Jun Soo Kwon

Neural correlates of clinical symptoms and cognitive dysfunctions in obsessive-compulsive disorder.

Although results from neuropsychological and neuroimaging studies have postulated the involvement of the frontal lobe and the subcortical brain regions in the pathophysiology of obsessive-compulsive disorder (OCD), neuroimaging studies have provided little evidence that cognitive abnormalities in patients with OCD are related to dysfunctions in these areas. This study was designed to determine whether the clinical features and cognitive deficits of OCD might be taken to reflect frontal-subcortical dysfunction. Fourteen patients with OCD and 14 case-matched normal subjects completed clinical and cognitive evaluation, including four sets of neuropsychological tests that assessed the executive functions and visual memory. Cerebral glucose metabolic rates were measured by using positron emission tomography (PET) with 18F-fluorodeoxyglucose. Behavioral and PET data were analyzed using statistical parametric mapping for group differences and behavioral-metabolic correlates. The right orbitofrontal cortex showed increased metabolic activity and the left parieto-occipital junction showed decreased metabolic activity in patients. Metabolism in the right hippocampus, the left putamen and the right parietal region was associated with the severity of obsessive-compulsive symptoms. Correlations between metabolic rates and neuropsychological test scores in the prefrontal cortex and the putamen occurred only in the patient group. These results suggest that patients with OCD have distinct features of brain metabolic activities for performing cognitive tasks as well as presenting obsessive-compulsive symptoms. In particular, the frontal-subcortical circuits might mediate not only symptomatic expression but also cognitive expression in patients with OCD.

Gender difference analysis of cortical thickness in healthy young adults with surface-based methods.

We have examined gender differences of cortical thickness using a 3-D surface-based method that enables more accurate measurement in deep sulci and localized regional mapping compared to volumetric analyses. Cortical thickness was measured using a direct method for calculating the distance between corresponding vertices from inner and outer cortical surfaces. We normalized cortical surfaces using 2-D surface registration and performed diffusion smoothing to reduce the variability of folding patterns and to increase the power of the statistical analysis. In stereotaxic space, significant localized cortical thickening in women was found extensively in frontal, parietal and occipital lobes, including the superior frontal gyrus (SFG), superior parietal gyrus (SPG), inferior frontal gyrus (IFG) and postcentral gyrus (PoCG) in the left hemisphere and mostly in the parietal lobe, including the SPG in the right hemisphere. In the temporal lobe, small regions of the left and right caudal superior temporal gyrus (STG) and the left temporal pole showed significantly greater cortical thickness in women. The temporal lobe shows relatively less significant thickening than other lobes in both hemispheres. In native space, significantly greater cortical thickness in women was detected in left parietal region, including SPG and PoCG. No significant local increases of cortical thickness were observed in men in both spaces. These findings suggest statistically significant cortical thickening in women in localized anatomical regions, which is consistent with several previous studies and may support a hypothesis of sexual dimorphism.

Increased default mode network connectivity associated with meditation

Areas associated with the default mode network (DMN) are substantially similar to those associated with meditation practice. However, no studies on DMN connectivity during resting states have been conducted on meditation practitioners. It was hypothesized that meditators would show heightened functional connectivity in areas of cortical midline activity. Thirty-five meditation practitioners and 33 healthy controls without meditation experience were included in this study. All subjects received 4.68-min resting state functional scanning runs. The posterior cingulate cortex and medial prefrontal cortex were chosen as seed regions for the DMN map. Meditation practitioners demonstrated greater functional connectivity within the DMN in the medial prefrontal cortex area (xyz=339-21) than did controls. These results suggest that the long-term practice of meditation may be associated with functional changes in regions related to internalized attention even when meditation is not being practiced.

Deficit of theory of mind in individuals at ultra-high-risk for schizophrenia

BACKGROUND Although a deficit in social cognition is regarded as an early indicator of schizophrenia, few studies have investigated social cognition in ultra-high-risk (UHR) individuals. METHODS Our investigation involved subjects at UHR for psychosis (N=33) and an age- and IQ-matched healthy control (HC) group (N=36). Two types of theory of mind (ToM) tasks and a neuropsychological test battery were measured. RESULTS Compared to the HC group, the UHR group performed significantly worse for ToM tasks, with the effect size at an intermediate level (0.64-0.68). Furthermore, the UHR group showed impaired performance in the executive and working memory tests, but not verbal memory tests. These deficits for ToM tests observed in the UHR group were significantly correlated with set-shifting tasks. CONCLUSIONS Deficits in social cognition may be modest at the prodromal stage of schizophrenia and may be attributed to prefrontal dysfunction. To prevent or delay transition to psychosis, there is a need for specific preventive strategies targeting social functioning for the UHR group.

White matter abnormalities associated with auditory hallucinations in schizophrenia: A combined study of voxel-based analyses of diffusion tensor imaging and structural magnetic resonance imaging

White matter (WM) abnormalities in schizophrenia may offer important clues to a better understanding of the disconnectivity associated with the disorder. The aim of this study was to elucidate a WM basis of auditory hallucinations in schizophrenia through the simultaneous investigation of WM tract integrity and WM density. Diffusion tensor images (DTIs) and structural T1 magnetic resonance images (MRIs) were taken from 15 hallucinating schizophrenic patients, 15 non-hallucinating schizophrenic patients and 22 normal controls. Voxel-based analyses and post-hoc region of interest analyses were obtained to compare the three groups on fractional anisotropy (FA) derived from DTI as well as WM density derived from structural MRIs. In both the hallucinating and non-hallucinating groups, FA of the WM regions was significantly decreased in the left superior longitudinal fasciculus (SLF), whereas WM density was significantly increased in the left inferior longitudinal fasciculus (ILF). The mean FA value of the left frontal part of the SLF was positively correlated with the severity score of auditory hallucinations in the hallucinating patient group. Our findings show that WM changes were mainly observed in the frontal and temporal areas, suggesting that disconnectivity in the left fronto-temporal area may contribute to the pathophysiology of schizophrenia. In addition, pathologic WM changes in this region may be an important step in the development of auditory hallucinations in schizophrenia.

Multicenter Voxel-Based Morphometry Mega-Analysis of Structural Brain Scans in Obsessive-Compulsive Disorder

OBJECTIVE Results from structural neuroimaging studies of obsessive-compulsive disorder (OCD) have been only partially consistent. The authors sought to assess regional gray and white matter volume differences between large samples of OCD patients and healthy comparison subjects and their relation with demographic and clinical variables. METHOD A multicenter voxel-based morphometry mega-analysis was performed on 1.5-T structural T1-weighted MRI scans derived from the International OCD Brain Imaging Consortium. Regional gray and white matter brain volumes were compared between 412 adult OCD patients and 368 healthy subjects. RESULTS Relative to healthy comparison subjects, OCD patients had significantly smaller volumes of frontal gray and white matter bilaterally, including the dorsomedial prefrontal cortex, the anterior cingulate cortex, and the inferior frontal gyrus extending to the anterior insula. Patients also showed greater cerebellar gray matter volume bilaterally compared with healthy subjects. Group differences in frontal gray and white matter volume were significant after correction for multiple comparisons. Additionally, group-by-age interactions were observed in the putamen, insula, and orbitofrontal cortex (indicating relative preservation of volume in patients compared with healthy subjects with increasing age) and in the temporal cortex bilaterally (indicating a relative loss of volume in patients compared with healthy subjects with increasing age). CONCLUSIONS These findings partially support the prevailing fronto-striatal models of OCD and offer additional insights into the neuroanatomy of the disorder that were not apparent from previous smaller studies. The group-by-age interaction effects in orbitofrontal-striatal and (para)limbic brain regions may be the result of altered neuroplasticity associated with chronic compulsive behaviors, anxiety, or compensatory processes related to cognitive dysfunction.

Impulsivity in Internet Addiction: A Comparison with Pathological Gambling

Internet addiction has been considered to be associated with poor impulse control. The aim of this study is to compare the trait impulsivity of those suffering from Internet addiction with that of individuals suffering from pathological gambling. Twenty-seven patients diagnosed with Internet addiction (age: 24.78±4.37 years), 27 patients diagnosed with pathological gambling (age: 25.67±3.97 years), and 27 healthy controls (age: 25.33±2.79 years) were enrolled in this study. All patients were men seeking treatment. Trait impulsivity and the severity of the Internet addiction and pathological gambling were measured by the Barratt Impulsiveness Scale-11, the Youngs Internet Addiction Test, and the South Oaks Gambling Screen, respectively. The Beck Depression Inventory and the Beck Anxiety Inventory were also administered to all subjects. Our results show that those suffering from Internet addiction showed increased levels of trait impulsivity which were comparable to those of patients diagnosed with pathological gambling. Additionally, the severity of Internet addiction was positively correlated with the level of trait impulsivity in patients with Internet addiction. These results state that Internet addiction can be conceptualized as an impulse control disorder and that trait impulsivity is a marker for vulnerability to Internet addiction.

Social cognition and neurocognition as predictors of conversion to psychosis in individuals at ultra-high risk

BACKGROUND While deficits in cognitive functions are frequently reported in psychotic disorders, further longitudinal research is needed to confirm the specific risk factors for the development of psychosis. We examined longitudinally the social-cognitive and neurocognitive function of individuals at ultra-high risk for schizophrenia who developed psychosis later as predictive markers. METHOD The investigators studied 49 subjects at ultra-high risk (UHR) for psychosis and 45 healthy controls. The UHR subjects were followed for up 5.2 years (mean: 2.8 years) and 13 of these subjects developed psychosis. Theory of mind (ToM) tasks and neuropsychological tests were administered at baseline. Analyses compared the UHR patients who later developed psychosis, those who did not develop, and healthy controls. To examine the cognitive variables to predict transition to psychosis, Cox regression analyses were conducted. RESULTS At baseline, we found significant differences among the three groups in social cognition according to the False Belief and cartoon tasks and in neurocognition according to tasks measuring executive function, working memory, verbal memory, and visual memory. Our study showed that a model combining working memory, visual memory, executive function, and ToM tasks was significantly predictive of time to conversion to psychosis. CONCLUSION This study indicated that UHR patients who later converted to psychosis performed more poorly on tasks involving social cognition and neurocognition than did those who did not convert. We suggest that these deficits can serve as specific markers to predict the development of psychosis.

Fractal dimension in human cortical surface: multiple regression analysis with cortical thickness, sulcal depth, and folding area.

Fractal dimension (FD) has been widely used to provide a quantitative description of structural complexity in the cerebral cortex. FD is an extremely compact measure of shape complexity, condensing all details into a single numeric value. We interpreted the variation of the FD in the cortical surface of normal controls through multiple regression analysis with cortical thickness, sulcal depth, and folding area related to cortical complexity. We used a cortical surface showing a reliable representation of folded gyri and manually parcellated it into frontal, parietal, temporal, and occipital regions for regional analysis. In both hemispheres the mean cortical thickness and folding area showed significant combination effects on cortical complexity and accounted for about 50% of its variance. The folding area was significant in accounting for the FD of the cortical surface, with positive coefficients in both hemispheres and several lobe regions, while sulcal depth was significant only in the left temporal region. The results may suggest that human cortex develops a complex structure through the thinning of cortical thickness and by increasing the frequency of folds and the convolution of gyral shape rather than by deepening sulcal regions. Through correlation analysis of FD with IQ and the number of years of education, the results showed that a complex shape of the cortical surface has a significant relationship with intelligence and education. Our findings may indicate the structural characteristics that are revealed in the cerebral cortex when the FD in human brain is increased, and provide important information about brain development. Hum Brain Mapp, 2006.

Similarity and disparity of obsessive-compulsive disorder and schizophrenia in MR volumetric abnormalities of the hippocampus-amygdala complex

Objectives: Given that obsessive-compulsive disorder (OCD) and schizophrenia may share clinical symptoms as well as functional brain abnormalities, this study was designed to clarify common and different morphological abnormalities in OCD and schizophrenia. Methods: Volumes of the hippocampus, the amygdala, and the thalamus were measured in three age and sex matched groups of 22 patients with OCD, 22 patients with schizophrenia, and 22 normal subjects using three dimensional magnetic resonance imaging. Volume tracing was performed manually on serial coronal slices with the references of sagittal or axial planes using internal landmarks. Results: Hippocampal volume was bilaterally reduced in both OCD and schizophrenic patients versus the normal controls. Left amygdala volume was significantly enlarged in patients with OCD but not in patients with schizophrenia versus the normal controls. The thalamus did not show any volumetric group differences. Conclusions: Non-specific hippocampal reduction in both the OCD and schizophrenic groups is likely to link to a clinical overlap between the two illnesses, whereas the left amygdala enlargement observed only in the OCD patients seems to be suggestive of a unique role for the amygdala in the pathophysiology of OCD.