Cortical complexity in bipolar disorder applying a spherical harmonics approach.

Recent studies using surface-based morphometry of structural magnetic resonance imaging data have suggested that some changes in bipolar disorder (BP) might be neurodevelopmental in origin. We applied a novel analysis of cortical complexity based on fractal dimensions in high-resolution structural MRI scans of 18 bipolar disorder patients and 26 healthy controls. Our region-of-interest based analysis revealed increases in fractal dimensions (in patients relative to controls) in left lateral orbitofrontal cortex and right precuneus, and decreases in right caudal middle frontal, entorhinal cortex, and right pars orbitalis, and left fusiform and posterior cingulate cortices. While our analysis is preliminary, it suggests that early neurodevelopmental pathologies might contribute to bipolar disorder, possibly through genetic mechanisms.

Patterns of cortical thinning in different subgroups of schizophrenia.

BACKGROUND: Alterations of cortical thickness have been shown in imaging studies of schizophrenia but it is unclear to what extent they are related to disease phenotype (including symptom profile) or other aspects such as genetic liability, disease onset and disease progression. AIMS: To test the hypothesis that cortical thinning would vary across different subgroups of patients with chronic schizophrenia, delineated according to their symptom profiles. METHOD: We compared high-resolution magnetic resonance imaging data of 87 patients with DSM-IV schizophrenia with 108 controls to detect changes in cortical thickness across the entire brain (P<0.05, false discovery rate-adjusted). The patient group was divided into three subgroups, consisting of patients with predominantly negative, disorganised or paranoid symptoms. RESULTS: The negative symptoms subgroup showed the most extensive cortical thinning, whereas thinning in the other subgroups was focused in prefrontal and temporal cortical subregions. CONCLUSIONS: Our findings support growing evidence of potential subtypes of schizophrenia that have different brain structural deficit profiles.

Cortical surface complexity in frontal and temporal areas varies across subgroups of schizophrenia.

Schizophrenia is assumed to be a neurodevelopmental disorder, which might involve disturbed development of the cerebral cortex, especially in frontal and medial temporal areas. Based on a novel spherical harmonics approach to measuring complexity of cortical folding, we applied a measure based on fractal dimension (FD) to investigate the heterogeneity of regional cortical surface abnormalities across subgroups of schizophrenia defined by symptom profiles. A sample of 87 patients with DSM-IV schizophrenia was divided into three subgroups (based on symptom profiles) with predominantly negative (n = 31), disorganized (n = 23), and paranoid (n = 33) symptoms and each compared to 108 matched healthy controls. While global FD measures were reduced in the right hemisphere of the negative and paranoid subgroups, regional analysis revealed marked heterogeneity of regional FD alterations. The negative subgroup showed most prominent reductions in left anterior cingulate, superior frontal, frontopolar, as well as right superior frontal and superior parietal cortices. The disorganized subgroup showed reductions in bilateral ventrolateral/orbitofrontal cortices, and several increases in the left hemisphere, including inferior parietal, middle temporal, and midcingulate areas. The paranoid subgroup showed only few changes, including decreases in the right superior parietal and left fusiform region, and increase in the left posterior cingulate cortex. Our findings suggest regional heterogeneity of cortical folding complexity, which might be related to biological subgroups of schizophrenia with differing degrees of altered cortical developmental pathology.

Memory decline shows stronger associations with estimated spatial patterns of amyloid deposition progression than total amyloid burden.

The development of amyloid imaging compounds has allowed in vivo imaging of amyloid deposition. In this study, we examined the spatial patterns of amyloid deposition throughout the brain using Pittsburgh Compound Blue ((11)C-PiB) positron emission tomography data from the Baltimore Longitudinal Study of Aging. We used a new methodology that allowed us to approximate spatial patterns of the temporal progression of amyloid plaque deposition from cross-sectional data. Our results are consistent with patterns of progression known from autopsy studies, with frontal and precuneus regions affected early and occipital and sensorimotor cortices affected later in disease progression--here, disease progression means lower-to-higher total amyloid burden. Furthermore, we divided participants into subgroups based on longitudinal change in memory performance, and demonstrated significantly different spatial patterns of the estimated progression of amyloid deposition between these subgroups. Our results indicate that the spatial pattern of amyloid deposition is related to cognitive performance and may be more informative than a biomarker reflecting total amyloid burden, the use of which is the current practice. This finding has broad implications for our understanding of the relationship between cognitive decline/resilience and amyloid deposition, as well as for the use of amyloid imaging as a biomarker in research and clinical applications.

Local cortical surface complexity maps from spherical harmonic reconstructions.

Altered cortical surface complexity and gyrification differences may be a potentially sensitive marker for several neurodevelopmental disorders. We propose to use spherical harmonic (SPH) constructions to measure cortical surface folding complexity. First, we demonstrate that the complexity measure is accurate, by applying our SPH approach and the more traditional box-counting method to von Koch fractal surfaces with known fractal dimension (FD) values. The SPH approach is then applied to study complexity differences between 87 patients with DSM-IV schizophrenia (with stable psychopathology and treated with antipsychotic medication; 48 male/39 female; mean age=35.5 years, SD=11.0) and 108 matched healthy controls (68 male/40 female; mean age=32.1 years, SD=10.0). The global FD for the right hemisphere in the schizophrenia group was significantly reduced. Regionally, reduced complexity was also found in temporal, frontal, and cingulate regions in the right hemisphere, and temporal and prefrontal regions in the left hemisphere. These results are discussed in terms of previously published findings. Finally, the anatomical implications of a reduced FD are highlighted through comparison of two subjects with vastly different complexity maps.

Phospholipase A2 activity in first episode schizophrenia: associations with symptom severity and outcome at week 12.

OBJECTIVES: Intracellular phospholipases A2 (inPLA2) are activated during monoaminergic neurotranismision and act as key enzymes in cell membrane repair and remodelling, neuroplasticity, neurodevelopment, apoptosis, synaptic pruning, neurodegenerative processes and neuroinflammation. Several independent studies found increased inPLA2 activity in drug-naïve first episode and chronic schizophrenia. This study investigates if inPLA2 activity is associated with symptoms severity and treatment response in first episode schizophrenia (FES). METHODS: InPLA2 activity was measured in serum of 35 young FES patients (mean age: 19.36 ± 3.32, mean duration of illness: 7.53 ± 6.28 months, 16 neuroleptic-naïve) before and after 12 weeks of treatment with second-generation antipsychotic medications (olanzapine, quetiapine or risperidone), as well as in 22 healthy controls matched for age. Psychopathology and social functioning were assessed at the same time points. RESULTS: Baseline inPLA2 activity was significantly increased in drug-naïve and treated FES patients compared to healthy controls. Baseline inPLA2 activity was also associated with severity of negative symptoms and lower functioning at baseline. Furthermore, baseline inPLA2 activity was associated with improvement in negative symptoms and functioning within the first 12 weeks of treatment. CONCLUSIONS: Intracellular PLA2 activity is increased in first episode schizophrenia and associated with symptom severity and outcome after 12 weeks of treatment. Future studies should investigate the implications of inPLA2 activity as a potential predictor of treatment response for different antipsychotic agents.

Algorithms to improve the reparameterization of spherical mappings of brain surface meshes.

A spherical map of a cortical surface is often used for improved brain registration, for advanced morphometric analysis (eg, of brain shape), and for surface-based analysis of functional signals recorded from the cortex. Furthermore, for intersubject analysis, it is usually necessary to reparameterize the surface mesh into a common coordinate system. An isometric map conserves all angle and area information in the original cortical mesh; however, in practice, spherical maps contain some distortion. Here, we propose fast new algorithms to reduce the distortion of initial spherical mappings generated using one of three common spherical mapping methods. The algorithms iteratively solve a nonlinear optimization problem to reduce distortion. Our results demonstrate that our correction process is computationally inexpensive and the resulting spherical maps have improved distortion metrics. We show that our corrected spherical maps improve reparameterization of the cortical surface mesh, such that the distance error measures between the original and reparameterized surface are significantly decreased.