Hippocampal morphometry in schizophrenia by high dimensional brain mapping

Abstract

Theories of the pathophysiology of schizophrenia have implicated the hippocampus, but controversy remains regarding hippocampal abnormalities in patients with schizophrenia. In vivo studies of hippocampal anatomy using high resolution magnetic resonance scanning and manual methods for volumetric measurement have yielded inconclusive results, perhaps because of the normal variability in hippocampal volume and the error involved in manual measurement techniques. To resolve this controversy, high dimensional transformations of a computerized brain template were used to compare hippocampal volumes and shape characteristics in 15 matched pairs of schizophrenia and control subjects. The transformations were derived from principles of general pattern matching and were constrained according to the physical properties of f luids. The analysis and comparison of hippocampal shapes based on these transformations were far superior to the comparison of hippocampal volumes or other global indices of hippocampal anatomy in showing a statistically significant difference between the two groups. In the schizophrenia subjects, hippocampal shape deformations were found to be localized to subregions of the structure that send projections to prefrontal cortex. The results of this study demonstrate that abnormalities of hippocampal anatomy occur in schizophrenia and support current hypotheses that schizophrenia involves a disturbance of hippocampalprefrontal connections. These results also show that comparisons of neuroanatomical shapes can be more informative than volume comparisons for identifying individuals with neuropsychiatric diseases, such as schizophrenia.

MR-based in vivo hippocampal volumetrics: 1. Review of methodologies currently employed

“…The method proposed by Webb et al 130 involves warping an atlas (obtained by manual volumetrics of 30 individuals) to the individual MR image. Another important automated method is the method used by Haller and co-workers, [131][132][133][134] which uses a high-dimensional fluid transformation to warp a template of the hippocampus and surrounding anatomical structures to an individual MR image. This method has also been validated, and was found to have less variability than manual tracing.…”

Mapping cortical change in Alzheimer's disease, brain development, and schizophrenia

“…Fox et al, 2001). All these efforts draw on methods from the rapidly growing field of computational anatomy (see e.g., Ashburner et al, 2003;Bankman, 1999: Bookstein, 2001: Chung, 2001: Csernansky et al, 1998Davatzikos, 1996Davatzikos, , 2001Drury and Van Essen, 1997;Evans et al, 1994;Fischl and Dale, 2000;Fitzpatrick and Sonka, 2000;Gee and Bajcsy, 1998;Gerig et al, 2001;Grenander and Miller, 1998;Leahy and Insana, 2001;Miller et al, 2002;Sereno et al, 1996;Thompson and Toga, 2003a,b;Thompson et al, 2000a,b, 2001a,b, cf. Toga, 1998Toga and Mazziotta, 2002; see other papers in this issue for recent developments and reviews).…”

Amygdala–hippocampal shape differences in schizophrenia: the application of 3D shape models to volumetric MR data

“…Csernansky et al, 1998) have evaluated shape, which may be importantly linked to neurodevelopmental influences. For example, there is evidence to suggest that shape deformations may be associated with the physical properties of morphogenetic mechanisms that directly impact on the particular shape of brain regions during neurodevelopment (Van Essen, 1997;Van Essen and Drury, 1997;Van Essen et al, 1998).…”

“…Bajcsy and Kovacic, 1989;Evans et al, 1991;Collins et al, 1992;Gee et al, 1993;Christensen et al, 1994Christensen et al, , 1996Christensen et al, , 1997Kelemen et al, 1999), and patternmatching methods derived from the theory of patterns by Grenander (1993) (e.g. Haller et al, 1997Csernansky et al, 1998). A clear trend in shape analysis is toward the movement from summary measures of whole structures or objects to measures of regional differences in shape, thus incorporating more information about the properties of shape than more simple volumetric measures.…”

“…A clear trend in shape analysis is toward the movement from summary measures of whole structures or objects to measures of regional differences in shape, thus incorporating more information about the properties of shape than more simple volumetric measures. Shape descriptions that are represented as high-dimensional features (Haller et al, 1996(Haller et al, , 1997Csernansky et al, 1998;Hogan et al, 2000;Wang et al, 2001) or features derived from a projection onto basis functions (Kelemen et al, 1999) are examples of this trend.…”