Publications by authors named "Dajung Kim"

21 Publications

  • Page 1 of 1

COVID-19 Antiviral and Treatment Candidates: Current Status.

Immune Netw 2021 Feb 15;21(1):e7. Epub 2021 Feb 15.

Department of Pharmacy, Korea University College of Pharmacy, Sejong 30019, Korea.

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 has severely impacted global health and economy. There is currently no effective approved treatment for COVID-19; although vaccines have been granted emergency use authorization in several countries, they are currently only administered to high-risk individuals, thereby leaving a gap in virus control measures. The scientific and clinical communities and drug manufacturers have collaborated to speed up the discovery of potential therapies for COVID-19 by taking advantage of currently approved drugs as well as investigatory agents in clinical trials. In this review, we stratified some of these candidates based on their potential targets in the progression of COVID-19 and discuss some of the results of ongoing clinical evaluations.
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http://dx.doi.org/10.4110/in.2021.21.e7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937511PMC
February 2021

Dopaminergic Regulation of Reward System Connectivity Underpins Pain and Emotional Suffering in Migraine.

J Pain Res 2021 9;14:631-643. Epub 2021 Mar 9.

Headache and Orofacial Pain Effort (H.O.P.E.), Biologic and Material Sciences & Prosthodontics, University of Michigan School of Dentistry, Ann Arbor, MI, 48109, USA.

Purpose: It has been suggested that reward system dysfunction may account for emotion and pain suffering in migraine. However, there is a lack of evidence whether the altered reward system connectivity is directly associated with clinical manifestations, including negative affect and ictal pain severity and, at the molecular level, the dopamine (DA) D2/D3 receptors (D2/3Rs) signaling implicated in encoding motivational and emotional cues.

Patients And Methods: We acquired resting-state functional MRI from interictal episodic migraine (EM) patients and age-matched healthy controls, as well as positron emission tomography (PET) with [C]raclopride, a selective radiotracer for DA D2/3Rs, from a subset of these participants. The nucleus accumbens (NAc) was seeded to measure functional connectivity (FC) and DA D2/3Rs availability based on its essential involvement in pain-related aversive/reward functions. Associations of the brain measures with positive/negative affect and ictal pain severity were also assessed.

Results: Compared with controls, the EM group showed weaker right NAc connectivity with areas implicated in pain and emotional regulation, such as the amygdala, rostral anterior cingulate cortex, hippocampus, and thalamus; but showed stronger left NAc connectivity with the dorsolateral prefrontal cortex and lingual gyrus. Moreover, among the altered NAc connectivities, only right NAc-amygdala connectivity was inversely correlated with DA D2/3Rs availability in migraine patients (diagnostic group-by-D2/3Rs interaction p < 0.007). At a clinical level, such weaker NAc-amygdala connectivity was associated with lower interictal positive affect and greater ictal pain severity over the head and facial extension area (pain area and intensity number summation, PAINS).

Conclusion: Together, our findings suggest that altered reward system connectivity, specifically between the NAc and amygdala, might be affected by endogenous DA D2/3Rs signaling, and such process might be a neural mechanism that underlies emotional and pain suffering in episodic migraineurs.
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http://dx.doi.org/10.2147/JPR.S296540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955762PMC
March 2021

Fabrication and Characterization of Polysaccharide Metallohydrogel Obtained from Succinoglycan and Trivalent Chromium.

Polymers (Basel) 2021 Jan 8;13(2). Epub 2021 Jan 8.

Department of Bioscience and Biotechnology, Microbial Carbohydrate Resource Bank (MCRB), Konkuk University, Seoul 05029, Korea.

In the present study, a polysaccharide metallohydrogel was successfully fabricated using succinoglycan and trivalent chromium and was verified via Fourier transform infrared spectroscopy, differential scanning calorimetry analysis, thermogravimetric analysis (TGA), field emission scanning electron microscopy, and rheological measurements. Thermal behavior analysis via TGA indicated that the final mass loss of pure succinoglycan was 87.8% although it was reduced to 65.8% by forming a hydrogel with trivalent chromium cations. Moreover, succinoglycan-based metallohydrogels exhibited improved mechanical properties based on the added concentration of Cr and displayed a 10 times higher compressive stress and enhanced storage modulus (G') of 230% at the same strain. In addition, the pore size of the obtained SCx could be adjusted by changing the concentration of Cr. Gelation can also be adjusted based on the initial pH of the metallohydrogel formulation. This was attributed to crosslinking between chromium trivalent ions and hydroxyl/carboxyl groups of succinoglycan, each of which exhibits a specific pH-dependent behavior in aqueous solutions. It could be used as a soft sensor to detect Cr in certain biological systems, or as a soft matrix for bioseparation that allows control of pore size and mechanical strength by tuning the Cr concentration.
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http://dx.doi.org/10.3390/polym13020202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827257PMC
January 2021

Differential alteration of fMRI signal variability in the ascending trigeminal somatosensory and pain modulatory pathways in migraine.

J Headache Pain 2021 Jan 7;22(1). Epub 2021 Jan 7.

Headache and Orofacial Pain Effort (H.O.P.E.), Department of Biologic and Materials Sciences & Prosthodontics, University of Michigan School of Dentistry, 1011 N. University Ave, Room 1014A, Ann Arbor, MI, 48109-1078, USA.

Background: The moment-to-moment variability of resting-state brain activity has been suggested to play an active role in chronic pain. Here, we investigated the regional blood-oxygen-level-dependent signal variability (BOLD) and inter-regional dynamic functional connectivity (dFC) in the interictal phase of migraine and its relationship with the attack severity.

Methods: We acquired resting-state functional magnetic resonance imaging from 20 migraine patients and 26 healthy controls (HC). We calculated the standard deviation (SD) of the BOLD time-series at each voxel as a measure of the BOLD signal variability (BOLD) and performed a whole-brain voxel-wise group comparison. The brain regions showing significant group differences in BOLD were used to define the regions of interest (ROIs). The SD and mean of the dynamic conditional correlation between those ROIs were calculated to measure the variability and strength of the dFC. Furthermore, patients' experimental pain thresholds and headache pain area/intensity levels during the migraine ictal-phase were assessed for clinical correlations.

Results: We found that migraineurs, compared to HCs, displayed greater BOLD in the ascending trigeminal spinal-thalamo-cortical pathways, including the spinal trigeminal nucleus, pulvinar/ventral posteromedial (VPM) nuclei of the thalamus, primary somatosensory cortex (S1), and posterior insula. Conversely, migraine patients exhibited lower BOLD in the top-down modulatory pathways, including the dorsolateral prefrontal (dlPFC) and inferior parietal (IPC) cortices compared to HCs. Importantly, abnormal interictal BOLD in the ascending trigeminal spinal-thalamo-cortical and frontoparietal pathways were associated with the patient's headache severity and thermal pain sensitivity during the migraine attack. Migraineurs also had significantly lower variability and greater strength of dFC within the thalamo-cortical pathway (VPM-S1) than HCs. In contrast, migraine patients showed greater variability and lower strength of dFC within the frontoparietal pathway (dlPFC-IPC).

Conclusions: Migraine is associated with alterations in temporal signal variability in the ascending trigeminal somatosensory and top-down modulatory pathways, which may explain migraine-related pain and allodynia. Contrasting patterns of time-varying connectivity within the thalamo-cortical and frontoparietal pathways could be linked to abnormal network integrity and instability for pain transmission and modulation.
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http://dx.doi.org/10.1186/s10194-020-01210-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791681PMC
January 2021

Succinoglycan dialdehyde-reinforced gelatin hydrogels with toughness and thermal stability.

Int J Biol Macromol 2020 Apr 23;149:281-289. Epub 2020 Jan 23.

Department of Bioscience and Biotechnology, Microbial Carbohydrate Resource Bank (MCRB), Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, South Korea; Institute for Ubiquitous Information Technology and Applications (UBITA), Center for Biotechnology Research in UBITA (CBRU), Konkuk University, Seoul 05029, South Korea. Electronic address:

Pure gelatin hydrogel (PG) has limited practical applications due to their thermal instability and unfavorable mechanical properties. To overcome these limitations, dually crosslinked hydrogels were developed by imparting chemical crosslinking to existing physically crosslinked gelatin hydrogel networks using succinoglycan dialdehyde (SGDA) as a macromolecular crosslinker. SGDA-reinforced gelatin hydrogels (SGDA/Gels) displayed an 11 times higher compressive stress under identical deformation strain and a 1040% improvement in storage modulus (G') than PG. In addition, chemical crosslinking induced by SGDA increased the thermal stability of SGDA/Gels, such that they did not decompose at 60 °C, as confirmed by oscillatory temperature ramp experiments. The newly synthesized SGDA/Gels with reinforced networks and thermal stability exhibit potential for long-term use as controlled drug delivery carriers and 3D cell culture scaffolds for tissue engineering.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.01.228DOI Listing
April 2020

Succinoglycan dialdehyde-reinforced gelatin hydrogels with toughness and thermal stability.

Int J Biol Macromol 2020 Apr 23;149:281-289. Epub 2020 Jan 23.

Department of Bioscience and Biotechnology, Microbial Carbohydrate Resource Bank (MCRB), Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, South Korea; Institute for Ubiquitous Information Technology and Applications (UBITA), Center for Biotechnology Research in UBITA (CBRU), Konkuk University, Seoul 05029, South Korea. Electronic address:

Pure gelatin hydrogel (PG) has limited practical applications due to their thermal instability and unfavorable mechanical properties. To overcome these limitations, dually crosslinked hydrogels were developed by imparting chemical crosslinking to existing physically crosslinked gelatin hydrogel networks using succinoglycan dialdehyde (SGDA) as a macromolecular crosslinker. SGDA-reinforced gelatin hydrogels (SGDA/Gels) displayed an 11 times higher compressive stress under identical deformation strain and a 1040% improvement in storage modulus (G') than PG. In addition, chemical crosslinking induced by SGDA increased the thermal stability of SGDA/Gels, such that they did not decompose at 60 °C, as confirmed by oscillatory temperature ramp experiments. The newly synthesized SGDA/Gels with reinforced networks and thermal stability exhibit potential for long-term use as controlled drug delivery carriers and 3D cell culture scaffolds for tissue engineering.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.01.228DOI Listing
April 2020

Clinical impact of anti-thymocyte globulin on survival and graft-versus-host disease in patients undergoing human leukocyte antigen mismatched allogeneic stem cell transplantation.

Korean J Intern Med 2020 03 10;35(2):429-437. Epub 2019 Jan 10.

Department of Internal Medicine, Kosin University Gospel Hospital, Busan, Korea.

Background/aims: Rabbit anti-thymocyte globulin (ATG) is usually incorporated in hematopoietic stem cell transplantation (HSCT) to reduce the incidence of graft-versus-host disease (GVHD). This study aimed to find optimal ATG doses in patients undergoing human leukocyte antigen (HLA)-mismatched allogeneic HSCT.

Methods: We retrospectively collected medical records from 352 consecutive patients with acute myeloid leukemia (n = 214), acute lymphoblastic leukemia (n = 62), or myelodysplastic syndrome (n = 76) in eight centers of Korea between 2005 and 2015. All patients received busulfan-based conditioning without total body irradiation (TBI) and received stem cells from HLA-mismatched donors.

Results: In the current study, 5-year overall survival rates of patients receiving low to medium doses of ATG (2.5 to 7.5 mg/kg) were higher than those receiving other doses of ATG (hazard ratio [HR], 0.528; 95% confidence interval [CI], 0.311 to 0.897; p = 0.018). The incidence rates of extensive chronic GVHD (ecGVHD) after administration of low to medium doses of ATG were lower than those after other doses of ATG (HR, 0.447; 95% CI, 0.224 ton 0.889; p = 0.022).

Conclusion: The low to medium doses of ATG may be associated with improving survival outcomes and reducing incidence of ecGVHD without enhancing the chances of relapse in patients with acute leukemia or myelodysplastic syndrome undergoing non-TBI-based HLA-mismatched allogeneic HSCT.
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http://dx.doi.org/10.3904/kjim.2018.317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061010PMC
March 2020

as a function-based high-throughput screening model for antinephrolithiasis agents in kidney stone patients.

Dis Model Mech 2018 11 16;11(11). Epub 2018 Nov 16.

Division of Urology, Department of Surgery, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 4V2, Canada

Kidney stone disease involves the aggregation of stone-forming salts consequent to solute supersaturation in urine. The development of novel therapeutic agents for this predominantly metabolic and biochemical disorder have been hampered by the lack of a practical pre-clinical model amenable to drug screening. Here, , an emerging model for kidney stone disease research, was adapted as a high-throughput functional drug screening platform independent of the multifactorial nature of mammalian nephrolithiasis. Through functional screening, the therapeutic potential of a novel compound commonly known as arbutin that specifically binds to oxalate, a key component of kidney calculi, was identified. Through isothermal titration calorimetry, high-performance liquid chromatography and atomic force microscopy, arbutin was determined to interact with calcium and oxalate in both free and bound states, disrupting crystal lattice structure, growth and crystallization. When used to treat patient urine samples, arbutin significantly abrogated calculus formation and outperformed potassium citrate in low pH urine conditions, owing to its oxalate-centric mode of action. The discovery of this novel antilithogenic compound via , independent of a mammalian model, brings greater recognition to this platform, for which metabolic features are primary outcomes, underscoring the power of as a high-throughput drug screening platform in similar disorders. This is the first description of the use of as the model system for a high-throughput chemical library screen. This article has an associated First Person interview with the first authors of the paper.
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http://dx.doi.org/10.1242/dmm.035873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262805PMC
November 2018

The Optimal Energy Level of Virtual Monochromatic Images From Spectral CT for Reducing Beam-Hardening Artifacts Due to Contrast Media in the Thorax.

AJR Am J Roentgenol 2018 09 5;211(3):557-563. Epub 2018 Jul 5.

3 Radiological Science, Catholic University of Daegu, Gyeongsangbuk-do, South Korea.

Objective: The purpose of this study is to determine the optimal energy level of virtual monochromatic images from spectral CT compared with conventional polychromatic images for reducing beam-hardening artifacts caused by contrast media in the thorax.

Materials And Methods: A total of 101 consecutive patients who underwent chest CT with contrast enhancement were retrospectively included in this study. The same contrast media and injection protocols were applied to the whole study population. Virtual monochromatic image datasets ranging from 70 to 200 keV and conventional polychromatic images were obtained. Readers' subjective image quality scores were recorded for conventional polychromatic and virtual monochromatic images obtained at 70, 100, 130, and 200 keV. Image noise, CT attenuation difference, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) were also obtained in each algorithm. Comparisons of parameters between algorithms were performed.

Results: The best subjective image quality score and significantly lower image noise were observed for 130-keV virtual monochromatic images compared with conventional polychromatic images (all p < 0.001). Also, CT attenuation differences were significantly lower for both 100- and 130-keV virtual monochromatic images than for conventional polychromatic images (all p < 0.001). Meanwhile, the lowest differences in CT attenuation were observed for 100-keV virtual monochromatic images compared with conventional polychromatic images. However, there were no significant differences in CT attenuation between 100- and 130-keV virtual monochromatic images. SNR was similar between 130-keV virtual monochromatic images and conventional polychromatic images, although both SNR and CNR decreased as the energy level increased.

Conclusion: Virtual monochromatic imaging reduced beam-hardening artifacts and improved image quality, and optimal evaluation of chest CT was best achieved at 100 and 130 keV.
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http://dx.doi.org/10.2214/AJR.17.19377DOI Listing
September 2018

Increased Low- and High-Frequency Oscillatory Activity in the Prefrontal Cortex of Fibromyalgia Patients.

Front Hum Neurosci 2016 14;10:111. Epub 2016 Mar 14.

Neuroscience Research Institute, Seoul National University College of MedicineSeoul, South Korea; Department of Brain and Cognitive Sciences, Seoul National University College of Natural SciencesSeoul, South Korea; Department of Neurosurgery, Seoul National University HospitalSeoul, South Korea.

Recent human neuroimaging studies have suggested that fibromyalgia (FM), a chronic widespread pain disorder, exhibits altered thalamic structure and function. Since the thalamus has extensive reciprocal connection with the cortex, structural and functional thalamic alterations in FM might be linked to aberrant thalamocortical oscillation. This study investigated the presence of abnormal brain rhythmicity in low- and high-frequency bands during resting state in patients with FM and their relationship to clinical pain symptom. Spontaneous magnetoencephalography (MEG) activity was recorded in 18 females with FM and 18 age- and sex-matched healthy control (HC) subjects. The most remarkable finding was that FM patients had general increases in theta, beta and gamma power along with a slowing of the dominant alpha peak. Increased spectral powers in the theta-band were primarily localized to the left dorsolateral prefrontal (DLPFC) and orbitofrontal cortex (OFC). Beta and gamma over-activation were localized to insular, primary motor and primary and secondary somatosensory (S2) cortices, as well as the DLPFC and OFC. Furthermore, enhanced high-frequency oscillatory activities in the DLPFC and OFC were associated with higher affective pain scores in patients with FM. Our results demonstrate that FM patients feature enhanced low- and high-frequency oscillatory activity in the brain areas related to cognitive and emotional modulation of pain. Increased low- and high-frequency activity of the prefrontal cortex may contribute to persistent perception of pain in FM. Therapeutic intervention based on manipulating neural oscillation to restore normal thalamocortical rhythmicity may be beneficial to pain relief in FM.
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http://dx.doi.org/10.3389/fnhum.2016.00111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789463PMC
March 2016

Correction: Dye adsorption mechanisms in TiO2 films, and their effects on the photodynamic and photovoltaic properties in dye-sensitized solar cells.

Phys Chem Chem Phys 2016 Feb;18(7):5659

Konkuk University-Fraunhofer ISE Next Generation Solar Cell Research Center, Konkuk University, Seoul 143-701, Korea. and Department of Advanced Materials Chemistry, Korea University (Sejong Campus), Sejong 30019, Korea. and Center for Photovoltaic Materials, Korea University (Sejong Campus), Sejong 30019, Korea.

Correction for 'Dye adsorption mechanisms in TiO2 films, and their effects on the photodynamic and photovoltaic properties in dye-sensitized solar cells' by Kyung-Jun Hwang et al., Phys. Chem. Chem. Phys., 2015, 17, 21974-21981.
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http://dx.doi.org/10.1039/c6cp90022dDOI Listing
February 2016

Outcomes of acute kidney injury patients with and without cancer.

Ren Fail 2015 Nov 22;37(10):332-7. Epub 2015 Oct 22.

a Department of Internal Medicine , College of Medicine, Kosin University , Seo-gu, Busan , South Korea.

Incidence of AKI in hospitalized patients with cancer is increasing, but there have been few studies on AKI in patients with cancer. We conducted a retrospective cohort study in a South Korean tertiary care hospital. A total of 2211 consecutive patients (without cancer 61.5%; with cancer 38.5%) were included over a 140-month period. Predictors of all-cause death were examined using the Kaplan-Meier method and the Cox proportional hazards model. The main contributing factors of AKI were sepsis (31.1%) and ischemia (52.7%). AKI was multifactorial in 78% of patients with cancer and in 71% of patients without cancer. Hospital mortality rates were higher in patients with cancer (42.8%) than in patients without cancer (22.5%) (p = 0.014). In multivariate analyses, diabetes mellitus (DM) and cancer diagnosis were associated with hospital mortality. Cancer diagnosis was independently associated with mortality [odds ratio = 3.010 (95% confidence interval, 2.340-3.873), p = 0.001]. Kaplan-Meier analysis revealed that subjects with DM and cancer (n = 146) had lower survival rates than subjects with DM and without cancer (n = 687) (log rank test, p = 0.001). The presence of DM and cancer was independently associated with mortality in AKI patients both with and without cancer. Studies are warranted to determine whether proactive measures may limit AKI and improve outcomes.
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http://dx.doi.org/10.3109/0886022X.2015.1074489DOI Listing
November 2015

Disinhibition of the primary somatosensory cortex in patients with fibromyalgia.

Pain 2015 Apr;156(4):666-674

MEG Center, Department of Neurosurgery, Seoul National University Hospital, Seoul, South Korea Neuroscience Research Institute, Seoul National University Medical Research Center, Seoul, South Korea Department of Rehabilitation, Radboud University Medical Center, Nijmegen, the Netherlands Sensory Organ Research Institute, Seoul National University Medical Research Center, Seoul, South Korea Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, South Korea Division of Rheumatology, Department of Internal Medicine, Eulji University School of Medicine, Eulji General Hospital, Seoul, South Korea Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea Division of Rheumatology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, South Korea.

Fibromyalgia (FM) is a chronic widespread pain condition linked to central sensitization. Altered excitability of sensorimotor cortex has been proposed as an underlying pathology of FM. This study aimed to investigate intracortical excitability of the primary somatosensory cortex (S1) and its potential role in clinical pain in patients with FM. Somatosensory evoked magnetic fields were recorded in 17 right-handed females with FM and 21 age-, sex-, and handedness-matched healthy control subjects. Paired-pulse median nerve stimulation was delivered to the left and right wrist. We assessed the peak-to-peak amplitudes of the N20m-P35m and peak amplitude of each N20m and P35m component. Paired-pulse suppression (PPS) of the second response was quantified as the ratio of the amplitudes of the second to the first response. Patients with FM displayed significantly higher PPS ratio for the N20m-P35m in both hemispheres, indicating reduced intracortical inhibition in the S1. Notably, PPS ratio for the P35m was higher in patients with FM than in healthy controls, whereas no differences were apparent in PPS ratio for the N20m in both hemispheres. For both the N20m-P35m and the P35m in the left hemisphere, PPS ratios were positively associated with the sensory pain on the short-form McGill Pain Questionnaire. This study demonstrated that intracortical inhibition in the S1 is compromised bilaterally in patients with FM, and the extent of disinhibition can be closely associated with increased clinical pain. Our results suggest that changes of intracortical inhibition of the S1 may contribute to the pathophysiology of FM pain.
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http://dx.doi.org/10.1097/j.pain.0000000000000096DOI Listing
April 2015

Impaired pre-attentive auditory processing in fibromyalgia: A mismatch negativity (MMN) study.

Clin Neurophysiol 2015 Jul 18;126(7):1310-8. Epub 2014 Oct 18.

Interdisciplinary Program in Neuroscience, Seoul National University College of Natural Sciences, Seoul, Republic of Korea; MEG Center, Department of Neurosurgery, Seoul National University Hospital, Seoul, Republic of Korea; Neuroscience Research Institute, Seoul National University Medical Research Center, Seoul, Republic of Korea; Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Republic of Korea. Electronic address:

Objective: Fibromyalgia (FM) patients often show deficits in cognitive functions such as attention and working memory. We assumed that pre-attentive information processing, a crucial element in human perception and cognition, would be altered in FM patients. Thus, the objective of this study was to determine whether FM patients exhibit alterations in pre-attentive processing as assessed by auditory mismatch negativity (MMN).

Methods: Auditory evoked magnetic fields were recorded in FM patients (n=18) and healthy control subjects (n=21) during a duration-deviant auditory oddball paradigm. The magnetic mismatch negativity (MMNm) was obtained by subtracting responses to standard tones from responses to deviant tones. Pressure pain thresholds over the thenar and trapezius muscles were determined using an algometer.

Results: MMNm peak amplitudes in right hemispheres were attenuated, and the directional asymmetry coefficient of the MMNm amplitude was lower in FM patients, indicating a more leftward asymmetry than in healthy control subjects. Smaller right MMNm amplitude was associated with lower pressure pain thresholds of thenar muscles in FM patients.

Conclusions: Our results suggested that pre-attentive processing of auditory information is impaired in FM patients.

Significance: This study provided neurophysiological evidence of impaired pre-attentive sensory change detection in FM.
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http://dx.doi.org/10.1016/j.clinph.2014.10.012DOI Listing
July 2015

Altered white matter integrity in the corpus callosum in fibromyalgia patients identified by tract-based spatial statistical analysis.

Arthritis Rheumatol 2014 Nov;66(11):3190-9

Seoul National University Hospital and Seoul National University College of Natural Sciences, Seoul, Republic of Korea.

Objective: Although recent imaging studies of fibromyalgia (FM) have converged on a dysfunction of central pain processing as the primary pathophysiologic cause of the disorder, microstructural changes of the white matter (WM) suggestive of abnormalities in the anatomic connectivity of the brain have not been extensively examined. The aim of this study was to investigate WM integrity and its possible relationship to pain symptoms in women with FM.

Methods: Nineteen FM patients and 21 age-, sex-, and education-matched healthy control subjects were included in the study and underwent diffusion-weighted imaging. Group differences in WM integrity, which were assessed via fractional anisotropy (FA), was investigated by applying tract-based spatial statistics.

Results: As compared with the healthy control group, the FM group showed a single cluster with lower FA in the left body of the corpus callosum, which was found to be connected to the bilateral sensorimotor cortices (P < 0.05, corrected for multiple comparisons). Furthermore, FA values in the cluster were negatively associated with sensory pain, as measured by the Short-Form McGill Pain Questionnaire, as well as with the relative magnitude of sensory pain versus affective pain (calculated by dividing the sensory score by the affective score).

Conclusion: Findings of the current study demonstrated that patients with FM had disrupted WM microstructure in the body of the corpus callosum, which was associated with clinical pain intensity. Our results suggest that abnormal interhemispheric transfer might contribute to the heightened pain perception. Our findings further strengthen the hypothesis of centrally augmented pain processing in patients with FM.
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http://dx.doi.org/10.1002/art.38771DOI Listing
November 2014

Posterior cerebellar vermal deficits in bipolar disorder.

J Affect Disord 2013 Sep 12;150(2):499-506. Epub 2013 Jun 12.

Interdisciplinary Program in Neuroscience, Seoul National University, Seoul, South Korea.

Background: Based on growing evidence of the crucial role of the cerebellum in emotional regulation, we sought to identify cerebellar structural deficits in a large sample of patients with bipolar disorder (BD).

Methods: Cerebellar gray matter density was examined in 49 BD patients (24 medication-naive and 25 medication-treated) and 50 carefully matched healthy individuals, using voxel-based morphometry with a high-resolution spatially unbiased atlas template of the human cerebellum. This recently developed methodology is specifically optimized for the assessment of cerebellar structures. We further explored whether antimanic treatment could attenuate cerebellar structural deficits.

Results: BD patients showed a greater reduction in gray matter density of the posterior cerebellar regions, including the bilateral vermi and the right crus relative to healthy individuals (corrected p<.05). A stepwise linear reduction in gray matter density was observed in bilateral vermal regions between healthy individuals, medication-treated, and medication-naive BD patients. Furthermore, positive correlations of longer duration of illness with bilateral vermal gray matter deficits were observed only in medication-naive BD patients, but not in patients with medication history.

Limitations: This study adopted a cross-sectional design. The automatic intensity-normalization method for the measurement of cerebellar gray matter density may have a limitation in providing detailed anatomical information at a cerebellar folia level.

Conclusions: The current findings suggest that BD-related deficits in the posterior cerebellar regions, which appear to progress over the course of illness, could potentially be ameliorated by proper treatment with mood stabilizers.
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http://dx.doi.org/10.1016/j.jad.2013.04.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5510461PMC
September 2013

Prefrontal cortical deficits in type 1 diabetes mellitus: brain correlates of comorbid depression.

Arch Gen Psychiatry 2012 Dec;69(12):1267-76

CONTEXT Neural substrates that may be responsible for the high prevalence of depression in type 1 diabetes mellitus (T1DM) have not yet been elucidated. OBJECTIVE To investigate neuroanatomic correlates of depression in T1DM. DESIGN Case-control study using high-resolution brain magnetic resonance images. SETTINGS Joslin Diabetes Center and McLean Hospital, Massachusetts, and Seoul National University Hospital, South Korea. PARTICIPANTS A total of 125 patients with T1DM (44 subjects with ≥1 previous depressive episodes [T1DM-depression group] and 81 subjects who had never experienced depressive episodes [T1DM-only group]), 23 subjects without T1DM but with 1 or more previous depressive episodes (depression group), and 38 healthy subjects (control group). MAIN OUTCOME MEASURES Spatial distributions of cortical thickness for each diagnostic group were compared with the control group using a surface-based approach. Among patients with T1DM, associations between metabolic control measures and cortical thickness deficits were examined. RESULTS Thickness reduction in the bilateral superior prefrontal cortical regions was observed in the T1DM-depression, T1DM-only, and depression groups relative to the control group at corrected P < .01. Conjunction analyses demonstrated that thickness reductions related to the influence of T1DM and those related to past depressive episode influence were observed primarily in the superior prefrontal cortical region. Long-term glycemic control levels were associated with superior prefrontal cortical deficits in patients with T1DM (β = -0.19, P = .02). CONCLUSIONS This study provides evidence that thickness reduction of prefrontal cortical regions in patients with T1DM, as modified by long-term glycemic control, could contribute to the increased risk for comorbid depression.
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http://dx.doi.org/10.1001/archgenpsychiatry.2012.543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681445PMC
December 2012

The neurobiological role of the dorsolateral prefrontal cortex in recovery from trauma. Longitudinal brain imaging study among survivors of the South Korean subway disaster.

Arch Gen Psychiatry 2011 Jul;68(7):701-13

Department of Psychiatry and Interdisciplinary Program in Neuroscience, Seoul National University College of Medicine and College of Natural Sciences, 28 Yongon-dong, Jongno-gu, 110-744 Seoul, South Korea.

Context: A multiwave longitudinal neuroimaging study in a cohort of direct survivors of a South Korean subway disaster, most of whom recovered from posttraumatic stress disorder 5 years after trauma, provided a unique opportunity to investigate the brain correlates of recovery from a severe psychological trauma.

Objectives: To investigate region-specific brain mobilization during successful recovery from posttraumatic stress disorder by assessing cortical thickness multiple times from early after trauma to recovery, and to examine whether a brain-derived neurotrophic factor gene polymorphism was associated with this brain mobilization.

Design: Five-year follow-up case-control study conducted from 2003-2007.

Setting: Seoul National University and Hospital.

Participants: Thirty psychologically traumatized disaster survivors and 36 age- and sex-matched control group members recruited from the disaster registry and local community, respectively, who contributed 156 high-resolution brain magnetic resonance images during 3 waves of assessments.

Main Outcome Measures: Cerebral cortical thickness measured in high-resolution anatomic magnetic resonance images using a validated cortical thickness analysis tool and its prospective changes from early after trauma to recovery in trauma-exposed individuals and controls.

Results: Trauma-exposed individuals had greater dorsolateral prefrontal cortical (DLPFC) thickness 1.42 years after trauma (right DLPFC, 5.4%; left superior frontal cortex, 5.8%; and left inferior frontal cortex, 5.3% [all clusters, P ≤ .01]) relative to controls. Thicknesses gradually normalized over time during recovery. We found a positive linear trend, with trauma-exposed individuals with a valine/valine genotype having the greatest DLPFC cortical thickness, followed by those with a methionine genotype and controls (P < .001 for trend). Greater DLPFC thickness was associated with greater posttraumatic stress disorder symptom reductions and better recovery.

Conclusion: The DLPFC region might play an important role in psychological recovery from a severely traumatic event in humans.
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http://dx.doi.org/10.1001/archgenpsychiatry.2011.70DOI Listing
July 2011

Laterobasal amygdalar enlargement in 6- to 7-year-old children with autism spectrum disorder.

Arch Gen Psychiatry 2010 Nov;67(11):1187-97

Department of Psychiatry, Seoul National University, Seoul, South Korea.

Context: There is substantial imaging evidence for volumetric abnormalities of the amygdala in younger children with autism spectrum disorder (ASD). The amygdala can be divided into functionally distinct laterobasal, superficial, and centromedial subregions. To date, we are not aware of any in vivo reports specifically assessing subregional amygdalar abnormalities in individuals with ASD.

Objectives: To evaluate alterations in subregional amygdalar morphology in children with ASD compared with typically developing (TD) children and to examine the relationships with ASD symptom severity.

Design: A cross-sectional study encompassing a narrow age range of children with ASD and age-matched TD children that evaluated magnetic resonance imaging-defined subregional morphology of the amygdala using a novel subregional analytic method.

Setting: Participants were recruited and clinically evaluated through the University of Washington Autism Center and imaged at the Diagnostic Imaging Sciences Center at the University of Washington. Imaging data were analyzed through the Brain Imaging Laboratory at the Seoul National University.

Participants: Fifty-one children 6 to 7 years of age (ASD, n = 31 and TD, n = 20) were assessed using magnetic resonance imaging and behavioral measures.

Main Outcome Measures: Volume and subregional measures of the amygdala and measures of social and communication functioning.

Results: The ASD group exhibited larger right and left amygdalae, by 12.7% and 11.0%, respectively, relative to the TD group. Subregional analysis revealed that the ASD group had enlarged laterobasal amygdalar subregions, relative to the TD group, after adjusting for age, sex, and hemispheric cerebral volume (P < .05, false discovery rate corrected and with clustered surface points >15). Exploratory analyses revealed that there were linear trends comparing a strictly defined subgroup of children with autistic disorder, who exhibited the greatest extent of laterobasal enlargement, followed by a subgroup of children with pervasive developmental disorder not otherwise specified and then the group of TD children (P for linear trend <.001). There were linear trends between enlargement of laterobasal subregions and lower levels of social and communication functioning (P < .001, P < .001, and P = .001 for 3 areas in the right laterobasal subregion; P < .001 for 1 area in the left laterobasal subregion).

Conclusion: The current study demonstrates bilateral enlargement of laterobasal subregions of the amygdala in 6- to 7-year-old children with ASD and that subregional alterations are associated with deficits in social and communicative behavior.
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http://dx.doi.org/10.1001/archgenpsychiatry.2010.148DOI Listing
November 2010

Clinical response of quetiapine in rapid cycling manic bipolar patients and lactate level changes in proton magnetic resonance spectroscopy.

Prog Neuropsychopharmacol Biol Psychiatry 2007 Aug 24;31(6):1182-8. Epub 2007 Apr 24.

Department of Psychiatry, Seoul National University College of Medicine, Seoul National University Hospital, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, Republic of Korea.

The aim of the current study was to evaluate the relationship between quetiapine's effect on the improvement of mood symptoms in bipolar patients and brain metabolite level changes as measured by proton magnetic resonance spectroscopy ((1)H-MRS). Rapid cycling bipolar patients in the manic state were recruited and treated with quetiapine for 12 weeks. Clinical assessment was performed using the Young Mania Rating Scale (YMRS), the 17-item Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impression-Severity scale (CGI-S) at baseline and weekly intervals during the 12-week period. In order to evaluate metabolite level changes over time, (1)H-MRS scans were acquired at baseline and week 12. There were significant reductions in YMRS scores (by 43.0%), HDRS scores (by 27.5%) and CGI-S score (by 44.6%) over the 12 week-period. Lactate levels significantly decreased over the 12-week study period (22.4%). This change in lactate levels was more prominent in quetiapine responders than in non-responders. Additionally, there was a positive correlation between changes in lactate levels and those in YMRS scores (r=0.52, p=0.003). Our findings suggest that quetiapine's antimanic and antidepressant efficacy in patients with rapid cycling bipolar disorder may potentially be related to decreased lactate levels in frontal regions of the brain.
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http://dx.doi.org/10.1016/j.pnpbp.2007.04.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731791PMC
August 2007

Decreased GABA levels in anterior cingulate and basal ganglia in medicated subjects with panic disorder: a proton magnetic resonance spectroscopy (1H-MRS) study.

Prog Neuropsychopharmacol Biol Psychiatry 2007 Mar 1;31(2):403-11. Epub 2006 Dec 1.

Department of Psychiatry, Hangang Sacred Heart Hospital, Hallym University Medical Center, Seoul, South Korea.

The purpose of this study was to investigate the brain gamma-aminobutyric acid (GABA) concentration and its relationship with clinical variables in patients with panic disorder (PD). Single voxel proton magnetic resonance spectroscopy ((1)H-MRS) scan was performed on 22 medicated subjects with PD and 25 age and sex-matched healthy comparison subjects. GABA and other metabolite levels were measured in the anterior cingulate cortex (ACC) and basal ganglia. GABA levels were significantly lower in the ACC and basal ganglia of PD patients relative to comparison subjects. Lactate and choline concentrations in the ACC in PD patients were also higher than in the comparison subjects. Our data suggested in part that alterations of the GABA function and the energy metabolism in ACC and basal ganglia may play an important role in the pathophysiology of panic disorder.
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http://dx.doi.org/10.1016/j.pnpbp.2006.10.011DOI Listing
March 2007