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Background: Major depressive disorder (MDD) is a mood disorder associated with disruptions in emotional control. Previous studies have investigated abnormal regional activity and connectivity within the fronto-limbic circuit. However, condition-specific connectivity changes and their association with the pathophysiology of MDD remain unexplored. This study investigated effective connectivity in the fronto-limbic circuit induced by negative emotional processing from patients with MDD. Methods: Thirty-four unmedicated female patients with MDD and 28 healthy participants underwent event-related functional magnetic resonance imaging at 7T while viewing emotionally negative and neutral images. Brain regions whose dynamics are driven by experimental conditions were identified by using statistical parametric mapping. Effective connectivity among regions of interest was then estimated by using dynamic causal modeling. Results: Patients with MDD had lower activation of the orbitofrontal cortex (OFC) and higher activation of the parahippocampal gyrus (PHG) than healthy controls (HC). In association with these regional changes, we found that patients with MDD did not have significant modulatory connections from the primary visual cortex (V1) to OFC, whereas those connections of HC were significantly positively modulated during negative emotional processing. Regarding the PHG activity, patients with MDD had greater modulatory connection from the V1, but reduced negative modulatory connection from the OFC, compared with healthy participants. Conclusions: These results imply that disrupted effective connectivity among regions of the OFC, PHG, and V1 may be closely associated with the impaired regulation of negative emotional processing in the female patients with MDD.

Emotions are experienced differently by individuals, and thus, it is important to account for individuals' experienced emotions to understand their physiological responses to emotional stimuli. The present study investigated the physiological responses to a fear-inducing stimulus and examined whether these responses can predict experienced fear. A total of 230 participants were presented with neutral and fear-inducing film clips, after which they self-rated their experienced emotions. Physiological measures (skin conductance level and response: SCL, SCR, heart rate: HR, pulse transit time: PTT, fingertip temperature: FT, and respiratory rate: RR) were recorded during the stimuli presentation. We examined the correlations between the physiological measures and the participants' experienced emotional intensity, and performed a multiple linear regression to predict fear intensity based on the physiological responses. Of the participants, 92.5% experienced the fear emotion, and the average intensity was 5.95 on a 7-point Likert scale. Compared to the neutral condition, the SCL, SCR, HR, and RR increased significantly during the fear-inducing stimulus presentation whereas FT and PTT decreased significantly. Fear intensity correlated positively with SCR and HR and negatively with SCL, FT, PTT, and RR. The multiple linear regression demonstrated that fear intensity was predicted by a combination of SCL, SCR, HR, FT, and RR. Our findings indicate that the physiological responses to experiencing fear are associated with cholinergic, sympathetic, and α-adrenergic vascular activation as well as myocardial β-sympathetic excitation, and support the use of multimodal physiological signals for quantifying emotions.

Neuroimaging studies on the characteristics of hypersexual disorder have been accumulating, yet alternations in brain structures and functional connectivity in individuals with problematic hypersexual behavior (PHB) has only recently been studied. This study aimed to investigate gray matter deficits and resting-state abnormalities in individuals with PHB using voxel-based morphometry and resting-state connectivity analysis. Seventeen individuals with PHB and 19 age-matched healthy controls participated in this study. Gray matter volume of the brain and resting-state connectivity were measured using 3T magnetic resonance imaging. Compared to healthy subjects, individuals with PHB had significant reductions in gray matter volume in the left superior temporal gyrus (STG) and right middle temporal gyrus. Individuals with PHB also exhibited a decrease in resting-state functional connectivity between the left STG and left precuneus and between the left STG and right caudate. The gray matter volume of the left STG and its resting-state functional connectivity with the right caudate both showed significant negative correlations with the severity of PHB. The findings suggest that structural deficits and resting-state functional impairments in the left STG might be linked to PHB and provide new insights into the underlying neural mechanisms of PHB.

This study was conducted to whether the administration of mexiletine, a Na+ channel blocker, impacts the recovery from demyelination. Under anesthesia, 0.1% ethidium bromide was injected into the dorsal funiculus (T3), followed by a mexiletine or saline treatment. Motor evoked potential (MEP) recordings and luxol fast blue stainings were performed at one, seven, 14, and 21 days post-operatively. Conduction was delayed during demyelination, but the mexiletine-injected group demonstrated shortened latencies and reductions in the demyelination area when compared to the control. These results suggest that systemic mexiletine plays a positive role in protecting neural tissues from demyelination.

Recent advances in optical imaging techniques have made it possible to monitor neural activity and provided powerful tools to reveal the spatiotemporal patterns of neural activity. We used optical imaging to determine whether nerve injury affects excitability of the sensory cortex. Male Sprague-Dawley rats were subjected to neuropathic surgery consisting of a tight ligation and transection of the left tibial and sural nerves while under pentobarbital anesthesia. The rats were reanesthetized with urethane two weeks post-operatively, and the exposed cortex surfaces were stained with a voltage-sensitive dye (di-2-ANEPEQ). After electrical stimulation of the receptive field, optical signals from the cerebral cortex were recorded using an optical imaging system. Increased optical intensity and an enlarged area of activation were observed in the cerebral cortex of neuropathic rats during electrical stimulation compared to normal or sham-operated rats. Higher electric stimulation resulted in more intensity and a larger area of activation in neuropathic rats. These results suggest that cortical excitability, resulting from peripheral stimulation, may be affected by nerve injury, which indicates a degree of neural plasticity.

The purpose of this study was to measure the average corpus callosum volume of normal Koreans (aged in their 20s or 40s) and to analyze the effects of gender, age, and body parameters, such as height and weight on corpus callosum size. Magnetic resonance brain images were recorded for 68 people in their 20s (29 men, 39 women) and 91 in their 40s (36 men, 55 women). Intracranial volume was calculated using cerebral size and corpus callosum volume was normalized by covariance method. To investigate the effect of gender and age on corpus callosum volume, two-way analysis of variance, which used gender (two levels) and age (two levels) as independent variables, was employed. Multiple regression analysis was carried out to investigate the effect of body parameters, such as height and weight, according to the age and gender on the changes in corpus callosum volume. The average corpus callosum volume of Korean men (11.09 cm(3)) was larger than that of Korean women (9.61 cm(3)). There was no significant difference in corpus callosum volume between 20s (10.43 cm(3)) and 40s (10.12 cm(3)). There was a positive relationship between body weight and corpus callosum volume for 20s, but not for 40s.

As imaging technology develops, magnetic resonance imaging (MRI) has furthered our understanding of brain function by clarifying the anatomical structure and generating functional imaging data related to information processing in pain conditions. Recent studies have reported that manganese (Mn(2+))-enhanced MRI (MEMRI) provides valuable information about the functions of the central nervous system. The aim of this study was to identify specific brain regions activated during noxious electric stimulation using high-resolution MEMRI. Male Sprague Dawley rats were divided into three groups: naive, sham electrical stimulation, and noxious electric stimulation. Under urethane with α-chloralose mixture anesthesia, a catheter was placed in the external carotid artery to administrate 20% mannitol and manganese chloride (25mM MnCl2). Noxious electric stimulation (2Hz, 10V) was applied to the hind paw with a needle electrode. Stimulation-induced neuronal activation was detected using 4.7-T MRI. In response to noxious electrical stimulation, remarkable Mn(2+)-enhanced signals were observed in the agranular insular cortex, auditory cortex, primary somatosensory cortex of the hind limb, and granular and dysgranular insular cortex, which correspond to sensory tactile electric stimulus to the hindpaws. These results indicate that the combination of MEMRI with activity-induced Mn(2+)-dependent contrast can delineate functional areas in the rat brain.

Functional deficits after spinal cord injury have originated not only from the direct physical damage itself, but from the secondary biochemical and pathological changes. Apoptotic cell death has been seen around the periphery of an injured site and has been known to ultimately progress to necrosis and infarction. We have initiated the present study focusing on the role of apoptosis in the secondary injury of the brain after acute spinal cord injury (SCI), and conducted a series of experiments, the study examining the morphological changes in the brain following the spinal injury. Under pentobarbital anesthesia, male Sprague–Dawley rats were subjected to SCI model. Rats were laminectomized and SCI was induced using NYU spinal impactor at T9 segment. The behavioral test was performed. Electrophysiologically, motor evoked potentials (MEPs) were recorded. The animals were subjected to morphological study at 12, 24, 48, 72 h, and 1 week, postoperatively. Locomotor deficits were observed after SCI, and changes in the amplitudes and latencies of the MEPs were observed. The morphological changes were evidenced by terminal TUNEL staining and Calbindin-D 28K immunohistochemistry. The TUNEL-positive cells were located at the brain motor cortex after SCI. TUNEL-positive cells were seldom found 4 h after injury. In addition, Calbindin-D 28K immunoreactive neurons were observed in the motor cortex after injury. These results suggest that apoptosis may play an important role in the pathophysiology of the brain motor cortex following acute spinal cord injury and functions that were deteriorated after SCI may be related to these electrophysiological and morphological changes.

It has been well documented that there is opioid resistance in neuropathic pain. This indicates that the endogenous opioid system may not be involved effectively in modulating neuropathic pain. The present study sought to determine if activation of the descending pain inhibition system might produce analgesia in the animal neuropathic model we developed. Under ketamine anesthesia, male Sprague-Dawley rats were chronically implanted with stimulating electrodes in the ventral periaqueductal gray matter (PAG) and both the tibial and sural nerves of the sciatic nerve branches were severed. Pain sensitivity was measured with a von Frey filament and acetone applied to the sensitive area for 1 week postoperatively. Rats with neuropathic pain syndrome after transection of the tibial and sural nerves were tested as to the analgesic effects of ventral PAG stimulation for an additional two weeks. Electrical stimulation of the ventral PAG turned out to be highly effective in alleviating neuropathic pain. Mechanical allodynia and cold allodynia were reduced by PAG stimulation. Naloxone reversed the antiallodynic effects of ventral PAG stimulation. These results suggest that activation of the descending pain inhibition system including the ventral PAG reduces neuropathic pain syndrome and that opiates are involved in this system.

We have previously demonstrated that electrical stimulation of the ventral periaqueductal gray matter (PAG) produced analgesia in neuropathic pain in rats. Opioids were also shown to be involved in analgesic effects. This study sought to determine whether opiates microinjected into the ventral PAG produce analgesia. Male Sprague-Dawley rats were chronically implanted with a guide cannula in the PAG under pentobarbital anesthesia and both the tibial and sural nerves were completely cut. Pain sensitivity was postoperatively measured with a von Frey filament and acetone applied to the sensitive area for I week. Opioids such as [D-Ala 2 ,N-MePhe 4 ,Gly(ol) 5 ]-enkephalin (DAMGO) and [D-Pen 2 ,D-Pen 5 ].-enkephalin (DPDPE) were injected into the PAG. DAMGO, a μ-opioid agonist, and DPDPE, a δ-opioid agonist, were highly effective in reducing neuropathic pain. These effects were reversed by naloxone. These results suggest that the neurons in the ventral PAG are activated by opioids to produce analgesia and that specific opioid receptors are involved in the descending pain inhibition system from the PAG.

The average cerebellar volume of Korean men (135.19 cm3) is larger than that of Korean women (123.06 cm3), and that of subjects in their twenties (134.28 cm3) is larger than that of subjects in their forties (121.83 cm3). Atrophy of the cerebellum is more markedly observed in men than in women. There is a relation between body weight and cerebellar volume for men, but not for women.

FK506 has been originally classified as an immunosuppressant and is known to exhibit neurotrophic actions in vitro and protective effects on some neurological conditions. We investigated the neuroprotective effects of FK506 on kainic acid (KA)-induced neuronal death in organotypic hippocampal slice cultures (OHSCs). After an 18 h KA (5 microM) treatment, significantly neuronal death was detected in the CA3 region using propidium iodide staining. However, neuronal death was significantly prevented at 24 and 48 h after treatment with 0.1 microM FK506. Using cresyl violet staining, we also observed that an increased number of CA3 neurons survived in the 0.1 microM FK506 group compared to the KA only group. Based on the results of the Western blot analysis, the expressions of 5-lipoxygenase and caspase-3 were reduced 24h after 0.1 microM FK506 treatment. The levels of superoxide dismutase (SOD) and phospho-Akt expression were increased by treatment with 0.1 microM FK506. These results suggest that FK506 may have a positive role in protecting neurons against cell death in the KA injury model of OHSCs.

This study aimed to investigate the hypothesis that a transient increase in oxygen level administered to subjects increases the BOLD effect in brain regions associated with verbal cognitive functioning and enhances performance accuracy. A verbal task was presented while brain images were scanned by a 3T fMRI system. The accuracy rate on the verbal task was enhanced during 30% oxygen administration compared to 21% oxygen administration. The neural activations were observed at the occipital, parietal, temporal and frontal lobes, during both 21% and 30% oxygen administration. Increased brain activations were observed in the right middle frontal gyrus, right inferior frontal gyrus, right superior frontal gyrus, cingulate gyrus, left middle temporal gyrus, and left fusiform gyrus with 30% oxygen administration. These results suggest that a higher concentration of breathed oxygen increases saturation of blood oxygen in the brain, and facilitates verbal cognitive performance.

Single unit responses of the primary somatosensory (SI) cortical neurons to the stimulation of the forepaw single digit were monitored in anesthetized rats before and after subcutaneous injection of lidocaine to an ipsilateral homologous receptive field (IHRF). Quantitative determination of the temporal changes of afferent sensory transmission was done by analyzing poststimulus time histograms of unit responses. Temporary deafferentation to the IHRF induced immediate, but reversible suppression of afferent sensory transmission in the SI cortex and this suppression lasts up to 35 min post-deafferentation period (during 10-15 min, -21.81 +/- 5.9%, P < 0.01). This result suggests that temporary absence of afferent inflow from the digit to the SI cortex may exert interhemispheric modulation of afferent sensory transmission in the opposite somatosensory cortex of anesthetized rats.

Electrical stimulation of the commissural region of the nucleus tractus solitarius (NTS) inhibits the tail-flick reflex evoked by noxious heat. This antinociception can be measured in the awake or pentobarbital anesthetized rat at current intensities that do not induce overt behavioral side effects. Glutamate microinjections into the NTS, but not immediately surrounding the NTS, also inhibit the tail-flick reflex, demonstrating that activation of NTS cell bodies, and not fibers of passage, mediates antinociception from this region. In contrast, morphine microinjections into the NTS have no effect on the tail-flick reflex in anesthetized rats. These findings provide further evidence that the NTS is involved in the modulation of nociception.

Stimulation of the periaqueductal gray matter (PAG) is known to modulate nociception at the spinal level. Several studies have suggested that nociception may also be modulated via ascending projections from the PAG. To study this hypothesis, the descending pathway was selectively disrupted immediately caudal to the PAG in 28 rats. Twenty-eight additional rats served as non-lesioned controls. All animals were chronically implanted with a stimulating electrode in the PAG, and antinociception was assessed using tests involving spinally and supraspinally mediated responses (tail-flick and hot-plate tests, respectively). Significantly fewer lesioned than non-lesioned rats showed stimulation-produced analgesia (SPA) in the tail-flick test (4 of 28 vs 14 of 28, respectively). In contrast, no significant difference in the incidence of SPA occurred between lesioned and non-lesioned rats in the hot-plate test. These findings demonstrate that nociception can be modulated at the supraspinal, as well as spinal, level.