Aberrant Resting-state Functional Connectivity in Complex Regional Pain Syndrome: A Network-based Statistics Analysis

Complex regional pain syndrome (CRPS) is a chronic neuropathic pain disorder. Pain catastrophizing, characterized by magnification, rumination, and helplessness, increases perceived pain intensity and mental distress in CRPS patients. As functional connectivity patterns in CRPS remain largely unknown, we aimed to investigate functional connectivity alterations in CRPS patients and their association with pain catastrophizing using a whole-brain analysis approach. Twenty-one patients with CRPS and 49 healthy controls were included in the study for clinical assessment and resting-state functional magnetic resonance imaging. Between-group differences in whole-brain functional connectivity were examined through a Network-based Statistics analysis. Associations between altered functional connectivity and the extent of pain catastrophizing were also assessed in CRPS patients. Relative to healthy controls, CRPS patients showed higher levels of functional connectivity in the bilateral somatosensory subnetworks (components 1~2), but lower functional connectivity within the prefronto-posterior cingulate (component 3), prefrontal (component 4), prefronto-parietal (component 5), and thalamo-anterior cingulate (component 6) subnetworks (p<0.05, family-wise error corrected). Higher levels of functional connectivity in components 1~2 (β=0.45, p=0.04) and lower levels of functional connectivity in components 3~6 (β=-0.49, p=0.047) were significantly correlated with higher levels of pain catastrophizing in CRPS patients. Higher functional connectivity in the somatosensory subnetworks implicating exaggerated pain perception and lower functional connectivity in the prefronto-parieto-cingulo-thalamic subnetworks indicating impaired cognitive-affective pain processing may underlie pain catastrophizing in CRPS.

The Effect of Hormonal Changes During the Menstrual Cycle on the Brain: Focusing on Structural and Functional Neuroimaging Studies / 생물치료정신의학

It is well known that sex hormones are potential modulators of brain functions and women experience dynamic hormonal changes during the menstrual cycle. Previous animal studies have reported that the variations in sex hormones over the menstrual cycle may affect cognitive function, emotion, and behavior by altering structures and functional connectivity of the brain. Considering the prevalence of certain neuropsychiatric disorders such as mood and anxiety disorders is relatively high in women, as compared with men, fluctuations of sex hormones over the menstrual cycle may influence the human brain and potentially underlie sex differences in clinical features of several neuropsychiatric disorders. There is, however, little evidence regarding the exact mechanisms underlying the effects of sex hormones on the human brain. In this review, we focused on studies to examine structural and functional changes over the menstrual cycles in women and aimed to provide an up-to-date overview of neuroimaging studies regarding the effects of sex hormonal fluctuations on the brain and behaviors.

The Effect of Hormonal Changes During the Menstrual Cycle on the Brain: Focusing on Structural and Functional Neuroimaging Studies / 생물치료정신의학

It is well known that sex hormones are potential modulators of brain functions and women experience dynamic hormonal changes during the menstrual cycle. Previous animal studies have reported that the variations in sex hormones over the menstrual cycle may affect cognitive function, emotion, and behavior by altering structures and functional connectivity of the brain. Considering the prevalence of certain neuropsychiatric disorders such as mood and anxiety disorders is relatively high in women, as compared with men, fluctuations of sex hormones over the menstrual cycle may influence the human brain and potentially underlie sex differences in clinical features of several neuropsychiatric disorders. There is, however, little evidence regarding the exact mechanisms underlying the effects of sex hormones on the human brain. In this review, we focused on studies to examine structural and functional changes over the menstrual cycles in women and aimed to provide an up-to-date overview of neuroimaging studies regarding the effects of sex hormonal fluctuations on the brain and behaviors.

A Review on Neuronavigated Repetitive Transcranial Magnetic Stimulation and Its Antidepressant Effect / 생물치료정신의학

Repetitive transcranial magnetic stimulation (rTMS) is widely recognized as an effective and noninvasive neuromodulation for treating depression, and has been applied in a wide range of clinical settings. However, previous studies often reported inconsistent antidepressant effects that may be due to differences in the rTMS protocols such as coil placement. The typical simulation site for rTMS depression protocol is the left dorsolateral prefrontal cortex (DLPFC). Targeting the exact site of the left DLPFC while considering individual brain structure has been challenging due to the non-invasive nature of rTMS. Several researchers have applied various targeting methods to overcome the abovementioned issue. Most of the previous studies have applied the “5-cm rule” or the “international 10-20 system,” which is easily applicable. Recently, researchers started to apply a neuronavigation system that targets the stimulation site based on neuroimaging of each individual. Pros and cons of targeting methods have been discussed in terms of validity and reliability of targeting stimulation sites, differences in treatment responses, as well as considerations of individual characteristics. Therefore, the current review focuses on the targeting methods of stimulation site and the treatment effects of depression in previous studies. For discussion, we divided neuronavigation methods into using fixed coordinates and using individualized targets. Furthermore, the limitations of each targeting method are discussed that may potentially contribute to the development of the optimal rTMS protocol for depression treatment.

A Group of Descending Glutamatergic Neurons Activated by Stress in Corticolimbic Regions Project to the Nucleus Accumbens

The nucleus accumbens (NAc) is the major component of the ventral striatum that regulates stress-induced depression. The NAc receives dopaminergic inputs from the ventral tegmental area (VTA), and the role of VTA-NAc neurons in stress response has been recently characterized. The NAc also receives glutamatergic inputs from various forebrain structures including the prelimbic cortex (PL), basolateral amygdala (BLA), and ventral hippocampus (vHIP), whereas the role of those glutamatergic afferents in stress response remains underscored. In the present study, we investigated the extent to which descending glutamatergic neurons activated by stress in the PL, BLA, and vHIP project to the NAc. To specifically label the input neurons into the NAc, fluorescent-tagged cholera toxin subunit B (CTB), which can be used as a retrograde neuronal tracer, was injected into the NAc. After two weeks, the mice were placed under restraint for 1 h. Subsequent histological analyses indicated that CTB-positive cells were detected in 170~680 cells/mm² in the PL, BLA, and vHIP, and those CTB-positive cells were mostly glutamatergic. In the PL, BLA, and vHIP regions analyzed, stress-induced c-Fos expression was found in 20~100 cells/mm². Among the CTB-positive cells, 2.6% in the PL, 4.2% in the BLA, and 1.1% in the vHIP were co-labeled by c-Fos, whereas among c-Fos-positive cells, 7.7% in the PL, 19.8% in the BLA, and 8.5% in the vHIP were co-labeled with CTB. These results suggest that the NAc receives a significant but differing proportion of glutamatergic inputs from the PL, BLA, and vHIP in stress response.

Multi-voxel magnetic resonance spectroscopy of cerebral metabolites in healthy dogs at 1.5 Tesla

This study was conducted to measure the difference in levels of cerebral metabolites in the right and left hemispheres, gray (GM) and white matter (WM), imaging planes, and anatomical regions of healthy dogs to establish normal variations. Eight male Beagle dogs (1 to 4 years of age; mean age, 2 years) with no evidence of neurologic disease were studied. Using the multi-voxel technique on a 1.5 Tesla magnetic resonance imaging scanner, metabolite values (N-acetyl aspartate [NAA], choline [Cho], creatine [Cr]) were obtained from the frontoparietal WM, parietal GM, temporal GM, occipital GM, thalamus, cerebellum, mid-brain, and pons. There was no significant difference in levels of these metabolites between the right and left in any locations or between the GM and WM in the cerebral hemispheres. However, there were significant differences in metabolite ratios within imaging planes. The NAA/Cr was lower in the cerebellum than other regions and the thalamus had a higher Cho/Cr and lower NAA/Cho ratio than in other regions. The spectral and metabolic values will provide a useful internal reference for clinical practice and research involving multi-voxel magnetic resonance spectroscopy. Measurement of metabolite values in the transverse plane is recommended for comparing levels of regional metabolites.

Analysis of Various Artifacts Produced by Spectral-Domain Optical Coherence Tomography Based on Macular Pathologies

PURPOSE: To report the frequency, severity and various types of artifacts associated with spectral-domain optical coherence tomography (SD-OCT) based on macular pathologies. METHODS: Data was collected retrospectively from 116 eyes of 116 subjects. SD-OCT (3D-1000, Topcon Corp., Japan) imaging was performed in 40 healthy eyes, 45 eyes with intraretinal pathology (IRP) and 31 eyes with subretinal pathology (SRP). The scan protocol was 12x6 mm radial scan. The frequency and types of artifacts were investigated in each scan and were analyzed based on macular disease. Additionally, the effect of artifacts on the measurement of macular thickness was studied. RESULTS: Errors occurred in 77 eyes (66.38%). Inner retinal boundary misidentification (IRBM) was the most common error (25.86%), with the frequencies of other types of artifacts being 10.34% for off-center fixation, 15.52% for degraded image and 8.6% for outer retinal boundary misidentification (ORBM). The overall error rate of SD-OCT in the retinal pathology group was much higher than that in the normal group. Macular thickness was underestimated in the IRP group because the outer retinal boundary of the IRP group tended to be misidentified toward the inner retina (p<0.01). CONCLUSIONS: SD-OCT can frequently cause various types of artifacts in patients with macular disease. When interpreting OCT images, the artifacts of SD-OCT should be considered in order to obtain accurate macular thickness and to prevent erroneous clinical decisions.

A Case of Neurosyphilis with Acute Optic Neuritis and Trochlear Nerve Palsy in Human Immunodeficiency Virus Infected Male

With the increase in human immunodeficiency virus (HIV) infection, the incidence of syphilis also increased worldwide presenting with diverse clinical manifestations. We experienced a case of symptomatic early neurosyphilis manifesting as optic neuritis and trochlear nerve palsy with typical skin lesions of secondary syphilis in an HIV-Infected patient. Intravenous penicillin and oral steroid were administered for 2 weeks. Skin lesions improved after a week, and ocular lesions resolved completely after eight weeks of treatment.

Comparison of Macular Thickness Measurements Between Fourier-Domain and Time-Domain Optical Coherence Tomography in Normal Eyes and Eyes With Macular Diseases

PURPOSE: To define and measure macular thickness and volume using Fourier domain OCT (FD OCT) and compare the values with Stratus OCT in normal eyes and eyes with macular disease. METHODS: On the same day, macular thicknesses of the ETDRS 9 subfield and total macular volumes were measured in 35 eyes of 23 normal subjects and 19 diseased eyes of 24 patients with FD OCT and Stratus OCT. The macular cube scan protocol for FD OCT and the fast macular thickness map protocol for Stratus OCT were used to measure macular thicknesses. RESULTS: Foveal thickness of the central subfield in FD OCT (251.49+/-79.45 micrometer) was thicker than the value of Stratus OCT (210.26+/-60.57 micrometer) (p<0.001) in all eyes. Total macular volume was 7.72+/-1.06 mm3 and 7.04+/-0.96 mm3 for FD OCT and Stratus OCT, respectively (p<0.001). Retina thickness of the ETDRS 9 subfields in FD OCT was thicker than the value obtained using Stratus OCT. In addition, foveal thickness differences were statistically significant in both the normal and diseased eye groups. CONCLUSIONS: Macular thickness and total macular volume as measured by the FD OCT were larger than the values obtained using the Stratus OCT in both the normal and the diseased eye groups. The measuring algorithm of FD OCT defines the top of RPE as the outer retinal boundary, but Stratus OCT defines the outer retinal boundary as the IS/OS junction of the photoreceptor. Therefore, macular thicknesses of FD OCT are thicker than those of Stratus OCT. This difference should be considered when comparing the results of FD OCT with those of Stratus OCT.

The Effect of Intravitreal Bevacizumab Injection in Eales' Disease

PURPOSE: To report on 2 cases of Eales' disease that were successfully regressed with laser photocoagulation and intravitreal bevacizumab (Avastin; Genetech, Inc, San Francisco, California, USA) injection. CASE SUMMARY: Two male patients (30 years and, 40 years of age,) with a history of recurrent vitreous hemorrhage were diagnosed with Eales' disease. The 2 patients had peripheral retina neovascularization and active phlebitis in fundus fluorescein angiography. No other findings were observed in their eyes in the general examination. Scatter laser photocoagulation and intravitreal bevacizumab injection were performed. After 1 month follow-up, neovascularization completely regressed. There was no complication or recurrent vitreous hemorrhage at the 1 year follow up. CONCLUSIONS: Intravitreal bevacizumab injection, as combination treatment of laser photocoagulation, may be helpful in the regression of neovascularization due to Eales' disease.

A Study of the Vascular Network of the Iris Using Flat Preparation

PURPOSE: This study was performed to examine the vascular network of the human iris using flat preparation. METHODS: The ciliary body-iris structures were separated from human eyeballs, and a portion of the irises were treated with trypsin to remove the pigment granules. These iris tissues were unfolded and placed onto glass slides using flat preparation, and the vascular network of each iris was examined by fluorescein microscopy. The ciliary body-iris structures separated from the remaining eyes were stained with hematoxylin-eosin without trypsin treatment and were examined by light microscopy. RESULTS: The long posterior ciliary artery formed several branches before entering the iris root, and such branches formed the major arterial circle of the iris with diverse diameters in the vicinity of the iris root and the ciliary process. In the pupillary margin, the iris vasculature network formed a cone shape and then formed an arcade by connecting to adjacent vasculatures. In the vicinity of the collarette, the iris vasculature network formed the minor arterial circle of the iris with diverse diameters perpendicular to the arcade of the iris network located in the pupillary margin. In the pupillary margin, the capillaries were somewhat thick and connected to the irregular traveling iris vein. CONCLUSIONS: The above findings explain the human iris vascular network and provide a theoretical basis for the sectoral filling of the iris vasculature seen in fluorescein iris angiography.

The Clear Oil-drop Residue After Intravitreal Injection: Comparison between Different Brands of Triamcinolone Acetonide

PURPOSE: To investigate the characteristics of the clear oil-drop residue observed in the vitreous cavity after intravitreal injection of different brands of triamcinolone acetonide (TA), and to compare this ingredient's effects in those products. METHODS: Intravitreal injections of four different brands of triamcinolone acetonide (4 mg/0.1 mL), which are commercially available in Korea, were given to 40 eyes for the treatment of macular edema due to a variety of causes from October 2005 through February 2006. Regular slit-lamp biomicroscopy of fundus had been performed periodically with digital image acquisition equipment after injection of TA for at least two months. We analyzed the characteristics of this residue and compared the number and size of this residue in each product. RESULTS: Four TA products commercially available in Korea were used, with vehicles composed of preservatives and suspending agents. There were differences between products in respect to ingredients and content, as well as the characteristics of the intravitreal clear oil droplet-like residue. CONCLUSIONS: Each TA product has a variable frequency and variable amounts of clear oil droplet-like residue, which seems to be a component of the vehicle. This variation could generate differences in efficacy, side effects, and retaining duration. It should be verified whether commercial TA products are consistently safe and effective.

Combined Central Retinal Vein and Artery Occlusion After Retrobulbar Anesthesia: A Case Report

PURPOSE: To report central retinal vein and artery occlusion after retrobulbar anesthesia for a cataract operation. CASE SUMMARY: A 65-year-old woman was transferred to our facility 4 days after she had undergone cataract extraction with IOL implantation. She could count fingers and had a relative afferent papillary defect in her left eye. As seen upon fundus examination, dot-shaped, circular-shaped irregular, and partially linear-shaped retinal hemorrhages were evident. Fluorescein angiography revealed that branch arteries around the nasal and temporal areas were not filled, and that the filling of veins was delayed. After two weeks, the patient was only able to recognize hand motion, and her intraocular pressure was 10 mmHg. According to a fundus examination, the size and quantity of retinal hemorrhages increased, and a pale, macular edema was observed. Following fluorescein angiography, the filling defect of branch vessels on the nasal and temporal areas was still evident, and the blocked fluorescence of capillaries on the fundus was prominent. After two months, she could still only recognize hand motion, and her intraocular pressure had increased to 35 mmHg; we therefore diagnosed a neovascular glaucoma. CONCLUSIONS: A patient experienced a serious central retinal vessel occlusion after retrobulbar anesthesia for cataract extraction. Retrobulbar injections should therefore be administered with great caution to prevent this outcome.

Suprachoroidal Hemorrhage During Pars Plana Vitrectomy Associated with Valsalva Maneuver

PURPOSE: To report a suprachoroidal hemorrhage by Valsalva maneuver during vitrectomy under general anesthesia. CASE SUMMARY: A healthy 26-year-old man had vitrectomy under general anesthesia due to rhegmatogenous retinal detachment in his right eye. During scleral indentation and endolaser photocoagulation, he took a sudden and severe bucking reflex because the effect of general anesthesia was insufficient. After the bucking reflex, suprachoroidal hemorrhage occurred in his right eye. Immediate IOP elevation and hyperfluorocarbon tamponade was performed to remove the suprachoroidal hemorrhage and reattach the retina and choroid. The patient's corrected visual acuity was 20/50 and slender crescent shaped choroidal rupture remained around the temporal area of the macula, unlike traumatic choroidal rupture. Following fluorescein angiography, staining was evident at the choroidal rupture site; no fluorescein leakage was evident. CONCLUSIONS: We report a case of acute suprachoroidal hemorrhage which we investigated by fundus examination and fluorescein angiography.