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During rubber hand illusion (RHI), participants feel that a rubber (fake) hand is their own (i.e., embodiment of the rubber hand) if the unseen real hand and seen rubber hand are stroked synchronously (i.e., visuo-tactile stimuli). The RHI is also evoked if the real and rubber hands are placed in the same position (i.e., visual-proprioceptive congruency), which can be performed using a mirror setting. Using electroencephalography (EEG) and mirror settings, we compared μ rhythm (8–13 Hz) event-related desynchronization (ERD; an index of sensorimotor activation) while watching the movements of embodied or non-embodied rubber hands, which was preceded by an observation of the rubber hand with or without synchronous visuo-tactile stimuli. The illusory ownership of the fake hand was manipulated using visual continuity with (RHI) and without (non-RHI) a fake forearm. Resultantly, an ownership-dependent μ rhythm ERD was found when delivering visuo-tactile stimuli; a greater and more persistent μ rhythm ERD during the rubber hand movement was identified in the RHI in comparison to the non-RHI condition. However, no difference was observed between the two when observing the fake hand alone. These findings suggest the possibility that a self-related multisensory interaction between body representation (top-down processing) and visuo-tactile inputs (bottom-up processing) before a fake hand movement produces ownership-dependent sensorimotor activations during subsequent movement observations. [ABSTRACT FROM AUTHOR]

The rubber hand illusion (RHI) is a perceptual illusion, whereby a fake hand is recognized as one's own hand when a fake hand and felt real hand are stroked synchronously. RHI strength is mainly assessed using a questionnaire rating and proprioceptive drift (PD). PD is characterized by the proprioceptively sensed location of the participant's own hand shifting toward the location of the fake hand after RHI. However, the relationship between the two measures of hand ownership and location remains controversial due to mixed findings: some studies report correlations between them, while others show that they are independent. Here, we demonstrated significant PD without RHI using delayed visual feedback. In this RHI study, video images of the fake hand were delivered to the subjects, and four delay intervals of visual feedback (80, 280, 480, and 680ms) were introduced. In four of six conditions, the delay interval was fixed throughout the condition. In the other two conditions, four delays were delivered in a predetermined order (i.e., serial condition; higher predictability) or in a pseudo-random order (i.e., random condition; low predictability). For the four conditions with a fixed delay, the questionnaire ratings and PD declined significantly when the delay interval exceeded circa 300ms. In both the serial and random conditions, no illusory ownership of the fake hand was reported in the questionnaire. In contrast, greater PD was found in the random condition but not in the serial condition. Our findings suggest that hand ownership and localization are caused by distinct multisensory integration processes. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate whether default mode network (DMN) connectivity and brain white matter integrity at baseline were associated with severe cognitive impairments at baseline and poor cognitive outcomes after shunt placement in patients with idiopathic normal pressure hydrocephalus (iNPH).Methods: Twenty consecutive patients with iNPH whose symptoms were followed for 6 months after shunt placement and 10 healthy controls (HCs) were enrolled. DMN connectivity and brain white matter integrity at baseline in the patients with iNPH and HCs were detected by using resting-state functional magnetic resonance imaging (MRI) with independent component analysis and diffusion tensor imaging, respectively, and these MRI indexes were compared between the patients with iNPH and HCs. Performance on neuropsychological tests for memory and executive function and on the gait test was assessed in the patients with iNPH at baseline and 6 months after shunt placement. We divided the patients with iNPH into the relatively preserved and reduced DMN connectivity groups using the MRI indexes for DMN connectivity and brain white matter integrity, and the clinical measures were compared between the relatively preserved and reduced DMN connectivity groups.Results: Mean DMN connectivity in the iNPH group was significantly lower than that in the HC group and was significantly positively correlated with Rey auditory verbal learning test (RAVLT) immediate recall scores and frontal assessment battery (FAB) scores. Mean fractional anisotropy of the whole-brain white matter skeleton in the iNPH group was significantly lower than that in the HC group. The reduced DMN connectivity group showed significantly worse performance on the RAVLT at baseline and significantly worse improvement in the RAVLT immediate recall and recognition scores and the FAB scores than the preserved DMN connectivity group. Moreover, the RAVLT recognition score highly discriminated patients with relatively preserved DMN connectivity from those with relatively reduced DMN connectivity.Conclusions: Our findings indicated that iNPH patients with reduced DMN connectivity relative to the severity of brain white matter disruption have severe memory deficits at baseline and poorer cognitive outcomes after shunt placement. However, further larger-scale studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

In the rubber hand illusion (RHI), the subject recognizes a fake hand as his or her own. We recently found that the observation of embodied fake hand movement elicited mu-rhythm (8–13 Hz) desynchronization on electroencephalography (EEG), suggesting brain activation in the sensorimotor regions. However, it is known that mu-rhythm desynchronization during action observation is confounded with occipital alpha-rhythm desynchronization, which is modulated by attention. This study examined the independence of brain activities in the sensorimotor and occipital regions relating to the movement observation under the RHI. The invisible participant's left and fake right hands were stroked simultaneously, which was interrupted by unexpected fake hand movements. A mirror-reversed image of the fake hand was shown on a monitor in front of the participant with a delay of 80, 280, or 480 ms. Illusion strength decreased as a function of the delay. EEG independent component analysis (ICA) and ICA clustering revealed six clusters with observation-induced desynchronization of 8–13 Hz frequency band. In the right sensorimotor cluster, mu-rhythm desynchronization was the greatest under the 80-ms delay, while alpha-rhythm desynchronization of the occipital clusters did not show delay-dependence. These results suggest that brain activation in the sensorimotor areas (i.e., mu-rhythm desynchronization) induced by embodied fake hand movement is independent of that in the occipital areas (alpha-rhythm desynchronization). [ABSTRACT FROM AUTHOR]

Bodily self-consciousness consists of agency (i.e., the feeling of controlling one's actions and causing external events) and body ownership (i.e., the feeling that one's body belongs to one's self). If a visual presentation of a virtual (fake) hand matches the active movement of a real hand, both the agency and body ownership of the virtual hand are induced [i.e., the active virtual hand illusion (VHI)]. However, previous active VHI studies have rarely considered the effects of goal-related movement errors (i.e., motor performance) on the senses of agency and ownership. Hence, the current study aimed to clarify the relationship between the active VHI and motor performance. To induce the VHI, 18 healthy subjects (three men and 15 women; 20.7 ± 7.3 years) were required to continuously move a virtual hand around a circle at a predetermined speed (i.e., spatial and temporal goals) using their active hand movements. While moving the virtual hand actively, five visual feedback delays were introduced: 90, 210, 330, 450, and 570 ms. It was found that the subjective ratings of both the agency and body ownership of the virtual hand decreased as a function of the delay intervals, whereas most of the spatial and temporal movement errors linearly increased. Using multiple regression analyses, we examined whether the agency and ownership ratings could be explained effectively by both the delay and movement errors. The results demonstrated that the agency was determined not only by the delay but also by the movement variability, whereas the body ownership was mostly determined by the delay. These findings suggest a possibility that the goal-related motor performance of the active VHI influences the agency judgment more strongly, while its effect on the ownership judgment is weaker. [ABSTRACT FROM AUTHOR]

Cervical myelopathy (CM) caused by spinal cord compression can lead to reduced hand dexterity. However, except for the 10 sec grip-and-release test, there is no objective assessment system for hand dexterity in patients with CM. Therefore, we evaluated the hand dexterity impairment of patients with CM objectively by asking them to perform a natural prehension movement. Twenty-three patients with CM and 30 age-matched controls were asked to reach for and grasp a small object with their right thumb and index finger and to subsequently lift and hold it. To examine the effects of tactile afferents from the fingers, objects with surface materials of differing textures (silk, suede, and sandpaper) were used. All patients also underwent the Japanese Orthopedic Association (JOA) test. Preoperative patients showed significantly greater grip aperture during reach-to-grasp movements and weaker grip force than controls only while attempting to lift the most slippery object (silk). Patients, immediately after surgery, (n=15) tended to show improvements in the JOA score and in reaction time and movement time with respect to reaching movements. Multiple regression analysis demonstrated that some parameters of the prehension task could successfully predict subjective evaluations of dexterous hand movements based on JOA scores. These results suggest that quantitative assessments using prehension movements could be useful to objectively evaluate hand dexterity impairment in patients with CM. [ABSTRACT FROM AUTHOR]

Background: We aimed to clarify associations between pre-admission risk scores (CHADS2, CHA2DS2-VASc, and HAS-BLED) and 2-year clinical outcomes in ischemic stroke or transient ischemic attack (TIA) patients with non-valvular atrial fibrillation (NVAF) using a prospective, multicenter, observational registry. Methods: From 18 Japanese stroke centers, ischemic stroke or TIA patients with NVAF hospitalized within 7 days after onset were enrolled. Outcome measures were defined as death/disability (modified Rankin Scale score ≥3) at 2 years, 2-year mortality, and ischemic or hemorrhagic events within 2 years. Results: A total of 1,192 patients with NVAF (527 women; mean age, 78 ± 10 years), including 1,141 ischemic stroke and 51 TIA, were analyzed. Rates of death/disability, mortality, and ischemic or hemorrhagic events increased significantly with increasing pre-admission CHADS2 (p for trend <0.001 for death/disability and mortality, p for trend = 0.024 for events), CHA2DS2-VASc (p for trend <0.001 for all), and HAS-BLED (p for trend = 0.004 for death/disability, p for trend <0.001 for mortality, p for trend = 0.024 for events) scores. Pre-admission CHADS2 (OR per 1 point, 1.52; 95% CI 1.35–1.71; p <0.001 for death/disability; hazard ratio (HR) per 1 point, 1.23; 95% CI 1.12–1.35; p <0.001 for mortality; HR per 1 point, 1.14; 95% CI 1.02–1.26; p = 0.016 for events), CHA2DS2-VASc (1.55, 1.41–1.72, p < 0.001; 1.21, 1.12–1.30, p < 0.001; 1.17, 1.07–1.27, p < 0.001; respectively), and HAS-BLED (1.33, 1.17–1.52, p < 0.001; 1.23, 1.10–1.38, p < 0.001; 1.18, 1.05–1.34, p = 0.008; respectively) scores were independently associated with all outcome measures. Conclusions: In ischemic stroke or TIA patients with NVAF, all pre-admission risk scores were independently associated with death/disability at 2 years and 2-year mortality, as well as ischemic or hemorrhagic events within 2 years. [ABSTRACT FROM AUTHOR]

Body ownership and agency are fundamental to self-consciousness. These bodily experiences have been intensively investigated using the rubber hand illusion, wherein participants perceive a fake hand as their own. After presentation of the illusion, the position of the participant's hand then shifts toward the location of the fake hand (proprioceptive drift). However, it remains controversial whether proprioceptive drift is able to provide an objective measurement of body ownership, and whether agency also affects drift. Using the virtual hand illusion (VHI), the current study examined the effects of body ownership and agency on proprioceptive drift, with three different visuo-motor tasks. Twenty healthy adults (29.6 ± 9.2 years old) completed VH manipulations using their right hand under a 2 × 2 factorial design (active vs. passive manipulation, and congruent vs. incongruent virtual hand). Prior to and after VH manipulation, three different tasks were performed to assess proprioceptive drift, in which participants were unable to see their real hands. The effects of the VHI on proprioceptive drift were task-dependent. When participants were required to judge the position of their right hand using a ruler, or by reaching toward a visual target, both body ownership and agency modulated proprioceptive drift. Comparatively, when participants aligned both hands, drift was influenced by ownership but not agency. These results suggest that body ownership and agency might differentially modulate various body representations in the brain. [ABSTRACT FROM AUTHOR]

Recently, neurorehabilitation that uses virtual reality systems is being applied in clinical settings to deal with issues such as phantom limb pain (PLP) as an alternative to mirror box therapy. One of the weak points of mirror box therapy is that the desired analgesia effect might not be confirmed in some patients. One hypothesis to explain this phenomenon is that the subjective sense of the length of a phantom limb is different from that of an intact limb. Since the gap between body representation in the brain and actual sensory feedback is considered one of the causes of PLP, different lengths of a subjective phantom limb are a serious problem for mirror box therapy and similar VR-based rehabilitation methods. We are thus developing a VR system that displays an avatar that has the same length as the subjective phantom limb. The purpose of the current study is to determine the feasibility of the VR system – specifically, whether it has enough effect on sense of agency (SoA) and sense of ownership (SoO) for healthy subjects – before conducting experiments for actual phantom limb patients. To this end, we developed a VR system in which a virtual avatar performs a motion identical to that of the subject by means of a motion capturing device (Kinect V2). The subject wears a 3D head mounted display (Oculus Rift DK2) to experience seeing through the eyes of the avatar. Six conditions of avatar representation were used: two appearances of a normal human arm and a robot arm and three lengths of the arm (short, medium, and long). The subject executes elbow flexion-extension movement of the right arm, which causes the same movement in the VR avatar’s arm. After the induction movement, the subjective sense of the length of the right arm is measured by a pointing gesture of the left hand. Twelve subjects participated in this experiment. Results showed that the subjective length of the arm was changed according to the length of the displayed arm in the VR environment. From the results of a questionnaire, we found that there is no negative effect on SoA. SoO when the subjects watch the natural human avatar is stronger than when the robot arm is shown. These results are positive, thus confirming the basic potential of the proposed VR system. In conclusion, the change of self-body appearance of a VR avatar has enough effect on subjective sense of arm length. Since the subjective sense of arm length is strongly related to body representation in the brain, we believe that the system can be a platform for research on embodied-brain science systems. [ABSTRACT FROM AUTHOR]

Aims: This study was performed to determine the short-term risk-benefit profiles of patients treated with oral antic- oagulation for acute ischemic stroke or transient ischemic attack using a multicenter, prospective registry. Methods: A total of 1137 patients (645 men, 77 ± 10 years old) with acute ischemic stroke/transient ischemic attack taking warfarin (662 patients) or non-vitamin K antagonist oral anticoagulants (dabigatran in 205, rivaroxaban in 245, apixaban in 25 patients) for nonvalvular atrial fibrillation who completed a three-month follow-up survey were studied. Choice of anticoagulants was not randomized. Primary outcome measures were stroke/systemic embolism and major bleeding. Results: Both warfarin and non-vitamin K antagonist oral anticoagulants were initiated within four days after stroke/ transient ischemic attack onset in the majority of cases. Non-vitamin K antagonist oral anticoagulant users had lower ischemia- and bleeding-risk indices (CHADS2, CHA2DS2-VASc, HAS-BLED) and milder strokes than warfarin users. The three-month cumulative rate of stroke/systemic embolism was 3.06% (95% CI 1.96%-4.74%) in warfarin users and 2.84% (1.65%-4.83%) in non-vitamin K antagonist oral anticoagulant users (adjusted HR 0.96, 95% CI 0.44-2.04). The rate of major bleeding was 2.61% (1.60%-4.22%) and 1.11% (0.14%-1.08%), respectively (HR 0.63, 0.19-1.78); that for intracranial hemorrhage was marginally significantly lower in non-vitamin K antagonist oral anticoagulant users (HR 0.17, 0.01-1.15). Major bleeding did not occur in non-vitamin K antagonist oral anticoagulant users with a CHADS2 score <4 or those with a discharge modified Rankin Scale score ≤2. Conclusions: Stroke or systemic embolism during the initial three-month anticoagulation period after stroke/transient ischemic attack was not frequent as compared to previous findings regardless of warfarin or non-vitamin K antagonist oral anticoagulants were used. Intracranial hemorrhage was relatively uncommon in non-vitamin K antagonist oral anticoagulant users, although treatment assignment was not randomized. Early initiation of non-vitamin K antagonist oral anticoagulants during the acute stage of stroke/transient ischemic attack in real-world clinical settings seems safe in bleeding-susceptible Japanese population. [ABSTRACT FROM AUTHOR]

Information regarding squalene synthases (SQSs) from prokaryotes is scarce. We aimed to characterize the SQS from Methylococcus capsulatus. We studied its reaction mechanism by kinetic analysis and evaluated the structure of the substrate/inhibitor-binding sites via homology modeling. The cloned M. capsulatus SQS was expressed in Escherichia coli and purified by nickel-nitrilotriacetic acid column chromatography. Interestingly, M. capsulatus SQS was water-soluble and did not require any detergent for its higher activity, unlike other SQSs studied previously; supplementation of any type of detergent inhibited enzyme activity. The specific activity and the kinetic values (Km and kcat) for the substrate farnesyl diphosphate and NADPH are reported. The substrate analog farnesyl methylenediphosphonate showed potent inhibition toward the enzyme. We prepared the sitespecific mutants directed at potential active-site residues 58DXX61E62D (S1 site) and 213DXX216D217D (S2 site), which were assumed to be involved in the binding of the substrate farnesyl diphosphate through the Mg2+ion. We first demonstrated that the S1 site and the two basic residues (R55 and K212) were responsible for the binding of farnesyl diphosphate. Furthermore, we examined the catalytic roles of the highly conserved aromatic residues and demonstrated that the Y164 residue abstracts the proton of cation 5, which is produced during the first half-reaction (Scheme 1), to afford presqualene diphosphate, and that the W224 residue stabilizes the intermediary cation 5 via the cation-π interaction. Furthermore, we confirm for the first time that the F32 and the Y51 residues also stabilize the carbocation intermediate(s) generated during the second half-reaction. [ABSTRACT FROM AUTHOR]

Successive tactile stimuli, delivered one to each hand, are referred to spatial representation before they are ordered in time (Yamamoto and Kitazawa in Nat Neurosci 4:759–765 ). In the present study, we examined if this applies even when they are delivered unilaterally to fingers of a single hand. Tactile stimuli were delivered left-to-rightward relative to the body (2nd–3rd–4th) or in reverse with stimulus onset asynchrony of 100 ms. Simultaneously with the delivery of tactile stimuli, three of nine small squares arranged in a matrix of 3 × 3 were turned on as if they appeared near the tips of the fingers. Although subjects were instructed to ignore the visual stimuli and make a forced choice between the two orders of tactile stimuli, the correct-judgment probability depended on the direction of visual stimuli. It was greater than 95% when the direction of visual stimuli matched that of the tactile stimuli, but less than 50% when they were opposite to each other. When the right hand was rotated counterclockwise on the horizontal plane (90°) so that the fingers were pointing to the left, the preferred direction of visual stimuli that yielded the peak correct judgment was also rotated, although not to the full extent. These results show that subjects cannot be basing their tactile temporal order judgment solely on a somatotopic map, but rather on a spatial map on which both visual and tactile signals converge. [ABSTRACT FROM AUTHOR]

Using transcranial magnetic stimulation (TMS), we examined whether sensory input from a finger affects activity of the ipsilateral primary motor cortex (M1) when human subjects hold a virtual object bimanually and whether this ipsilateral activation varies under different contexts. Subjects used both index fingers to hold two plates, which were subjected to unpredictable pulling loads from torque motors. Loads were delivered in a random sequence to either plate or concurrently to both, although the latter occurred most frequently. Finger forces vertical to the plates and surface electromyographs from the first dorsal interosseous muscles were recorded bilaterally during the task. TMS was sometimes applied over the finger area of the left M1 at variable times relative to load onset to examine cortical excitability. Strength of TMS was set around the active motor threshold of the right finger muscle while subjects waited for loading to the handheld plates. When one plate was singly loaded, the M1 contralateral to the loaded finger was activated, causing automatic force increases in the finger. In addition, the ipsilateral M1 was activated during such loading, associated with transient force increases in the contralateral nonloaded finger. Activations in the ipsilateral M1 were also observed during concurrent loading, when activations were stronger than those following single loading of the contralateral plate. Ipsilateral activations weakened when concurrent loading was less frequent. These results suggest interactions between bilateral sensorimotor cortices during bimanual coordinated movements, with strength varying by context. [ABSTRACT FROM AUTHOR]

A correction to the article "Effects of visual stimuli on temporal order judgments of unimanual finger stimuli" that was published in the September 13, 2007 issue is presented.