Questionnaire survey on the prevention and development of cervical cancer in patients with systemic lupus erythematosus in Japan.

OBJECTIVES: The aim is to evaluate the prevention and development of cervical cancer in systemic lupus erythematosus (SLE) patients in Japan and its background based on a questionnaire survey. METHODS: The questionnaire was handed to 460 adult female SLE patients at 12 medical institutions. The participants were grouped by age, and data related to their human papillomavirus vaccination status, age at first coitus, cervical cancer screening, and diagnosis of cervical cancer were analysed. RESULTS: A total of 320 responses were received. Patients aged 35-54 years included a higher proportion of patients whose age at first coitus was <20 years. This group also showed a higher rate of cervical cancer/dysplasia. Only nine patients had a human papillomavirus vaccination history. Adequate frequency of cervical cancer screening was slightly higher (52.1%) among SLE patients than in the Japanese general population. However, 23% of the patients had never undergone examination, primarily because of a feeling of troublesome. The incidence of cervical cancer was significantly higher among SLE patients. One reason for this may be associated with the use of immunosuppressants, although the difference was not significant. CONCLUSIONS: SLE patients are at a higher risk of cervical cancer and dysplasia. Rheumatologists should proactively recommend vaccination and screening examinations for SLE female patients.

Distinct decrease in peripheral lymphocytes in EBER-positive cases of MTX-LPD.

OBJECTIVES: To determine the clinical characteristics of methotrexate-associated lymphoproliferative disorder (MTX-LPD). METHODS: In this study, 12 RA patients who developed MTX-LPD were assessed. The peripheral blood lymphocyte (PBL) count at the onset of MTX-LPD was compared to that 6 months before the onset, in Epstein-Barr virus-encoded RNA (EBER)-positive and -negative subgroups. We examined the change in the PBL count after MTX withdrawal. In patients with relapsed LPD, changes in the PBL count before relapse were also examined. RESULTS: Regression of LPD after MTX withdrawal was noted in eight patients. In these patients, the PBL count was decreased at the onset of MTX-LPD compared to 6 months before the onset; the decrease was significantly more prominent in EBER-positive patients. In cases of spontaneous regression of LPD, the PBL count recovered quickly after MTX withdrawal. Four of eight patients showed a recurrence of LPD after they improved following MTX withdrawal. These patients also exhibited a decreased PBL count at recurrence compared to 6 months before recurrence. CONCLUSION: A decrease in the PBL count might be involved in the pathogenesis of MTX-LPD, especially in EBER-positive cases and in patients with LPD relapse after MTX withdrawal following initial improvement.

Ventral striatum links motivational and motor networks during operant-conditioned movement in rats.

Voluntary actions require motives. It is already known that the medial prefrontal cortex (MPFC) assess the motivational values. However, it remains unclear how the motivational process gains access to the motor execution system in the brain. Here we present evidence that the ventral striatum (VS) plays a hub-like role in mediating motivational and motor processing in operant behavior. We used positron emission tomography (PET) to detect the neural activation areas associated with motivational action. Using obtained regions, partial correlation analysis was performed to examine how the motivational signals propagate to the motor system. The results revealed that VS activity propagated to both MPFC and primary motor cortex through the thalamus. Moreover, muscimol injection into the VS suppressed the motivational behavior, supporting the idea of representations of motivational signals in VS that trigger motivational behavior. These results suggest that the VS-thalamic pathway plays a pivotal role for both motivational processing through interactions with the MPFC and for motor processing through interactions with the motor BG circuits.

Neuroanatomical correlates of brain-computer interface performance.

Brain-computer interfaces (BCIs) offer a potential means to replace or restore lost motor function. However, BCI performance varies considerably between users, the reasons for which are poorly understood. Here we investigated the relationship between sensorimotor rhythm (SMR)-based BCI performance and brain structure. Participants were instructed to control a computer cursor using right- and left-hand motor imagery, which primarily modulated their left- and right-hemispheric SMR powers, respectively. Although most participants were able to control the BCI with success rates significantly above chance level even at the first encounter, they also showed substantial inter-individual variability in BCI success rate. Participants also underwent T1-weighted three-dimensional structural magnetic resonance imaging (MRI). The MRI data were subjected to voxel-based morphometry using BCI success rate as an independent variable. We found that BCI performance correlated with gray matter volume of the supplementary motor area, supplementary somatosensory area, and dorsal premotor cortex. We suggest that SMR-based BCI performance is associated with development of non-primary somatosensory and motor areas. Advancing our understanding of BCI performance in relation to its neuroanatomical correlates may lead to better customization of BCIs based on individual brain structure.

Dynamic neural network reorganization associated with second language vocabulary acquisition: a multimodal imaging study.

It remains unsettled whether human language relies exclusively on innately privileged brain structure in the left hemisphere or is more flexibly shaped through experiences, which induce neuroplastic changes in potentially relevant neural circuits. Here we show that learning of second language (L2) vocabulary and its cessation can induce bidirectional changes in the mirror-reverse of the traditional language areas. A cross-sectional study identified that gray matter volume in the inferior frontal gyrus pars opercularis (IFGop) and connectivity of the IFGop with the caudate nucleus and the superior temporal gyrus/supramarginal (STG/SMG), predominantly in the right hemisphere, were positively correlated with L2 vocabulary competence. We then implemented a cohort study involving 16 weeks of L2 training in university students. Brain structure before training did not predict the later gain in L2 ability. However, training intervention did increase IFGop volume and reorganization of white matter including the IFGop-caudate and IFGop-STG/SMG pathways in the right hemisphere. These "positive" plastic changes were correlated with the gain in L2 ability in the trained group but were not observed in the control group. We propose that the right hemispheric network can be reorganized into language-related areas through use-dependent plasticity in young adults, reflecting a repertoire of flexible reorganization of the neural substrates responding to linguistic experiences.

Simulating developmental diversity: Impact of neural stochasticity on atypical flexibility and hierarchy.

Introduction: Investigating the pathological mechanisms of developmental disorders is a challenge because the symptoms are a result of complex and dynamic factors such as neural networks, cognitive behavior, environment, and developmental learning. Recently, computational methods have started to provide a unified framework for understanding developmental disorders, enabling us to describe the interactions among those multiple factors underlying symptoms. However, this approach is still limited because most studies to date have focused on cross-sectional task performance and lacked the perspectives of developmental learning. Here, we proposed a new research method for understanding the mechanisms of the acquisition and its failures in hierarchical Bayesian representations using a state-of-the-art computational model, referred to as in silico neurodevelopment framework for atypical representation learning. Methods: Simple simulation experiments were conducted using the proposed framework to examine whether manipulating the neural stochasticity and noise levels in external environments during the learning process can lead to the altered acquisition of hierarchical Bayesian representation and reduced flexibility. Results: Networks with normal neural stochasticity acquired hierarchical representations that reflected the underlying probabilistic structures in the environment, including higher-order representation, and exhibited good behavioral and cognitive flexibility. When the neural stochasticity was high during learning, top-down generation using higher-order representation became atypical, although the flexibility did not differ from that of the normal stochasticity settings. However, when the neural stochasticity was low in the learning process, the networks demonstrated reduced flexibility and altered hierarchical representation. Notably, this altered acquisition of higher-order representation and flexibility was ameliorated by increasing the level of noises in external stimuli. Discussion: These results demonstrated that the proposed method assists in modeling developmental disorders by bridging between multiple factors, such as the inherent characteristics of neural dynamics, acquisitions of hierarchical representation, flexible behavior, and external environment.

Eosinophilic granulomatous with polyangiitis complicated by swelling of the oral cavity floor and cervical soft tissue as initial manifestation mimicking IgG4-related disease: A case report.

Eosinophilic granulomatous polyangiitis is a systemic vasculitis associated with bronchial asthma and eosinophilic sinusitis. Here, we describe an unusual presentation of eosinophilic granulomatous polyangiitis that initially manifested as swelling of the oral cavity floor and cervical soft tissue. A 58 year-old Japanese man was diagnosed with bronchial asthma during childhood but did not receive regular medication. Prior to this presentation, he had a persistent cough for over 1 month, and a local physician diagnosed him with bronchial asthma. However, 6 months later, his cough worsened, and a blood test revealed elevated eosinophil levels. Immediately afterward, swelling of the floor of the oral cavity and cervical soft tissue developed. Cellulitis was suspected and antimicrobial treatment was initiated; however, the symptoms persisted and abdominal pain developed. An endoscopic examination revealed duodenitis and a duodenal ulcer. The patient was diagnosed with eosinophilic granulomatous polyangiitis based on three items of the 2022 American College of Rheumatology/European College of Rheumatology classification criteria: obstructive airway disease, blood eosinophil count ≥1 × 109 cells/L, and extravascular eosinophilic infiltration with a score of 10. Oral prednisolone (70 mg/day), intravenous cyclophosphamide (500 mg/m2), and subcutaneous mepolizumab (300 mg every 4 weeks) were administered. The patient's symptoms improved after these treatments, and the eosinophil count and inflammatory marker levels declined. When swelling of the oral cavity floor and cervical soft tissue following an increase in eosinophilia and allergic symptoms occurs, it is crucial to consider the likelihood of eosinophilic granulomatous polyangiitis and collaborate with otolaryngologists and dentists to ensure its prompt identification.

Cortical current source estimation from electroencephalography in combination with near-infrared spectroscopy as a hierarchical prior.

Previous simulation and experimental studies have demonstrated that the application of Variational Bayesian Multimodal EncephaloGraphy (VBMEG) to magnetoencephalography (MEG) data can be used to estimate cortical currents with high spatio-temporal resolution, by incorporating functional magnetic resonance imaging (fMRI) activity as a hierarchical prior. However, the use of combined MEG and fMRI is restricted by the high costs involved, a lack of portability and high sensitivity to body-motion artifacts. One possible solution for overcoming these limitations is to use a combination of electroencephalography (EEG) and near-infrared spectroscopy (NIRS). This study therefore aimed to extend the possible applications of VBMEG to include EEG data with NIRS activity as a hierarchical prior. Using computer simulations and real experimental data, we evaluated the performance of VBMEG applied to EEG data under different conditions, including different numbers of EEG sensors and different prior information. The results suggest that VBMEG with NIRS prior performs well, even with as few as 19 EEG sensors. These findings indicate the potential value of clinically applying VBMEG using a combination of EEG and NIRS.

Basal ganglia-cortical connectivity underlies self-regulation of brain oscillations in humans.

Brain-computer interfaces provide an artificial link by which the brain can directly interact with the environment. To achieve fine brain-computer interface control, participants must modulate the patterns of the cortical oscillations generated from the motor and somatosensory cortices. However, it remains unclear how humans regulate cortical oscillations, the controllability of which substantially varies across individuals. Here, we performed simultaneous electroencephalography (to assess brain-computer interface control) and functional magnetic resonance imaging (to measure brain activity) in healthy participants. Self-regulation of cortical oscillations induced activity in the basal ganglia-cortical network and the neurofeedback control network. Successful self-regulation correlated with striatal activity in the basal ganglia-cortical network, through which patterns of cortical oscillations were likely modulated. Moreover, basal ganglia-cortical network and neurofeedback control network connectivity correlated with strong and weak self-regulation, respectively. The findings indicate that the basal ganglia-cortical network is important for self-regulation, the understanding of which should help advance brain-computer interface technology.

Positive effect of inaudible high-frequency components of sounds on glucose tolerance: a quasi-experimental crossover study.

Although stress significantly impacts on various metabolic syndromes, including diabetes mellitus, most stress management techniques are based on psychological and subjective approaches. This study examined how the presence or absence of the inaudible high-frequency component (HFC) of sounds, which activates deep-brain structures, affects glucose tolerance in healthy participants using the oral glucose tolerance test (OGTT). Sounds containing HFC suppressed the increase in glucose levels measured by incremental area under the curve in the OGTT compared with the otherwise same sounds without HFC. The suppression effect of HFC was more prominent in the older age group and the group with high HbA1c. This suggests that sounds with HFC are more effective in improving glucose tolerance in individuals at a higher risk of glucose intolerance.

Differential contribution of the supplementary motor area to stabilization of a procedural motor skill acquired through different practice schedules.

Behavioral studies have suggested that the stabilization of motor memory varies depending on the practice schedule. The neural substrates underlying this schedule-dependent difference in memory stabilization are not known. Here, we evaluated the effects of 1-Hz repetitive transcranial magnetic stimulation (rTMS) applied to different cortical regions and sham after one session of training (Day 1) of sequential motor skills acquired through blocked (each sequence was completely trained before training the next)-practice schedules and random (random training of 3 sequences)-practice schedules. The recall of sequences learned on Day 1 by Day 2 was measured in different groups of healthy volunteers. The rTMS over the supplementary motor area (SMA) but not over control regions or over the primary motor cortex (M1) immediately after practice or over SMA 6 h later reduced recall relative to sham only in the blocked-practice group. In contrast, recall in the random-practice group was unaffected by rTMS. These results document a differential contribution of the SMA to the stabilization of motor memories acquired through different practice schedules. More generally, they indicate that the anatomical substrates underlying motor-memory stabilization (or their temporal operation) do differ depending on the practice schedule.

Deep Feature Extraction for Resting-State Functional MRI by Self-Supervised Learning and Application to Schizophrenia Diagnosis.

In this study, we propose a deep-learning technique for functional MRI analysis. We introduced a novel self-supervised learning scheme that is particularly useful for functional MRI wherein the subject identity is used as the teacher signal of a neural network. The neural network is trained solely based on functional MRI-scans, and the training does not require any explicit labels. The proposed method demonstrated that each temporal volume of resting state functional MRI contains enough information to identify the subject. The network learned a feature space in which the features were clustered per subject for the test data as well as for the training data; this is unlike the features extracted by conventional methods including region of interests (ROIs) pooling signals and principal component analysis. In addition, applying a simple linear classifier to the per-subject mean of the features (namely "identity feature"), we demonstrated that the extracted features could contribute to schizophrenia diagnosis. The classification accuracy of our identity features was comparable to that of the conventional functional connectivity. Our results suggested that our proposed training scheme of the neural network captured brain functioning related to the diagnosis of psychiatric disorders as well as the identity of the subject. Our results together highlight the validity of our proposed technique as a design for self-supervised learning.

Bilateral Optic Disc Swelling with Preserved Visual Function Associated with Giant Cell Arteritis.

A 68-year-old Japanese man was introduced to our hospital for optic disc swelling (ODS) in his both eyes (OU). Other than floaters in his right eye, he did not report any symptoms including blurred vision, visual field defect, and ocular pain. Light reflex was prompt and complete OU, and critical flicker frequency was within the normal range OU. By fluorescein angiography, hyperfluorescence was detected on optic discs OU; however, no fluorescein leakage or filling defect was observed. By Goldmann perimetry, enlargement of the Mariotte blind spot was revealed OU, while no central scotoma or remarkable visual field defects were detected. By neuroimaging and lumbar puncture, papilledema due to intracranial pressure elevation was denied. Based on the reassessment of fundus findings, narrowing and segmental whitening/sheathing of peripapillary vessels predominantly to arterioles were realized, and systemic arteritis was suspected. Based on the subject age, elevation of erythrocyte sedimentation rate, positron emission tomography findings in the aorta, and MRI findings in temporal arteries, underlying giant cell arteritis (GCA) was diagnosed. After the start of systemic and local steroid therapies, ODS improved OU. Although rare, bilateral ODS with no visual disturbance can occur in patients with GCA. This case emphasizes the importance of careful assessment of ocular findings to reach the correct diagnosis of even a rare cause of ODS.

Conjunctival Chemosis and Annular Ciliochoroidal Detachments Detected by Anterior-Segment Optical Coherence Tomography in a Case of Systemic Lupus Erythematosus.

A 61-year-old Japanese woman presented to our hospital for treatment of systemic serositis associated with systemic lupus erythematosus (SLE). At the initial ophthalmologic examination, her best-corrected visual acuity was 1.2 and 0.6 in her right and left eyes, respectively. Slit-lamp examination showed marked chemosis in both eyes (OU). Swept source-based, anterior-segment optical coherence tomography (AS-OCT) clearly showed conjunctival elevations corresponding to the chemosis in all scan directions OU. In some scans, hyporeflective spaces with luminal structures corresponding to dilated lymphatic channels and nonluminal structures corresponding to interstitial fluid accumulation were seen clearly under the conjunctival epithelium and/or in the parenchyma. In all scan directions, the supraciliary space was seen clearly, suggesting the presence of an annular ciliochoroidal detachment. Fundus examinations showed retinal edema temporal to the optic nerve head and subfoveal serous retinal detachments OU. Ocular effusions resolved by 2 weeks after the start of steroid pulse therapy, and pleural effusions and ascites resolved and pericardial effusion decreased by 2 months. AS-OCT can be useful for understanding the mechanism(s) of the less common anterior-segment ocular manifestations of SLE.

Three-Dimensional Convolutional Autoencoder Extracts Features of Structural Brain Images With a "Diagnostic Label-Free" Approach: Application to Schizophrenia Datasets.

There has been increasing interest in performing psychiatric brain imaging studies using deep learning. However, most studies in this field disregard three-dimensional (3D) spatial information and targeted disease discrimination, without considering the genetic and clinical heterogeneity of psychiatric disorders. The purpose of this study was to investigate the efficacy of a 3D convolutional autoencoder (3D-CAE) for extracting features related to psychiatric disorders without diagnostic labels. The network was trained using a Kyoto University dataset including 82 patients with schizophrenia (SZ) and 90 healthy subjects (HS) and was evaluated using Center for Biomedical Research Excellence (COBRE) datasets, including 71 SZ patients and 71 HS. We created 16 3D-CAE models with different channels and convolutions to explore the effective range of hyperparameters for psychiatric brain imaging. The number of blocks containing two convolutional layers and one pooling layer was set, ranging from 1 block to 4 blocks. The number of channels in the extraction layer varied from 1, 4, 16, and 32 channels. The proposed 3D-CAEs were successfully reproduced into 3D structural magnetic resonance imaging (MRI) scans with sufficiently low errors. In addition, the features extracted using 3D-CAE retained the relation to clinical information. We explored the appropriate hyperparameter range of 3D-CAE, and it was suggested that a model with 3 blocks may be related to extracting features for predicting the dose of medication and symptom severity in schizophrenia.

A case of rheumatoid arthritis with multiple lung rheumatoid nodules successfully treated with tofacitinib.

Sporadic cases of rheumatoid nodules (RNs) in the lung during treatment with tumour necrosis factor (TNF) inhibitors have been reported, but no treatment has been established. Here, we report a case of symptomatic lung RNs refractory to abatacept (ABT) and intravenous cyclophosphamide (IVCY) that improved with tofacitinib (TOF) treatment. A 75-year-old Japanese woman with a 10-year history of rheumatoid arthritis (RA) presented with a cough and haemoptysis during treatment with etanercept (ETN). Radiographic examinations revealed multiple nodules that were diagnosed as lung RNs via biopsy. The ETN was discontinued and ABT followed by IVCY was introduced; however, neither was sufficiently effective against the lung RNs. Thereafter, TOF was started and the lung RNs improved rapidly. The precise mechanisms that induce RNs during treatment with TNF inhibitors are unknown. Cytokines (IL-23 and IL-6) are suspected to be involved. TOF may be a reasonable strategy for treating symptomatic lung RNs.

Differential effect of double-pulse TMS applied to dorsal premotor cortex and precuneus during internal operation of visuospatial information.

Human neuro-imaging studies have often reported co-activation of the dorsal premotor cortex (PMd) and the posterior parietal cortex (PPC) during internal operation of visuospatial information, referred to here as "visuospatial mental operation". However, the functions assigned to the PMd and PPC during these tasks are still unclear. Here, we examined the significance of these two areas for a visuospatial mental operation using the transcranial magnetic stimulation (TMS) technique. Subjects performed a task in which a visuospatial mental operation was required. A localization study conducted prior to the TMS experiment using functional magnetic resonance imaging (fMRI) revealed that the PMd and the medial part of the PPC, precuneus (PCu), were specifically activated during the visuospatial mental operation. Then, we impeded the activities of the PMd and the PCu in the right hemisphere during the same task using double-pulse TMS to determine whether these activities were necessary for the task. The TMS was applied at different times in relation to the visuospatial mental operation cue. Consequently, only the TMS applied at 300 ms after the cue affected the task performance. Furthermore, we found that the TMS at this time to each area differentially affected the performance: TMS to the PMd hindered the performance of the task whereas TMS to the PCu facilitated it without a speed/accuracy trade-off. These effects were not found in the control condition that lacked a visuospatial mental operation. These findings suggest that the PMd and the PCu are involved in differential aspects of visuospatial mental operations.

Stimulus-response profile during single-pulse transcranial magnetic stimulation to the primary motor cortex.

We examined the stimulus-response profile during single-pulse transcranial magnetic stimulation (TMS) by measuring motor-evoked potentials (MEPs) with electromyographic monitoring and hemodynamic responses with functional magnetic resonance imaging (fMRI) at 3 Tesla. In 16 healthy subjects, single TMS pulses were irregularly delivered to the left primary motor cortex at a mean frequency of 0.15 Hz with a wide range of stimulus intensities. The measurement of MEP proved a typical relationship between stimulus intensity and MEP amplitude in the concurrent TMS-fMRI environment. In the population-level analysis of the suprathreshold stimulation conditions, significant increases in hemodynamic responses were detected in the motor/somatosensory network, reflecting both direct and remote effects of TMS, and also the auditory/cognitive areas, perhaps related to detection of clicks. The stimulus-response profile showed both linear and nonlinear components in the direct and remote motor/somatosensory network. A detailed analysis suggested that the nonlinear components of the motor/somatosensory network activity might be induced by nonlinear recruitment of neurons in addition to sensory afferents resulting from movement. These findings expand our basic knowledge of the quantitative relationship between TMS-induced neural activations and hemodynamic signals measured by neuroimaging techniques.

[Neural Basis of "Breath of Aun"].

Many musical expressions exist in various cultures of the world, where multiple performers autonomously synchronize without a conductor or a metronome, and achieve an undisturbed musical performance by "breath of Aun". As a typical example, we considered the ritual performing art of Kecak in Bali, Indonesia, and performed simultaneous electroencephalogram (EEG) measurements on multiple participants during a Kecak performance. The study revealed that the inter-individual synchronization of the EEG during and after the performance was enhanced as compared to that before the performance. The author will also discuss the relation between synchronization of brain function and society and the culture of Bali.

Plastic frontal pole cortex structure related to individual persistence for goal achievement.

Persistent goal-directed behaviours result in achievements in many fields. However, the underlying neural mechanisms of persistence and the methods that enhance the neuroplasticity underlying persistence, remain unclear. We here demonstrate that the structural properties of the frontal pole cortex (FPC) before tasks contain information that can classify Achievers and Non-achievers (goal-directed persistence) participating in three tasks that differ in time scale (hours to months) and task domains (cognitive, language, and motor learning). We also found that most Achievers exhibit experience-dependent neuroplastic changes in the FPC after completing language and motor learning tasks. Moreover, we confirmed that a coaching strategy that used subgoals modified goal-directed persistence and increased the likelihood of becoming an Achiever. Notably, we discovered that neuroplastic changes in the FPC were facilitated by the subgoal strategy, suggesting that goal-striving, using effective coaching, optimizes the FPC for goal persistence.