People with high empathy show increased cortical activity around the left medial parieto-occipital sulcus after watching social interaction of on-screen characters.

People with high empathy interpret others' mental states in daily social interactions. To investigate their characteristics of social cognitive processing, we compared neuromagnetic activities between 20 males with high empathy and 23 males with low empathy while watching social interactions between two characters. Twenty stories of four-panel comic strips were presented; the first three panels described social interactions, and the last panel described empathic/nonempathic behaviors. People with high empathy exhibited increased cortical activity in the right occipital region, medial part of the bilateral superior frontal gyri, and right posterior insula while watching social interaction scenes, which suggests that they paid attention to others' faces and bodies, and inferred others' mental states. They also exhibited increased cortical activity in the left superior frontal gyrus while watching empathic behaviors. Moreover, they exhibited increased cortical activity in the region around the left medial parieto-occipital sulcus, which is related to self-projection, while passively watching both empathic and nonempathic endings. Taken together, these results suggest that people with high empathy pay attention to others and actively infer others' mental states while watching social interactions and that they reconstruct others' mental states and intentions through self-projection after watching a sequence of others' behaviors.

Bisphenol A and rotenone induce S-nitrosylation of protein disulfide isomerase (PDI) and inhibit neurite outgrowth of primary cultured cells of the rat hippocampus and PC12 cells.

Bisphenol A (BPA) interferes the function and development of the central nervous system (CNS), resulting in behavioral abnormalities and memory loss. S-nitrosylation of protein disulfide isomerase (PDI) is increased in brains with sporadic Alzheimer's disease and Parkinson's disease. The aim of the present study was to clarify the role of nitric oxide (NO) in BPA-induced neurotoxicity. Since rotenone induces NO-mediated neurodegeneration through S-nitrosylation of PDI, it was used as a positive control. First, rats were treated with BPA and rotenone, and S-nitrosylation of PDI was detected in rat brain microsomes. BPA and rotenone decreased RNase oxidation activity of PDI concomitant with S-nitrosylation of PDI. Next, to clarify S-nitrosylation of PDI by BPA and rotenone in rat brains, we treated the rat pheochromocytoma cell line PC12 and primary cultured neuron cells from the rat hippocampus with BPA (5 and 10 µM) and rotenone (100 or 200 nM). BPA induced S-nitrosylation of PDI, while NG-monomethyl-L-arginine (L-NMMA), a NOS inhibitor, exerted the opposite effects. Finally, to evaluate the toxicity of BPA in the CNS, we investigated its effects on neurite outgrowth of PC12 and primary cultured neuron cells. BPA inhibited neurite outgrowth of these cells, while L-NMMA reversed this inhibition. The involvement of PDI activity in neurite outgrowth was also examined, and bacitracin, a PDI inhibitor, is shown to decrease neurite outgrowth. Furthermore, the overexpression of PDI, but not a catalytically inactive PDI mutant, enhanced neurite outgrowth. These results suggested that S-nitrosylation of PDI induced by excessive NO caused BPA-induced neurotoxicity.

Brain activity associated with the rubber foot illusion.

The internal representation of the body is constantly updated by sensory information based on interactions with the environment. The internal representation of the hand can be experimentally manipulated with the rubber hand illusion (RHI) paradigm. Brain activity during the RHI provides insight into the neural mechanisms underpinning the reconstruction of the internal representation of the hand. Recently, the RHI paradigm has been employed for the lower limb, revealing that the illusion is also induced in the lower limb (rubber foot illusion; RFI). However, the neural correlates of the RFI remain unknown. We used functional magnetic resonance imaging (fMRI) to examine brain activity during the RFI. Forty-four healthy volunteers participated in the fMRI experiment. Significant increases in activation were observed in the bilateral medial and middle frontal gyri, left supplemental motor area, bilateral inferior parietal lobuli, precunei, calcarine cortices, and cerebellar hemispheres; and in the vermis and bilateral thalami during the right RFI. During the left RFI, significant increases in activation were observed in the bilateral medial, middle, and superior frontal gyri; left inferior frontal gyrus and supplemental motor area, bilateral inferior parietal lobuli and middle temporal gyri, and in the left cerebellar hemisphere, vermis, and bilateral thalami. Conjunction analysis revealed that the prefrontal cortex including the bilateral medial and middle frontal gyri, parietal cortex including the bilateral inferior parietal lobuli, and cerebellum including the bilateral cerebellar hemispheres and vermis were conjointly activated during the right and left RFIs. The distribution of co-activated brain areas during the RFI was similar to the previously reported distribution of brain areas activated during the RHI. Co-activation of these brain areas may be associated with the reconstruction of the internal representation of the body. The fact that these areas are activated both in the RFI and RHI will have implications for the treatment of patients with disturbed internal bodily representation.

A Descending Circuit Derived From the Superior Colliculus Modulates Vibrissal Movements.

The superior colliculus (SC) is an essential structure for the control of eye movements. In rodents, the SC is also considered to play an important role in whisking behavior, in which animals actively move their vibrissae (mechanosensors) to gather tactile information about the space around them during exploration. We investigated how the SC contributes to vibrissal movement control. We found that when the SC was unilaterally lesioned, the resting position of the vibrissae shifted backward on the side contralateral to the lesion. The unilateral SC lesion also induced an increase in the whisking amplitude on the contralateral side. To explore the anatomical basis for SC involvement in vibrissal movement control, we then quantitatively evaluated axonal projections from the SC to the brainstem using neuronal labeling with a virus vector. Neurons of the SC mainly sent axons to the contralateral side in the lower brainstem. We found that the facial nucleus received input directly from the SC, and that the descending projections from the SC also reached the intermediate reticular formation and pre-Bötzinger complex, which are both considered to contain neural oscillators generating rhythmic movements of the vibrissae. Together, these results indicate the existence of a neural circuit in which the SC modulates vibrissal movements mainly on the contralateral side, via direct connections to motoneurons, and via indirect connections including the central pattern generators.

Effect of electrical stimulation of the infralimbic and prelimbic cortices on anxiolytic-like behavior of rats during the elevated plus-maze test, with particular reference to multiunit recording of the behavior-associated neural activity.

Fear and anxiety affect the activities of daily living and require concerted management, such as coping strategies, to preserve quality of life. The infralimbic (IL) and prelimbic (PL) medial prefrontal cortices have been implicated in the regulation of fear- and anxiety-like behavior, but their roles in overcoming fear- and anxiety-like behavior remain unknown. We investigated the anxiolytic-like effects of electrical stimulation of the IL and PL cortices in rats during the elevated plus-maze test. IL stimulation led to a significantly higher percentage of time spent and entries in the open arms, whereas PL stimulation did not have any significant behavioral effects. Subsequently, we recorded multiunit activity from the IL and PL cortices in rats using a wireless telemetry device, to determine whether activation of the IL occurs when rats enter the open arms in the elevated plus-maze test. The firing rate of IL neurons increased 1-3 s prior to entry from the closed arm to the open arm, whereas there were no corresponding changes in the firing rate of PL neurons. Taken together, the present findings suggest that the IL plays a key role in exerting active action to overcome anxiety-like behavior.

Region-specific deletions of the glutamate transporter GLT1 differentially affect seizure activity and neurodegeneration in mice.

Glial glutamate transporter GLT1 plays a key role in the maintenance of extracellular glutamate homeostasis. Recent human genetic studies have suggested that de novo mutations in GLT1 (EAAT2) cause early-onset epilepsy with multiple seizure types. Consistent with these findings, global GLT1 null mice show lethal spontaneous seizures. The consequences of GLT1 dysfunction vary between different brain regions, suggesting that the role of GLT1 dysfunction in epilepsy may also vary with brain regions. In this study, we generated region-specific GLT1 knockout mice by crossing floxed-GLT1 mice with mice that express the Cre recombinase in a particular domain of the ventricular zone. Selective deletion of GLT1 in the diencephalon, brainstem and spinal cord is sufficient to reproduce the phenotypes (excess mortality, decreased body weight, and lethal spontaneous seizure) of the global GLT1 null mice. By contrast, dorsal forebrain-specific GLT1 knockout mice showed nonlethal complex seizures including myoclonic jerks, hyperkinetic running, spasm and clonic convulsion via the activation of NMDA receptors during a limited period from P12 to P14 and selective neuronal death in cortical layer II/III and the hippocampus. Thus, GLT1 dysfunction in the dorsal forebrain is involved in the pathogenesis of infantile epilepsy and GLT1 in the diencephalon, brainstem and spinal cord may play a critical role in preventing seizure-induced sudden death.

Neural activity in the prelimbic and infralimbic cortices of freely moving rats during social interaction: Effect of isolation rearing.

Sociability promotes a sound daily life for individuals. Reduced sociability is a central symptom of various neuropsychiatric disorders, and yet the neural mechanisms underlying reduced sociability remain unclear. The prelimbic cortex (PL) and infralimbic cortex (IL) have been suggested to play an important role in the neural mechanisms underlying sociability because isolation rearing in rats results in impairment of social behavior and structural changes in the PL and IL. One possible mechanism underlying reduced sociability involves dysfunction of the PL and IL. We made a wireless telemetry system to record multiunit activity in the PL and IL of pairs of freely moving rats during social interaction and examined the influence of isolation rearing on this activity. In group-reared rats, PL neurons increased firing when the rat showed approaching behavior and also contact behavior, especially when the rat attacked the partner. Conversely, IL neurons increased firing when the rat exhibited leaving behavior, especially when the partner left on its own accord. In social interaction, the PL may be involved in active actions toward others, whereas the IL may be involved in passive relief from cautionary subjects. Isolation rearing altered social behavior and neural activity. Isolation-reared rats showed an increased frequency and decreased duration of contact behavior. The increased firing of PL neurons during approaching and contact behavior, observed in group-reared rats, was preserved in isolation-reared rats, whereas the increased firing of IL neurons during leaving behavior, observed in group-reared rats, was suppressed in isolation-reared rats. This result indicates that isolation rearing differentially alters neural activity in the PL and IL during social behavior. The differential influence of isolation rearing on neural activity in the PL and IL may be one of the neural bases of isolation rearing-induced behavior.

Effects of a self-management program on antiemetic-induced constipation during chemotherapy among breast cancer patients: a randomized controlled clinical trial.

Research on patient-reported outcomes indicates that constipation is a common adverse effect of chemotherapy, and the use of 5-hydroxytryptamine (serotonin; 5HT3) receptor antagonists aggravates this condition. As cancer patients take multiple drugs as a part of their clinical management, a non-pharmacological self-management (SM) of constipation would be recommended. We aimed to evaluate the effectiveness of a SM program on antiemetic-induced constipation in cancer patients. Thirty patients with breast cancer, receiving 5HT3 receptor antagonists to prevent emesis during chemotherapy were randomly assigned to the intervention or control group. The SM program consisted of abdominal massage, abdominal muscle stretching, and education on proper defecation position. The intervention group started the program before the first chemotherapy cycle, whereas patients in the wait-list control group received the program on the day before their second chemotherapy cycle. The primary outcome was constipation severity, assessed by the constipation assessment scale (CAS, sum of eight components). The secondary outcome included each CAS component (0-2 points) and mood states. A self-reported assessment of satisfaction with the program was performed. The program produced a statistically and clinically significant alleviation of constipation severity (mean difference in CAS, -3.00; P = 0.02), decrease in the likelihood of a small volume of stool (P = 0.03), and decrease in depression and dejection (P = 0.02). With regards to program satisfaction, 43.6 and 26.4 % patients rated the program as excellent and good, respectively. Our SM program is effective for mitigating the symptoms of antiemetic-induced constipation during chemotherapy.

Effect of the angle of shoulder flexion on the reach trajectory of children with spastic cerebral palsy.

Many children with cerebral palsy (CP) use a wheelchair during activities of daily living and often extend their hand upward and downward to reach objects in a seated position in a wheelchair. However, the effect of shoulder position on reaching movements of children with CP is not established. The purpose of this study was to determine the effect of the angle of shoulder flexion on the reach trajectory of children with spastic CP. Seven children with mild CP [Manual Ability Classification System (MACS) levels I-II], five children with severe CP (MACS levels III-V) and six typically developing (TD) children participated. We prepared the device to have a top board with variable tilting angle in order to reduce the effect of gravity imposing on reaching movements. By using this device, the subjects could extend their arm by sliding it on the board to push a target button. The reaching movements were performed with the more affected hand at three angles (60°, 90° and 120°) of shoulder flexion and captured using a camera motion analysis system. Subjects in the TD and mild CP groups reached the target at 60°, 90° and 120° of shoulder flexion. Subjects of the severe CP group reached the target at 60° and 90° of shoulder flexion, but two of the subjects could not reach the target at 120° of shoulder flexion. The TD and mild CP groups showed smooth and almost straight trajectories at all three angles of shoulder flexion; however, the reach trajectory in the subjects with severe CP changed with the angle of shoulder flexion. A large angle of shoulder flexion induced great outward deviation in the trajectory. These findings suggest that the difficulty of the reaching task is changed depending on the shoulder joint angle in children with severe CP and that therapeutic interventions for children with severe CP should be provided in a manner appropriate for the shoulder joint angle.

Asymmetric activation of the primary motor cortex during observation of a mirror reflection of a hand.

Mirror therapy is an effective technique for pain relief and motor function recovery. It has been demonstrated that magnetic 20-Hz activity is induced in the primary motor cortex (M1) after median nerve stimulation and that the amount of the stimulus-induced 20-Hz activity is decreased when the M1 is activated. In the present study, we investigated how the image or the mirror reflection of a hand holding a pencil modulates the stimulus-induced 20-Hz activity in the M1. Neuromagnetic brain activity was recorded from 13 healthy right-handed subjects while they were either viewing directly their hand holding a pencil or viewing a mirror reflection of their hand holding a pencil. The 20-Hz activity in the left or the right M1 was examined after the right or the left median nerve stimulation, respectively, and the suppression of the stimulus-induced 20-Hz in the M1 by viewing directly one hand holding a pencil or by viewing the mirror image of the hand holding a pencil was assumed to indicate the activation of the M1. The results indicated that the M1 innervating the dominant hand was suppressed either by viewing directly the dominant hand holding a pencil or by viewing the mirror image of the non-dominant hand holding a pencil. On the other hand, the M1 innervating the non-dominant hand was activated by viewing the mirror image of the dominant hand holding a pencil, but was not activated by viewing directly the non-dominant hand holding a pencil. The M1 innervating either the dominant or the non-dominant hand, however, was not activated by viewing the hand on the side ipsilateral to the M1 examined or the mirror image of the hand on the side contralateral to the M1 exaimined. Such activation of the M1 might induce some therapeutic effects of mirror therapy.

Modulation of stimulus-induced 20-Hz activity during lower extremity motor imagery.

Using magnetoencephalography, we measured 20-Hz activity induced after the common peroneal nerve (CPN) stimulation in 15 healthy subjects during the execution of foot movement or its motor imagery, and examined whether the 20-Hz activity is suppressed during motor imagery of foot movement. The prominent 20-Hz activity was contralaterally induced in the paracentral area after CPN stimulation, and it was almost completely suppressed during execution of the foot movement and partially suppressed during its motor imagery. These results suggest that the modulation of the 20-Hz activity is a useful indicator of the motor imagery of foot movement.

A mirror reflection of a hand modulates stimulus-induced 20-Hz activity.

Mirror therapy is one of the promising rehabilitation therapeutic interventions but the neural basis of the therapeutic effect remains unknown. It has been reported that the 20-Hz rhythmic activity is induced in the primary motor cortex after median nerve stimulation and the amount of the induced activity is decreased when the primary motor cortex is activated. In the present study, to elucidate the neural mechanisms underlying mirror therapy, we investigated whether the mirror reflection of a hand holding a pencil modulates the stimulus-induced 20-Hz activity. Neuromagnetic brain activities were recorded from 11 healthy right-handed subjects while they were viewing their hand holding a pencil or its mirror reflection. The right median nerve was stimulated and the stimulus-induced 20-Hz activity over the left rolandic cortex dominantly innervating right-hand movements was quantified. The stimulus-induced 20-Hz activity was strongly suppressed when subjects viewed the right hand holding a pencil or the mirror reflection of the left hand looking like the right hand holding a pencil, compared with when subjects viewed the left hand holding a pencil or the mirror reflection of the right hand looking like the left hand holding a pencil. These results suggest that the human left primary motor cortex is strongly activated when the subjects view not only the right hand holding a pencil but also the mirror reflection of the left hand looking like the right hand holding a pencil. This may be one of the neural mechanisms responsible for the therapeutic effect of mirror therapy.

Glutamate transporters regulate lesion-induced plasticity in the developing somatosensory cortex.

Glutamate transporters are involved in neural differentiation, neuronal survival, and synaptic transmission. In the present study, we examined glutamate transporter 1 (GLT1) expression in the neonatal somatosensory cortex of C57BL/6 mice, and pursued its role in somatosensory development by comparing barrel development between GLT1 knock-out and control mice. During the first few neonatal days, a critical period for barrels, GLT1 expression is strikingly upregulated in cortical astrocytes, whereas it was downregulated in neuronal elements to below the detection threshold. GLT1 knock-out neonates developed normally in terms of body growth, cortical histoarchitecture, barrel formation, and critical period termination. However, when row C whiskers were lesioned during the critical period, reduction of lesioned row C barrels and reciprocal expansion of intact row B/D barrels were both milder in GLT1 knock-out mice than in control littermates. Accordingly, the map plasticity index, calculated as (B + D)/2C, was significantly lowered in GLT1 knock-out mice. We also found that extracellular glutamate levels in the neonatal somatosensory cortex were significantly elevated in GLT1 knock-out mice. Diminished lesion-induced plasticity was further found in mutant mice lacking glutamate-aspartate transporter (GLAST), an astrocyte-specific glutamate transporter throughout development. Therefore, glutamate transporters regulate critical period plasticity by enhancing expansion of active barrels and shrinkage of inactive barrels. Because cortical contents of glutamate receptors and GLAST were unaltered in GLT1 knock-out mice, this action appears to be mediated, at least partly, by keeping the ambient glutamate level low. Considering an essential role of glutamate receptors in the formation of whisker-related thalamocortical synapse patterning, glutamate transporters thus facilitate their activity-dependent remodeling.

The potential role of glutamate transporters in the pathogenesis of normal tension glaucoma.

Glaucoma, a progressive optic neuropathy due to retinal ganglion cell (RGC) degeneration, is one of the leading causes of irreversible blindness. Although glaucoma is often associated with elevated intraocular pressure (IOP), IOP elevation is not detected in a significant subset of glaucomas, such as normal tension glaucoma (NTG). Moreover, in some glaucoma patients, significant IOP reduction does not prevent progression of the disease. Thus, understanding IOP-independent mechanisms of RGC loss is important. Here, we show that mice deficient in the glutamate transporters GLAST or EAAC1 demonstrate spontaneous RGC and optic nerve degeneration without elevated IOP. In GLAST-deficient mice, the glutathione level in Müller glia was decreased; administration of glutamate receptor blocker prevented RGC loss. In EAAC1-deficient mice, RGCs were more vulnerable to oxidative stress. These findings suggest that glutamate transporters are necessary both to prevent excitotoxic retinal damage and to synthesize glutathione, a major cellular antioxidant and tripeptide of glutamate, cysteine, and glycine. We believe these mice are the first animal models of NTG that offer a powerful system for investigating mechanisms of neurodegeneration in NTG and developing therapies directed at IOP-independent mechanisms of RGC loss.

Stimulus-related 20-Hz activity of human cortex modulated by the way of presenting hand actions.

The neural mechanisms underlying recognition of presented hand actions are not well understood. Rolandic rhythmic activity of about 20 Hz is reproducibly induced after median nerve stimulation and has been reported to be related to various types of movements including actual movement, motor imagery and action observation. We recorded neuromagnetic brain activity from 11 healthy subjects to investigate whether the way to present hand actions modulates the 20-Hz activity after median nerve stimulation. The stimulus-related 20-Hz activity was prominently evoked in the contralateral sensorimotor cortex around 0.5-1.0 s after median nerve stimulation and was almost completely suppressed during executing actual hand action. The suppression of the stimulus-related 20-Hz activity was also observed during viewing the similar action of another person's hand. Furthermore, the suppression during viewing the action of another person's hand presented in the same direction as the subject's hand was significantly larger than that during viewing it presented in the opposite direction and was closer to that during executing subject's own hand action. These results indicate that the stimulus-related rolandic 20-Hz activity was modulated by the way to present hand actions, and suggest that the 20-Hz activity is related to neural mechanisms underlying recognition of presented hand actions.

Synthesis of novel pentafluorosulfanylfurans. Two retro-Diels-Alder approaches.

The first examples of furan substituted with an SF5 group are reported. 3-pentafluorosulfanylfurans were prepared from their respective 2-pentafluorosulfanyl-5-cyano-7-oxabicyclo[2.2.1]hept-2-ene precursors via retro-Diels-Alder reactions. Also, a tandem cycloaddition/retrocycloaddition reaction between 4-phenyloxazole and 1-pentafluorosulfanylhex-1-yne was used to prepare 3-pentafluorosulfanyl-4-butylfuran. [reaction: see text].

Kelvin-wave cascade on a vortex in superfluid 4He at a very low temperature.

A study by computer simulation is reported of the behavior of a quantized vortex line at a very low temperature when there is continuous excitation of low-frequency Kelvin waves. There is no dissipation except by phonon radiation at a very high frequency. It is shown that nonlinear coupling leads to a net flow of energy to higher wave numbers and to the development of a simple spectrum of Kelvin waves that is insensitive to the strength and frequency of the exciting drive. The results are likely to be relevant to the decay of turbulence in superfluid 4He at very low temperatures.

Functional changes of glial glutamate transporter GLT-1 during ischemia: an in vivo study in the hippocampal CA1 of normal mice and mutant mice lacking GLT-1.

Glutamate transporters remove glutamate from the extracellular space and maintain it below neurotoxic levels under normal conditions. However, the dynamics under ischemic conditions remain to be determined. In the present study, we evaluated the function of the glial glutamate transporter (GLT-1) during brain ischemia by using an in vivo brain microdialysis technique in GLT-1 mutant mice. A microdialysis probe was placed in the hippocampal CA1 of GLT-1 mutant and wild-type mice, and glutamate levels were measured during 5 and 20 min ischemia. The glutamate levels in mice lacking GLT-1 were significantly higher than the corresponding glutamate levels in wild-type mice during 5 min ischemia. Delayed neuronal death was induced in the CA1 of the mice lacking GLT-1 but not in the CA1 of the wild-type mice. When ischemia was elongated to the duration of 20 min, the glutamate levels in wild-type mice were significantly higher than the corresponding glutamate levels in mice lacking GLT-1 during the last 12.5 min of 20 min ischemia. Acute neuronal death was also observed in the CA1 of wild-type mice. These results suggest that GLT-1 takes up extracellular glutamate to protect neurons in the early stage of ischemia and then releases glutamate, triggering acute neuronal death, when ischemic conditions are elongated. The function of GLT-1 may change from neuroprotective to neurodegenerative during ischemia.