Three-dimensional mapping of temporo-limbic regions and the lateral ventricles in schizophrenia: gender effects.

BACKGROUND: Local alterations in morphological parameters are poorly characterized in several brain regions widely implicated in schizophrenia neuropathology. METHODS: Surface-based anatomical modeling was applied to magnetic resonance data to obtain three-dimensional (3D) average anatomical maps and measures of location, shape, asymmetry, and volume for the lateral ventricles, hippocampus, amygdala, and superior temporal gyrus in schizophrenic (n = 25; 15 male) and normal subjects (n = 28; 15 male) matched for demographic variables. For all regions, intra-group variability was visualized and group differences assessed statistically to discriminate local alterations in anatomy across sex and diagnosis. RESULTS: Posterior hippocampal volumes, lengths, and widths were reduced in patients. The right amygdala showed volume increases in schizophrenia patients versus controls. Ventricular enlargements, pronounced in the left hemisphere, occurred in the superior and lateral dimensions in patients, and these effects interacted with gender. Superior horn anterior extremes, inferior horn volumes, and hippocampal asymmetries exhibited gender effects. Significant group differences were absent in superior temporal gyrus parameters. Finally, regional variability profiles differed across groups. CONCLUSIONS: Clear morphometric differences of the lateral ventricles, hippocampus, and amygdala indicate regional displacements and shape distortions in several functional systems in schizophrenia. Alterations in these structures as mapped in 3D may provide the foundation for establishing brain abnormalities not previously defined at such a local level.

Three-dimensional mapping of gyral shape and cortical surface asymmetries in schizophrenia: gender effects.

OBJECTIVE: People with schizophrenia exhibit abnormalities in brain structure, often in the left hemisphere. Disturbed structural lateralization is controversial, however, and effects appear mediated by gender. The authors mapped differences between schizophrenic and normal subjects in gyral asymmetries, complexity, and variability across the entire cortex. METHOD: Asymmetry and shape profiles for 25 schizophrenic patients (15 men) and 28 demographically similar normal subjects (15 men) were obtained for 38 gyral regions, including the sylvian fissure and temporal and postcentral gyri, by using magnetic resonance data and a novel surface-based mesh-modeling approach. Cortical complexity was examined for sex and diagnosis effects in lobar regions. Intragroup variability was quantified and visualized to assess regional group abnormalities at the cortical surface. RESULTS: The patients showed greater variability in frontal areas than the comparison subjects. They also had significant deviations in gyral complexity asymmetry in the superior frontal cortex. In temporoparietal regions, significant gyral asymmetries were present in both groups. Sex differences were apparent in superior temporal gyral measures, and cortical complexity in inferior frontal regions was significantly greater in men. CONCLUSIONS: Cortical variability and complexity show regional abnormalities in the frontal cortex potentially specific to schizophrenia. The results indicate highly significant temporoparietal gyral asymmetries in both diagnostic groups, contrary to reports of less lateralization in schizophrenia. Substantially larger study groups are necessary to isolate smaller deviations in surface asymmetries, if present in schizophrenia, suggesting their diagnostic value is minimal.

Sulcal variability in the Alzheimer's brain: correlations with cognition.

We mapped the three dimensional (3D) extents and variability of selected sulci in the Alzheimer's brain and explored the relationship between sulcal pattern and patient's cognitive performance. High-resolution MRIs of 10 patients with probable Alzheimer's disease (AD) were linearly transformed into a standard "normalized" 3D atlas (known as the Talairach coordinate system) and, on each relevant slice, contours of the left and right Sylvian fissure, anterior and posterior calcarine, callosal, parietooccipital, and cingulate sulci and the floor of the temporal horn of the lateral ventricle were traced. These landmarks were chosen because of their relative invariant location across individuals and because they demarcate functional boundaries relevant in AD. The sulcal contours were resolved into two-dimensional surfaces that cut through a brain volume. All 10 patients' sulcal surfaces were averaged to determine their mean spatial locations in the Talairach coordinate system. The 3D spatial extents of each patient's sulci were compared with their disease severity based on neuropsychological performance. The 3D sulcal variability, within the "normalized" atlas space, ranged from 4.0 mm for the left callosal sulcus to 9.1 mm for the left Sylvian fissure. Significant correlations were found among the spatial extents for the posterior floor of the right temporal horn of the lateral ventricle (r = -0.89, p < 0.001 for vertical extent) and right anterior calcarine sulcus (r = -0.75, p < 0.01 for anterior-posterior extent) with copying ability of the Rey-Osterrieth Complex Figure; the right anterior calcarine also had a significant relationship (r = -0.72, p = 0.02 for anterior-posterior extent) with performance on the Block Design subtest from the Wechsler Adult Intelligence Scale-Revised. Verbal fluency performance measured by the Controlled Oral Word Association Test was significantly related to the left cingulate (r = 0.91, p < 0.001 for anterior-posterior extent, and r = -0.82, p < 0.01 for vertical extent) and right cingulate (r = -0.72, p < or = 0.02 for vertical extent) sulci. This exploratory study is the first to evaluate the relationship between 3D sulcal variability and cognition; our preliminary findings suggest that the 3D pattern of sulci in the AD brain is related to the severity of the disease as reflected by cognitive performance. In the Talairach brain atlas, sulcal variability, within an AD population, approaches 1 cm. This large variability requires correction when functional imaging data are transformed into the Talairach atlas space to "normalize" individual morphologic differences.

Mapping morphology of the corpus callosum in schizophrenia.

The nature and extent of callosal morphological alterations in schizophrenia remain unresolved. A parametric surface modeling approach using magnetic resonance (MR) images was employed. This provided spatially accurate representations of midsagittal callosal surfaces in schizophrenic patients (n = 25; 15 males) and normal controls (n = 28; 15 males). Areas of functionally relevant callosal channels and measures reflecting callosal shape were visualized and compared across groups. To register neuroanatomical landmarks surrounding the corpus callosum, each three-dimensional MR volume was scaled according to Talairach AC-PC distance, and raw distances included as covariates in multivariate analyses. Results revealed: (i) a marked vertical displacement of the corpus callosum in patients (P < 0.01); (ii) increases in curvature of superior and inferior callosal surfaces (P < 0.001); and (iii) significant increases in maximum widths in anterior and posterior regions in male patients compared to male controls; as well as (iv) increased patterns of callosal variability in female patients but no effects of diagnosis between female groups. These findings demonstrate a clear index of structural neuropathology in male schizophrenic patients. Displacement and curvature increases were highly correlated with structural differences in surrounding neuroanatomical regions, including increased volume of the lateral ventricles (P < 0.01).

Cortical variability and asymmetry in normal aging and Alzheimer's disease.

The onset of Alzheimer's disease (AD) is accompanied by a complex and distributed pattern of neuroanatomic change, difficult to distinguish clinically from dynamic alterations in normal aging. Extreme variations in the sulcal patterns of the human cortex have made it difficult to identify diffuse and focal variations in cortical structure in neurodegenerative disease. We report the first comprehensive 3D statistical analysis of deep sulcal structure in vivo, in both normal aging and dementia. High-resolution 3D T1-weighted fast SPGR (spoiled GRASS) MRI volumes were acquired from 10 patients diagnosed with AD (NINCDS-ARDRA criteria; age: 71.9 +/- 10.7 years) and 10 normal subjects matched for age (72.9 +/- 5.6 years), gender, educational level and handedness. Scans were digitally transformed into Talairach stereotaxic space. To determine specific patterns of cortical variation in dementia patients, 3D average and probabilistic maps of primary deep sulci were developed for both normal and AD groups. Major sulci (including supracallosal, cingulate, marginal, parieto-occipital, anterior and posterior calcarine sulci, and Sylvian fissures) were modeled as complex systems of 3D surfaces using a multi-resolution parametric mesh approach. Variations and asymmetries in their extents, curvature, area and surface complexity were evaluated. Three-dimensional maps of anatomic variability, structural asymmetry and local atrophy indicated severe regionally selective fiber loss in AD. A midsagittal area loss of 24.5% at the corpus callosum's posterior midbody (P < 0.025) matched increases in structural variability in corresponding temporo-parietal projection areas. Confidence limits on 3D cortical variation, visualized in 3D, exhibited severe increases in AD from 2 to 4 mm at the callosum to a peak SD of 19.6 mm at the posterior left Sylvian fissure. Normal Sylvian fissure asymmetries (right higher than left; P < 0.0005), mapped for the first time in three dimensions, were accentuated in AD (P < 0.0002), and were greater in AD than in controls (P < 0.05). Severe AD-related increases in 3D variability and asymmetry may reflect disease-related disruption of the commissural system connecting bilateral temporal and parietal cortical zones, regions known to be at risk of early metabolic dysfunction, perfusion deficits and selective neuronal loss in AD.

Cortical change in Alzheimer's disease detected with a disease-specific population-based brain atlas.

We report the first detailed population-based maps of cortical gray matter loss in Alzheimer's disease (AD), revealing prominent features of early structural change. New computational approaches were used to: (i) distinguish variations in gray matter distribution from variations in gyral patterns; (ii) encode these variations in a brain atlas (n = 46); (iii) create detailed maps localizing gray matter differences across groups. High resolution 3D magnetic resonance imaging (MRI) volumes were acquired from 26 subjects with mild to moderate AD (age 75.8+/-1.7 years, MMSE score 20.0+/-0.9) and 20 normal elderly controls (72.4+/-1.3 years) matched for age, sex, handedness and educational level. Image data were aligned into a standardized coordinate space specifically developed for an elderly population. Eighty-four anatomical models per brain, based on parametric surface meshes, were created for all 46 subjects. Structures modeled included: cortical surfaces, all major superficial and deep cortical sulci, callosal and hippocampal surfaces, 14 ventricular regions and 36 gyral boundaries. An elastic warping approach, driven by anatomical features, was then used to measure gyral pattern variations. Measures of gray matter distribution were made in corresponding regions of cortex across all 46 subjects. Statistical variations in cortical patterning, asymmetry, gray matter distribution and average gray matter loss were then encoded locally across the cortex. Maps of group differences were generated. Average maps revealed complex profiles of gray matter loss in disease. Greatest deficits (20-30% loss, P<0.001-0.0001) were mapped in the temporo-parietal cortices. The sensorimotor and occipital cortices were comparatively spared (0-5% loss, P>0.05). Gray matter loss was greater in the left hemisphere, with different patterns in the heteromodal and idiotypic cortex. Gyral pattern variability also differed in cortical regions appearing at different embryonic phases. 3D mapping revealed profiles of structural deficits consistent with the cognitive, metabolic and histological changes in early AD. These deficits can therefore be (i) charted in a living population and (ii) compared across individuals and groups, facilitating longitudinal, genetic and interventional studies of dementia.