Decision-Making with Predictions of Others' Likely and Unlikely Choices in the Human Brain.

For better decisions in social interactions, humans often must understand the thinking of others and predict their actions. Since such predictions are uncertain, multiple predictions may be necessary for better decision-making. However, the neural processes and computations underlying such social decision-making remain unclear. We investigated this issue by developing a behavioral paradigm and performing functional magnetic resonance imaging and computational modeling. In our task, female and male participants were required to predict others' choices in order to make their own value-based decisions, as the outcome depended on others' choices. Results showed, to make choices, the participants mostly relied on a value difference (primary) generated from the case where others would make a likely choice, but sometimes they additionally used another value difference (secondary) from the opposite case where others make an unlikely choice. We found that the activations in the posterior cingulate cortex (PCC) correlated with the primary difference while the activations in the right dorsolateral prefrontal cortex (rdlPFC) correlated with the secondary difference. Analysis of neural coupling and temporal dynamics suggested a three-step processing network, beginning with the left amygdala signals for predictions of others' choices. Modulated by these signals, the PCC and rdlPFC reflect the respective value differences for self-decisions. Finally, the medial prefrontal cortex integrated these decision signals for a final decision. Our findings elucidate the neural process of constructing value-based decisions by predicting others and illuminate their key variables with social modulations, providing insight into the differential functional roles of these brain regions in this process.

Headache in systemic lupus erythematosus: The LUNA registry cross-sectional study.

OBJECTIVES: This study investigated the clinically relevant factors for headaches in patients with systemic lupus erythematosus (SLE) using a registry from a Japanese multicenter cohort. METHODS: This cross-sectional study analysed the clinical information of patients with SLE who experienced headache episodes using the Migraine Disability Assessment (MIDAS) questionnaire. Significant findings in the comparisons between patients with headache (HA patients) and those without headache (non-HA patients) and in the comparisons depending on the grades of headache-induced disability in daily life based on the MIDAS scores were evaluated. Multivariate logistic regression analyses were performed to identify the relevant factors for headache. RESULTS: We analyzed 369 patients (median age, 45 years; female, 90.8%), including 113 HA patients who were significantly younger than non-HA patients (p < .005). HA patients had significantly higher frequencies of photosensitivity, rashes, and mucosal ulcers than non-HA patients (p < .05). Age and photosensitivity were significantly associated with headache (odds ratio (OR) 0.93, 95% confidence interval (CI) 0.95-0.99; OR 2.11, 95% CI 1.29-3.49, respectively). In the HA patients, hypocomplementemia was significantly associated with a disability of more than mild grade (OR 2.89, 95% CI 1.14-7.74), while rash was significantly observed in those presenting with moderate and severe disability. CONCLUSION: This study suggests that photosensitivity is a relevant manifestation of headache in patients with SLE. Persistent hypocomplementemia can contribute to headache-induced disability in daily life, whereas a rash may be a dominant manifestation in patients presenting with moderate/severe headache-induced disability.

Clinical characteristics and treatment of elderly onset adult-onset Still's disease.

Adult-onset Still's disease (AOSD)-a systemic inflammatory disease-often occurs at a young age. Recently, elderly onset patient proportion has been increasing; however, data are limited. To evaluate the characteristics of elderly patients with AOSD in a multicenter cohort, we retrospectively analyzed 62 patients with AOSD at five hospitals during April 2008-December 2020. Patients were divided into two groups according to age at disease onset: younger-onset (≤ 64 years) and elderly onset (≥ 65 years). Clinical symptoms, complications, laboratory findings, treatment, and outcomes were compared. Twenty-six (41.9%) patients developed AOSD at age ≥ 65 years. The elderly onset group had a lower frequency of sore throat (53.8% vs. 86.1%), higher frequency of pleuritis (46.2% vs. 16.7%), and higher complication rates of disseminated intravascular coagulation (30.8% vs. 8.3%) and macrophage activation syndrome (19.2% vs. 2.8%) than the younger onset group. Cytomegalovirus infections were frequent in elderly onset patients (38.5% vs. 13.9%) but decreased with early glucocorticoid dose reduction and increased immunosuppressant and tocilizumab use. Elderly AOSD is not uncommon; these patients have different characteristics than younger-onset patients. Devising a way to control disease activity quickly while managing infections may be an important goal in elderly AOSD.

[Rapid Screening System for Paralytic Shellfish Toxins in Bivalves by Oligonucleotide Lateral Flow Immunoassay].

The mouse bioassay (MBA) for paralytic shellfish toxins (PSTs) in bivalves has been used as an official method in Japan. It is necessary to develop an alternative method to animal experiments in PSTs assay because 3Rs (Replacement, Reduction, and Refinement) of animal experiments are required from the animal welfare point of view. Various methods such as HPLC-FL, receptor binding assay, LC-MS/MS and ELISA have been established to detect PSTs without performing animal experiments. The present study was undertaken to develop a screening method using oligonucleotide lateral flow immunoassay (OLFIA) for detecting PSTs in bivalves. The screening level was defined as positive at 2 MU/g of MBA that is the half regulation limit of PSTs monitoring in Japan. All 20 positive (equal to or more than 2 MU/g) samples judged from MBA showed a positive reaction in the OLFIA. No positive samples resulted in a false negative reaction. The OLFIA exhibited high accuracy at 2 MU/g of screening criteria. The authors demonstrated here that the OLFIA can be useful for rapid detection of PSTs in bivalves.

The implication of interferon-γ-producing immunocompetent cells for evaluating disease activity and severity in adult-onset Still's disease.

OBJECTIVE: To investigate the relationship between interferon-γ (IFN-γ), IFN-γ-producing immunocompetent cells, their related cytokines, and the clinical features in adult-onset Still's disease (AOSD). METHODS: Twenty-five patients with AOSD before initiating treatment (acute AOSD), 9 patients after remission (remission AOSD), and 12 healthy controls (HC) were included. Circulating IFN-γ-producing CD4+ and CD8+ cells, natural killer (NK) cells, and IFN-γ production in NK cells were evaluated by flow cytometry. Serum levels of IFN-γ, interleukin (IL)-6, IL-12, IL-15, and IL-18 were also measured. The obtained results were statistically analyzed with clinical findings. RESULTS: Serum levels of IFN-γ, IL-6, IL-12, IL-18, intracellular expression of IFN-γ in CD4+, CD8+, and NK cells were significantly higher in acute AOSD than in HC. The proportion of NK cells was significantly lower in acute AOSD than in HC. Serum levels of IFN-γ and IFN-γ expression in CD4+ cells were significantly correlated with serum ferritin levels. The proportion of NK cells had a significant inverse correlation with serum IFN-γ levels. A lower proportion of NK cells was significantly noted in patients refractory to initial immunosuppressive treatment. In remission AOSD, serum levels of IL-6, IL-12, and IL-18 were significantly higher than in HC. CONCLUSION: Increased serum levels of IFN-γ, increased expression of IFN-γ in CD4+ cells, and decreased NK cell proportion correlate with disease activity in AOSD. Moreover, a lower proportion of NK cells may be useful for predicting a refractory clinical course. Meanwhile, increased serum levels of IL-6, IL-12, and IL-18 may persist after clinical remission.

Painless Panniculitis upon the Treatment of Clinically Amyopathic Dermatomyositis with Anti-MDA5 Antibody.

Panniculitis, a rare cutaneous manifestation in patients with dermatomyositis (DM), usually presents as a painful erythematous lesion. We herein report a 32-year-old woman with panniculitis that appeared as an indurated plaque without pain or redness after a 4-month episode of clinically amyopathic DM during treatment with prednisolone and tacrolimus. She experienced no pain; however, the firmness and extent gradually worsened. Based on our findings, including the histopathological results, DM panniculitis was diagnosed. Azathioprine was additionally administered, leading to remission. DM panniculitis can develop as a painless induration during immunosuppressive treatment, and azathioprine may be a useful treatment.

Neuroplastic Reorganization Induced by Sensory Augmentation for Self-Localization During Locomotion.

Sensory skills can be augmented through training and technological support. This process is underpinned by neural plasticity in the brain. We previously demonstrated that auditory-based sensory augmentation can be used to assist self-localization during locomotion. However, the neural mechanisms underlying this phenomenon remain unclear. Here, by using functional magnetic resonance imaging, we aimed to identify the neuroplastic reorganization induced by sensory augmentation training for self-localization during locomotion. We compared activation in response to auditory cues for self-localization before, the day after, and 1 month after 8 days of sensory augmentation training in a simulated driving environment. Self-localization accuracy improved after sensory augmentation training, compared with the control (normal driving) condition; importantly, sensory augmentation training resulted in auditory responses not only in temporal auditory areas but also in higher-order somatosensory areas extending to the supramarginal gyrus and the parietal operculum. This sensory reorganization had disappeared by 1 month after the end of the training. These results suggest that the use of auditory cues for self-localization during locomotion relies on multimodality in higher-order somatosensory areas, despite substantial evidence that information for self-localization during driving is estimated from visual cues on the proximal part of the road. Our findings imply that the involvement of higher-order somatosensory, rather than visual, areas is crucial for acquiring augmented sensory skills for self-localization during locomotion.

Development of Arthritis as the Initial Involvement in Adult-Onset Cutaneous Polyarteritis Nodosa: Two Cases and Literature Review.

Articular symptoms are commonly present in polyarteritis nodosa (PAN). Meanwhile, they may occur as the initial and main involvement of PAN, raising a concern of a delay in a definitive diagnosis of disease unless the histological evidence is obtained. Herein, we report two cases of cutaneous PAN (c-PAN) in which arthritis developed as the initial clinical episode of disease and we argued, through a review of the literature, the clinical feature of patients presenting with arthritis as the initial symptom of PAN. To our knowledge, only six cases have been reported in the English literature, and all six patients were categorized as having c-PAN. Of those patients, four had arthritis with indicating destructive changes. A median of 9 years elapsed prior to the induction of immunosuppressive treatment despite the fact that the other reviewed cases as well as our two patients, who received treatment significantly earlier, showed no evidence of joint destruction. Taken together, this report suggests that the early induction of therapy based on the definitive diagnosis of PAN may be required for preventing joint disruption even though it is not easy to make a diagnosis of PAN unless biopsied tissue can provide the evidence of necrotizing vasculitis.

Clinical characteristics of patients with myalgia as the initial manifestation of small and medium-sized vasculitis: a retrospective study.

Myalgia is a common symptom in small and medium-sized systemic vasculitis, sometimes occurring as the initial or only clinical manifestation of vasculitis. This study investigated the clinical features and diagnostic process in patients presenting with myalgia as the initial symptom of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) or polyarteritis nodosa (PAN). We included 93 patients diagnosed with AAV or PAN by retrospectively reviewing their clinical records at the initial diagnosis. Clinical findings and diagnostic methods were assessed in patients with myalgia. Of 93 patients, myalgia was observed in 21 (22.6%) patients, with diagnostic classifications of microscopic polyangiitis (MPA) in 12 (52.4%), granulomatosis with polyangiitis in 2 (9.5%), eosinophilic granulomatosis with polyangiitis in 2 (9.5%), and PAN in 5 (23.8%). Myalgia was present in the lower extremities of all patients; more than 80% of patients had pain in the calf muscle. In 10 patients with myalgia, including 7 with MPA and 3 with PAN, muscle biopsy was performed because myalgia was the main symptom and no other impaired organs were suitable for biopsy. Consequently, 8 patients had necrotizing vasculitis, leading to MPA or PAN diagnosis, although muscle pathology was not evaluated in patients without myalgia. Muscle magnetic resonance imaging was useful in determining the biopsy site. Myalgia, especially in the lower limbs, may be an initial clinical sign of vasculitis, particularly in MPA or PAN patients. Moreover, the histological evidence of muscular vasculitis can contribute to a definite diagnosis especially in patients presenting with myalgia as an early symptom of AAV or PAN.

Moyamoya syndrome related to systemic lupus erythematosus developing during pregnancy: a case-based review.

Moyamoya syndrome (MMS) is a chronic cerebrovascular disorder characterized by occlusion or stenosis of the internal carotid arteries with the formation of abnormal collateral vascular networks. Moreover, the development of MMS, which is a distinct category from "moyamoya disease," is attributed to the underlying disease, while some cases of MMS related to systemic lupus erythematosus (SLE) have been previously reported. Herein, we present the case of a 29-year-old Japanese woman with SLE in whom intracranial hemorrhage ascribable to MMS developed during pregnancy. Craniotomy was performed to remove hematoma, and prednisolone, tacrolimus, and hydroxychloroquine were consecutively administered. She ultimately achieved remission and childbearing without the relapse of cerebrovascular event. To our knowledge, this is the first report of MMS associated with SLE in pregnancy. Through reviewing published English articles and our case, it was suggested that the pathogenesis of SLE is implicated in the development of moyamoya vasculopathy leading to cerebrovascular events. Moreover, pregnancy may affect the bleeding from the fragile collateral vessel wall.

Macrophage activation syndrome in adult dermatomyositis: a case-based review.

Macrophage activation syndrome (MAS) is a severe and life-threatening syndrome associated with autoimmune diseases, characterized by fever, hepatosplenomegaly, and pancytopenia. Dermatomyositis (DM) is one of the causes of MAS; however, its clinical characteristics in DM patients remain unclear. This study aimed to present a case of anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive DM complicated by MAS in a 29-year-old woman and to review the literatures including similar cases. Even though symptoms and cytopenia of our patient were refractory to combination therapy, including glucocorticoids, immunosuppressants, and plasma exchange, the administration of rituximab (RTX) resulted in rapid clinical improvement and glucocorticoid reduction. The literature review revealed 18 adult patients with DM associated MAS. Most patients developed MAS within 3 months from DM onset. A monotherapy of glucocorticoid was insufficient to control the disease, and the mortality of MAS in DM was higher than that of MAS in other rheumatic diseases, despite being treated by various means. RTX may be an effective treatment for patients with DM complicated by MAS who are refractory to conventional therapy. Anti-MDA5 antibody could influence the development of MAS; however, further investigations are needed to elucidate the association between myositis-specific antibody and MAS.

Cerebrospinal fluid biomarkers implicated in the pathogenesis of anti-neutrophil cytoplasmic antibody-related hypertrophic pachymeningitis.

OBJECTIVE: Hypertrophic pachymeningitis (HP) related to anti-neutrophil cytoplasmic antibody (ANCA) is the most frequently seen immune-mediated HP. We investigated cerebrospinal fluid (CSF) biomarkers related to the pathogenesis of ANCA-related HP (ANCA-HP). METHODS: The levels of B cell activation factor of the tumor necrosis factor family (BAFF), a proliferation-inducing ligand (APRIL), and transforming growth factor beta 1 (TGF-ß1) in the CSF were compared between patients with ANCA-HP (n = 12), other types of immune-mediated HP (other HP; n = 12), multiple sclerosis (MS; n = 14), and non-inflammatory neurological disorders (NIND; n = 10). In addition, we evaluated whether ANCA would be detected in CSF. RESULTS: CSF levels of BAFF, APRIL, and TGF-ß1 were significantly increased in ANCA-HP and other HP. In particular, BAFF and APRIL levels were significantly correlated with the IgG index in ANCA-HP. In other HP, BAFF and APRIL levels were significantly correlated with cell counts and protein levels in CSF. Of 12 patients with ANCA-HP, the CSF of 7 patients (58%) tested positive for myeloperoxidase (MPO)- or proteinase 3 (PR3)-ANCA, while none of the CSF samples from other HP, MS, or NIND patients tested positive. CONCLUSION: The levels of BAFF, APRIL, and TGF-ß1 may serve as useful CSF biomarkers for assessing the disease activity of immune-mediated HP. Moreover, BAFF and APRIL in the CSF may be implicated in the pathogenesis of ANCA-HP via promoting autoreactive B cells, while detecting MPO- or PR3-ANCA in the CSF may be found in some patients with ANCA-HP.Key Points• CSF BAFF, APRIL, and TGF-ß1 levels increase significantly in immune-mediated HP.• CSF BAFF and APRIL levels are significantly correlated with IgG index in ANCA-HP.• Detection of MPO- or PR3-ANCA in the CSF is found in some patients with ANCA-HP.• BAFF, APRIL, and ANCA in the CSF may be implicated in the pathogenesis of ANCA-HP.

Acquired Amegakaryocytic Thrombocytopenia in Adult-onset Still's Disease: Successful Combination Therapy with Tocilizumab and Cyclosporine.

Adult-onset Still's disease (AOSD) sometimes demonstrates hematologic disorder, whereas acquired amegakaryocytic thrombocytopenia (AAT) involvement is extremely rare. We herein report a 67-year-old woman with relapse of AOSD who concomitantly developed AAT. Thrombocytopenia along with high disease activity of AOSD was resistant to high-dose prednisolone, even in combination with methotrexate and tacrolimus. However, alternative treatment with cyclosporine after administering tocilizumab resulted in the improvement of thrombocytopenia, ultimately demonstrating that combination therapy based on suppressing the intractable disease activity of AOSD and subsequently adding a reliable immunosuppressant was required to achieve remission.

[Determination of Nonvolatile Amines in Foods by HPLC Following Fluorescamine Derivatization].

A method was developed for the determination of nonvolatile amines, such as histamine, tyramine, putrescine, and cadaverine, in foods. These nonvolatile amines were extracted from a sample with 5% trichloroacetic acid, and the extract was purified using an InertSep MC-1 cartridge column. The four amines were derivatized with fluorescamine, determined by HPLC with a fluorescence detector, and confirmed by LC-MS/MS. The average recoveries (n=5) and the relative standard deviations from 11 foods (pacific saury, dried mackerel, canned mackerel in brine, canned tuna in oil, fish sauce, surimi, rice-koji miso, soy sauce, gouda cheese, red wine, and beer) spiked at 100 mg/kg were 81-100% and 0.4-3.1%, respectively.

Computing Social Value Conversion in the Human Brain.

Social signals play powerful roles in shaping self-oriented reward valuation and decision making. These signals activate social and valuation/decision areas, but the core computation for their integration into the self-oriented decision machinery remains unclear. Here, we study how a fundamental social signal, social value (others' reward value), is converted into self-oriented decision making in the human brain. Using behavioral analysis, modeling, and neuroimaging, we show three-stage processing of social value conversion from the offer to the effective value and then to the final decision value. First, a value of others' bonus on offer, called offered value, was encoded uniquely in the right temporoparietal junction (rTPJ) and also in the left dorsolateral prefrontal cortex (ldlPFC), which is commonly activated by offered self-bonus value. The effective value, an intermediate value representing the effective influence of the offer on the decision, was represented in the right anterior insula (rAI), and the final decision value was encoded in the medial prefrontal cortex (mPFC). Second, using psychophysiological interaction and dynamic causal modeling analyses, we demonstrated three-stage feedforward processing from the rTPJ and ldPFC to the rAI and then from rAI to the mPFC. Further, we showed that these characteristics of social conversion underlie distinct sociobehavioral phenotypes. We demonstrate that the variability in the conversion underlies the difference between prosocial and selfish subjects, as seen from the differential strength of the rAI and ldlPFC coupling to the mPFC responses, respectively. Together, these findings identified fundamental neural computation processes for social value conversion underlying complex social decision making behaviors.SIGNIFICANCE STATEMENT In daily life, we make decisions based on self-interest, but also in consideration for others' status. These social influences modulate valuation and decision signals in the brain, suggesting a fundamental process called value conversion that translates social information into self-referenced decisions. However, little is known about the conversion process and its underlying brain mechanisms. We investigated value conversion using human fMRI with computational modeling and found three essential stages in a progressive brain circuit from social to empathic and decision areas. Interestingly, the brain mechanism of conversion differed between prosocial and individualistic subjects. These findings reveal how the brain processes and merges social information into the elemental flow of self-interested decision making.

Cerebellar activation associated with model-based estimation of tool-use consequences.

BACKGROUND: Dexterous tool use is considered to be underpinned by model-based control relying on acquired internal models of tools. In particular, this is the case in situations where available sensory feedback regarding the consequences of tool use is restricted. In the present study, we conducted an fMRI study to identify cerebellar involvement in model-based estimation of tool-use consequences using tracking tasks with different levels of visual feedback. METHODS: Twenty healthy right-handed adults participated in this study. These participants tracked a moving target on a screen with a cursor controlled by a joystick using their right hand during fMRI scanning. For each trial, the level of visual feedback for cursor position was randomly selected from three task conditions, namely, Precise, Obscure, and No conditions. RESULTS: A conjunction analysis across all task conditions found extensive activation of the right cerebellum, covering the anterior lobe (lobule V) and inferior posterior lobe (lobule VIII). Also, contrasts among the three task conditions revealed additional significant activation of the left superior posterior lobe (Crus I) in the No compared to the Precise condition. Furthermore, a post hoc psychophysiological interaction analysis revealed conditional modulation of functional coupling between the right, but not the left, cerebellar region and right frontoparietal regions that are involved in self-body perception. CONCLUSIONS: Our data show that the left Crus I is the only region that was more active in a condition where no visual feedback for cursor position was available. This suggests that the left Crus I region plays a role in model-based estimation of tool-use consequences based on an acquired internal model of tools.

Characteristics of Circulating Natural Killer Cells and Their Interferon-γ Production in Active Adult-onset Still Disease.

OBJECTIVE: To investigate the characteristics of circulating natural killer (NK) cells and their interferon (IFN)-γ-producing ability in adult-onset Still disease (AOSD). METHODS: Peripheral blood mononuclear cells were obtained from 22 patients in the acute phase of AOSD (acute AOSD); 7 of the 22 patients after treatment (remission AOSD), and 11 healthy controls (HC). NK cells and their IFN-γ expression levels were analyzed by flow cytometry. Additionally, the cytokine receptors of interleukin (IL)-12, IL-15, and IL-18 on NK cells were also evaluated. RESULTS: The frequency of NK cells was significantly lower in acute AOSD than in HC. NK cell counts significantly increased in remission AOSD. Expression of IL-12 and IL-15 receptors on NK cells was significantly increased in acute AOSD, whereas that of IL-18 receptor indicated no significant difference among 3 groups. IFN-γ expression in NK cells was significantly higher in acute AOSD than in HC, and significantly decreased in remission AOSD. The absolute number of NK cells and IFN-γ-expressing NK cells revealed an inverse correlation with serum ferritin levels in acute AOSD. In 2 distinct subsets of NK cells, CD56dim NK cells significantly exhibited higher IFN-γ expression than CD56bright NK cells in acute AOSD. CONCLUSION: In acute AOSD, NK cells displayed lower proportion, whereas they had higher ability for IFN-γ production than in HC; moreover, upregulation of IL-12 and IL-15 receptors on NK cells may promote IFN-γ production. In addition, disease activity may be implicated in regulating the number of NK cells and IFN-γ-expressing NK cells in AOSD.

Propylthiouracil-induced Otitis Media with Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

We herein report a case of otitis media with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) induced by propylthiouracil (PTU). A 30-year-old Japanese woman with Graves' disease, who was treated with PTU, reported with otitis media with sensorineural hearing loss bilaterally and trigeminal neuralgia on the left side, as well as elevated serum levels of myeloperoxidase-ANCA. Prior treatment with antibiotics was ineffective even after tympanostomy. However, clinical remission was immediately achieved after initiating prednisolone together with PTU withdrawal. These findings suggest that PTU therapy induces localized otological involvement as the concept of OMAAV.