that modify APOE-ε4-associated cognitive decline. We conduct cross-ancestry APOE-ε4-stratified and interaction GWAS using harmonized cognitive data from 32,778 participants, including 29,354 non-Hispanic White and 3,424 non-Hispanic Black individuals. Our primary outcome is late-life cognition, measured using harmonized composite scores for memory, executive function, and language, modeled as continuous traits reflecting both normative cognitive aging and disease-related decline. We identify two genome-wide significant loci in APOE-ε4 carriers, reaching genome-wide significance for executive function. These loci also demonstrate nominal associations across the other domains, suggesting broad effects on cognition. In non-carriers, we identify a genome-wide significant association at ITGB8 restricted to executive function, and another locus associated with language. We further link these loci to SEMA6D, GRIN3A, and ITGB8 through expression and methylation databases. Post-GWAS analyses implicate additional genes including SLCO1A2, and DNAH11. Genetic correlation analyses reveal differences by APOE-ε4 status for immune-related traits, suggesting immune-related predispositions may exacerbate cognitive risk in APOE-ε4 carriers.

Humans↗

PubMed2026

Big data and psychiatry: advances, constraints and future directions.

Early work in psychiatry research, often involving single sites, small samples, and limited variables, has shifted to contemporary research involving multiple sites, large samples, and many variables. Such research raises important questions, including concerns about data quality and methodological rigor, uncertainty about its key lessons, issues regarding clinical relevance, and questions about how to optimize future advances. Here we consider these questions and concerns against the context of big data work on community and register-based surveys, cohort and biobank studies, electronic health records, digital phenotyping, brain imaging, genomics and other -omics, and randomized controlled trials. The development of large datasets allowing well-powered analyses is a major milestone, but sample size alone does not guarantee more precise estimates, and ongoing attention to the quality and rigor of big data collation and analysis is needed. Big data research has fostered trans-disciplinarity and given insights into mechanisms underlying psychiatric disorders, but also emphasizes the intricacy, heterogeneity and variability of such mechanisms, and the importance of triangulating between large-scale and small-scale research. The complexity of psychiatric phenotypes and psychobiological mechanisms contributes to the difficulty in bridging from big data to clinical application; big data research reinforces the importance of holding our diagnoses of psychiatric disorders lightly and providing explanations of these conditions humbly; and future work needs to be more attentive to clinical issues. There is enormous scope for further building databases relevant to psychiatry, but advances in conceptual models and asking the right questions are equally valuable. The full impact of big data, including artificial intelligence analyses, remains to be seen, but overenthusiastic support should be tempered by a better understanding of its strengths and limitations. At its best, such work will contribute in an iterative and integrative way to advancing our knowledge of psychiatric disorders and mental health.

Big data↗

PubMed2025

S-GMAS: Genome-Wide Mediation Analysis With Brain Subcortical Shape Mediators.

Mediation analysis is widely utilized in neuroscience to investigate the role of brain image phenotypes in the neurological pathways from genetic exposures to clinical outcomes. However, it is still difficult to conduct mediation analyses with whole genome-wide exposures and brain subcortical shape mediators due to several challenges including (i) large-scale genetic exposures, that is, millions of single-nucleotide polymorphisms (SNPs); (ii) nonlinear Hilbert space for shape mediators; and (iii) statistical inference on the direct and indirect effects. To tackle these challenges, this paper proposes a genome-wide mediation analysis framework with brain subcortical shape mediators. First, to address the issue caused by the high dimensionality in genetic exposures, a fast genome-wide association analysis is conducted to discover potential genetic variants with significant genetic effects on the clinical outcome. Second, the square-root velocity function representations are extracted from the brain subcortical shapes, which fall in an unconstrained linear Hilbert subspace. Third, to identify the underlying causal pathways from the detected SNPs to the clinical outcome implicitly through the shape mediators, we utilize a shape mediation analysis framework consisting of a shape-on-scalar model and a scalar-on-shape model. Furthermore, the bootstrap resampling approach is adopted to investigate both global and spatial significant mediation effects. Finally, our framework is applied to the corpus callosum shape data from the Alzheimer's Disease Neuroimaging Initiative.

Humans↗

PubMed2025

A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study.

BACKGROUND: Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group. METHODS: T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9). RESULTS: PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges' g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges' g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (p corrected  = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (p corrected  = .001). CONCLUSIONS: PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

Humans↗

PubMed2025

The Consortium for Clarity in ADRD Research Through Imaging (CLARiTI): Overview of consortium sites and anticipated enrollment.

INTRODUCTION: The Consortium for Clarity in Alzheimer's disease related dementias (ADRD) Research Through Imaging (CLARiTI) is a study that aims to collect standardized imaging and plasma biomarkers on 2000 Clinical Core participants enrolled across all Alzheimer's Disease Research Centers (ADRC) sites. We sought to summarize the known heterogeneity across centers regarding scientific focus and initial enrollment plans for CLARiTI. METHODS: We developed and distributed a survey capturing information on the 36 CLARiTI site's theme/expertise, recruitment plans, and the intersection of CLARiTI with other ADRC imaging efforts. RESULTS: Anticipated CLARiTI enrollees spanned 11 different categories of suspected etiologies underlying impairment. A wide range of risk factors were endorsed across sites regarding the enrollment of unimpaired individuals. Variability also existed regarding site-level strategies in enrollment into CLARiTI versus other imaging efforts. DISCUSSION: We anticipate that the 2000 individuals that will enroll into CLARiTI will reflect the clinical heterogeneity already in place across the ADRC network. HIGHLIGHTS: The ADRC Consortium for Clarity in ADRD Research Through Imaging (CLARiTI) will leverage and contribute to the existing Alzheimer's Disease Research Centers (ADRC) program by supporting standardized imaging and plasma collection across all centers. We summarize the variation in scientific focus and enrollment plans across ADRC sites participating in CLARiTI. The anticipated CLARiTI cohort will reflect the clinical heterogeneity that already exists across the ADRC network. CLARiTI will contribute to scientific goals related to the detection of multi-etiological signatures relevant for Alzheimer's disease and related disorders (ADRDs).

Humans↗

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↗

PubMed2007

Temporal and spatial variation in age-specific survival rates of a long-lived mammal, the Hawaiian monk seal.

Estimates of variability in pinniped survival rates are generally based on observations at single sites, so it is not certain whether observed rates represent the whole population. Here, we provide a comprehensive analysis of spatio-temporal variation in age-specific survival rates for endangered Hawaiian monk seals (Monachus schauinslandi) based on capture-recapture analyses of more than 85% of the pups weaned in this population over the last two decades. Uniquely, these data have been collected from six subpopulations, encompassing all major breeding sites across its 1800 km long core range. Analyses of individual subpopulations revealed similar patterns in age-specific survival, characterized by the relatively low survival rates from weaning to 2 years of age, intermediate rates to 4 years of age, and then by relatively high 'mature' survival rates until 17 years of age, after which a senescent decline was observed. Juvenile, subadult and adult survival rates all varied significantly over time. Trends in survival among subpopulations were coherent with their relative geographical positions, suggesting regional structuring and connectedness within the archipelago. Survival rates for different age classes tended to be positively correlated, suggesting that similar factors may influence the survival for seals of all ages.

Animals↗

PubMed2006

PET of brain amyloid and tau in mild cognitive impairment.

BACKGROUND: Amyloid senile plaques and tau neurofibrillary tangles are neuropathological hallmarks of Alzheimer's disease that accumulate in the cortical regions of the brain in persons with mild cognitive impairment who are at risk for Alzheimer's disease. Noninvasive methods to detect these abnormal proteins are potentially useful in developing surrogate markers for drug discovery and diagnostics. METHODS: We enrolled 83 volunteers with self-reported memory problems who had undergone neurologic and psychiatric evaluation and positron-emission tomography (PET). On the basis of cognitive testing, 25 volunteers were classified as having Alzheimer's disease, 28 as having mild cognitive impairment, and 30 as having no cognitive impairment (healthy controls). PET was performed after injection of 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP), a molecule that binds to plaques and tangles in vitro. All subjects also underwent 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) PET, and 72 underwent magnetic resonance imaging (MRI). RESULTS: Global values for FDDNP-PET binding (average of the values for the temporal, parietal, posterior cingulate, and frontal regions) were lower in the control group than in the group with mild cognitive impairment (P<0.001), and the values for binding in the group with mild cognitive impairment were lower than in the group with Alzheimer's disease (P<0.001). FDDNP-PET binding differentiated among the diagnostic groups better than did metabolism on FDG-PET or volume on MRI. CONCLUSIONS: FDDNP-PET scanning can differentiate persons with mild cognitive impairment from those with Alzheimer's disease and those with no cognitive impairment. This technique is potentially useful as a noninvasive method to determine regional cerebral patterns of amyloid plaques and tau neurofibrillary tangles.

Aged↗

PubMed2006

Asymmetries of cortical shape: Effects of handedness, sex and schizophrenia.

Some evidence suggests that sex, handedness and disease processes associated with schizophrenia affect the magnitude and/or direction of structural brain asymmetries. There are mixed findings, however, on how these factors influence cerebral torque, when torque is assessed with linear or volumetric measurements. We obtained MRI data from 67 healthy (30 males, 10 non-dextrals) and 84 schizophrenia subjects (60 males; 16 non-dextrals) and applied cortical pattern matching to spatially relate and compare differences in the surface morphology of the two cerebral hemispheres at high spatial resolution. Asymmetry indices, computed at thousands of matched hemispheric locations, were used to examine effects of sex, handedness and schizophrenia on hemispheric shape asymmetries while controlling for age and the other factors. Highly significant and discriminative right-frontal and left parietal-occipital surface expansions and protrusions (petalias) were mapped within groups. Although hemispheric shape asymmetries appeared less pronounced within female non-dextrals, asymmetry indices were not shown to differ significantly across sex, hand preference or diagnosis, or to reveal interactions of handedness with sex or diagnosis. Our 3D maps of spatially detailed anterior and posterior hemispheric shape asymmetries reflect subtle geometric distortions in hemispheric surface morphology that cannot be characterized with 2D or volumetric methods. Inter-individual variations in hemispheric torque appear minimally influenced by sex, dextrality or disease status. Biological factors driving language dominance or other lateralized brain functions dissociable from handedness, may more closely relate to hemispheric shape asymmetries, while the lateralization of other discrete brain regions may be more influenced by sexually dimorphic factors or by schizophrenia pathophysiology.

Cerebral Cortex↗

PubMed2006

Dynamic mapping of hippocampal development in childhood onset schizophrenia.

Prior cross-sectional anatomic brain imaging studies of the hippocampus in schizophrenia have generally shown loss in total hippocampal volume although the progressive course of these changes remains unknown. We report the first prospective sub-regional maps of hippocampal development in childhood onset schizophrenia (COS), reconstructed from serial brain MRI scans of 29 children with COS scanned every 2 years (87 scans) and compared to 31 controls matched for age, sex, and scan interval (94 scans). As expected, the COS subjects showed significant bilateral deficits (9-10%) in total hippocampal volume which remained consistent between age 9 and 26. However sub-regional maps showed heterogeneous changes with loss of hippocampal volume in both anterior as well as posterior ends while the body of the hippocampus gained in volume suggesting that hippocampal subunits are differentially affected in schizophrenia.

Adolescent↗

PubMed2006

3D pattern of brain abnormalities in Fragile X syndrome visualized using tensor-based morphometry.

Fragile X syndrome (FraX), a genetic neurodevelopmental disorder, results in impaired cognition with particular deficits in executive function and visuo-spatial skills. Here we report the first detailed 3D maps of the effects of the Fragile X mutation on brain structure, using tensor-based morphometry. TBM visualizes structural brain deficits automatically, without time-consuming specification of regions-of-interest. We compared 36 subjects with FraX (age: 14.66+/-1.58 S.D., 18 females/18 males), and 33 age-matched healthy controls (age: 14.67+/-2.2 S.D., 17 females/16 males), using high-dimensional elastic image registration. All 69 subjects' 3D T1-weighted brain MRIs were spatially deformed to match a high-resolution single-subject average MRI scan in ICBM space, whose geometry was optimized to produce a minimal deformation target. Maps of the local Jacobian determinant (expansion factor) were computed from the deformation fields. Statistical maps showed increased caudate (10% higher; p = 0.001) and lateral ventricle volumes (19% higher; p = 0.003), and trend-level parietal and temporal white matter excesses (10% higher locally; p = 0.04). In affected females, volume abnormalities correlated with reduction in systemically measured levels of the Fragile X mental retardation protein (FMRP; Spearman's r < -0.5 locally). Decreased FMRP correlated with ventricular expansion (p = 0.042; permutation test), and anterior cingulate tissue reductions (p = 0.0026; permutation test) supporting theories that FMRP is required for normal dendritic pruning in fronto-striatal-limbic pathways. No sex differences were found; findings were confirmed using traditional volumetric measures in regions of interest. Deficit patterns were replicated by performing statistics after logarithmic transformation, which may be more appropriate for tensor-valued data. Investigation of how these anomalies emerge over time will accelerate our understanding of FraX and its treatment.

Adult↗

PubMed2006

Relationships between IQ and regional cortical gray matter thickness in healthy adults.

Prior studies show positive correlations between full-scale intelligence quotient (FSIQ) and cerebral gray matter measures. Few imaging studies have addressed whether general intelligence is related to regional variations in brain tissue and the associated influences of sex. Cortical thickness may more closely reflect cytoarchitectural characteristics than gray matter density or volume estimates. To identify possible localized relationships, we examined FSIQ associations with cortical thickness at high spatial resolution across the cortex in healthy young adult (age 17-44 years) men (n = 30) and women (n = 35). Positive relationships were found between FSIQ and intracranial gray and white matter but not cerebrospinal fluid volumes. Significant associations with cortical thickness were evident bilaterally in prefrontal (Brodmann's areas [BAs] 10/11, 47) and posterior temporal cortices (BA 36/37) and proximal regions. Sex influenced regional relationships; women showed correlations in prefrontal and temporal association cortices, whereas men exhibited correlations primarily in temporal-occipital association cortices. In healthy adults, greater intelligence is associated with larger intracranial gray matter and to a lesser extent with white matter. Variations in prefrontal and posterior temporal cortical thickness are particularly linked with intellectual ability. Sex moderates regional relationships that may index dimorphisms in cognitive abilities, overall processing strategies, or differences in structural organization.

Adolescent↗

PubMed2006

Measuring brain variability by extrapolating sparse tensor fields measured on sulcal lines.

Modeling and understanding the variability of brain structures is a fundamental problem in neurosciences. Improved mathematical representations of structural brain variation are needed to help detect and understand genetic or disease related sources of abnormality, as well as to improve statistical power when integrating functional brain mapping data across subjects. In this paper, we develop a new mathematical model of normal brain variation based on a large set of cortical sulcal landmarks (72 per brain) delineated in each of 98 healthy human subjects scanned with 3D MRI (age: 51.8+/-6.2 years). We propose an original method to compute an average representation of the sulcal curves, which constitutes the mean anatomy. After affine alignment of the individual data across subjects, the second order moment distribution of the sulcal position is modeled as a sparse field of covariance tensors (symmetric, positive definite matrices). To extrapolate this information to the full brain, one has to overcome the limitations of the standard Euclidean matrix calculus. We propose an affine-invariant Riemannian framework to perform computations with tensors. In particular, we generalize radial basis function (RBF) interpolation and harmonic diffusion partial differential equations (PDEs) to tensor fields. As a result, we obtain a dense 3D variability map that agrees well with prior results on smaller subject samples. Moreover, "leave one (sulcus) out" tests show that our model is globally able to recover the missing information on brain variation when there is a consistent neighboring pattern of variability. Finally, we propose an innovative method to analyze the asymmetry of brain variability. As expected, the greatest asymmetries are found in regions that includes the primary language areas. Interestingly, any such asymmetries in anatomical variance, if it remains after anatomical normalization, could explain why there may be greater power to detect group activation in one hemisphere versus the other in fMRI studies.

Algorithms↗

PubMed2006

Reduced neocortical thickness and complexity mapped in mesial temporal lobe epilepsy with hippocampal sclerosis.

We mapped the profile of neocortical thickness and complexity in patients with mesial temporal lobe epilepsy (MTLE) and hippocampal sclerosis. Thirty preoperative high-resolution magnetic resonance imaging scans were acquired from 15 right (mean age: 31.9 +/- 9.7 standard deviation [SD] years) and 15 left (mean age: 30.8 +/- 8.4 SD years) MTLE patients who were seizure-free for 2 years after anteriomesial temporal resection. Nineteen healthy controls were also scanned (mean age: 24.8 +/- 3.9 SD years). A cortical pattern matching technique mapped thickness across the entire neocortex. Mesial temporal structures were not included in this analysis. Cortical models were remeshed in frequency space to compute their fractal dimension (surface complexity). Both MTLE groups showed up to 30% bilateral decrease in cortical thickness, in the frontal poles, frontal operculum, orbitofrontal, lateral temporal, and occipital regions. In both groups, cortical complexity was decreased in multiple lobar regions. Significant linkages were found relating longer duration of epilepsy to greater cortical thickness reduction in the superior frontal and parahippocampal gyrus ipsilateral to the side of seizure onset. The pervasive extrahippocampal structural deficits may result from chronic seizure propagation or may reflect other causes such as initial precipitating factors leading to MTLE.

Adult↗

PubMed2006

Detection and mapping of hippocampal abnormalities in autism.

Brain imaging studies of the hippocampus in autism have yielded inconsistent results. In this study, a computational mapping strategy was used to examine the three-dimensional profile of hippocampal abnormalities in autism. Twenty-one males with autism (age: 9.5+/-3.3 years) and 24 male controls (age: 10.3+/-2.4 years) underwent a volumetric magnetic resonance imaging scan at 3 Tesla. The hippocampus was delineated, using an anatomical protocol, and hippocampal volumes were compared between the two groups. Hippocampal traces were also converted into three-dimensional parametric surface meshes, and statistical brain maps were created to visualize morphological differences in the shape and thickness of the hippocampus between groups. Parametric surface meshes and shape analysis revealed subtle differences between patients and controls, particularly in the right posterior hippocampus. These deficits were significant even though the groups did not differ significantly with traditional measures of hippocampal volume. These results suggest that autism may be associated with subtle regional reductions in the size of the hippocampus. The increased statistical and spatial power of computational mapping methods provided the ability to detect these differences, which were not found with traditional volumetric methods.

Adolescent↗

PubMed2006

Mapping cortical thickness in children with 22q11.2 deletions.

The 22q11.2 deletion syndrome (velocardiofacial/DiGeorge syndrome, 22q11.2DS) involves cardiac and craniofacial anomalies, marked deficits in visuospatial cognition, and elevated rates of psychosis. Although the mechanism is unknown, characteristic brain alterations may predispose to development of psychosis and cognitive deficits in 22q11DS. We applied cortical pattern matching and new methods for measuring cortical thickness in millimeters to structural magnetic resonance images of 21 children with confirmed 22q11.2 deletions and 13 demographically matched healthy comparison subjects. Thickness was mapped at 65 536 homologous points, based on 3-dimensional distance from the cortical gray-white matter interface to the external gray-cerebrospinal fluid boundary. A pattern of regionally specific cortical thinning was observed in superior parietal cortices and right parietooccipital cortex, regions critical for visuospatial processing, and bilaterally in the most inferior portion of the inferior frontal gyrus (pars orbitalis), a key area for language development. Several of the 30 genes encoded in the deleted segment are highly expressed in the developing brain and known to affect early neuronal migration. These brain maps reveal how haploinsufficiency for such genes can affect cortical development and suggest a possible underlying pathophysiology of the neurobehavioral phenotype.

Aging↗

PubMed2006

3D pattern of brain atrophy in HIV/AIDS visualized using tensor-based morphometry.

UNLABELLED: 35% of HIV-infected patients have cognitive impairment, but the profile of HIV-induced brain damage is still not well understood. Here we used tensor-based morphometry (TBM) to visualize brain deficits and clinical/anatomical correlations in HIV/AIDS. To perform TBM, we developed a new MRI-based analysis technique that uses fluid image warping, and a new alpha-entropy-based information-theoretic measure of image correspondence, called the Jensen-Rényi divergence (JRD). METHODS: 3D T1-weighted brain MRIs of 26 AIDS patients (CDC stage C and/or 3 without HIV-associated dementia; 47.2+/-9.8 years; 25M/1F; CD4+ T-cell count: 299.5+/-175.7/microl; log10 plasma viral load: 2.57+/- 1.28 RNA copies/ml) and 14 HIV-seronegative controls (37.6+/-12.2 years; 8M/6F) were fluidly registered by applying forces throughout each deforming image to maximize the JRD between it and a target image (from a control subject). The 3D fluid registration was regularized using the linearized Cauchy-Navier operator. Fine-scale volumetric differences between diagnostic groups were mapped. Regions were identified where brain atrophy correlated with clinical measures. RESULTS: Severe atrophy ( approximately 15-20% deficit) was detected bilaterally in the primary and association sensorimotor areas. Atrophy of these regions, particularly in the white matter, correlated with cognitive impairment (P = 0.033) and CD4+ T-lymphocyte depletion (P = 0.005). CONCLUSION: TBM facilitates 3D visualization of AIDS neuropathology in living patients scanned with MRI. Severe atrophy in frontoparietal and striatal areas may underlie early cognitive dysfunction in AIDS patients, and may signal the imminent onset of AIDS dementia complex.

Acquired Immunodeficiency Syndrome↗