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

Abstract

Evidence suggests that some structural brain abnormalities in schizophrenia are neurodevelopmental in origin. There is also growing evidence to suggest that shape deformations in brain structure may reflect abnormalities in neurodevelopment. While many magnetic resonance (MR) imaging studies have investigated brain area and volume measures in schizophrenia, fewer have focused on shape deformations. In this MR study we used a 3D shape representation technique, based on spherical harmonic functions, to analyze left and right amygdala-hippocampus shapes in each of 15 patients with schizophrenia and 15 healthy controls matched for age, gender, handedness and parental socioeconomic status. Left/right asymmetry was also measured for both shape and volume differences. Additionally, shape and volume measurements were combined in a composite analysis. There were no differences between groups in overall volume or shape. Left/right amygdalahippocampal asymmetry, however, was significantly larger in patients than controls for both relative volume and shape. The local brain regions responsible for the left/right asymmetry differences in patients with schizophrenia were in the tail of the hippocampus (including both the inferior aspect adjacent to parahippocampal gyrus and the superior aspect adjacent to the lateral geniculate nucleus and more anteriorly to the cerebral peduncles) and in portions of the amygdala body (including the anterior-superior aspect adjacent to the basal nucleus). Also, in patients, increased volumetric asymmetry tended to be correlated with increased left/right shape asymmetry. Furthermore, a combined analysis of volume and shape asymmetry resulted in improved differentiation between groups. Classification function analyses correctly classified 70% of cases using volume, 73.3% using shape, and 87% using combined volume and shape measures. These findings suggest that shape provides important new information toward characterizing the pathophysiology of schizophrenia, and that combining volume and shape measures provides improved group discrimination in studies investigating brain abnormalities in schizophrenia. An evaluation of shape deformations also suggests local abnormalities in the amygdala-hippocampal complex in schizophrenia.

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

“…Using a deformable shape method, which combines geometric properties of hippocampal boundaries, statistical characterization of normal shape variation, and manually defined boundary points, Shen et al 137 demonstrated excellent agreement between automatic and manual volumetrics of the hippocampus. Shenton et al 138 have used an active, flexible deformable shape model for the automatic volumetrics of the amygdala-hippocampal complex to investigate volumetric changes in schizophrenia. These automated methods mark the onset of a new era in structural neuroimaging.…”

Shape of caudate nucleus and its cognitive correlates in neuroleptic-naive schizotypal personality disorder

“…There have been many approaches to shape characterization, which has resulted in a specialized area of computer science expertise (recently review by Shenton et al [2002]). Quantitative descriptions of shape have included approaches such as the generation of skeletons or a medial axis to characterize features of a shape (Golland et al 1999).…”

“…Furthermore, the quantitative analysis of shape, we believe, provides a complementary approach to the quantitative analysis of volume of structural brain abnormalities in neuropsychiatric disorders, because shape changes might occur with little or no change in volume. As suggested by prior shape studies of the hippocampus in adult schizophrenia (Csernansky et al 1998;Shenton et al 2002;Wang et al 2001), quantitative shape analyses might be more sensitive than volumetric measures for detecting small changes in volume or volume changes that might be restricted to subregions of brain structures. Here, we use an approach that is conceptually less complex than prior methods (e.g., Csernansky et al 1998;Shenton et al 2002;Thompson et al 2000;Wang et al 2001) for measuring the shape of brain structures and have been able to detect group differences that complement our prior volumetric findings.…”

“…Of note, the shape of the caudate nucleus might be distorted in developmental disorders, such as schizophrenia, because midline and medial C-shaped structures in the brain are thought to be sensitive to developmental forces and tensions (Van Essen 1997;Van Essen and Drury 1997). For example, the cavum septum pellucidum (Kwon et al 1998;Nopoulos et al 1996), the corpus callosum, and the hippocampus (Csernansky et al 1998;Frumin et al 2002;Shenton et al 2002;Thompson et al 2000) each have been reported to have distorted shapes in schizophrenia. Furthermore, the quantitative analysis of shape, we believe, provides a complementary approach to the quantitative analysis of volume of structural brain abnormalities in neuropsychiatric disorders, because shape changes might occur with little or no change in volume.…”

An MRI study of spatial probability brain map differences between first-episode schizophrenia and normal controls

“…However, relatively few pathology-specific probability maps have been created ; Thompson et al, 1997). Instead of using probability maps, pathology-specific variations have been investigated using shape analysis of specific ROIs (Csernansky et al, 1998;Shenton et al, 2002), but shape analysis does not provide information on spatial distribution, especially the relative location of ROIs together with neighboring brain regions.…”