Elsevier

NeuroImage

Volume 43, Issue 3, 15 November 2008, Pages 440-446
NeuroImage

Symmetric abnormalities in sulcal patterning in schizophrenia

https://doi.org/10.1016/j.neuroimage.2008.07.034Get rights and content

Abstract

To compare the morphology of the cerebral cortex and its characteristic pattern of gyri and sulci in individuals with and without schizophrenia, T1-weighted magnetic resonance scans were collected, along with clinical and cognitive information, from 33 individuals with schizophrenia and 30 healthy individuals group-matched for age, gender, race and parental socioeconomic status. Sulcal depth was measured across the entire cerebral cortex by reconstructing surfaces of cortical mid-thickness (layer 4) in each hemisphere and registering them to the human PALS cortical atlas. Group differences in sulcal depth were tested using methods for cluster size analysis and interhemispheric symmetry analysis. A significant group difference was found bilaterally in the parietal operculum, where the average sulcal depth was shallower in individuals with schizophrenia. In addition, group differences in sulcal depth showed significant bilateral symmetry across much of the occipital, parietal, and temporal cortices. In individuals with schizophrenia, sulcal depth in the left hemisphere was correlated with the severity of impaired performance on tests of working memory and executive function.

Introduction

Schizophrenia is thought to have its origins in neurodevelopment (Lewis and Lieberman, 2000). Evidence for this hypothesis includes observations of (i) abnormalities of cognition and social interaction that precede the clinical syndrome and remain relatively unchanged during the course of illness; (ii) prenatal and perinatal insults that increase the risk of developing the illness; and (iii) facial and dermatological anomalies in patients with schizophrenia that reflect aberrant development of the ectodermal germ layer (see Arnold et al., 2005 for review). Moreover, post-mortem studies of the brains of patients with schizophrenia have revealed evidence of abnormal neuronal migration and synaptogenesis (Arnold et al., 2005, Rapoport et al., 2005). Finally, several of the “vulnerability” genes that have been recently associated with schizophrenia play prominent roles in neurodevelopment (Kozlovsky et al., 2002, Toro and Deakin, 2006). In keeping with the hypothesis that schizophrenia is a neurodevelopmental disorder, in vivo neuroimaging studies provide evidence of irregularities in the morphology of cerebral gyri (Arnold et al., 2005). For example, Kikinis et al. (1994) compared the pattern of sulci on the lateral surface of the temporal lobe in individuals with and without schizophrenia and reported a bias towards vertically aligned sulcal trajectories in the individuals with schizophrenia.

The study of normal and abnormal configurations of cortical gyri has been greatly facilitated by the development of the tools of computational neuroanatomy (Csernansky et al., 2004). Toga and colleagues developed statistical variability maps for cortical sulci in normal individuals (Thompson et al., 1996, Thompson et al., 1997), and using such methods, abnormalities in the normal patterning of sulci have been reported in schizophrenia subjects (Narr et al., 2004). In addition, DeQuardo et al. (1999) and Jou et al. (2005) applied similar methods to characterize abnormalities of sulcal patterning in subjects with schizophrenia subjects and their relatives, respectively. Computational methods have been used to study the patterning of cortical sulci in patients with other neurodevelopmental diseases, including autism (Piven et al., 1990, Courchesne et al., 1993) and William's syndrome (Van Essen et al., 2006, Kippenhan et al., 2005).

Recently, a population-based, surface and landmark-based ‘PALS’ atlas of human cerebral cortex has been developed (Van Essen, 2005) and used to demonstrate cortical folding abnormalities in disease conditions (Van Essen et al., 2006, Nordahl et al., 2007). The PALS atlas utilizes a surface-based registration process to compare groups of individuals with and without neuropsychiatric disease, and to assess the hemispheric symmetry of group differences. In the present study, we used the PALS atlas and associated surface-based registration methods to compare the pattern of cortical sulcal depths in individuals with and without schizophrenia matched for age, gender and parental socioeconomic status. We found a bilateral difference between groups in the depth of the cortex in the parietal operculum. Further, in the subjects with schizophrenia, a measure of sulcal depth in this region of the left hemisphere was associated with the severity of cognitive deficits.

Section snippets

Participants

Thirty-three individuals with schizophrenia and 30 healthy individuals, matched in age, gender, race, and parental socioeconomic status, gave written informed consent for participation in this study after the risks and benefits of participation were explained to them. The demographic and clinical characteristics of these groups are summarized in Table 1. The diagnosis of each individual was based on criteria from the Diagnostic and Statistical Manual for Mental Disorders—Fourth Edition (DSM-IV)

Group differences

Fig. 1 shows the average fiducial cortical surfaces generated for the schizophrenia and control groups. Visual inspection of these representations suggested subtle group differences in sulcal patterning. For example, the posterior ramus of the Sylvian fissure was oriented more vertically in the left hemisphere of the schizophrenia subjects than in the healthy individuals, and correspondingly, the supramarginal gyrus was more dorsal in the schizophrenia subjects than in the healthy individuals

Discussion

The primary objective of this study was to compare the morphology of the cerebral cortex and its characteristic pattern of gyri and sulci in individuals with schizophrenia and healthy individuals, matched for gender, age and parental socioeconomic status. We identified a bilateral sulcal depth abnormality in the parietal operculum of individuals with schizophrenia. However, the results do not reveal whether the underlying structural abnormalities are in cortical gray matter, in underlying white

Acknowledgments

This research was supported by PHS grants P50 MH071616 (Conte Center for the Neuroscience of Mental Disorders at Washington University School of Medicine); R01 MH058564; and the Human Brain Project (NIMH, NSF, NCI, NLM, NASA). The authors would like to thank the Conte Center Administration and Assessment Core for performing all clinical and cognitive assessments; the Biostatistics and Data Management Core for assistance with data management and analysis; John Harwell for software development;

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