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Background: Advance care planning (ACP) is a widely advocated strategy to improve outcomes at end-of-life care for patients suffering from heart failure (HF). However, finding the right time to start ACP is challenging for healthcare providers because it is often a sensitive issue for patients with HF and their families. We interviewed patients with cardiovascular diseases regarding ACP readiness and investigated the relationship between the ACP desire and multiple clinical prognostic parameters., Method: Eighty-one patients (average age 81.8 ± 10.3 years old, 42 men, 62 cases of HF) who introduced cardiac rehabilitation were inquired about previous ACP experience, a desire for ACP, understanding of their cardiovascular diseases, and lifestyle-associated questionnaires. Multiple logistic regression analyses were employed to identify the clinical parameters associated with ACP desire. Patients who desired ACP were also asked about their preferences for medical care at the end-of-life., Results: Nine patients (11.1%) had previous experience with ACP, and 28 (34.6%) preferred to implement ACP. Patients who did not want to implement ACP were 54.3%. Patients with HF showed a higher acceptance rate of ACP (odds ratio [OR] 5.56, p = 0.015). Interestingly, patients harboring skeletal muscle frailty showed lower ACP acceptance, while patients with non-frailty rather positively wanted to implement ACP. Two types of prognosis evaluation scales, such as the Enhanced Feedback for Effective Cardiac Treatment (EFFECT) risk score and the Japanese Version of Supportive and Palliative Care Indicators Tool (SPICT-JP), identified 31 patients (38.3%) needing ACP; however, 19 (61.3%) did not want ACP. The wish not to attempt resuscitation and life-prolonging treatment at the end-of-life reached approximately 70% among patients who requested ACP., Conclusions: Although patients with HF tended to be ready for implementing ACP, the presence of skeletal muscle frailty was negatively associated with ACP preference. Indeed, patients who should be considered ACP were not carried out and did not desire it. Earlier introduction of ACP into patients before having skeletal muscle frailty may be considered., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fukue, Naito, Kimura, Ono, Sato, Takaki and Ikeda.)

Primary Objective: To examine whether vibration to the palm of the hand induces motor activity in the forearm muscles of individuals with post-stroke and healthy young adults. We hypothesized that the vibration would induce antagonistic muscle activities via the motor cortex., Research Design: Observational study using the between- and within-subjects mixed design., Methods and Procedures: Vibratory stimulation was applied to the palm of the paretic and non-paretic hands in seven post-stroke hemiplegia, and of the right hand in 22 healthy young adults in the eyes-closed and eyes-open conditions. Surface electromyography (sEMG) was recorded from the forearm extensors and flexors and the sEMG amplitudes were analyzed., Main Outcomes and Results: The extensor activities were significantly larger than that of the flexors in all hands. Especially, the extensor activities were augmented when the eyes were open in the paretic and non-paretic hands. Moreover, there was greater muscle activity in the non-paretic hand compared with the paretic hand., Conclusions: These novel findings revealed that vibration to the palm augmented the activity of the antagonistic forearm extensors, especially in the paretic hand, which was induced via top-down cortical modulation. Thus, it can be utilized to improve the impaired forearm extensors in post-stroke rehabilitation.

Background: Biomarker assessments for nivolumab monotherapy efficacy in previously treated patients with non-small cell lung cancer (NSCLC) remain unclear. We evaluated whether body mass index (BMI) and Glasgow prognostic score (GPS) are useful for assessing the efficacy of nivolumab alone as a second-line treatment in patients with pretreated NSCLC., Methods: Data of 99 patients treated with second-line nivolumab monotherapy for NSCLC between January 2016 and December 2019 were evaluated for prognostic values of BMI and GPS to assess their usefulness in predicting progression-free survival (PFS) and overall survival (OS)., Results: The Eastern Cooperative Oncology Group-performance status (PS) independently predicted the second-line nivolumab monotherapeutic effect; good PS (0-1) correlated with significantly longer PFS (4.3 vs. 1.9 months, log-rank; p = 0.0004) and OS (17.7 vs. 4.6 months, log-rank; p < 0.0001) than poor PS. BMI independently predicted survival, with high BMI (≥22.1 kg/m 2 ) associated with significantly longer OS (19.1 vs. 8.5 months, log-rank; p = 0.0023) than low BMI (<22.1 kg/m 2 ). However, GPS showed no significant difference for PFS or OS., Conclusion: Among patients with NSCLC treated with nivolumab monotherapy as second-line treatment, PS was significantly correlated with both PFS and OS and BMI with OS. Thus, BMI could be a useful predictor of survival in these patients., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

The human brain has the capacity to drastically alter its somatotopic representations in response to congenital or acquired limb deficiencies and dysfunctions. The main purpose of the present study was to elucidate such extreme adaptability in the brain of an active top wheelchair racing Paralympian (participant P1) who has congenital paraplegia (dysfunction of bilateral lower limbs). Participant P1 has undergone long-term wheelchair racing training using bilateral upper limbs and has won a total of 19 medals in six consecutive summer Paralympic games as of 2021. We examined the functional and structural changes in the foot section of the primary motor cortex (M1) in participant P1 as compared to able-bodied control participants. We also examined the functional and structural changes in three other individuals (participants P2, P3, and P4) with acquired paraplegia, who also had long-term non-use period of the lower limbs and had undergone long-term training for wheelchair sports (but not top athletes at the level of participant P1). We measured brain activity in all the participants using functional magnetic resonance imaging (MRI) when bimanual wrist extension-flexion movement was performed, and the structural MRI images were collected. Compared to 37 control participants, participant P1 showed significantly greater activity in the M1 foot section during the bimanual task, and significant local GM expansion in this section. Significantly greater activity in the M1 foot section was also observed in participant P4, but not in P2 and P3, and the significant local GM expansion was observed in participant P2, but not in P3 and P4. Thus, functional or structural change was observed in an acquired paraplegic participant, but was not observed in all the paraplegic participants. The functional and structural changes typically observed in participant P1 may represent extreme adaptability of the human brain. We discuss the results in terms of a new idea of hyper-adaptation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Morita, Hirose, Kimura, Takemura, Asada and Naito.)

Purpose: Nivolumab + ipilimumab (nivo + ipi) is highly efficacious but has high toxicity. Standard treatment in advanced melanoma is four doses of nivo + ipi followed by nivo alone. Whether four doses of nivo + ipi are needed is unclear., Methods: The Adaptively Dosed ImmunoTherapy Trial (ADAPT-IT) study (NCT03122522) is a multicenter, single-arm phase II clinical trial. Patients received two doses of nivo (1 mg/kg) + ipi (3 mg/kg) followed by a computed tomography scan at week 6. Patients without new lesions or index lesion tumor growth of > 4% had protocol-defined early favorable antitumor effect (FATE) and ceased nivo + ipi, transitioning to nivo monotherapy. Patients without FATE at week 6 received the standard third and fourth doses of nivo + ipi followed by nivo monotherapy. The primary end point was response rate by RECIST 1.1 at week 12. Secondary end points included additional efficacy assessments and safety., Results: Sixty patients were enrolled; 41 patients (68%) had FATE at week 6 and met criteria for stopping nivo + ipi. Best overall response rates by RECIST at week 12 or any time afterward were 48% (95% CI, 35 to 62) and 58% (95% CI, 45 to 71), respectively. With a median follow-up of 25 months, the estimated 18-month progression-free survival and overall survival are 52% and 80%, respectively. Fifty seven percent of patients had grade 3-5 treatment-related toxicity., Conclusion: The efficacy and toxicity of standard four dose nivo + ipi induction therapy in melanoma is likely driven by the first two doses. An interim computed tomography scan after two doses guided cessation of combination dosing and identified almost all responders. Longer follow-up and further study are needed to fully understand the implications of a shortened induction course of nivo + ipi., Competing Interests: Michael A. PostowConsulting or Advisory Role: Bristol Myers Squibb, Novartis, Array BioPharma, NewLink Genetics, Incyte, Merck, Eisai, PfizerResearch Funding: Bristol Myers Squibb (Inst), Novartis (Inst), Array BioPharma (Inst), Infinity Pharmaceuticals (Inst), Regenix (Inst), Merck (Inst), AstraZeneca/MedImmune (Inst) Debra A. GoldmanEmployment: RegeneronStock and Other Ownership Interests: Johnson & Johnson Alexander N. ShoushtariConsulting or Advisory Role: Immunocore, Bristol Myers SquibbResearching Funding: Immunocore, Bristol Myers Squibb, Xcovery, Polaris, Novartis (Inst), Pfizer (Inst)Patents, Royalties, Other Intellectual Property: UpToDate Allison Betof WarnerHonoraria: LG ChemConsulting or Advisory Role: Nanbiotix, Iovance Biotherapeutics, Novartis, Shanghai Jo’Ann Medical Technology, BluePath Solutions, PfizerResearch Funding: Leap Therapeutics Margaret K. CallahanEmployment: Bristol-Myers Squibb (I), Celgene (I), Kleo Pharmaceuticals (I), Bristol-Myers Squibb (I)Consulting or Advisory Role: AstraZeneca, Moderna Therapeutics, Merck, ImmunocoreResearching Funding: Bristol Myers Squibb (Inst)Other Relationship: Clinical Care Options, Potomac Center for Medical Education Omar EtonSpeakers’ Bureau: MerckResearching Funding: Bristol Myers Squibb (Inst) Suresh G. NairStock and Other Ownership Interests: Moderna Therapeutics, Novavax, Biotech, Gilead SciencsResearch Funding: Bristol-Myers Squibb, Merck, Nektar (Inst) Katherine S. PanageasStock and Other Ownership Interests: AstraZeneca, Pfizer, Sunesis Pharmaceuticals Jedd D. WolchokStock and Other Ownership Interests: Tizona Therapeutics, Inc, Adaptive Biotechnologies, Imvaq Therapeutics, Beigene, Linnaeus Therapeutics, Arsenal IO, Geogiamune, LLC, Maverick Therapeutics, Apricity Therapeutics, Trieza TherapeuticsConsulting or Advisory Role: Bristol-Myers Squibb, Merck, Sellas Life Sciences, Lilly, Tizona Therapeutics, Inc,, Amgen, Chugai Pharma, Adaptive Biotechnologies, Ascentage Pharma, PsiOxus Therapeutics, F-Start Biotechnology, Surface Biotechnology, Apricity Therapeutics, PsiOxus Therapeutics, F-Star Biotechnology, Surface Oncology, Apricity Therapeutics, PsiOxus Therapeutics, Astellas Pharma, Recepta Biopharma, Arsenal IO, Boehringer Ingelheim, AstraZeneca, Daiichi Sankyo,Inc, Dragonfly Therapeutics, Geogiamune, Kyowa Kirin Pharmaceutical, Maverick Therapeutics, Werewolf Therapeutics, Trishula Therapeutics, Idera, Imvq Therapeutics, Biscara TherapeuticsResearch Funding: Bristol Myers Squibb (Inst), Genentech/Roche (Inst), Merck Sharp & Dohme (Inst)Patents, Royalties, Other Intellectual Property: I am a co-inventor on an issued patent for DNA vaccines for treatment for cancer in companion animals, I am a co-inventor on a patent for use of oncolytic Newcaste Disease virus, I am a co-inventor and receive royalties for a blood test for monitoring myeloid derived suppressor cells. I am co-inventor and receive royalties for a petent for immune modulating antibododies. I am a co-inventor on a patent for CAR+ T cells targeting differentiation antigens as means to treat cancer. I am a co-inventor on a patent for Anti-CD40 agonist mAb fused to Monophosphory Lipid A (MPL) for cancer therapy, Alphavirus Replicon Particles Expressing TRP2, Engineered Vaccinia Viruses for Cancer Immunotherapy, Recombinant Poxviruses for Cancer Immunotherapy Paul B. ChapmanConsulting or Advisory Role: Merck, Pfizer, Black Diamond TherapeuticsResearch Funding: Pfizer, NCI (Inst), GenentechNo other potential conflicts of interest were reported.

Background: Pyruvate dehydrogenase complex (PDHC) deficiency is an inborn error of metabolism that causes lactic acidosis and neurodevelopmental changes. Five causative genes have been identified: PDHA1, PDHB, DLAT, DLD, and PDHX. Four neurological phenotypes have been reported: neonatal encephalopathy with lactic acidosis, non-progressive infantile encephalopathy, Leigh syndrome, and relapsing ataxia. Of these, neonatal encephalopathy has the worst mortality and morbidity and there is no effective treatment., Subjects and Methods: We studied two girls who were clinically diagnosed with PDHC deficiency as neonates; they were subsequently found to have PDHA1 mutations. The clinical diagnosis was based on white matter loss and a lateral ventricular septum on fetal MRI, spasticity of the lower extremities, and lactic acidosis worsening after birth. Intravenous ketogenic diets were started within 24 h after birth. The ketogenic ratio was increased until the blood lactate level was controlled, while monitoring for side effects., Results: In both cases, the lactic acidosis improved immediately with no apparent side effects. Both children had better developmental outcomes than previously reported cases; neither exhibited epilepsy., Conclusions: Intravenous ketogenic diet therapy is a treatment option for neonatal-onset PDHC deficiency. Further studies are needed to optimize this therapy., (Copyright © 2021 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Canine degenerative myelopathy (DM) is a progressive neurodegenerative disease of the spinal cord. The diagnosis is based on the observation of clinical signs, genetic testing, and exclusion of other spinal cord diseases, and a definitive diagnosis of DM can only be confirmed by postmortem histopathological findings. The aim of this study was to investigate the diagnostic ability of diffusion tensor imaging (DTI) for DM. Eight DM-affected Pembroke Welsh Corgis, thirteen dogs with thoracolumbar intervertebral disk herniation (IVDH), and six healthy control dogs were included. All dogs were scanned using a 3.0-T MRI system. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were calculated for each intervertebral disk level slice between T8-T9 and L2-L3 intervertebral disk levels, and the entire area of the thoracolumbar spinal cord between T8-T9 and L2-L3 intervertebral disk levels (T8-L3 region). The ADC and FA values of the T8-L3 region were significantly lower in the DM group than in the IVDH group. The ADC values for the T8-L3 region had a moderate negative correlation with clinical duration (r s = -0.723, P=0.043); however, the FA values of other intervertebral disk levels and T8-L3 region had no correlation with clinical durations. The measurement of DTI indices can be used to quantitatively assess neurodegeneration and may have diagnostic value for DM. In particular, the ADC value of the T8-L3 region may aid in making a non-invasive premortem diagnosis of DM.

A 67-year-old Japanese man was admitted to our hospital with severe coronavirus disease 2019 (COVID-19) in March 2020. Mechanical ventilation was initiated 8 days after admission, due to severe respiratory failure. Multiple severe complications such as liver dysfunction, arrhythmia, brain infarction, and venous thromboembolism were also observed. We initially diagnosed Coombs test-positive warm autoimmune hemolytic anemia. Corticosteroids proved ineffective and anemia worsened with severe erythroid hypoplasia (0.5% erythroblasts in bone marrow), so we diagnosed pure red cell aplasia (PRCA). We also identified massive infiltration of cytotoxic T-lymphocytes expressing CD8, granzyme B, and perforin in bone marrow. Systemic cyclosporine was started, with full resolution of anemia and no need for blood transfusions after 4 weeks. We believe that this represents the first report of COVID-19-associated PRCA successfully treated using cyclosporine., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Improving deteriorated sensorimotor functions in older individuals is a social necessity in a super-aging society. Previous studies suggested that the declined interhemispheric sensorimotor inhibition observed in older adults is associated with their deteriorated hand/finger dexterity. Here, we examined whether bimanual digit exercises, which can train the interhemispheric inhibitory system, improve deteriorated hand/finger dexterity in older adults. Forty-eight healthy, right-handed, older adults (65-78 years old) were divided into two groups, i.e., the bimanual (BM) digit training and right-hand (RH) training groups, and intensive daily training was performed for 2 months. Before and after the training, we evaluated individual right hand/finger dexterity using a peg task, and the individual state of interhemispheric sensorimotor inhibition by analyzing ipsilateral sensorimotor deactivation via functional magnetic resonance imaging when participants experienced a kinesthetic illusory movement of the right-hand without performing any motor tasks. Before training, the degree of reduction/loss of ipsilateral motor-cortical deactivation was associated with dexterity deterioration. After training, the dexterity improved only in the BM group, and the dexterity improvement was correlated with reduction in ipsilateral motor-cortical activity. The capability of the brain to inhibit ipsilateral motor-cortical activity during a simple right-hand sensory-motor task is tightly related to right-hand dexterity in older adults., (© 2021. The Author(s).)

Interhemispheric inhibition (IHI) between the left and right primary motor cortices (M1) plays an important role when people perform an isolated unilateral limb movement. Moreover, negative blood oxygenation-level dependent signal (deactivation) obtained from the M1 ipsilateral to the limb could be a surrogate IHI marker. Studies have reported deactivation in the hand section of the ipsilateral M1 during simple unilateral hand movement. However, deactivation in the foot section during unilateral foot movement has not been reported. Therefore, IHI between the foot sections of the bilateral M1s has been considered very weak or absent. Thirty-seven healthy adults performed active control of the right foot and also passively received vibration to the tendon of the tibialis anterior muscle of the right foot, which activates the foot section of the contralateral M1, with brain activity being examined through functional magnetic resonance imaging. The vibration and active tasks significantly and non-significantly, respectively, deactivated the foot section of the ipsilateral M1, with a corresponding 86% and 60% of the participants showing decreased activity. Thus, there could be IHI between the foot sections of the bilateral M1s. Further, our findings demonstrate between-task differences and similarities in cross-somatotopic deactivation.

Background: Allergen immunotherapy (AIT) is a specific treatment of administering clinically important allergens to patients who have allergic diseases. In Japan, the standardized house dust mite (HDM) allergen for subcutaneous immunotherapy (SCIT) was approved in 2015, and we then introduced rush-immunotherapy (rush-IT) using the standardized HDM allergen for HDM-sensitive asthmatics. However, little data are available on the safety and effectiveness of rush-HDM-IT, especially for Japanese asthmatics., Objective: The objective of this study was to examine the safety and clinical effectiveness of rush-IT using the standardized HDM for HDM-sensitive Japanese asthmatics., Methods: Thirteen HDM-sensitive asthmatics who received rush-HDM-IT and 12 HDM-sensitive asthmatic controls were enrolled. To evaluate the safety, the number of systemic reaction (SR) events, including anaphylaxis, was assessed. To evaluate the effectiveness, changes in the treatment step, dose of inhaled corticosteroid, and asthma control after rush-HDM-IT and the subsequent maintenance SCIT were assessed. Changes in the HDM-induced production of type 2 cytokines from peripheral blood mononuclear cells were also evaluated., Results: Among the 12 patients who received rush-IT, 4 (30.7%) experienced a SR and 3 (23.1%) experienced anaphylaxis. However, the anaphylaxis was not severe (grade 3) in all cases, and they recovered in a short time. The treatment step of asthma was better and the dose of inhaled corticosteroid was lower in the rush-HDM-IT group than in the control group. The HDM-induced production of both interleukin (IL)-5 and IL-13 from peripheral blood mononuclear cells was significantly lower in the rush-HDM-IT group than in the control group., Conclusion: Rush-HDM-IT can be performed relatively safely in Japanese asthmatics. Furthermore, rush-HDM-IT and the subsequent maintenance SCIT provided clinical improvement in asthma patients, and was accompanied by the suppression of HDM-specific Th2-mediated systemic immune responses., Competing Interests: Conflict of Interest: MN received fees for speaking from Torii Pharmaceutical Co., Ltd. The rest of the authors declare no conflicts of interest., (Copyright © 2021. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.)

Canine degenerative myelopathy (DM) is a progressive and fatal neurodegenerative disease. However, a definitive diagnosis of DM can only be achieved by postmortem histopathological examination of the spinal cord. The purpose of this study was to investigate whether the volumetry of DRG using the ability of water-excitation magnetic resonance imaging (MRI) to visualize the DRG in dogs has premortem diagnostic value for DM. Eight dogs with DM, twenty-four dogs with intervertebral disc herniation (IVDH), and eight control dogs were scanned using a 3.0-tesla MRI system, and water-excitation images were obtained to visualize and measure the volume of DRG, normalized by body surface area. The normalized mean DRG volume between each spinal cord segment and mean volume of all DRG between T8 and L2 in the DM group was significantly lower than that in the control and the IVDH groups ( P = 0.011, P = 0.002, respectively). There were no correlations within the normalized mean DRG volume between DM stage 1 and stage 4 ( r s = 0.312, P = 0.128, respectively). In conclusion, DRG volumetry by the water-excitation MRI provides a non-invasive and quantitative assessment of neurodegeneration in DRG and may have diagnostic potential for DM.

The superior longitudinal fascicle/fasciculus (SLF) is a major white matter tract connecting the frontal and parietal cortices in humans. Although the SLF has often been analyzed as a single entity, several studies have reported that the SLF is segregated into three distinct branches (SLF I, II, and III). They have also reported the right lateralization of the SLF III volume and discussed its relationship with lateralized cortical functions in the fronto-parietal network. However, to date, the homogeneity or heterogeneity of the age dependency and lateralization properties of SLF branches have not been fully clarified. Through this study, we aimed to clarify the age dependency and lateralization of SLF I-III by analyzing diffusion-weighted MRI (dMRI) and quantitative R1 (qR1) map datasets collected from a wide range of age groups, mostly comprising right-handed children, adolescents, adults, and seniors (6 to 81 years old). The age dependency in dMRI measurement (fractional anisotropy, FA) was heterogeneous among the three SLF branches, suggesting that these branches are regulated by distinct developmental and aging processes. Lateralization analysis on SLF branches revealed that the right SLF III was larger than the left SLF III in adults, replicating previous reports. FA measurement also suggested that, in addition to SLF III, SLF II was lateralized to the right hemisphere in adolescents and adults. We further found a left lateralization of SLF I in qR1 data, a microstructural measurement sensitive to myelin levels, in adults. These findings suggest that the SLF sub-bundles are distinct entities in terms of age dependency and lateralization., Competing Interests: Declaration of competing interest None., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In people with normal sight, mental simulation (motor imagery) of an experienced action involves a multisensory (especially kinesthetic and visual) emulation process associated with the action. Here, we examined how long-term blindness influences sensory experience during motor imagery and its neuronal correlates by comparing data obtained from blind and sighted people. We scanned brain activity with functional magnetic resonance imaging (fMRI) while 16 sighted and 14 blind male volunteers imagined either walking or jogging around a circle of 2 m radius. In the training before fMRI, they performed these actions with their eyes closed. During scanning, we explicitly instructed the blindfolded participants to generate kinesthetic motor imagery. After the experimental run, they rated the degree to which their motor imagery became kinesthetic or spatio-visual. The imagery of blind people was more kinesthetic as per instructions, while that of the sighted group became more spatio-visual. The imagery of both groups commonly activated bilateral frontoparietal cortices including supplementary motor areas (SMA). Despite the lack of group differences in degree of brain activation, we observed stronger functional connectivity between the SMA and cerebellum in the blind group compared to that in the sighted group. To conclude, long-term blindness likely changes sensory emulation during motor imagery to a more kinesthetic mode, which may be associated with stronger functional coupling in kinesthetic brain networks compared with that in sighted people. This study adds valuable knowledge on motor cognition and mental imagery processes in the blind.

Self-consciousness is a personality trait associated with an individual's concern regarding observable (public) and unobservable (private) aspects of self. Prompted by previous functional magnetic resonance imaging (MRI) studies, we examined possible gray-matter expansions in emotion-related and default mode networks in individuals with higher public or private self-consciousness. One hundred healthy young adults answered the Japanese version of the Self-Consciousness Scale (SCS) questionnaire and underwent structural MRI. A voxel-based morphometry analysis revealed that individuals scoring higher on the public SCS showed expansions of gray matter in the emotion-related regions of the cingulate and insular cortices and in the default mode network of the precuneus and medial prefrontal cortex. In addition, these gray-matter expansions were particularly related to the trait of "concern about being evaluated by others", which was one of the subfactors constituting public self-consciousness. Conversely, no relationship was observed between gray-matter volume in any brain regions and the private SCS scores. This is the first study showing that the personal trait of concern regarding public aspects of the self may cause long-term substantial structural changes in social brain networks.

Although studies have determined the neutrophil-lymphocyte ratio (NLR) to be a useful prognostic predictor in various human cancers, little is known regarding its preoperative prognostic significance in feline mammary tumors (FMTs). Thus, the present study aimed to determine the prognostic utility of preoperative peripheral blood NLR in malignant FMTs. Accordingly, medical records of 34 cats that had undergone mastectomy were searched, after which those histopathologically confirmed to have malignant FMTs were included. Univariate analysis was used to determine the effect of each variable on one-year survival time. Factors determined to be significant during univariate analysis were subsequently included for multivariate analysis. Receiver operating characteristic analysis was used to assess the accuracy of the tests for predicting one-year survival. Univariate analysis showed that a high NLR and large tumor size were significantly associated with shorter survival times (P < 0.01, for both). No significant differences in other factors were observed. Multivariate analysis showed that a high NLR (hazard ratio, 25.03; 95% confidence interval, 2.98-210.40; P < 0.01), but not tumor size and age, was an independent prognostic factor for poor outcomes. The sensitivity and specificity of the NLR (cut-off, 5.67) for predicting one-year survival were 93.8% and 88.9%, respectively. This study suggests that the NLR could potentially be used as a preoperative prognostic factor in FMTs. Preoperative NLR may help to establish therapeutic modalities by allowing prognostic evaluation among cats with mammary tumors., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Hand/finger dexterity is well-developed in humans, and the primary motor cortex (M1) is believed to play a particularly important role in it. Here, we show that efficient recruitment of the contralateral M1 and neuronal inhibition of the ipsilateral M1 identified by simple hand motor and proprioceptive tasks are related to hand/finger dexterity and its ontogenetic development. We recruited healthy, right-handed children ( n  = 21, aged 8-11 years) and adults ( n  = 23, aged 20-26 years) and measured their brain activity using functional magnetic resonance imaging during active and passive right-hand extension-flexion tasks. We calculated individual active control-related activity (active-passive) to evaluate efficient brain activity recruitment and individual task-related deactivation (neuronal inhibition) during both tasks. Outside the scanner, participants performed 2 right-hand dexterous motor tasks, and we calculated the hand/finger dexterity index (HDI) based on their individual performance. Participants with a higher HDI exhibited less active control-related activity in the contralateral M1 defined by the active and passive tasks, independent of age. Only children with a higher HDI exhibited greater ipsilateral M1 deactivation identified by these tasks. The results imply that hand/finger dexterity can be predicted by recruitment and inhibition styles of the M1 during simple hand sensory-motor tasks., (© The Author(s) 2020. Published by Oxford University Press.)

A swarm robotic system is a system in which multiple robots cooperate to fulfill a macroscopic function. Many swarm robots have been developed for various purposes. This study aims to design swarm robots capable of executing spatially distributed tasks effectively, which can be potentially used for tasks such as search-and-rescue operation and gathering scattered garbage in rooms. We propose a simple decentralized control scheme for swarm robots by extending our previously proposed non-reciprocal-interaction-based model. Each robot has an internal state, called its workload . Each robot first moves randomly to find a task, and when it does, its workload increases, and then it attracts its neighboring robots to ask for their help. We demonstrate, via simulations, that the proposed control scheme enables the robots to effectively execute multiple tasks in parallel under various environments. Fault tolerance of the proposed system is also demonstrated.

Visual self-face and proprioceptive postural recognition predominantly activate the right inferior frontoparietal cortices in human right-handers at the population level. In the present study, prompted by the finding that left-handedness may alter lateralized cortical organization for language, sensory-motor, and cognitive functions observed in right-handers, we investigated individual variations in right-dominant use of the cortices in 50 right-handers and 50 left-handers during self-body recognition (self-face and proprioceptive) tasks. We also investigated possible between-tasks differences in this right-dominant use, and possible atypical left-right reversed lateralization (right-dominance for language and left-dominance for self-body recognition) in left-handers. We measured brain activity using functional magnetic resonance imaging while participants performed a proprioceptive postural recognition task (experiencing illusory movements of the left and the right hands), a visual self-face recognition (self-other distinction) task, and a language (verb generation) task. To evaluate hemispheric dominance, we computed individual lateralization indices for the inferior frontoparietal activities in these tasks. Left-handedness altered the right-hemispheric dominance that was observed in the majority of right-handed participants in both self-body recognition tasks. In the left-handed group, during proprioceptive recognition, participants with right-lateralization, bilaterality, or left-lateralization were equally distributed, and during self-face recognition, right-lateralization was still observed, though the number of participants who demonstrated left-lateralization increased. Atypical left-right reversed lateralization was only observed in left-handed participants, but during both self-body recognition tasks. The present study provides novel and valuable knowledge about right-hemispheric dominance in self-body recognition affected by left-handedness. We discuss how functional lateralization of self-body recognition is shaped in human brain, in terms of handedness, language lateralization, and development., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In this study, we demonstrate the involvement of left frontoparietal cortices in neural processes for task-switching between skilled movements. Functional magnetic resonance imaging was conducted while thirty-two right-handed healthy participants performed two sequential finger-movement tasks with their left hands. One group (n = 16) trained these tasks through random-practice (tasks were either switched or repeated trial by trial) on one day and blocked-practice (successive intensive practice of each task) on the next day, while the remaining participants practiced in the reverse order. On the first day, performance of both tasks improved in all participants, suggesting that the two skilful tasks can be learned in both practice schedules. However, during the random-practice, the performance in the switched trials initially deteriorated and gradually approached to that in the repeated trials as the practice proceeded. The left (mainly inferior) frontoparietal cortices showed greater preparatory activity for the switched trials compared with the repeated trials in a left-hemispheric dominant manner, and the left intraparietal activity decreased as the performance of the switched trials improved. The results indicate that neural processes for task-switching are associated with the greater preparatory activity in the left inferior frontoparietal cortices, and the efficient switching may proceed concomitantly with the left intraparietal activity reduction., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aims/introduction: Although nerve conduction study (NCS) using a standard electromyography system (EMGS) is considered to be the gold standard in evaluating diabetic polyneuropathy, this examination requires expensive equipment and well-trained technicians. We aimed to validate a point-of-care device, NC-stat/DPNCheck™, that has been developed for widespread use of NCS in diabetic polyneuropathy., Materials and Methods: Diabetes patients underwent two kinds of NCS: DPNCheck™ and electromyography system. Inter-/intrarater reliability of DPNCheck™ were also determined by the intraclass correlation coefficient., Results: A total of 57 patients were evaluated. The parameters of NCS between the two methods correlated well (r = 0.7734 for the sural nerve conduction velocity, r = 0.6155 for the amplitude of sural nerve action potential). The intraclass correlation coefficients were excellent (intrarater: the velocity 0.767, the amplitude 0.811; interrater: the velocity 0.974, the amplitude 0.834)., Conclusions: The point-of-care device has excellent reproducibility and good agreement with standard electromyography system. The device might be useful to evaluate diabetic polyneuropathy., (© 2019 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Interpersonal rhythmic interaction is one of the fundamental behaviors that allow humans to socially interact with others. In this study, we provide novel neuroimaging evidence that being followed by other agents in such an interaction is pleasant for humans. Using functional magnetic resonance imaging, we measured the brain activity of 17 participants while they performed a virtual drum-hitting task, in one of the following conditions: a) alternating with a virtual agent that would always copy their hitting pace, or b) alternating with a virtual agent that would randomly hit the drum. The participants reported a significantly higher subjective feeling of being followed by the agent in the first condition. Moreover, almost all participants preferred the agent that followed their drum-hitting rhythm. The activity of the caudate nucleus, which is one of the reward-related brain structures, was found to be associated with the subjective feeling of being followed, suggesting that the sense of being the leader, in an interpersonal rhythmic interaction, creates a pleasant feeling., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Performing tasks activates relevant brain regions in adults while deactivating task-irrelevant regions. Here, using a well-controlled motor task, we explored how deactivation is shaped during typical human development and whether deactivation is related to task performance. Healthy right-handed children (8-11 years), adolescents (12-15 years), and young adults (20-24 years; 20 per group) underwent functional magnetic resonance imaging with their eyes closed while performing a repetitive button-press task with their right index finger in synchronization with a 1-Hz sound. Deactivation in the ipsilateral sensorimotor cortex (SM1), bilateral visual and auditory (cross-modal) areas, and bilateral default mode network (DMN) progressed with development. Specifically, ipsilateral SM1 and lateral occipital deactivation progressed prominently between childhood and adolescence, while medial occipital (including primary visual) and DMN deactivation progressed from adolescence to adulthood. In adults, greater cross-modal deactivation in the bilateral primary visual cortices was associated with higher button-press timing accuracy relative to the sound. The region-specific deactivation progression in a developmental period may underlie the gradual promotion of sensorimotor function segregation required in the task. Task-induced deactivation might have physiological significance regarding suppressed activity in task-irrelevant regions. Furthermore, cross-modal deactivation develops to benefit some aspects of task performance in adults., (© 2019 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc.)

Sensorimotor function is a fundamental brain function in humans, and the cerebrocerebellar circuit is essential to this function. In this study, we demonstrate how the cerebrocerebellar circuit develops both functionally and anatomically from childhood to adulthood in the typically developing human brain. We measured brain activity using functional magnetic resonance imaging while a total of 57 right-handed, blindfolded, healthy children (aged 8-11 years), adolescents (aged 12-15 years), and young adults (aged 18-23 years) (n = 19 per group) performed alternating extension-flexion movements of their right wrists in precise synchronization with 1-Hz audio tones. We also collected their diffusion MR images to examine the extent of fiber maturity in cerebrocerebellar afferent and efferent tracts by evaluating the anisotropy-sensitive index of hindrance modulated orientational anisotropy (HMOA). During the motor task, although the ipsilateral cerebellum and the contralateral primary sensorimotor cortices were consistently activated across all age groups, the functional connectivity between these two distant regions was stronger in adults than in children and adolescents, whereas connectivity within the local cerebellum was stronger in children and adolescents than in adults. The HMOA values in cerebrocerebellar afferent and efferent tracts were higher in adults than in children (some were also higher than in adolescents). The results indicate that adult-like cerebrocerebellar functional coupling is not completely achieved during childhood and adolescence, even for fundamental sensorimotor brain function, probably due to anatomical immaturity of cerebrocerebellar tracts. This study clearly demonstrated the principle of "local-to-distant" development of functional brain networks in the human cerebrocerebellar sensorimotor network.

Motor action is prepared in the human brain for rapid initiation at the appropriate time. Recent non-invasive decoding techniques have shown that brain activity for action preparation represents various parameters of an upcoming action. In the present study, we demonstrated that a freely chosen effector can be predicted from brain activity measured using functional magnetic resonance imaging (fMRI) before initiation of the action. Furthermore, the activity was related to response time (RT). We measured brain activity with fMRI while 12 participants performed a finger-tapping task using either the left or right hand, which was freely chosen by them. Using fMRI decoding, we identified brain regions in which activity during the preparatory period could predict the hand used for the upcoming action. We subsequently evaluated the relationship between brain activity and the RT of the upcoming action to determine whether correct decoding was associated with short RT. We observed that activity in the supplementary motor area, dorsal premotor cortex (PMd), and primary motor cortex (M1) measured before action execution predicted the hand used to perform the action with significantly above-chance accuracy (approximately 70%). Furthermore, in most participants, the RT was shorter in trials for which the used hand was correctly predicted by activity in the PMd and M1. The present study showed that preparatory activity in cortical motor areas represents information about the effector used for an upcoming action, and that well-formed motor representations in these regions are associated with reduced response times., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Severe asthma is a complex disease with heterogeneous features and involves type 2 airway inflammation, including eosinophil accumulation. Surrogate biomarkers, fraction of exhaled nitric oxide (FeNO) and blood eosinophil count (b-EOS), may predict eosinophilic airway inflammation. Here we investigated clinical characteristics of severe asthma phenotype using a combined analysis of FeNO and b-EOS., Methods: This retrospective study examined clinical data of patients with severe asthma (N = 107; median age, 64 years) treated at Saitama Medical University Hospital from 2009 to 2016. Thresholds of FeNO and b-EOS for sputum eosinophil ratio ≥2% were determined using receiver operating characteristic curve (ROC) analysis. Clinical characteristics were analyzed after classifying patients into four subgroups according to these thresholds., Results: Of 39 induced sputum samples examined, ROC area under the curve for predicting sputum eosinophilia was 82.0% (p = 0.001) for b-EOS and 77.0% (p = 0.006) for FeNO at optimal cut-off values of ≥300/μL and ≥25 ppb, respectively. The number of sensitized allergens was higher in the high FeNO/low b-EOS and high FeNO/high b-EOS subgroups (p < 0.05). The prevalence of chronic sinusitis was higher in the low FeNO/high b-EOS and high FeNO/high b-EOS subgroups (p = 0.04). The high FeNO/high b-EOS subgroup included the largest proportion (approximately 40%) of patients experiencing frequent severe exacerbations. Both low FeNO/low b-EOS and high FeNO/low b-EOS subgroups showed less severe exacerbations., Conclusions: Combined evaluation of FeNO and b-EOS can identify patients with frequent exacerbations and stratify the appropriate therapy for type 2 inflammation-predominant severe asthma., (Copyright © 2018 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

We recently reported that right-side dominance of the inferior parietal lobule (IPL) in self-body recognition (proprioceptive illusion) task emerges during adolescence in typical human development. Here, we extend this finding by demonstrating that functional lateralization to the right IPL also develops during adolescence in another self-body (specifically a self-face) recognition task. We collected functional magnetic resonance imaging (fMRI) data from 60 right-handed healthy children (8-11 years), adolescents (12-15 years), and adults (18-23 years; 20 per group) while they judged whether a presented face was their own (Self) or that of somebody else (Other). We also analyzed fMRI data collected while they performed proprioceptive illusion task. All participants performed self-face recognition with high accuracy. Among brain regions where self-face-related activity (Self vs. Other) developed, only right IPL activity developed predominantly for self-face processing, with no substantial involvement in other-face processing. Adult-like right-dominant use of IPL emerged during adolescence, but was not yet present in childhood. Adult-like common activation between the tasks also emerged during adolescence. Adolescents showing stronger right-lateralized IPL activity during illusion also showed this during self-face recognition. Our results suggest the importance of the right IPL in neuronal processing of information associated with one's own body in typically developing humans.

An obesity-related prediabetic state is characterised by metabolic abnormalities such as post-glucose load hyperglycaemia and dyslipidaemia and consequently increases the risk for type 2 diabetes and cardiovascular disease. This study aimed to investigate the effects of Lactobacillus casei strain Shirota (LcS) on metabolic abnormalities in obese prediabetic subjects in a randomised, double-blind, placebo-controlled trial. Herein, 100 obese subjects (body mass index ≥25), who had moderate post-load hyperglycaemia (1-hr post-load plasma glucose (PG) levels ≥180 mg/dl during the oral glucose tolerance test), consumed LcS-fermented milk or placebo milk daily for 8 weeks. The post-load PG and fasting blood markers were evaluated. Although post-load PG levels were not significantly different between the groups, 1-hr post-load PG, glycoalbumin, and HbA1c levels decreased at 8 weeks compared with the baseline levels only in the LcS group (p=0.036, p=0.002, and p=0.006, respectively). The reduction in glycoalbumin levels was statistically significantly greater in the LcS group than in the placebo group (p=0.030). Stratified analyses revealed significantly improved 1-hr post-load PG and glycoalbumin levels in the LcS group compared with the placebo group among subjects with severe glucose intolerance (2-hr post-load PG levels higher than the median at baseline; p=0.036 and p=0.034, respectively). In terms of lipidic outcomes, total, low-density lipoprotein, and non-high-density lipoprotein cholesterol levels were significantly lower in the LcS group than in the placebo group (p=0.023, p=0.022, and p=0.008, respectively). These findings suggest that LcS may favourably affect metabolic abnormalities in obese prediabetic subjects, though the effects on glycaemic control may be limited.

Background: Carnitine palmitoyltransferase (CPT) II deficiency is one of the most common forms of mitochondrial fatty acid oxidation disorder (FAOD). However, newborn screening (NBS) for this potentially fatal disease has not been established partly because reliable indices are not available., Methods: We diagnosed CPT II deficiency in a 7-month-old boy presenting with hypoglycemic encephalopathy, which apparently had been missed in the NBS using C16 and C18:1 concentrations as indices. By referring to his acylcarnitine profile from the NBS, we adopted the (C16+C18:1)/C2 ratio (cutoff 0.62) and C16 concentration (cutoff 3.0nmol/mL) as alternative indices for CPT II deficiency such that an analysis of a dried blood specimen collected at postnatal day five retroactively yielded the correct diagnosis. Thereafter, positive cases were assessed by measuring (1) the fatty acid oxidation ability of intact lymphocytes and/or (2) CPT II activity in the lysates of lymphocytes. The diagnoses were then further confirmed by genetic analysis., Results: The disease was diagnosed in seven of 21 newborns suspected of having CPT II deficiency based on NBS. We also analyzed the false-negative patient and five symptomatic patients for comparison. Values for the NBS indices of the false-negative, symptomatic patient were lower than those of the seven affected newborns. Although it was difficult to differentiate the false-negative patient from heterozygous carriers and false-positive subjects, the fatty acid oxidation ability of the lymphocytes and CPT II activity clearly confirmed the diagnosis. Among several other indices proposed previously, C14/C3 completely differentiated the seven NBS-positive patients and the false-negative patient from the heterozygous carriers and the false-positive subjects. Genetic analysis revealed 16 kinds of variant alleles. The most prevalent, detected in ten alleles in nine patients from eight families, was c.1148T>A (p.F383Y), a finding in line with those of several previous reports on Japanese patients., Conclusions: These findings suggested that CPT II deficiency can be screened by using (C16+C18:1)/C2 and C16 as indices. An appropriate cutoff level is required to achieve adequate sensitivity albeit at the cost of a considerable increase in the false-positive rate, which might be reduced by using additional indices such as C14/C3., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Functional lateralization can be an indicator of brain maturation. We have consistently shown that, in the adult brain, proprioceptive processing of muscle spindle afferents generating illusory movement of the right hand activates inferior frontoparietal cortical regions in a right-side dominant manner in addition to the cerebrocerebellar motor network. Here we provide novel evidence regarding the development of the right-dominant use of the inferior frontoparietal cortical regions in humans using this task. We studied brain activity using functional magnetic resonance imaging while 60 right-handed blindfolded healthy children (8-11 years), adolescents (12-15 years), and young adults (18-23 years) (20 per group) experienced the illusion. Adult-like right-dominant use of the inferior parietal lobule (IPL) was observed in adolescents, while children used the IPL bilaterally. In contrast, adult-like lateralized cerebrocerebellar motor activation patterns were already observable in children. The right-side dominance progresses during adolescence along with the suppression of the left-sided IPL activity that emerges during childhood. Therefore, the neuronal processing implemented in the adult's right IPL during the proprioceptive illusion task is likely mediated bilaterally during childhood, and then becomes right-lateralized during adolescence at a substantially later time than the lateralized use of the cerebrocerebellar motor system for kinesthetic processing., (© The Author 2017. Published by Oxford University Press.)

Proprioception is somatic sensation that allows us to sense and recognize position, posture, and their changes in our body parts. It pertains directly to oneself and may contribute to bodily awareness. Likewise, one's face is a symbol of oneself, so that visual self-face recognition directly contributes to the awareness of self as distinct from others. Recently, we showed that right-hemispheric dominant activity in the inferior fronto-parietal cortices, which are connected by the inferior branch of the superior longitudinal fasciculus (SLF III), is associated with proprioceptive illusion (awareness), in concert with sensorimotor activity. Herein, we tested the hypothesis that visual self-face recognition shares brain regions active during proprioceptive illusion in the right inferior fronto-parietal SLF III network. We scanned brain activity using functional magnetic resonance imaging while twenty-two right-handed healthy adults performed two tasks. One was a proprioceptive illusion task, where blindfolded participants experienced a proprioceptive illusion of right hand movement. The other was a visual self-face recognition task, where the participants judged whether an observed face was their own. We examined whether the self-face recognition and the proprioceptive illusion commonly activated the inferior fronto-parietal cortices connected by the SLF III in a right-hemispheric dominant manner. Despite the difference in sensory modality and in the body parts involved in the two tasks, both tasks activated the right inferior fronto-parietal cortices, which are likely connected by the SLF III, in a right-side dominant manner. Here we discuss possible roles for right inferior fronto-parietal activity in bodily awareness and self-awareness., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Proprioceptive signals originating from skeletal muscles and joints contribute to the formation of both the human body schema and the body image. In this chapter, we introduce various types of bodily illusions that are elicited by proprioceptive inputs, and we discuss distinct functions implemented by different parietal cortices. First, we illustrate the primary importance of the motor network in the processing of proprioceptive (kinesthetic) signals originating from muscle spindles. Next, we argue that the right inferior parietal cortex, in concert with the inferior frontal cortex (both regions connected by the inferior branch of the superior longitudinal fasciculus-SLF III), may be involved in the conscious experience of body image. Further, we hypothesize other functions of distinct parietal regions: the association between internal hand motor representation with external object representation in the left inferior parietal cortex, visuo-kinesthetic processing in the bilateral posterior parietal cortices, and the integration of somatic signals from different body parts in the higher-order somatosensory parietal cortices. Our results indicate that a distinct parietal region, in concert with its anatomically and functionally connected frontal regions, probably plays specialized roles in the processing of body-related information.

Humans experience significant physical and mental changes from birth to adulthood, and a variety of perceptual, cognitive and motor functions mature over the course of approximately 20 years following birth. To deeply understand such developmental processes, merely studying behavioral changes is not sufficient; simultaneous investigation of the development of the brain may lead us to a more comprehensive understanding. Recent advances in noninvasive neuroimaging technologies largely contribute to this understanding. Here, it is very important to consider the development of the brain from the perspectives of "structure" and "function" because both structure and function of the human brain mature slowly. In this review, we first discuss the process of structural brain development, i.e., how the structure of the brain, which is crucial when discussing functional brain development, changes with age. Second, we introduce some representative studies and the latest studies related to the functional development of the brain, particularly for visual, facial recognition, and social cognition functions, all of which are important for humans. Finally, we summarize how brain science can contribute to developmental study and discuss the challenges that neuroimaging should address in the future.

It is generally believed that the human right cerebral hemisphere plays a dominant role in corporeal awareness, which is highly associated with conscious experience of the physical self. Prompted by our previous findings, we examined whether the right frontoparietal activations often observed when people experience kinesthetic illusory limb movement are supported by a large-scale brain network connected by a specific branch of the superior longitudinal fasciculus fiber tracts (SLF I, II, and III). We scanned brain activity with functional magnetic resonance imaging (MRI) while nineteen blindfolded healthy volunteers experienced illusory movement of the right stationary hand elicited by tendon vibration, which was replicated after the scanning. We also scanned brain activity when they executed and imagined right hand movement, and identified the active brain regions during illusion, execution, and imagery in relation to the SLF fiber tracts. We found that illusion predominantly activated the right inferior frontoparietal regions connected by SLF III, which were not substantially recruited during execution and imagery. Among these regions, activities in the right inferior parietal cortices and inferior frontal cortices showed right-side dominance and correlated well with the amount of illusion (kinesthetic illusory awareness) experienced by the participants. The results illustrated the predominant involvement of the right inferior frontoparietal network connected by SLF III when people recognize postural changes of their limb. We assume that the network bears a series of functions, specifically, monitoring the current status of the musculoskeletal system, and building-up and updating our postural model (body schema), which could be a basis for the conscious experience of the physical self., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The human brain can generate a continuously changing postural model of our body. Somatic (proprioceptive) signals from skeletal muscles and joints contribute to the formation of the body representation. Recent neuroimaging studies of proprioceptive bodily illusions have elucidated the importance of three brain systems (motor network, specialized parietal systems, right inferior fronto-parietal network) in the formation of the human body representation. The motor network, especially the primary motor cortex, processes afferent input from skeletal muscles. Such information may contribute to the formation of kinematic/dynamic postural models of limbs, thereby enabling fast online feedback control. Distinct parietal regions appear to play specialized roles in the transformation/integration of information across different coordinate systems, which may subserve the adaptability and flexibility of the body representation. Finally, the right inferior fronto-parietal network, connected by the inferior branch of the superior longitudinal fasciculus, is consistently recruited when an individual experiences various types of bodily illusions and its possible roles relate to corporeal awareness, which is likely elicited through a series of neuronal processes of monitoring and accumulating bodily information and updating the body representation. Because this network is also recruited when identifying one's own features, the network activity could be a neuronal basis for self-consciousness., (Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

Motor performance fluctuates trial by trial even in a well-trained motor skill. Here we show neural substrates underlying such behavioral fluctuation in humans. We first scanned brain activity with functional magnetic resonance imaging while healthy participants repeatedly performed a 10 s skillful sequential finger-tapping task. Before starting the experiment, the participants had completed intensive training. We evaluated task performance per trial (number of correct sequences in 10 s) and depicted brain regions where the activity changes in association with the fluctuation of the task performance across trials. We found that the activity in a broader range of frontoparietocerebellar network, including the bilateral dorsolateral prefrontal cortex (DLPFC), anterior cingulate and anterior insular cortices, and left cerebellar hemisphere, was negatively correlated with the task performance. We further showed in another transcranial direct current stimulation (tDCS) experiment that task performance deteriorated, when we applied anodal tDCS to the right DLPFC. These results indicate that fluctuation of brain activity in the nonmotor frontoparietocerebellar network may underlie trial-by-trial performance variability even in a well-trained motor skill, and its neuromodulation with tDCS may affect the task performance.

Performing a complex sequential finger movement requires the temporally well-ordered organization of individual finger movements. Previous behavioural studies have suggested that the brain prepares a whole sequence of movements as a single set, rather than the movements of individual fingers. However, direct neuroimaging support for this hypothesis is lacking and, assuming it to be true, it remains unclear which brain regions represent the information of a prepared sequence. Here, we measured brain activity with functional magnetic resonance imaging while 14 right-handed healthy participants performed two types of well-learned sequential finger movements with their right hands. Using multi-voxel pattern analysis, we examined whether the types of the forthcoming sequence could be predicted from the preparatory activities of nine regions of interest, which included the motor, somatosensory and posterior parietal regions in each hemisphere, bilateral visual cortices, cerebellum and basal ganglia. We found that, during preparation, the activity of the contralateral motor regions could predict which of the two sequences would be executed. Further detailed analysis revealed that the contralateral dorsal premotor cortex and supplementary motor area were the key areas that contributed to the prediction consistently across participants. These contrasted with results from execution-related brain activity where a performed sequence was successfully predicted from the activities in the broad cortical sensory-motor network, including the bilateral motor, parietal and ipsilateral somatosensory cortices. Our study supports the hypothesis that temporary well-organized sequences of movements are represented as a set in the brain, and that preparatory activity in higher-order motor regions represents information about upcoming motor actions., (© 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Dental pulp cells (DPCs) of various species have been studied for their potentials of differentiation into functional neurons and secretion of neurotrophic factors. In canine, DPCs have only been studied for cell surface markers and differentiation, but there is little direct evidence for therapeutic potentials for neurological disorders. The present study aimed to further characterize canine DPCs (cDPCs), particularly focusing on their neuroregenerative potentials. It was also reported that superparamagnetic iron oxide (SPIO) particles were useful for labeling of MSCs and tracking with magnetic resonance imaging (MRI). Our data suggested that cDPCs hold higher proliferation capacity than bone marrow stromal cells, the other type of mesenchymal stem cells which have been the target of intensive research. Canine DPCs constitutively expressed neural markers, suggesting a close relationship to the nervous system in their developmental origin. Canine DPCs promoted neuritogenesis of PC12 cells, most likely through secretion of neurotrophic factors. Furthermore, SPIO nanoparticles could be effectively transported to cDPCs without significant cytotoxicity and unfavorable effects on neuritogenesis. SPIO-labeled cDPCs embedded in agarose spinal cord phantoms were successfully visualized with a magnetic resonance imaging arousing a hope for noninvasive cell tracking in transplantation studies.

We present a case of a 32-year-old diabetic woman with Prader-Willi syndrome who developed severe ketoacidosis caused by a sodium-glucose cotransporter 2 (SGLT2) inhibitor, a novel class of antihyperglycemic agents, during a strict low-carbohydrate diet. At admission, a serum glucose level of 191 mg/dL was relatively low, though laboratory evaluations showed severe ketoacidosis. This is the first report of ketoacidosis caused by a SGLT2 inhibitor. It is necessary to not only pay attention when using a SGLT2 inhibitor in patients following a low-carbohydrate diet, but also to start a low-carbohydrate diet in patients treated with a SGLT2 inhibitor because of a high risk for developing ketoacidosis.

The purpose of this study was to clarify the effect of Chinese propolis on the expression level of neurotrophic factors in dental pulp cells (DPCs). We also investigated that the effects of the conditioned medium (CM) of DPCs stimulated by the propolis against oxidative and endoplasmic reticulum (ER) stresses in human neuroblastoma SH-SY5Y cells, and on neurite extensions in rat adrenal pheochromocytoma PC12 cells. To investigate the effect of the propolis on the levels of neurotrophic factors in DPCs, we performed a qRT-PCR experiment. As results, NGF, but not BDNF and NT-3, in DPCs was significantly elevated by the propolis in a concentration-dependent manner. H2O2-induced cell death was significantly inhibited by the treatment with the CM of DPCs. In addition, the treatment with the propolis-stimulated CM of DPCs had a more protective effect than that with the CM of DPCs. We also examine the effect of the propolis-stimulated CM of DPCs against a tunicamycin-induced ER stress. The treatment with the propolis-stimulated CM as well as the CM of DPCs significantly inhibited tunicamycin-induced cell death. Moreover, the treatment with the propolis-stimulated CM of DPCs significantly induced neurite outgrowth from PC12 cells than that with the CM of DPCs. These results suggest that the CM of DPCs as well as DPCs will be an efficient source of new treatments for neurodegenerative diseases and that the propolis promote the advantage of the CM of DPCs via producing neurotrophic factors., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Recent functional magnetic resonance imaging (fMRI) decoding techniques allow us to predict the contents of sensory and motor events or participants' mental states from multi-voxel patterns of fMRI signals. Sparse logistic regression (SLR) is a useful pattern classification algorithm that has the advantage of being able to automatically select voxels to avoid over-fitting. However, SLR suffers from over-pruning, in which many voxels that are potentially useful for prediction are discarded., New Method: We propose an ensemble solution for over-pruning, called "Iterative Recycling" (iRec), in which sparse classifiers are trained iteratively by recycling over-pruned voxels., Results: Our simulation demonstrates that iRec can effectively rectify over-pruning in SLR and improve its classification accuracy. We also conduct an fMRI experiment in which eight healthy volunteers perform a finger-tapping task with their index or middle fingers. The results indicate that SLR with iRec (iSLR) can predict the finger used more accurately than SLR. Further, iSLR is able to identify a voxel cluster representing the finger movements in the biologically plausible contralateral primary sensory-motor cortices in each participant. We also successfully dissociated the regularly arranged representation for each finger in the cluster., Conclusion and Comparison With Other Methods: To the best of our knowledge, ours is the first study to propose a solution for over-pruning with ensemble-learning that is applicable to any sparse algorithm. In addition, from the viewpoint of machine learning, we provide the novel idea of using the sparse classification algorithm to generate accurate divergent base classifiers., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)

This commentary builds on a companion article in which Kim et al compare brain activation in elite, expert, and novice archers during a simulated target aiming task (Kim et al. 2014. Cogn Behav Neurol. 27:173-182). With the archery study as our starting point, we address 4 neural processes that may be responsible in general for elite athletes' superior performance over experts and novices: neural efficiency, cortical expansion, specialized processes, and internal models. In Kim et al's study, the elite archers' brains showed more activity in the supplementary motor area and the cerebellum than those of the novices and experts, and showed minimal widespread activity, especially in frontal areas involved with executive control. Kim et al's results are consistent with the idea of specialized neural processes that help coordinate motor planning and control. As athletes become more skilled, these processes may mediate the reduction in widespread activity in regions mapping executive control, and may produce a shift toward more automated processing. Kim et al's finding that activity in the cerebellum rose with increasing skill is consistent both with expansion of the finger representational area in the cerebellum and with internal models that simulate how archers manipulate the bow and arrow when aiming. Kim et al prepare the way for testing of neuromodulation techniques to improve athletic performance, refine highly technical job skills, and rehabilitate patients.

We report a 21-year-old male patient with dentatorubral-pallidoluysian atrophy (DRPLA) showing progressive myoclonus epilepsy (PME), who responded to levetiracetam (LEV) at an initial dose of 1,000 mg/day. The patient developed epilepsy at the age of 10 years, and also showed intellectual regression. Various antiepileptic drugs showed no effects on generalized tonic seizures, tonic-clonic seizures, and myoclonus. Addition of LEV (1,000 mg/day) led to the reduction of myoclonus and tonic-clonic seizures, and improved the EEG and sleep-wake rhythm. He had a better appetite and gain weight. It is suggested that LEV may improve quality of life in patients with DRPLA, in addition to reducing the frequency of epileptic seizures.

Internal (neuronal) representations in the brain are modified by our experiences, and this phenomenon is not unique to sensory and motor systems. Here, we show that different impressions obtained through social interaction with a variety of agents uniquely modulate activity of dorsal and ventral pathways of the brain network that mediates human social behavior. We scanned brain activity with functional magnetic resonance imaging (fMRI) in 16 healthy volunteers when they performed a simple matching-pennies game with a human, human-like android, mechanical robot, interactive robot, and a computer. Before playing this game in the scanner, participants experienced social interactions with each opponent separately and scored their initial impressions using two questionnaires. We found that the participants perceived opponents in two mental dimensions: one represented "mind-holderness" in which participants attributed anthropomorphic impressions to some of the opponents that had mental functions, while the other dimension represented "mind-readerness" in which participants characterized opponents as intelligent. Interestingly, this "mind-readerness" dimension correlated to participants frequently changing their game tactic to prevent opponents from envisioning their strategy, and this was corroborated by increased entropy during the game. We also found that the two factors separately modulated activity in distinct social brain regions. Specifically, mind-holderness modulated activity in the dorsal aspect of the temporoparietal junction (TPJ) and medial prefrontal and posterior paracingulate cortices, while mind-readerness modulated activity in the ventral aspect of TPJ and the temporal pole. These results clearly demonstrate that activity in social brain networks is modulated through pre-scanning experiences of social interaction with a variety of agents. Furthermore, our findings elucidated the existence of two distinct functional networks in the social human brain. Social interaction with anthropomorphic or intelligent-looking agents may distinctly shape the internal representation of our social brain, which may in turn determine how we behave for various agents that we encounter in our society., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

How very long-term (over many years) motor skill training shapes internal motor representation remains poorly understood. We provide valuable evidence that the football brain of Neymar da Silva Santos Júnior (the Brasilian footballer) recruits very limited neural resources in the motor-cortical foot regions during foot movements. We scanned his brain activity with a 3-tesla functional magnetic resonance imaging (fMRI) while he rotated his right ankle at 1 Hz. We also scanned brain activity when three other age-controlled professional footballers, two top-athlete swimmers and one amateur footballer performed the identical task. A comparison was made between Neymar's brain activity with that obtained from the others. We found activations in the left medial-wall foot motor regions during the foot movements consistently across all participants. However, the size and intensity of medial-wall activity was smaller in the four professional footballers than in the three other participants, despite no difference in amount of foot movement. Surprisingly, the reduced recruitment of medial-wall foot motor regions became apparent in Neymar. His medial-wall activity was smallest among all participants with absolutely no difference in amount of foot movement. Neymar may efficiently control given foot movements probably by largely conserving motor-cortical neural resources. We discuss this possibility in terms of over-years motor skill training effect, use-dependent plasticity, and efficient motor control.

The human brain processes every sensation evoked by altered posture and builds up a constantly changing postural model of the body. This is called a body schema, and somatic signals originating from skeletal muscles and joints, i.e. proprioceptive signals, largely contribute its formation. Recent neuroimaging techniques have revealed neuronal substrates for human body schema. A dynamic limb position model seems to be computed in the central motor network (represented by the primary motor cortex). Here, proprioceptive (kinesthetic) signals from muscle spindles are transformed into motor commands, which may underlie somatic perception of limb movement and facilitate its efficient motor control. Somatic signals originating from different body parts are integrated in the course of hierarchical somatosensory processing, and activity in higher-order somatosensory parietal cortices is capable of representing a postural model of the entire body. The left fronto-parietal network associates internal motor representation with external object representation, allowing the embodiment of external objects. In contrast, the right fronto-parietal regions connected by the most inferior branch of superior longitudinal fasciculus fibers seem to have the functions of monitoring bodily states and updating body schema. We hypothesize that activity in these right-sided fronto-parietal regions is deeply involved in corporeal self-consciousness.

Aims/introduction: Previously, it was observed that long-term ingestion of a probiotic strain Lactobacillus casei Shirota (LcS) ameliorates insulin resistance and glucose intolerance in rats fed a high-fat diet. In the present study, we examined its possible role in the autonomic nervous system during LcS-induced modulations in glucose and lipid metabolism or cardiovascular functions., Materials and Methods: The present study examined the effects of intragastric (IG) LcS injection on autonomic nerve tones in anesthetized rats by electrophysiological method., Results: We found that an IG injection of LcS suppressed neural activity of sympathetic nerves supplying the white adipose tissue of urethane-anesthetized rats in a dose-dependent manner, whereas sympathetic nerve outflow to brown adipose tissue was not affected by the IG LcS injection. Furthermore, the IG LcS injection reduced efferent sympathetic nerve outflow to the adrenal gland and liver, but did not alter gastric vagal nerve activity, renal sympathetic nerve activity, as well as mean arterial pressure. To test the involvement of afferent vagal nerves and the abdominal organs, we examined the adrenal sympathetic response to an LcS injection in rats with ablated afferent vagal nerves, and found that the adrenal sympathetic nerve response to LcS was inhibited in vagotomized rats. In addition, we found that oral ingestion of LcS attenuated the hyperglycemic response to glucose loading and blood glycerol levels in conscious rats., Conclusions: Our data suggest that LcS might affect tissue-specific autonomic nerves through the afferent vagal nerve pathway to modulate glucose and lipid metabolism.

When confronted with complex visual scenes in daily life, how do we know which visual information represents our own hand? We investigated the cues used to assign visual information to one's own hand. Wrist tendon vibration elicits an illusory sensation of wrist movement. The intensity of this illusion attenuates when the actual motionless hand is visually presented. Testing what kind of visual stimuli attenuate this illusion will elucidate factors contributing to visual detection of one's own hand. The illusion was reduced when a stationary object was shown, but only when participants knew it was controllable with their hands. In contrast, the visual image of their own hand attenuated the illusion even when participants knew that it was not controllable. We suggest that long-term knowledge about the appearance of the body and short-term knowledge about controllability of a visual object are combined to robustly extract our own body from a visual scene.

Considerable progress has been made in developing models of cerebellar function in sensorimotor control, as well as in identifying key problems that are the focus of current investigation. In this consensus paper, we discuss the literature on the role of the cerebellar circuitry in motor control, bringing together a range of different viewpoints. The following topics are covered: oculomotor control, classical conditioning (evidence in animals and in humans), cerebellar control of motor speech, control of grip forces, control of voluntary limb movements, timing, sensorimotor synchronization, control of corticomotor excitability, control of movement-related sensory data acquisition, cerebro-cerebellar interaction in visuokinesthetic perception of hand movement, functional neuroimaging studies, and magnetoencephalographic mapping of cortico-cerebellar dynamics. While the field has yet to reach a consensus on the precise role played by the cerebellum in movement control, the literature has witnessed the emergence of broad proposals that address cerebellar function at multiple levels of analysis. This paper highlights the diversity of current opinion, providing a framework for debate and discussion on the role of this quintessential vertebrate structure.