3D Cortical Surface Asymmetry and Variability Profiles in First Episode Schizophrenia

7th International Conference on Functional Mapping of the Human Brain, Brighton, England, June 2001.

Introduction:
Some disturbances of normal asymmetries are reported in cortical and subcortical regions in schizophrenia. In peri-sylvian regions however, findings are mixed with reports of normal, reduced and even reversed structural lateralization. Recently, we observed normal temporo-parietal cortical surface asymmetries in chronically ill patients with schizophrenia compared to matched controls, although hemisphere by diagnostic group interactions showed small effect sizes and potentially large Type II error (1). It was therefore our goal to replicate these measurements in a larger independent sample of first episode patients with schizophrenia. Furthermore, we assessed in 3D, potential differences in sulcal stereotaxic location and cortical variability in groups defined by sex and diagnosis, given that both might influence structural asymmetries and their functional homologues.

Methods
High-resolution (256x256x124; 1.5 mm separation) T1-weighted MR images were acquired from schizophrenia patients (n=31m/11f) and control subjects (n=16m/17f) matched for demographic variables. Image volumes were aligned and scaled along the AC-PC line to correct for head orientation and allow for inter-individual comparisons. After surface extractions, shape profiles were obtained for 38 gyral regions by manually following neuroanatomic landmarks. Surface warping and mesh modeling algorithms were then used to track complex surface representations and anatomies of the sylvian fissure, temporal sulci and postcentral sulcus in 3D stereotaxic space in each group (2). Patterns of within-group variability were visualized by quantifying the root mean square magnitude of displacement vectors required to match equivalent points from sulcal surfaces. Sulcal parameters measured in stereotaxic co-ordinates chosen to best characterize asymmetries were assessed statistically using multivariate analyses with hemisphere as a repeated measure.

Results
Schizophrenia groups exhibited increased patterns of variability overall, particularly in frontal cortices. In all groups variability was greatest in posterior association areas. Statistical analyses revealed significant asymmetries in sylvian fissure posterior and superior extrema and slopes (all p < 0.0001) in both patients and controls. Slopes and superior extrema were greater in the right hemisphere and posterior extrema greater in the left, consistent with previous findings. Similarly, slopes and posterior and superior extrema of the superior temporal sulcus showed significant asymmetries (p < 0.0001; 0.01 and 0.0001 respectively) in both diagnostic groups. Moreover, inferior temporal sulcal posterior extrema and posterior central sulcal anterior extrema showed significant asymmetries (p < 0.002, and p < 0.0001) in both patients with schizophrenia and controls. Finally, slopes of the sylvian fissure and post central sulcus were greater in male compared to female subjects (both p < 0.04).

Conclusion
Significant gyral asymmetries were observed in temporo-parietal regions in first episode schizophrenia consistent with previous findings (1). Reductions or reversals in structural lateralization are therefore assumed absent in schizophrenia, at least at the cortical surface. Males however, exhibited some increased hemispheric asymmetries compared to females, possibly influenced by steroid hormones in development. Finally, some regional alterations in frontal cortical variability may suggest increased localized vulnerability in first episode patients that are complementary with hypotheses of prefrontal pathology in schizophrenia.

References
1. Narr et al., Am J of Psychiatry 2001; In Press
2. Thompson et al., J. Comp. Assist. Tomography 1997;21:567-81.

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