Jong-Min Lee

Automated 3-D extraction and evaluation of the inner and outer cortical surfaces using a Laplacian map and partial volume effect classification

Accurate reconstruction of the inner and outer cortical surfaces of the human cerebrum is a critical objective for a wide variety of neuroimaging analysis purposes, including visualization, morphometry, and brain mapping. The Anatomic Segmentation using Proximity (ASP) algorithm, previously developed by our group, provides a topology-preserving cortical surface deformation method that has been extensively used for the aforementioned purposes. However, constraints in the algorithm to ensure topology preservation occasionally produce incorrect thickness measurements due to a restriction in the range of allowable distances between the gray and white matter surfaces. This problem is particularly prominent in pediatric brain images with tightly folded gyri. This paper presents a novel method for improving the conventional ASP algorithm by making use of partial volume information through probabilistic classification in order to allow for topology preservation across a less restricted range of cortical thickness values. The new algorithm also corrects the classification of the insular cortex by masking out subcortical tissues. For 70 pediatric brains, validation experiments for the modified algorithm, Constrained Laplacian ASP (CLASP), were performed by three methods: (i) volume matching between surface-masked gray matter (GM) and conventional tissue-classified GM, (ii) surface matching between simulated and CLASP-extracted surfaces, and (iii) repeatability of the surface reconstruction among 16 MRI scans of the same subject. In the volume-based evaluation, the volume enclosed by the CLASP WM and GM surfaces matched the classified GM volume 13% more accurately than using conventional ASP. In the surface-based evaluation, using synthesized thick cortex, the average difference between simulated and extracted surfaces was 4.6 +/- 1.4 mm for conventional ASP and 0.5 +/- 0.4 mm for CLASP. In a repeatability study, CLASP produced a 30% lower RMS error for the GM surface and a 8% lower RMS error for the WM surface compared with ASP.

Development of Korean Standard Brain Templates

We developed age, gender and ethnic specific brain templates based on MR and Positron-Emission Tomography (PET) images of Korean normal volunteers. Seventy-eight normal right-handed volunteers (M/F=49/29) underwent 3D T1-weighted SPGR MR and F-18-FDG PET scans. For the generation of standard templates, an optimal target brain that has the average global hemispheric shape was selected for each gender. MR images were then spatially normalized by linear transformation to the target brains, and normalization parameters were reapplied to PET images. Subjects were subdivided into 2 groups for each gender: the young/midlife (<55 yr) and the elderly groups. Young and elderly MRI/PET templates were composed by averaging the spatially normalized images. Korean templates showed different shapes and sizes (mean length, width, and height of the brains were 16.5, 14.3 and 12.1 cm for man, and 15.6, 13.5 and 11.4 cm for woman) from the template based on Caucasian (18.3, 14.2, and 13.3 cm). MRI and PET templates developed in this study will provide the framework for more accurate stereotactic standardization and anatomical localization.

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.

Dopaminergic modulation of resting-state functional connectivity in de novo patients with Parkinson's disease

Parkinsons disease (PD) is characterized by degenerative changes of nigral dopamine neurons, resulting in the dopaminergic denervation of the striatum. Resting state networks studies have demonstrated that dopamine modulates distinct network connectivity patterns in both a linear and a nonlinear fashion, but quantitative analyses of dopamine‐dependent functional connectivity secondary to PD pathology were less informative. In the present study, we performed a correlation analysis between striatal dopamine levels assessed quantitatively by FP‐CIT positron emission tomography imaging and resting‐state functional connectivity in 23 drug naïve de novo patients with PD to elucidate dopamine‐dependent functional networks. The major finding is that the patterns of dopamine‐dependent positive functional connectivity varied depending on the location of striatal seeds. Dopamine‐dependent functional connectivity with the caudate predominantly overlay pericentral cortical areas, whereas dopamine‐dependent structures functionally connected with the posterior putamen predominantly involved cerebellar areas. The dorsolateral frontal area overlapped as a dopamine‐dependent cortical region that was positively connected with the anterior and posterior putamen. On the other hand, cortical areas where functional connectivity from the posterior cingulate was negatively correlated with dopaminergic status in the posterior putamen were localized in the left anterior prefrontal area and the parietal area. Additionally, functional connectivity between the anterior putamen and mesiofrontal areas was negatively coupled with striatal dopamine levels. The present study demonstrated that dopamine‐dependent functional network connectivity secondary to PD pathology mainly exhibits a consistent pattern, albeit with some variation. These patterns may reflect the diverse effects of dopaminergic medication on parkinsonian‐related motor and cognitive performance. Hum Brain Mapp 35:5431–5441, 2014.

Distinctive Resting State Network Disruptions Among Alzheimer’s Disease, Subcortical Vascular Dementia, and Mixed Dementia Patients

BACKGROUNDnRecent advances in resting-state functional MRI have revealed altered functional networks in Alzheimers disease (AD), especially those of the default mode network (DMN) and central executive network (CEN). However, few studies have evaluated whether small vessel disease (SVD) or combined amyloid and SVD burdens affect the DMN or CEN.nnnOBJECTIVEnThe aim of this study was to evaluate whether SVD or combined amyloid and SVD burdens affect the DMN or CEN.nnnMETHODSnIn this cross-sectional study, we investigated the resting-state functional connectivity within DMN and CEN in 37 Pittsburgh compound-B (PiB)(+) AD, 37 PiB(-) subcortical vascular dementia (SVaD), 13 mixed dementia patients, and 65 normal controls.nnnRESULTSnWhen the resting-state DMN of PiB(+) AD and PiB(-) SVaD patients were compared, the PiB(+) AD patients displayed lower functional connectivity in the inferior parietal lobule while the PiB(-) SVaD patients displayed lower functional connectivity in the medial frontal and superior frontal gyri. Compared to the PiB(-) SVaD or PiB(+) AD, the mixed dementia patients displayed lower functional connectivity within the DMN in the posterior cingulate gyrus. When the resting-state CEN connectivity of PiB(+) AD and PiB(-) SVaD patients were compared, the PiB(-) SVaD patients displayed lower functional connectivity in the anterior insular region. Compared to the PiB(-) SVaD or PiB(+) AD, the mixed dementia patients displayed lower functional connectivity within the CEN in the inferior frontal gyrus.nnnCONCLUSIONSnOur findings suggest that in PiB(+) AD and PiB(-) SVaD, there is divergent disruptions in resting-state DMN and CEN. Furthermore, patients with combined amyloid and SVD burdens exhibited more disrupted resting-state DMN and CEN than patients with only amyloid or SVD burden.

Brain mechanisms of pain relief by transcutaneous electrical nerve stimulation: A functional magnetic resonance imaging study

Although the exact mechanism of TENS pain relief is unknown, it is believed that TENS impulses interrupt nociceptive signals at the dorsal horn of the spinal cord.

Change of Brain Functional Connectivity in Patients With Spinal Cord Injury: Graph Theory Based Approach.

Objective To investigate the global functional reorganization of the brain following spinal cord injury with graph theory based approach by creating whole brain functional connectivity networks from resting state-functional magnetic resonance imaging (rs-fMRI), characterizing the reorganization of these networks using graph theoretical metrics and to compare these metrics between patients with spinal cord injury (SCI) and age-matched controls. Methods Twenty patients with incomplete cervical SCI (14 males, 6 females; age, 55±14.1 years) and 20 healthy subjects (10 males, 10 females; age, 52.9±13.6 years) participated in this study. To analyze the characteristics of the whole brain network constructed with functional connectivity using rs-fMRI, graph theoretical measures were calculated including clustering coefficient, characteristic path length, global efficiency and small-worldness. Results Clustering coefficient, global efficiency and small-worldness did not show any difference between controls and SCIs in all density ranges. The normalized characteristic path length to random network was higher in SCI patients than in controls and reached statistical significance at 12%-13% of density (p<0.05, uncorrected). Conclusion The graph theoretical approach in brain functional connectivity might be helpful to reveal the information processing after SCI. These findings imply that patients with SCI can build on preserved competent brain control. Further analyses, such as topological rearrangement and hub region identification, will be needed for better understanding of neuroplasticity in patients with SCI.

Assessment of Functional Characteristics of Amnestic Mild Cognitive Impairment and Alzheimer’s Disease Using Various Methods of Resting-State FMRI Analysis

Resting-state functional magnetic resonance imaging (RS FMRI) has been widely used to analyze functional alterations in amnestic mild cognitive impairment (aMCI) and Alzheimers disease (AD) patients. Although many clinical studies of aMCI and AD patients using RS FMRI have been undertaken, conducting a meta-analysis has not been easy because of seed selection bias by the investigators. The purpose of our study was to investigate the functional differences in aMCI and AD patients compared with healthy subjects in a meta-analysis. Thus, a multimethod approach using regional homogeneity, amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and global brain connectivity was used to investigate differences between three groups based on previously published data. According to the choice of RS FMRI approach used, the patterns of functional alteration were slightly different. Nevertheless, patients with aMCI and AD displayed consistently decreased functional characteristics with all approaches. All approaches showed that the functional characteristics in the left parahippocampal gyrus were decreased in AD patients compared with healthy subjects. Although some regions were slightly different according to the different RS FMRI approaches, patients with aMCI and AD showed a consistent pattern of decreased functional characteristics with all approaches.

Nigrostriatal dopamine-independent resting-state functional networks in Parkinson's disease

As an indicator of synchronous neural activity, resting-state functional networks are influenced by neuropathological and neurochemical changes in degenerative diseases. To further advance understanding about neurochemical and neuropathological basis for resting-state functional maps, we performed a comparative analysis of resting-state functional connectivity in patients with Parkinsons disease (PD) and drug induced parkinsonism (DIP). Resting-state neuroimaging data were analyzed with a seed-based approach to investigate striatocortical functional connectivity and cortical functional connectivity within the default mode network, executive control network, and the dorsal attention network. The striatal subregions were divided into the more or less affected sides in terms of dopamine transporter uptake. Compared with DIP, PD exhibited an increased cerebellar connectivity from the more affected side of the caudate and the less affected sides of the anterior and the posterior putamen. Additionally, PD showed increased functional connectivity in the anterior prefrontal areas from the more affected side of the anterior putamen and from the less affected side of the posterior putamen. However, PD exhibited decreased cortical functional connectivity from the posterior cingulate cortex in the left temporal area. Finally, DIP patients showed decreased cortical functional connectivity from the dorsolateral prefrontal cortex in frontal and parietal areas compared with PD patients. In summary, the present study demonstrates that PD patients exhibited a unique resting state functional connectivity that may be associated with PD-related pathological changes beyond the dopaminergic system, whereas DIP patients showed altered functional connectivity within executive control network.

Olfactory performance and resting state functional connectivity in non-demented drug naïve patients with Parkinson's disease

Olfactory performance in Parkinsons disease (PD) is closely associated with subsequent cognitive decline. In the present study, we analyzed the olfaction‐dependent functional connectivity with a hypothesis that olfactory performance would influence functional connectivity within key brain areas of PD. A total of 110 nondemented drug‐naïve patients with PD were subdivided into three groups of high score (PD‐H, nu2009=u200923), middle score (PD‐M, nu2009=u200964), and low score (PD‐L, nu2009=u200923) based on olfactory performance. We performed the resting‐state functional connectivity with seed region of interest in the posterior cingulate cortex (PCC) and caudate. An analysis of functional connectivity revealed that PD‐L patients exhibited a significant attenuation of cortical functional connectivity with the PCC in the bilateral primary sensory areas, right frontal areas, and right parietal areas compared to PD‐H or PD‐M patients. Meanwhile, PD‐L patients exhibited a significant enhancement of striatocortical functional connectivity in the bilateral occipital areas and right frontal areas compared to PD‐H or PD‐M patients. In the voxel‐wise correlation analysis, olfactory performance was positively associated with cortical functional connectivity with the PCC in similar areas of attenuated cortical connectivity in PD‐L patients relative to PD‐H patients. On the other hand, the cortical functional connectivity with the caudate was negatively correlated with olfactory performance in similar areas of increased connectivity in PD‐L patients relative to PD‐H patients. The present study demonstrated that resting state functional connectivity exhibits a distinctive pattern depending on olfactory performance, which might shed light on a meaningful relationship between olfactory impairment and cognitive dysfunction in PD. Hum Brain Mapp 36:1716–1727, 2015.