Sun Hyung Kim

Brain Size and Cortical Structure in the Adult Human Brain

We investigated the scale relationship between size and cortical structure of human brains in a large sample of magnetic resonance imaging data. Cortical structure was estimated with several measures (cortical volume, surface area, and thickness, sulcal depth, and absolute mean curvature in sulcal regions and sulcal walls) using three-dimensional surface-based methods in 148 normal subjects (n [men/women]: 83/65, age [mean +/- standard deviation]: 25.0 +/- 4.9 years). We found significantly larger scaling exponents than geometrically predicted for cortical surface area, absolute mean curvature in sulcal regions and in sulcal walls, and smaller ones for cortical volume and thickness. As brain size increases, the cortex thickens only slightly, but the degree of sulcal convolution increases dramatically, indicating that human cortices are not simply scaled versions of one another. Our results are consistent with previous hypotheses that greater local clustering of interneuronal connections would be required in a larger brain, and fiber tension between local cortical areas would induce cortical folds. We suggest that sex effects are explained by brain size effects in cortical structure at a macroscopic and lobar regional level, and that it is necessary to consider true relationships between cortical measures and brain size due to the limitations of linear stereotaxic normalization.

Early brain development in infants at high risk for autism spectrum disorder

Brain enlargement has been observed in children with autism spectrum disorder (ASD), but the timing of this phenomenon, and the relationship between ASD and the appearance of behavioural symptoms, are unknown. Retrospective head circumference and longitudinal brain volume studies of two-year olds followed up at four years of age have provided evidence that increased brain volume may emerge early in development. Studies of infants at high familial risk of autism can provide insight into the early development of autism and have shown that characteristic social deficits in ASD emerge during the latter part of the first and in the second year of life. These observations suggest that prospective brain-imaging studies of infants at high familial risk of ASD might identify early postnatal changes in brain volume that occur before an ASD diagnosis. In this prospective neuroimaging study of 106 infants at high familial risk of ASD and 42 low-risk infants, we show that hyperexpansion of the cortical surface area between 6 and 12 months of age precedes brain volume overgrowth observed between 12 and 24 months in 15 high-risk infants who were diagnosed with autism at 24 months. Brain volume overgrowth was linked to the emergence and severity of autistic social deficits. A deep-learning algorithm that primarily uses surface area information from magnetic resonance imaging of the brain of 6–12-month-old individuals predicted the diagnosis of autism in individual high-risk children at 24 months (with a positive predictive value of 81% and a sensitivity of 88%). These findings demonstrate that early brain changes occur during the period in which autistic behaviours are first emerging.

The Effect of Meditation on Brain Structure: Cortical Thickness Mapping and Diffusion Tensor Imaging

A convergent line of neuroscientific evidence suggests that meditation alters the functional and structural plasticity of distributed neural processes underlying attention and emotion. The purpose of this study was to examine the brain structural differences between a well-matched sample of long-term meditators and controls. We employed whole-brain cortical thickness analysis based on magnetic resonance imaging, and diffusion tensor imaging to quantify white matter integrity in the brains of 46 experienced meditators compared with 46 matched meditation-naïve volunteers. Meditators, compared with controls, showed significantly greater cortical thickness in the anterior regions of the brain, located in frontal and temporal areas, including the medial prefrontal cortex, superior frontal cortex, temporal pole and the middle and interior temporal cortices. Significantly thinner cortical thickness was found in the posterior regions of the brain, located in the parietal and occipital areas, including the postcentral cortex, inferior parietal cortex, middle occipital cortex and posterior cingulate cortex. Moreover, in the region adjacent to the medial prefrontal cortex, both higher fractional anisotropy values and greater cortical thickness were observed. Our findings suggest that long-term meditators have structural differences in both gray and white matter.

Sulcal morphology changes and their relationship with cortical thickness and gyral white matter volume in mild cognitive impairment and Alzheimer's disease.

We investigated the changes of sulcal shape (average mean curvature in folded regions and sulcal depth) in mild cognitive impairment (MCI) and Alzheimers disease (AD) using quantitative surface-based methods in a large sample of magnetic resonance imaging data. Moreover, we observed their relationships with cortical thickness and gyral white matter (WM) volume, while considering age effect. This study involved 85 normal controls (n [men/women]: 36/49, age [mean+/-SD]: 71.1+/-4.9 years), and 100 MCI (44/56, 71.8+/-6.5) and 145 AD subjects (53/92, 72.7+/-7.3). We found significantly lower average mean curvature (greater sulcal widening) and shallower sulcal depth with disease progression from controls to MCI and MCI to AD. The most remarkable change in MCI and AD was sulcal widening observed in the temporal lobe (average mean curvature, control [mean]: 0.564, MCI: 0.534 (5.3% decrease from control), AD: 0.486 (13.8% and 9.0% decrease from control and MCI respectively)). Of the four measurements, the sulcal widening measurement showed the highest sensitivity in revealing group differences between control and MCI, which might be useful for detecting early dementia. Significant reductions in cortical thickness and gyral WM volume also occurred in MCI and AD. Multiple regression analysis demonstrated that a wider and shallower sulcal shape was primarily associated with decreased cortical thickness and gyral WM volume in each group. Age-related trends for the sulcal shape were not strongly found when cortical thickness and gyral WM volume were considered.

Cortical thickness abnormality in juvenile myoclonic epilepsy

Previous studies on gray matter concentration changes in patients with juvenile myoclonic epilepsy (JME) are inconsistent. To investigate cortical abnormality in JME differently, we measured the cortical thickness in 19 JME patients and 18 normal controls. Results showed that the cortical thicknesses of superior/middle/medial frontal gyri, and superior/middle/ inferior temporal gyri were decreased in JME patients. Moreover, cortical thicknesses of precentral gyrus and medial orbital gyrus of right hemispheres were negatively correlated with disease duration. These findings suggest that JME brains have cortical gray matter atrophy in the frontal and temporal lobes.

Thalamus surface shape deformity in obsessive-compulsive disorder and schizophrenia.

The authors performed a three-dimensional shape deformation analysis to clarify the various patterns of specific thalamic nuclei abnormality using three age-matched and sex-matched groups of 22 patients with obsessive-compulsive disorder (OCD), 22 patients with schizophrenia and 22 control participants. Compared with the healthy volunteers, the anterior, lateral outward surface deformities of the thalamus were significant in OCD patients, whereas the posterior, medial outward deformities of the thalamus were prominent in schizophrenia patients. In terms of thalamic asymmetry, both OCD and schizophrenia patients exhibited the loss of a leftward pattern of asymmetry on the posterior, medial surface of the thalamus. Different patterns of shape abnormality of specific thalamic nuclei may be related to the different phenomenology of OCD and schizophrenia.

Deformable model with surface registration for hippocampal shape deformity analysis in schizophrenia.

Changes to the hippocampal structure have been reported as consistent structural abnormalities in schizophrenic patients and have been related to the learning and memory deficits in such patients. Although many magnetic resonance (MR) imaging studies have focused on the hippocampal volume, local structural changes were difficult to discriminate from normal neuroanatomical variations. 3D shape deformation analysis of the brain structure may reflect localized schizophrenic abnormalities. A deformable model, evolved from the ellipsoid to hippocampal surface, with 2562 vertexes, was developed to analyze the left and right hippocampus shapes in 22 schizophrenic patients and 22 healthy age and gender matched controls. One of the most critical issues in the shape analysis is the determination of homologous points between two objects. To determine more accurate corresponding points, an alignment procedure, consisting of coarse and fine steps, following a deformation process, was applied. The performance of the alignment process was tested using artificial data, to get the alignment error to within 3 degrees for each angle. A volume analysis indicated the hippocampal volume to be bilaterally reduced in schizophrenic patients compared to the normal controls, with a shape analysis showing a deformity pattern of the hippocampal surface. Bilateral inward deformities in the anterior and posterior hippocampus and a unilateral outward deformity in the right anterior hippocampus were observed, respectively.

Asymmetry analysis of deformable hippocampal model using the principal component in schizophrenia

The hippocampus is thought to play an important role in learning and memory processing, and impairments in memory, attention, and decision making are found commonly in schizophrenia. Although many studies have reported decreases in hippocampal volume in the left hemisphere in schizophrenia, regionally specific hippocampal volume loss has not been revealed consistently using volume analysis. Recently, many studies have analyzed shape asymmetry using 3‐D models; however, inconsistent results have been reported, mainly due to methodologic differences. We therefore used an active, flexible, deformable shape model for surface parameterization, and compared shape asymmetry based on principal component analysis (PCA) in the hippocampi of schizophrenic patients with those of the normal controls. Although the overall pattern of the statistical results did not change according to the number of principal components, the reconstructed results based on six major components were much more distinguishable. Although the left hemispheric hippocampal volume was larger than the right hemispheric was in this study, the difference was not significant. In shape asymmetry analysis, the right hemisphere hippocampus was bilaterally larger than the left hemisphere hippocampus was in the head of the superior CA1 and smaller in the tail and head of the inferior CA1. The asymmetry in the schizophrenia group was statistically smaller than that in the control group through reduction of the left hemisphere hippocampus volume. Hum Brain Mapp, 2005.

Hippocampal shape deformity analysis in obsessive–compulsive disorder

Abnormalities of orbital prefrontal cortex and caudate nuclei have, thus far, been the main findings regarding the pathophysiology of obsessive–compulsive disorder (OCD). On the other hand, neuroimaging studies have failed to reach a consensus with regard to the issue of hippocampal abnormalities in OCD patients. Shape analysis may facilitate a resolution of the discordance among these former studies by detecting local structural changes, thus enhancing power to discriminate structural differences. It has been suggested that neural circuitry interconnecting brain areas may critically influence the shape of neuroanatomical structures, serving as a rationale for better sensitivity of shape analysis compared to volume analysis, especially in detecting abnormalities of neural circuitry. Shape analysis of the hippocampus was performed in 22 matched pairs of OCD patients and normal control subjects. As a result, we observed a bilateral hippocampal shape deformity including the most prominent characteristic of downward displacement of the head. The hippocampal structural alteration observed in this study indicates that this structure may play a role in the pathophysiology of OCD. Also, further considering the hippocampal neural connections specific to its surface topography, these surface deformities may reflect developmental alterations in these patients with regard to the neural circuitry involving hippocampus.

Midsagittal structural differences and sexual dimorphism of the corpus callosum in obsessive-compulsive disorder

Neurobiological abnormalities in various brain regions, including the orbitofrontal cortex, basal ganglia, and thalamus, have been found in patients with obsessive-compulsive disorder (OCD), and impairment in white matter connectivity in these regions has recently been suggested. To investigate structural connectivity in OCD, we used the midsagittal area and thickness to assess the morphology of the corpus callosum (CC), the largest connecting fiber tract in the human brain. Midsagittal magnetic resonance images of the CC were acquired from 69 adult patients with OCD and 69 matched normal controls. We calculated and compared the total area and the areas of five subregions of the CC as well as the distances between 200 equidistant points on the top and bottom of lines on the surface of the CC in the two groups. The absolute total area of the CC was significantly larger in OCD patients than in controls when brain size, age, gender, and IQ were controlled. Significant enlargements in CC1, CC2, and CC5 were seen in OCD patients before correction for multiple comparisons. The thickness of the caudal part of the splenium was greater in OCD patients than in controls. The analysis according to gender showed that only male OCD patients differed from male controls with respect to the area of the CC. These findings reflect structural abnormalities in the CC, and especially in the splenium, in adult patients with OCD. Abnormal interhemispheric connectivity, including the parietotemporal and occipital areas, may affect the pathophysiology of OCD. Sexual dimorphism in the CC of OCD patients should be considered.