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1.
Neuroreport ; 34(3): 150-155, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36608144

ABSTRACT

Autism spectrum disorder (ASD) is characterized by social communicative disturbance. Social communication requires rapid processing and accurate cognition regarding others' emotional expressions. Previous electrophysiological studies have attempted to elucidate the processes underlying atypical face-specific N170 responses to emotional faces in ASD. The present study explored subliminal affective priming effects (SAPEs) on the N170 response and time-frequency analysis of intertrial phase coherence (ITPC) for the N170 in ASD. Fifteen participants [seven participants with ASD and eight typically developing (TD) controls] were recruited for the experiment. Event-related potentials were recorded with a 128-channel electroencephalography device while participants performed an emotional face judgment task. The results revealed enhanced N170 amplitude for supraliminal target-face stimuli when they were preceded by subliminal fearful-face stimuli, in both the ASD and TD groups. Interestingly, TD participants exhibited higher alpha-ITPC in the subliminal fearful-face priming condition in the right face-specific area in the N170 time window. In contrast, there were no significant differences in ITPC in any frequency bands between the subliminal fearful and neutral priming conditions in the ASD group. Asynchronous phase-locking neural activities in the face-specific area may underlie impaired nonconscious face processing in ASD, despite the presence of common features of SAPEs for the N170 component in both the ASD and TD groups.


Subject(s)
Autism Spectrum Disorder , Humans , Evoked Potentials/physiology , Electroencephalography , Emotions/physiology , Fear
2.
Front Neurosci ; 16: 1057021, 2022.
Article in English | MEDLINE | ID: mdl-36590300

ABSTRACT

Background: Human locomotion induces rhythmic movements of the trunk and head. Vestibular signaling is relayed to multiple regions in the brainstem and cerebellum, and plays an essential role in maintaining head stability. However, how the vestibular-cerebellar network contributes to the rhythmic locomotor pattern in humans is unclear. Transcranial alternating current stimulation (tACS) has been used to investigate the effects of the task-related network between stimulation regions in a phase-dependent manner. Here, we investigated the relationship between the vestibular system and the cerebellum during walking imagery using combined tACS over the left cerebellum and alternating current galvanic vestibular stimulation (AC-GVS). Methods: In Experiment 1, we tested the effects of AC-GVS alone at around individual gait stride frequencies. In Experiment 2, we then determined the phase-specificity of combined stimulation at the gait frequency. Combined stimulation was applied at in-phase (0° phase lag) or anti-phase (180° phase lag) between the left vestibular and left cerebellar stimulation, and the sham stimulation. We evaluated the AC-GVS-induced periodic postural response during walking imagery or no-imagery using the peak oscillatory power on the angular velocity signals of the head in both experiments. In Experiment 2, we also examined the phase-locking value (PLV) between the periodic postural responses and the left AC-GVS signals to estimate entrainment of the postural response by AC-GVS. Results: AC-GVS alone induced the periodic postural response in the yaw and roll axes, but no interactions with imagery walking were observed in Experiment 1 (p > 0.05). By contrast, combined in-phase stimulation increased yaw motion (0.345 ± 0.23) compared with sham (-0.044 ± 0.19) and anti-phase stimulation (-0.066 ± 0.18) during imaginary walking (in-phase vs. other conditions, imagery: p < 0.05; no-imagery: p ≥ 0.125). Furthermore, there was a positive correlation between the yaw peak power of actual locomotion and in-phase stimulation in the imagery session (imagery: p = 0.041; no-imagery: p = 0.177). Meanwhile, we found no imagery-dependent effects in roll peak power or PLV, although in-phase stimulation enhanced roll motion and PLV in Experiment 2. Conclusion: These findings suggest that combined stimulation can influence vestibular-cerebellar network activity, and modulate postural control and locomotion systems in a temporally sensitive manner. This novel combined tACS/AC-GVS stimulation approach may advance development of therapeutic applications.

3.
Neuroimage ; 239: 118325, 2021 10 01.
Article in English | MEDLINE | ID: mdl-34216773

ABSTRACT

Visual information involving facial identity and expression is crucial for social communication. Although the influence of facial features such as spatial frequency (SF) and luminance on face processing in visual areas has been studied extensively using grayscale stimuli, the combined effects of other features in this process have not been characterized. To determine the combined effects of different SFs and color, we created chromatic stimuli with low, high or no SF components, which bring distinct SF and color information into the ventral stream simultaneously. To obtain neural activity data with high spatiotemporal resolution we recorded face-selective responses (M170) using magnetoencephalography. We used a permutation test procedure with threshold-free cluster enhancement to assess statistical significance while resolving problems related to multiple comparisons and arbitrariness found in traditional statistical methods. We found that time windows with statistically significant threshold levels were distributed differently among the stimulus conditions. Face stimuli containing any SF components evoked M170 in the fusiform gyrus (FG), whereas a significant emotional effect on M170 was only observed with the original images. Low SF faces elicited larger activation of the FG and the inferior occipital gyrus than the original images, suggesting an interaction between low and high SF information processing. Interestingly, chromatic face stimuli without SF first activated color-selective regions and then the FG, indicating that facial color was processed according to a hierarchy in the ventral stream. These findings suggest complex effects of SFs in the presence of color information, reflected in M170, and unveil the detailed spatiotemporal dynamics of face processing in the human brain.


Subject(s)
Algorithms , Brain Mapping/methods , Facial Recognition/physiology , Magnetic Resonance Imaging/methods , Magnetoencephalography/methods , Spatio-Temporal Analysis , Visual Cortex/physiology , Visual Perception/physiology , Adult , Color , Fear , Female , Humans , Light , Male , Young Adult
4.
Plant Biotechnol (Tokyo) ; 38(1): 57-66, 2021 Mar 25.
Article in English | MEDLINE | ID: mdl-34177325

ABSTRACT

Licorice (Glycyrrhiza uralensis) is a medicinal plant that contains glycyrrhizin (GL), which has various pharmacological activities. Because licorice is a legume, it can establish a symbiotic relationship with nitrogen-fixing rhizobial bacteria. However, the effect of this symbiosis on GL production is unknown. Rhizobia were isolated from root nodules of Glycyrrhiza glabra, and a rhizobium that can form root nodules in G. uralensis was selected. Whole-genome analysis revealed a single circular chromosome of 6.7 Mbp. This rhizobium was classified as Mesorhizobium by phylogenetic analysis and was designated Mesorhizobium sp. J8. When G. uralensis plants grown from cuttings were inoculated with J8, root nodules formed. Shoot biomass and SPAD values of inoculated plants were significantly higher than those of uninoculated controls, and the GL content of the roots was 3.2 times that of controls. Because uninoculated plants from cuttings showed slight nodule formation, we grew plants from seeds in plant boxes filled with sterilized vermiculite, inoculated half of the seedlings with J8, and grew them with or without 100 µM KNO3. The SPAD values of inoculated plants were significantly higher than those of uninoculated plants. Furthermore, the expression level of the CYP88D6 gene, which is a marker of GL synthesis, was 2.5 times higher than in inoculated plants. These results indicate that rhizobial symbiosis promotes both biomass and GL production in G. uralensis.

5.
Sci Rep ; 11(1): 13179, 2021 06 23.
Article in English | MEDLINE | ID: mdl-34162993

ABSTRACT

Transcranial alternating current stimulation (tACS) at 20 Hz (ß) has been shown to modulate motor evoked potentials (MEPs) when paired with transcranial magnetic stimulation (TMS) in a phase-dependent manner. Repetitive paired-pulse TMS (rPPS) with I-wave periodicity (1.5 ms) induced short-lived facilitation of MEPs. We hypothesized that tACS would modulate the facilitatory effects of rPPS in a frequency- and phase-dependent manner. To test our hypothesis, we investigated the effects of combined tACS and rPPS. We applied rPPS in combination with peak or trough phase tACS at 10 Hz (α) or ß, or sham tACS (rPPS alone). The facilitatory effects of rPPS in the sham condition were temporary and variable among participants. In the ß tACS peak condition, significant increases in single-pulse MEPs persisted for over 30 min after the stimulation, and this effect was stable across participants. In contrast, ß tACS in the trough condition did not modulate MEPs. Further, α tACS parameters did not affect single-pulse MEPs after the intervention. These results suggest that a rPPS-induced increase in trans-synaptic efficacy could be strengthened depending on the ß tACS phase, and that this technique could produce long-lasting plasticity with respect to cortical excitability.


Subject(s)
Cortical Excitability/physiology , Evoked Potentials, Motor/physiology , Neuronal Plasticity/physiology , Transcranial Magnetic Stimulation/methods , Adult , Cross-Over Studies , Female , Humans , Male , Neurons/physiology , Single-Blind Method , Young Adult
6.
Data Brief ; 36: 106993, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33889696

ABSTRACT

This article describes data related to the research study entitled "The neural correlate of gait improvement by rhythmic sound stimulation in adults with Parkinson's disease - A functional magnetic resonance imaging study" [1]. We evaluated gait performance using the 10-meter walk test (10MWT) in adults with Parkinson's disease (PD) and age-matched healthy controls (HC). Gait speed (GS) and step length (SL) were calculated from the results of the 10MWT. We also evaluated neural activities in regions that were significantly activated by gait imagery in adults with PD using functional magnetic resonance imaging (fMRI). The correlation among GS, SL, and activation of blood oxygenation level-dependent (BOLD) signals by gait imagery in adults with PD. Both GS and SL were smaller in adults with PD than in HCs. The left parietal operculum (PO), left supplementary motor area (SMA), and right cerebellum were activated by gait imagery in adults with PD. No significant correlation was found in any pair of gait performance and neural activation of such regions. This data set could be reused for studies to investigate the relationship between gait performance and neural activities in adults with PD.

7.
Parkinsonism Relat Disord ; 84: 91-97, 2021 03.
Article in English | MEDLINE | ID: mdl-33607527

ABSTRACT

INTRODUCTION: Adults with Parkinson's disease (PD) experience gait disturbances that can sometimes be improved with rhythmic auditory stimulation (RAS); however, the underlying physiological mechanism for this improvement is not well understood. We investigated brain activation patterns in adults with PD and healthy controls (HC) using functional magnetic resonance imaging (fMRI) while participants imagined gait with or without RAS. METHODS: Twenty-seven adults with PD who could walk independently and walked more smoothly with rhythmic auditory cueing than without it, and 25 age-matched HC participated in this study. Participants imagined gait in the presence of RAS or white noise (WN) during fMRI. RESULTS: In the PD group, gait imagery with RAS activated cortical motor areas, including supplementary motor areas and the cerebellum, while gait imagery with WN additionally recruited the left parietal operculum. In HC, the induced activation was limited to cortical motor areas and the cerebellum for both the RAS and WN conditions. Within- and between-group analyses demonstrated that RAS reduced the activity of the left parietal operculum in the PD group but not in the HC group (condition-by-group interaction by repeated measures analysis of variance, p < 0.05). CONCLUSION: During gait imagery in adults with PD, the left parietal operculum was less activated by RAS than by WN, while no change was observed in HC, suggesting that rhythmic auditory stimulation may support the sensory-motor networks involved in gait, thus alleviating the overload of the parietal operculum and compensating for its dysfunction in these patients.


Subject(s)
Acoustic Stimulation , Cerebellar Cortex/physiopathology , Cues , Gait Disorders, Neurologic/physiopathology , Gait Disorders, Neurologic/rehabilitation , Motor Cortex/physiopathology , Neurological Rehabilitation , Parietal Lobe/physiopathology , Parkinson Disease/physiopathology , Parkinson Disease/rehabilitation , Acoustic Stimulation/methods , Aged , Aged, 80 and over , Animals , Cerebellar Cortex/diagnostic imaging , Female , Gait Disorders, Neurologic/diagnostic imaging , Gait Disorders, Neurologic/etiology , Humans , Imagination/physiology , Magnetic Resonance Imaging , Male , Motor Cortex/diagnostic imaging , Neurological Rehabilitation/methods , Outcome Assessment, Health Care , Parietal Lobe/diagnostic imaging , Parkinson Disease/complications , Parkinson Disease/diagnostic imaging
8.
Brain Behav ; 11(4): e02060, 2021 04.
Article in English | MEDLINE | ID: mdl-33528111

ABSTRACT

INTRODUCTION: Subliminal affective priming effects (SAPEs) refer to the phenomenon by which the presentation of an affective prime stimulus influences the subsequent affective evaluation of a target stimulus. Previous studies have reported that unconsciously processed stimuli affect behavioral performance more than consciously processed stimuli. However, the impact of SAPEs on the face-specific N170 component is unclear. We studied how SAPEs for fearful faces affected the N170 for subsequent supraliminal target faces using event-related potentials (ERPs). METHODS: Japanese adults (n = 44, 20 females) participated in this study. Subliminal prime faces (neutral or fearful) were presented for 17 ms, followed by a backward mask for 283 ms and 800 ms target faces (neutral, emotionally ambiguous, or fearful). 128-channel ERPs were recorded while participants judged the expression of target faces as neutral or fearful. Response rates and response times were also measured for assessing behavioral alterations. RESULTS: Although the behavioral results revealed no evidence of SAPEs, we found gender-related SAPEs in right N170 amplitude. Specifically, female participants exhibited enhanced right N170 amplitude for emotionally neutral faces primed by fearful faces, while male participants exhibited decreased N170 amplitude in fearful prime trials with fearful target faces. Male participants exhibited significant correlations between N170 amplitude and behavioral response time in the fearful prime-neutral target condition. CONCLUSIONS: Our ERP results suggest the existence of a gender difference in target-face processing preceded by subliminally presented face stimuli in the right occipito-temporal region.


Subject(s)
Facial Recognition , Sex Characteristics , Adult , Electroencephalography , Evoked Potentials , Facial Expression , Fear , Female , Humans , Male
10.
Brain Behav ; 10(6): e01649, 2020 06.
Article in English | MEDLINE | ID: mdl-32367678

ABSTRACT

INTRODUCTION: The right fusiform face area (FFA) is important for face recognition, whereas the left visual word fusiform area (VWFA) is critical for word processing. Nevertheless, the early stages of unconscious and conscious face and word processing have not been studied systematically. MATERIALS AND METHODS: To explore hemispheric differences for face and word recognition, we manipulated the visual field (left vs. right) and stimulus duration (subliminal [17 ms] versus supraliminal [300 ms]). We recorded P100 and N170 peaks with high-density ERPs in response to faces/objects or Japanese words/scrambled words in 18 healthy young subjects. RESULTS: Contralateral P100 was larger than ipsilateral P100 for all stimulus types in the supraliminal, but not subliminal condition. The face- and word-N170s were not evoked in the subliminal condition. The N170 amplitude for the supraliminal face stimuli was significantly larger than that for the objects, and right hemispheric specialization was found for face recognition, irrespective of stimulus visual hemifield. Conversely, the supraliminal word-N170 amplitude was not significantly modulated by stimulus type, visual field, or hemisphere. CONCLUSIONS: These results suggest that visual awareness is crucial for face and word recognition. Our study using hemifield stimulus presentation further demonstrates the robust right FFA for face recognition but not the left VWFA for word recognition in the Japanese brain.


Subject(s)
Facial Recognition , Electroencephalography , Evoked Potentials , Functional Laterality , Language , Pattern Recognition, Visual , Photic Stimulation
11.
Neurosci Lett ; 725: 134911, 2020 04 23.
Article in English | MEDLINE | ID: mdl-32171804

ABSTRACT

The relationship between facial identity and facial expression processing has long been debated. Although previous facial recognition models indicate that facial identity and facial expression processing are independent, psychological studies using the selective attention task (the Garner paradigm) have revealed an asymmetrical relationship between the perception of identity and emotional expressions in faces: while facial expression does not influence facial identity recognition, facial identity influences facial expression recognition. We used the Garner paradigm and recorded high-density event-related potentials (ERPs) to investigate the influence of facial identity on facial expression recognition. Twenty participants judged the expression of faces, while the irrelevant dimension of identity was either held constant (control condition) or varied (orthogonal condition). We recorded 128-channel EEGs while participants completed the facial expression task. We analyzed the two major components of early visual stages: P1 and N170. ERP results revealed a significant main effect of condition on the N170 latency. These results suggest that facial identity influences facial expression recognition in the N170 that reflects the structural encoding of faces. Thus, information on facial expression might be computed based on the unique structure of individual faces.


Subject(s)
Evoked Potentials, Visual/physiology , Facial Expression , Facial Recognition/physiology , Pattern Recognition, Visual/physiology , Photic Stimulation/methods , Adult , Female , Humans , Male , Reaction Time/physiology , Young Adult
12.
Arthritis Res Ther ; 22(1): 47, 2020 03 12.
Article in English | MEDLINE | ID: mdl-32164762

ABSTRACT

BACKGROUND: Peficitinib (ASP015K), a novel oral Janus kinase inhibitor, has demonstrated efficacy and safety for the treatment of rheumatoid arthritis (RA) in randomized, controlled trials of up to 52 weeks' duration. However, safety and effectiveness after long-term treatment have not been assessed. METHODS: This was an interim analysis of an ongoing open-label, multicenter extension study in RA patients who completed phase 2b (RAJ1; 12 weeks) and phase 3 (RAJ3 and RAJ4; 52 weeks) peficitinib studies in Asia (mainly Japan). Eligible patients (n = 843) received oral peficitinib once daily (100 mg, or 50 mg for patients transferring from RAJ1). The peficitinib dose could be increased (up to 150 mg) or reduced (to 50 mg) at the discretion of the investigator. Efficacy variables assessed included American College of Rheumatology (ACR) response rates, ACR components, and disease activity score in 28 joints based on C-reactive protein (DAS28-CRP). RESULTS: Results up to May 2018 are summarized. Mean peficitinib duration of exposure was 22.7 months and the maximum dose was 100 mg in most (66.5%) patients. ACR responses were maintained during the extension study, with ACR20/50/70 response rates of 71.6%, 52.1%, and 34.7% at week 0 and 78.9%, 61.4%, and 42.7% at end of treatment, respectively. ACR components and DAS28-CRP showed improvements from baselines of the preceding studies and continued to show improvements during the extension study. Treatment-emergent adverse events (TEAEs) were reported in 757/843 (89.8%) patients, the most common being nasopharyngitis (39.7%) and herpes zoster (11.7%). The majority of TEAEs were severity grade 1/2. Drug-related TEAEs leading to permanent study drug discontinuation occurred in 55/843 (6.5%) patients. Regarding AEs of special interest, the incidence per 100 patient-years of serious infections was 2.3 (95% CI 1.6 - 3.1), herpes zoster-related disease 6.8 (95% CI, 5.6 - 8.3), and malignancies 1.1 (95% CI, 0.7 - 1.8). One death from diffuse large B cell lymphoma during the study and one death from uterine sarcoma after the study were considered probably and possibly related to study drug, respectively. CONCLUSIONS: The effectiveness of peficitinib was maintained or improved during long-term administration and treatment up to 6 years was well tolerated in Asian patients with RA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01638013, registered retrospectively 11 July 2012.


Subject(s)
Adamantane/analogs & derivatives , Arthritis, Rheumatoid/drug therapy , Niacinamide/analogs & derivatives , Severity of Illness Index , Adamantane/adverse effects , Adamantane/therapeutic use , Adult , Aged , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/pathology , C-Reactive Protein/metabolism , Female , Herpes Zoster/chemically induced , Humans , Janus Kinase Inhibitors/adverse effects , Janus Kinase Inhibitors/therapeutic use , Japan , Male , Methotrexate/therapeutic use , Middle Aged , Nasopharyngitis/chemically induced , Niacinamide/adverse effects , Niacinamide/therapeutic use , Republic of Korea , Taiwan , Treatment Outcome
13.
Neurosci Res ; 156: 108-116, 2020 Jul.
Article in English | MEDLINE | ID: mdl-31730780

ABSTRACT

The adult human brain appears to have specialized and independent neural systems for the visual processing of faces and words: greater selectivity for faces in the right hemisphere (RH) while greater selectivity for words in the left hemisphere (LH). Nevertheless, the nature of functional differences between the hemispheres is still largely unknown. To elucidate the hemispheric specialization for face and word recognition, event-related magnetic fields (ERFs) were recorded in young adults while they passively viewed faces and words presented either in the right visual field or in the left visual field. If the neural correlates of face recognition and word recognition reflect the same lateralization profile, then the lateralization of the magnetic source of the M170 component should follow a similar profile, with a greater M170 response for faces in the RH and a greater M170 response for words in the LH. We observed the expected finding of a larger M170 in the LH for words. Unexpectedly, a larger M170 response in the RH for faces was not found. Thus, the hemispheric organization of face recognition is different from that of word recognition in terms of specificity.


Subject(s)
Facial Recognition , Pattern Recognition, Visual , Face , Functional Laterality , Humans , Photic Stimulation , Visual Perception , Young Adult
14.
Brain Stimul ; 13(2): 343-352, 2020.
Article in English | MEDLINE | ID: mdl-31711878

ABSTRACT

BACKGROUND: Transcranial alternating current stimulation (tACS) can entrain and enhance cortical oscillatory activity in a frequency-dependent manner. In our previous study (Nakazono et al., 2016), 20 Hz (ß) tACS significantly increased excitability of primary motor cortex compared with 10 Hz (α) tACS. α oscillations are a prominent feature of the primary visual cortex (V1) in a resting electroencephalogram. Hence, we investigated whether α and ß tACS can differentially influence multiple visual functions. METHODS: Firstly, we evaluated the after-effects of α and ß tACS on pattern-reversal (PR) and focal-flash (FF) visual evoked potentials (VEPs). Secondly, we determined the relationship between resting α oscillations and PR-VEPs modulated by tACS. Thirdly, the behavioral effects of tACS were assessed by contrast sensitivity. RESULTS: α tACS modulated the amplitudes of PR-VEPs, compared with ß tACS, but did not modulate the FF-VEPs. Time-frequency analysis revealed that α tACS facilitated event-related α phase synchronizations without increasing power, which consequently increased the PR-VEP amplitudes. There was a significant positive correlation between PR-VEP amplitudes and resting α oscillations. These findings suggested that α tACS modulated α oscillations, and affected visual functions of contrast and spatial frequency. Indeed, α tACS also improved subjects' contrast sensitivity at the behavioral level. Conversely, ß tACS increased posterior α activity, but did not change VEP amplitudes. CONCLUSIONS: α tACS can influence different neuronal populations from those influenced by ß tACS. Thus, our results provide evidence that α tACS sharpens multiple visual functions by modulating α oscillations in V1.


Subject(s)
Alpha Rhythm , Evoked Potentials, Visual , Transcranial Direct Current Stimulation/methods , Visual Cortex/physiology , Adult , Beta Rhythm , Female , Humans , Male , Motor Cortex/physiology
15.
Ann Rheum Dis ; 78(10): 1305-1319, 2019 10.
Article in English | MEDLINE | ID: mdl-31350269

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of the oral Janus kinase (JAK) inhibitor peficitinib versus placebo in Japanese patients with rheumatoid arthritis (RA). METHODS: In this multicentre, double-blind, parallel-group, placebo-controlled phase III study, patients with RA and inadequate response to methotrexate (MTX) were randomised 1:1:1 to placebo, peficitinib 100 mg once daily or peficitinib 150 mg once daily with MTX for 52 weeks. Based on baseline randomisation, at week 12, non-responders receiving placebo were switched to peficitinib until the end of treatment; the remaining patients were switched to peficitinib at week 28. Primary efficacy variables were American College of Rheumatology (ACR)20 response rate at week 12/early termination (ET) and change from baseline in van der Heijde-modified total Sharp score (mTSS) at week 28/ET. RESULTS: 519 patients were randomised and treated. Significantly more (p<0.001) peficitinib (58.6%, 100 mg; 64.4%, 150 mg) than placebo (21.8%) recipients achieved ACR20 response at week 12/ET. Significantly lower (p<0.001) mean changes from baseline in mTSS at week 28/ET occurred in peficitinib (1.62, 100 mg; 1.03, 150 mg) than placebo (3.37) recipients. Peficitinib was associated with haematological and biochemical parameter changes, and increased incidence of serious infections and herpes zoster-related disease. One death from suicide occurred in a patient in the placebo group after switching to peficitinib 100 mg. CONCLUSIONS: In Japanese patients with RA and inadequate response to MTX, peficitinib demonstrated significant superiority versus placebo in reducing RA symptoms and suppressing joint destruction. Peficitinib had an acceptable safety and tolerability profile, with no new safety signals compared with other JAK inhibitors. TRIAL REGISTRATION NUMBER: NCT02305849.


Subject(s)
Adamantane/analogs & derivatives , Antirheumatic Agents/administration & dosage , Arthritis, Rheumatoid/drug therapy , Immunosuppressive Agents/administration & dosage , Janus Kinase Inhibitors/administration & dosage , Niacinamide/analogs & derivatives , Adamantane/administration & dosage , Adamantane/adverse effects , Adult , Aged , Antirheumatic Agents/adverse effects , Double-Blind Method , Drug Substitution , Female , Herpes Zoster/chemically induced , Humans , Immunosuppressive Agents/adverse effects , Infections/chemically induced , Janus Kinase Inhibitors/adverse effects , Japan , Male , Methotrexate/administration & dosage , Middle Aged , Niacinamide/administration & dosage , Niacinamide/adverse effects , Severity of Illness Index , Treatment Outcome
16.
Ann Rheum Dis ; 78(10): 1320-1332, 2019 10.
Article in English | MEDLINE | ID: mdl-31350270

ABSTRACT

OBJECTIVES: To investigate the efficacy and safety of peficitinib, an oral Janus kinase inhibitor, in patients with rheumatoid arthritis (RA). METHODS: In this double-blind phase III study, patients with RA and an inadequate response to prior disease-modifying anti-rheumatic drugs (DMARDs) were randomised to peficitinib 100 mg once daily, peficitinib 150 mg once daily, placebo or open-label etanercept for 52 weeks' treatment; placebo-treated patients were switched at week 12 to peficitinib 100 or 150 mg once daily. The primary endpoint was American College of Rheumatology (ACR)20 response at week 12/early termination (ET). Secondary endpoints (assessed throughout) included ACR20, ACR50 and ACR70 response, changes from baseline in disease activity scores (DAS)28 and ACR core parameters, adverse events (AEs) and changes in clinical or laboratory measurements. RESULTS: In total, 507 patients received treatment. ACR20 response rates at week 12/ET were significantly higher in the peficitinib 100 mg (57.7%) and 150 mg (74.5%) groups versus placebo (30.7%) (p<0.001). ACR50/70 response rates were also higher for both peficitinib doses versus placebo. Improvements in ACR response were maintained until week 52. Changes from baseline in DAS28-C-reactive protein/erythrocyte sedimentation rate and the ACR core set were significantly greater for both peficitinib doses versus placebo at week 12/ET (p<0.001). AE incidence was similar across treatment arms. Incidence of serious infection and herpes zoster-related disease was higher with peficitinib versus placebo, but with no clear dose-dependent increase. CONCLUSIONS: In patients with RA and inadequate response to DMARDs, peficitinib 100 mg once daily or 150 mg once daily was efficacious in reducing RA symptoms and was well tolerated compared with placebo. TRIAL REGISTRATION NUMBER: NCT02308163.


Subject(s)
Adamantane/analogs & derivatives , Antirheumatic Agents/administration & dosage , Arthritis, Rheumatoid/drug therapy , Immunosuppressive Agents/administration & dosage , Janus Kinase Inhibitors/administration & dosage , Niacinamide/analogs & derivatives , Adamantane/administration & dosage , Adamantane/adverse effects , Adult , Aged , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/blood , Blood Sedimentation/drug effects , C-Reactive Protein/drug effects , Double-Blind Method , Drug Substitution , Female , Herpes Zoster/chemically induced , Humans , Immunosuppressive Agents/adverse effects , Infections/chemically induced , Janus Kinase Inhibitors/adverse effects , Japan , Male , Middle Aged , Niacinamide/administration & dosage , Niacinamide/adverse effects , Severity of Illness Index , Treatment Outcome
17.
Data Brief ; 22: 583-589, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30627613

ABSTRACT

It has been reported that it is possible to observe transient changes in resting-state functional connectivity (FC) in the attention networks of healthy adults during treatment with prism adaptation. by using functional magnetic resonance imaging (fMRI) (see "Prism adaptation changes resting-state functional connectivity in the dorsal stream of visual attention networks in healthy adults: A fMRI study" (Tsujimoto et al., 2018) [1]. Recent neuroimaging and neurophysiological studies support the idea that prism adaptation (PA) affects the visual attention and sensorimotor networks, which include the parietal cortex and cerebellum. These data demonstrate the effect of PA on resting-state functional connectivity between the primary motor cortex and cerebellum. Additionally, it evaluates changes of resting-state FC before and after PA in healthy individuals using fMRI. Analyses focus on FC between the primary motor cortex and cerebellum, and the correlation between changes in FC and its after-effects following a single PA session. Here, we show data that demonstrate the change in resting-state FC between the primary motor cortex and cerebellum, as well as a correlation between the change ratio of FC and the amplitude of the after-effect.

18.
Cortex ; 119: 594-605, 2019 10.
Article in English | MEDLINE | ID: mdl-30471844

ABSTRACT

Unilateral spatial neglect (USN) can be defined as a failure to orient to contra-lesional stimuli in the absence of either sensory or motor defects. Although the behavioral and clinical effects of prism adaptation (PA) are widely accepted, its underlying mechanisms are still controversial. However, recent neuroimaging and neurophysiological studies support the idea that PA affects the visual attention and sensorimotor networks including in the parietal cortex and cerebellum. We investigate the effect of PA on functional connectivity (FC) in attention and sensorimotor networks, evaluating changes of resting-state FC before and after PA in healthy individuals using functional magnetic resonance imaging (fMRI). MR sessions were conducted before PA, after PA (Post1), and 1 h after PA (Post2). The FC between the right frontal eye (FEF) field and the right intraparietal sulcus was significantly decreased at Post1 and that between the right FEF and the right anterior cingulate cortex was significantly increased after PA and recovered within 1 h. This is the first study to demonstrate transient changes of resting-state FC in the right dorsal attention network (DAN) by PA in healthy adults using fMRI. These results will contribute to the elucidation of the underling mechanism of PA therapy and to devising new therapies for USN and/or other higher cortical dysfunctions.


Subject(s)
Attention/physiology , Magnetic Resonance Imaging , Nerve Net/physiology , Perceptual Disorders/physiopathology , Adaptation, Physiological/physiology , Humans , Magnetic Resonance Imaging/methods , Neuroimaging/methods
19.
Physiol Rep ; 3(5)2015 May.
Article in English | MEDLINE | ID: mdl-25975645

ABSTRACT

Face identification and categorization are essential for social communication. The N170 event-related potential (ERP) is considered to be a biomarker of face perception. To elucidate the neural basis of species-dependent face processing, we recorded 128-ch high-density ERPs in 14 healthy adults while they viewed the images of morphed faces. The morphed stimuli contained different proportions of human and monkey faces, and the species boundary was shifted away from the center of the morph continuum. Three experiments were performed to determine how task requirement, facial orientation, and spatial frequency (SF) of visual stimuli affected ERPs. In an equal SF condition, the latency, and amplitude of the occipital P100 for upright faces were modulated in a monotonic-like fashion by the level of morphing. In contrast, the N170 latency for upright faces was modulated in a step-like fashion, showing a flexion point that may reflect species discrimination. Although N170 amplitudes for upright faces were not modulated by morph level, they were modulated in a monotonic-like fashion by inverted faces. The late positive (LP) component (350-550 msec) in the parietal region was modulated in a U-shaped function by morph level during a categorization task, but not in a simple reaction task. These results suggest that P100 reflects changes in the physical properties of faces and that N170 is involved in own-species selectivity. The LP component seems to represent species categorization that occurs 350 msec after stimulus onset.

20.
Biomicrofluidics ; 8(2): 024115, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24803964

ABSTRACT

We present facile strategies for the fabrication of two types of microfluidic devices made of hydrogels using the natural biopolymers, alginate, and gelatin as substrates. The processes presented include the molding-based preparation of hydrogel plates and their chemical bonding. To prepare calcium-alginate hydrogel microdevices, we suppressed the volume shrinkage of the alginate solution during gelation using propylene glycol alginate in the precursor solution along with sodium alginate. In addition, a chemical bonding method was developed using a polyelectrolyte membrane of poly-L-lysine as the electrostatic glue. To prepare gelatin-based microdevices, we used microbial transglutaminase to bond hydrogel plates chemically and to cross-link and stabilize the hydrogel matrix. As an application, mammalian cells (fibroblasts and vascular endothelial cells) were cultivated on the microchannel surface to form three-dimensional capillary-embedding tissue models for biological research and tissue engineering.

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