Narr KL, Thompson PM, Sharma T, Moussai J, Zoumalan CI, Toga AW
Laboratory of Neuro Imaging, Dept. Neurology, Division of Brain Mapping,
UCLA School of Medicine, Los Angeles CA 90095, USA,
Institute of Psychiatry, London
Objective. We applied comprehensive 3-dimensional brain mapping techniques using structural MR data to characterize macroscopic cerebral abnormalities in schizophrenic and normal populations. Furthermore, we attempted to isolate morphometric parameters that would discriminate groups defined by sex and diagnosis.
Background. Decades of in vivo imaging and post mortem studies have confirmed the presence of cerebral abnormalities in schizophrenic patients. Nevertheless, the volumetric analyses employed in most studies have failed to expose subtle morphological abnormalities that may be specific to schizophrenia neuropathology.
Design/Methods. We used surface-based anatomical modeling and brain atlasing approaches to map in 3D, cortical and subcortical systems widely implicated in schizophrenia. High-resolution (256x256x124; 1.5mm separation) T1-weighted MR images were acquired from 25 schizophrenic patients (10f/15m, mean age: 31.0±5.6 SD) and 28 controls (13f/15m, mean age: 30.5±8.7) matched for educational level and handedness. Each 3D volume was aligned and scaled according to Talairach AC-PC distance. Image data (16-bit) passed through a number of steps that included correction of signal intensity inhomogeneities, tissue segmentation, and cortical surface extraction and modeling. External and internal neuroanatomic regions, which included the (1) hippocampus; (2) amygdala; (3) lateral ventricles; (4) corpus callosum; and (5) primary internal and external sulcal trajectories, were reconstructed using surface-based mesh modeling algorithms after manual delineation of neuroanatomic regions. Information on intra-group variability and measures that included shape characteristics, stereotaxic location, volume and gray matter concentrations in all cortical and subcortical regions were visualized and compared between groups using statistical mapping techniques.
Results. Intra-group variability maps revealed unique profiles that suggested pathophysiological vulnerability in frontal and temporal cortices and in the hippocampus. Shape characteristics of subcortical regions including the lateral ventricles and corpus callosum segregated groups according to diagnosis and gender. Correlations between midsagittal callosal areas and sulcal asymmetries were sexually dimorphic and discriminated groups according to diagnosis. Temporo-parietal asymmetries, however, were not altered in patients, although patients exhibited a reduction in normal hemispheric asymmetry in frontal cortices. Volumes of the lateral ventricles were significantly greater in schizophrenic patients, while volumes of the hippocampus and superior temporal gyrus were reduced in patients compared to controls.
Conclusions. Variability maps indicated regional abnormalities in schizophrenic patients in dorsolateral and orbitofrontal cortices, in the superior temporal gyrus as well as in temporo-limbic regions. Differences in morphometric parameters, which may be disease-specific, were also observed in subcortical regions. Patterns of cortical surface asymmetries, however, were found not to be altered in temporal regions in schizophrenic patients. Overall, the 3D anatomical modeling approach used in this study indicates that disease and regionally specific pathophysiological processes may be isolated in schizophrenia at the macroscopic level.
Grant Support: (to P.T. and A.W.T.): NIMH/NIDA (P20 MH/DA52176), P41 NCRR (RR13642); (A.W.T.): NLM (LM/MH05639), NSF (BIR 93-22434), NCRR (RR05956) and NINCDS/NIMH (NS38753).
Paul Thompson, Ph.D.
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