Maeng-Keun Oh

Morphological alterations in the congenital blind based on the analysis of cortical thickness and surface area.

To explore the morphological aspects of the functional reorganization of the blinds visual cortex, we analyzed the regional cortical thickness and cortical surface area in the congenitally blind subjects (CB) compared to the late-onset blind (LB) and sighted controls (SC). Cortical thickness was calculated from high-resolution T1-weighted magnetic resonance images of 21 young CB (blind from birth, mean age=27.1 yr), 12 LB, and 35 young SC. Analysis of covariance of cortical layer thickness with global thickness, age, and gender as covariates was done node-by-node on the entire cortical surface. Further analysis of mean thickness and surface area was performed for 33 automatically parceled cortical regions. Voxel-based morphometry was also conducted to compare results with cortical thickness and surface area. We found increased cortical thickness in the regions involved in vision and eye movement, such as the pericalcarine sulcus, cingulate cortex, and right frontal eye field, but cortical thinning in the left somatosensory cortex and right auditory cortex of CB compared to SC. CB had significantly reduced surface extent in the primary and associated visual areas, which explains volumetric atrophies in the visual cortex of CB despite increased cortical thickness. Conversely, LB tended to have cortical thinning in the primary visual cortex with a slight or no significant reduction in the surface extent. These morphological alterations in CB may indicate cortical reorganization at the visual cortex in connection with other sensory cortices.

Cortical surface-based analysis of 18F-FDG PET: Measured metabolic abnormalities in schizophrenia are affected by cortical structural abnormalities

The purpose of the study is to propose a new framework for surface-based statistical parametric mapping of PET images using MRI-based cortical surface analysis, including partial volume correction, intensity normalization and spatial normalization on the cortical surface. Maximum PET intensities along the path between inner and outer layer of the cortical gray matter are mapped onto the cortical surface to generate a metabolic activity surface map. For the partial volume correction, the metabolic activity surface map was divided by the partial volume effect map. The regional metabolic activity was normalized by the global activity iteratively calculated at the surface nodes, statistically independent of the group, as measured by F statistics. After surface-based spatial normalization, a statistical evaluation of both cortical thickness and cortical metabolic activity was conducted on the normalized surfaces of 16 patients with schizophrenia and 16 age- and gender-matched healthy controls. The patients with schizophrenia were found to have significant cortical thinning in the temporal and inferior frontal cortices. Accordingly, their PET imaging was significantly affected by the partial volume effect, indicating that partial volume correction could change the statistical results. After correction of the partial volume effects, the patients showed hyperactivity in the temporal cortex, whereas hypoactivity in the prefrontal cortex, predominantly in the left hemisphere. Our results demonstrate that anatomical factors affect an analysis for functional data from the PET, and therefore the importance of combining anatomy and function in the analysis of imaging data for schizophrenia should be considered.

Reorganization of neural circuits in the blind on diffusion direction analysis

The neural reorganization of the visual cortex of early blind individuals was evaluated using voxel-by-voxel analysis of diffusion tensor images with regard to the diffusion direction, diffusion anisotropy and diffusivity. Reduced anisotropy and increased diffusivity was found mainly in the visual pathways of 18 early blind individuals as opposed to 25 sighted individuals. Alteration of the diffusion direction was detected not only in the visual pathways but also in nonvisual pathways such as the u fibers of the parietal lobe, the sagittal striatum, the pulvinar and the inferior and superior longitudinal fasciculi. The alteration of regional diffusion direction, reduced anisotropy and increased diffusivity in early blind individuals imply the neural reorganization for functional adaptation to the loss of visual input during the early development period.

Volumetric abnormalities in connectivity-based subregions of the thalamus in patients with chronic schizophrenia

OBJECTIVE The thalamus, which consists of multiple subnuclei, has been of particular interest in the study of schizophrenia. This study aimed to identify abnormalities in the connectivity-based subregions of the thalamus in patients with schizophrenia. METHODS Thalamic volume was measured by a manual tracing on superimposed images of T1-weighted and diffusion tensor images in 30 patients with schizophrenia and 22 normal volunteers. Cortical regional volumes automatically measured by a surface-based approach and thalamic subregional volumes measured by a connectivity-based technique were compared between the two groups and their correlations between the connected regions were calculated in each group. RESULTS Volume reduction was observed in the bilateral orbitofrontal cortices and the left cingulate gyrus on the cortical side, whereas in subregions connected to the right orbitofrontal cortex and bilateral parietal cortices on the thalamic side. Significant volumetric correlations were identified between the right dorsal prefrontal cortex and its related thalamic subregion and between the left parietal cortex and its related thalamic subregion only in the normal group. CONCLUSIONS Our results suggest that patients with schizophrenia have a structural deficit in the corticothalamic systems, especially in the orbitofrontal-thalamic system. Our findings may present evidence of corticothalamic connection problems in schizophrenia.

Increased GABA-A Receptor Binding and Reduced Connectivity at the Motor Cortex in Children with Hemiplegic Cerebral Palsy: A Multimodal Investigation Using 18F-Fluoroflumazenil PET, Immunohistochemistry, and MR Imaging

γ-aminobutyric acid (GABA)-A receptor–mediated neural transmission is important to promote practice-dependent plasticity after brain injury. This study investigated alterations in GABA-A receptor binding and functional and anatomic connectivity within the motor cortex in children with cerebral palsy (CP). Methods: We conducted 18F-fluoroflumazenil PET on children with hemiplegic CP to investigate whether in vivo GABA-A receptor binding is altered in the ipsilateral or contralateral hemisphere of the lesion site. To evaluate changes in the GABA-A receptor subunit after prenatal brain injury, we performed GABA-A receptor immunohistochemistry using rat pups with a diffuse hypoxic ischemic insult. We also performed diffusion tensor MR imaging and resting-state functional MR imaging on the same children with hemiplegic CP to investigate alterations in anatomic and functional connectivity at the motor cortex with increased GABA-A receptor binding. Results: In children with hemiplegic CP, the 18F-fluoroflumazenil binding potential was increased within the ipsilateral motor cortex. GABA-A receptors with the α1 subunit were highly expressed exclusively within cortical layers III, IV, and VI of the motor cortex in rat pups. The motor cortex with increased GABA-A receptor binding in children with hemiplegic CP had reduced thalamocortical and corticocortical connectivity, which might be linked to increased GABA-A receptor distribution in cortical layers in rats. Conclusion: Increased expression of the GABA-A receptor α1 subunit within the ipsilateral motor cortex may be an important adaptive mechanism after prenatal brain injury in children with CP but may be associated with improper functional connectivity after birth and have adverse effects on the development of motor plasticity.

SENSE factors for reliable cortical thickness measurement

The purposes of this study were to examine the effect of sensitivity encoding (SENSE) factors on cortical thickness measurements and to determine which SENSE factor to use to reliably measure cortical thickness in 3.0 T and 1.5 T T1-weighted MRI images. The 3D T1-TFE images were acquired from 11 healthy volunteers with 6 different SENSE acceleration factors from 1.0 (without SENSE acceleration) to 4.0 on a 1.5 T scanner, and 9 different SENSE factors from 1.0 to 6.0, plus a second-day 1.0 acquisition on a 3.0 T scanner. Cortical thickness was calculated for the entire cortical surface that was further subdivided into 33 regions. Repeated measures multivariate analysis of variance revealed that the main effect of SENSE factors (F=12.485, df=7, p=0.006) was a significant underestimation of cortical thickness at SENSE 5.0 (p=0.022) and 6.0 (p=0.011) at 3.0 T and at SENSE 4.0 (p<0.000) at 1.5 T. Repeated measures ANOVA showed that thickness measurements at the insula, superior temporal sulcus, the medial part of the superior frontal lobe, and cingulate cortex are highly affected by SENSE factors. SENSE factors affect thickness estimation more significantly at 1.5 T and thus 1.5 T imaging provides less reliable estimates using SENSE techniques. Faster imaging can be done without too much loss of reliability using a high SENSE factor, such as 3.0, at 3.0 T with acquisition time being inversely proportional to the SENSE factor.

Is the GABA System Related to the Social Competence Improvement Effect of Aripiprazole? An (18)F-Fluoroflumazenil PET Study.

Objective Patients with schizophrenia who are treated with aripiprazole experience some benefits including an improvement of social competence, but the underlying mechanism of this improvement has not been investigated yet. This study aimed to provide preliminary evidence that the GABA system may be involved in the effect of aripiprazole on social competence. Methods Seventeen outpatients with schizophrenia (9 taking aripiprazole and 8 taking risperidone) and 18 healthy controls underwent 18F-fluoroflumazenil PET, and GABAA receptor binding potential was compared between the three groups. Results Voxelwise one-way ANOVA showed that GABAA receptor binding potentials in the right medial prefrontal cortex (p=0.04) and right dorsolateral prefrontal cortex (p=0.02) were significantly lower in the aripiprazole group than the risperidone group, and those in the left frontopolar cortex (p=0.03) and right premotor cortex (p=0.02) were significantly lower in the aripiprazole group than the risperidone and control groups. Conclusion Our results suggest that aripiprazole administration results in increased GABA transmission in the prefrontal regions, and that these increases may be a neural basis of aripiprazoles clinical benefits on an improvement of social competence.

Neural responses to affective and cognitive theory of mind in children and adolescents with autism spectrum disorder.

Children and adolescents with Autism Spectrum Disorder (ASD) are characterized by an impaired Theory of Mind (ToM). Recent evidence suggested that two aspects of ToM (cognitive ToM versus affective ToM) are differentially impaired in individuals with ASD. In this study, we examined the neural correlates of cognitive and affective ToM in children and adolescents with ASD compared to typically developing children (TDCs). Twelve children and adolescents with ASD and 12 age, IQ matched TDCs participated in this functional MRI study. The ToM task involved the attribution of cognitive and affective mental states to a cartoon character based on verbal and eye-gaze cues. In cognitive ToM tasks, ASD participants recruited the medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and superior temporal gyrus (STG) to a greater extent than did TDCs. In affective ToM tasks, both ASD and TDC participants showed more activation in the insula and other subcortical regions than in cognitive ToM tasks. Correlational analysis revealed that greater activation of the mPFC/ACC regions was associated with less symptom severity in ASD patients. In sum, our study suggests that the recruitment of additional prefrontal resources can compensate for the successful behavioral performance in the ToM task in ASD participants.

A Network Analysis of 15O-H2O PET Reveals Deep Brain Stimulation Effects on Brain Network of Parkinson's Disease

Purpose As Parkinsons disease (PD) can be considered a network abnormality, the effects of deep brain stimulation (DBS) need to be investigated in the aspect of networks. This study aimed to examine how DBS of the bilateral subthalamic nucleus (STN) affects the motor networks of patients with idiopathic PD during motor performance and to show the feasibility of the network analysis using cross-sectional positron emission tomography (PET) images in DBS studies. Materials and Methods We obtained [15O]H2O PET images from ten patients with PD during a sequential finger-to-thumb opposition task and during the resting state, with DBS-On and DBS-Off at STN. To identify the alteration of motor networks in PD and their changes due to STN-DBS, we applied independent component analysis (ICA) to all the cross-sectional PET images. We analysed the strength of each component according to DBS effects, task effects and interaction effects. Results ICA blindly decomposed components of functionally associated distributed clusters, which were comparable to the results of univariate statistical parametric mapping. ICA further revealed that STN-DBS modifies usage-strengths of components corresponding to the basal ganglia-thalamo-cortical circuits in PD patients by increasing the hypoactive basal ganglia and by suppressing the hyperactive cortical motor areas, ventrolateral thalamus and cerebellum. Conclusion Our results suggest that STN-DBS may affect not only the abnormal local activity, but also alter brain networks in patients with PD. This study also demonstrated the usefulness of ICA for cross-sectional PET data to reveal network modifications due to DBS, which was not observable using the subtraction method.

Regional cerebral blood flow changes and performance deficit during a sustained attention task in schizophrenia: 15O-water positron emission tomography

Attention deficit has been reported in both schizophrenia patients and patients with major depressive disorder (MDD). The aim of this study was to elucidate the deficits in sustained attention and associated neural network dysfunctions in schizophrenia patients and MDD patients, and to investigate the difference between the two patient groups.