Masatoshi Takeda

Background: Simulated smiling, when an individual intentionally produces non-spontaneous smiles, can reportedly influence emotional and physiological states, but its neural and autonomic mechanisms remain unclear. Purpose: We examined whether one week of repeated simulated smiling with visual self-feedback would induce changes in brain function, autonomic nervous activity, and psychological state. Methods: Twenty healthy adults completed electroencephalogram, electrocardiogram, and psychological assessments before and then after a one-week intervention. Participants performed a daily home-based simulated smiling task while viewing their own facial expression by smartphone. During laboratory sessions before and after the one-week intervention, electroencephalogram (current source density and functional connectivity calculated by eLORETA), autonomic indices (cardio-sympathetic index, and cardio-parasympathetic index calculated by Lorenz plotting), and psychological measures (state-trait anxiety inventory) were recorded during resting and simulated smiling conditions. Results: Theta-band current source density in the medial prefrontal cortex significantly [BP1] decreased after the intervention, suggesting reduced cognitive control demands. At rest, alpha-band functional connectivity between occipital and parietal regions significantly increased after the intervention. Parasympathetic activity (cardio-parasympathetic index) increased during rest, while no autonomic changes were observed during the task. Psychological assessments showed reduction of state anxiety and increase in pleasant mood after completion of the one-week simulated smiling task. Conclusion: A brief, one-week program of repeated simulated smiling with visual self-feedback produced measurable improvements in psychological state and state-dependent alterations in central and autonomic activity. Given its simplicity, safety, and feasibility as a self-administered practice, simulated smiling may be a promising complementary approach for stress reduction and rehabilitation support.

In order to deal with the problem that the number of engineers and designers who are no longer able to think about themselves is increasing, we planned a “thinking practice workshop” using actual experiments and practiced it for university students. We set up four thinking scenes, actually thought and discussed each one. From the result of questionnaire, it was confirmed that the desired effect was achieved. It can be said that this workshop, including the result of practical cases in the company, is useful for engineers and designers to acquire the way to think through themselves.

Aim A substantial proportion of major depressive disorder patients are treatment-resistant to antidepressant therapy, who require augmentation drugs, or other treatments including electroconvulsive therapy or transcranial magnetic stimulation. Identifying treatment-resistant major depressive disorder patients before the actual administration of antidepressant is, however, often difficult. Accordingly, the serum biomarker to identify treatment-resistant patients will be helpful in clinical settings. This study aims to clarify the appropriate biomarkers for identification of treatment-resistant major depressive disorder. Method Given that immune-inflammatory processes are involved in the pathogenesis of major depressive disorder, it is possible that certain cytokine-related molecules could serve as clinically useful biomarkers of treatment-resistant major depressive disorder patients. In this study, we measured serum levels of tumor necrosis factor-alpha, interleukin 6, and soluble interleukin 6 receptor after major depressive disorder patients underwent antidepressant therapy. Results The serum level of soluble interleukin 6 receptor, but not interleukin 6 or tumor necrosis factor-alpha, was significantly higher in treatment-resistant major depressive disorder patients than in remitted patients, suggesting that serum soluble interleukin 6 receptor could be a good biomarker of treatment-resistant major depressive disorder. Receiver operating characteristic analysis confirmed that serum soluble interleukin-6 receptor level measurement was useful for identification of treatment-resistant major depressive disorder patients. Multiple regression analysis using the serum levels of the aforementioned cytokines as explanatory variables and the Quick Inventory of Depressive Symptomatology-Self Report score (QIDS-SR16) as a target variable showed that only serum soluble interleukin-6 receptor level could explain the severity of major depressive disorder. Conclusion Based on these results, we recommend measurement of serum soluble interleukin-6 receptor level to discriminate treatment-resistant major depressive disorder patients. High serum soluble interleukin-6 receptor level is associated with the pathogenesis of treatment-resistant major depressive disorder, suggesting the involvement of the interleukin 6 trans-signaling system in onset of treatment-resistant major depressive disorder.

The remarkable thing in particular in the aged society with a low birth rate is that the necessary energy to make sustainable society is weakened. From the mechanical engineering’s point of view for making better global environment, this paper recommends the industry-academia cooperation approach in which not only the engineering but also the business administration participates.

The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) recently included sensory processing abnormalities in the diagnostic criteria for individuals with autism spectrum disorder (ASD). However, there is no standard method for evaluating sensory abnormalities in individuals with ASD. Fifteen individuals with ASD and 15 age- and sex-matched controls were enrolled in this study. We compared objective pain sensitivity by measuring the pain detection threshold and pain tolerance to three different stimuli (electricity, heat, and cold). Then, we compared both subjective pain sensitivity, assessed by the visual analog scale (VAS), and quality of pain, assessed by the short-form McGill Pain Questionnaire (SF-MPQ), to determine the maximum tolerable pain intensities of each stimulation. The pain detection threshold and pain tolerance of individuals with ASD were not impaired, indicating that there were no differences in the somatic perception of pain between groups. However, individuals with ASD were hyposensitive to subjective pain intensity compared to controls (VAS; electrical: p = 0.044, cold: p = 0.011, heat: p = 0.042) and hyposensitive to affective aspects of pain sensitivity (SF-MPQ; electrical: p = 0.0071, cold: p = 0.042). Our results suggest that the cognitive pathways for pain processing are impaired in ASD and, furthermore, that our methodology can be used to assess pain sensitivity in individuals with ASD. Further investigations into sensory abnormalities in individuals with ASD are needed to clarify the pathophysiologic processes that may alter sensory processing in this disorder.

A pair of vertebrate-specific and brain-expressed pre-synaptic genes, NTNG1 and NTNG2, contributes to the Intellectual Quotient (IQ) test scores in a complementary manner. Single nucleotide polymorphisms (SNPs) of NTNG1 are associated with attenuated verbal comprehension (VC) or processing speed (PS) while NTNG2 SNPs affect working memory (WM) and perceptual organization (PO), forming cognitive endophenotypes in healthy and schizophrenia (SCZ)-affected human subjects. Regions of interest (ROIs), defined as 21 nucleotide (nu) long NTNG gene loci symmetrically embedding the IQ-affecting mutation alleles (VC/PS and WM/PO), underwent dramatic evolutionary changes from mice through primates to hominins, at the accelerated rates. Mutation alleles associated with the higher VC and WM IQ scores are found in the genomes of extinct hominins of Neolithic times, however, lower WM scores associated allele is also detectable in Mesolithic hunters genomes. Protein sequence of NTNG1 is 100% conserved among the primates, archaic and modern extinct hominins while NTNG2 underwent a recent selection sweep encoding a primate-specific S371A/V (~50,000 yrs BC), and a modern human (5,300 yrs BC) T346A substitutions. We show that a 500 mln yrs old genomic duplication of a synapse primordial gene provided a substrate for further synapse elaborations and its ultimate capacitive expansion of what evolved into a vertebrate cognitive superior complexity – intelligence.

We used a questionnaire to evaluate how patients with idiopathic normal-pressure hydrocephalus (iNPH) are examined in Medical Centers for Dementia (MCDs), which are qualified medical organizations for dementia patients in Japan. Ninety-eight of 205 MCDs responded to our questionnaire. Accordingly, more than 590 patients with iNPH underwent an MCD examination during the period of 1 year. In regards to the Guidelines for Management of iNPH, 40 of the 98 MCDs used neither the first nor second edition of the Guidelines, even though up-to-date information is available in the second edition of the Guidelines. At most MCDs, consultation with iNPH specialists was performed without a cerebrospinal fluid tap test. At more than half of the responding MCDs, doctors felt that the selection of appropriate candidates for shunt surgery differed from those selected by neurosurgeons. Moreover, 73 out of 87 MCDs argued that patients with iNPH should be examined by both dementia specialists and neurosurgeons after shunt surgery. These results suggest that doctors at MCDs should take advantage of up-to-date information and cooperate with iNPH specialists and neurosurgeons.

Patients with schizophrenia show various kinds of abnormality in eye movements. Recent studies showed that such abnormalities, including the shorter scanpath during free-viewing of natural images, is able to use as an efficient biomarker for schizophrenia. Here we extended our previous work (Miura et.al. 2014 Schizophr Res) and examined whether such difference in eye movements during free-viewing arises from the way in which their attention is drawn to specific features of the visual stimuli. The age-matched subjects (41 patients and 72 healthy controls) viewed 56 natural and/or complex images including faces, scenes and so on. During 8 seconds of viewing time for each image, eye movements were recorded using an eye tracker (EyeLink 1000). We calculated the saliency map of the images for low-level features (luminance, L-M, S-Lum and orientation) based on our previous work (Yoshida et.al. 2012 Curr. Biol.). Then we evaluated the time course of the saliency value at the position of the gaze. The luminance saliency was highest for the first fixation and went down during the 8-sec viewing time in the healthy controls. This is also true for patient group but the luminance saliency was consistently higher in the patients than in the healthy controls (repeated measures ANOVA, F_1,111=5.78, P=0.017). The saliency for other features showed different time course. By combining saliency values for different features (4 models * 8 time points), we constructed a classifier in which patients and controls are distinguished with 83% accuracy. These results suggest that the abnormality in eye movements during visual exploration can be explained, at least partly, by dysregulated saliency in the patients. Meeting abstract presented at VSS 2015

The dysbindin-1 gene (DTNBP1: dystrobrevin binding protein 1) is a promising schizophrenia susceptibility gene, known to localize almost exclusively to neurons in the brain, and participates in the regulation of neurotransmitter release, membrane-surface receptor expression, and synaptic plasticity. Sandy mice, with spontaneous Dtnbp1 deletion, display behavioral abnormalities relevant to symptoms of schizophrenia. However, it remains unknown if dysbindin-1 gain-of-function is beneficial or detrimental. To answer this question and gain further insight into the pathophysiology and therapeutic potential of dysbindin-1, we developed transgenic mice expressing human DTNBP1 (Dys1A-Tg) and analyzed their behavioral phenotypes. Dys1A-Tg mice were born viable in the expected Mendelian ratios, apparently normal and fertile. Primary screening of behavior and function showed a marginal change in limb grasping in Dys1A-Tg mice. In addition, Dys1A-Tg mice exhibited increased hyperlocomotion after methamphetamine injection. Transcriptomic analysis identified several up- and down-regulated genes, including the immediate-early genes Arc and Egr2, in the prefrontal cortex of Dys1A-Tg mice. The present findings in Dys1A-Tg mice support the role of dysbindin-1 in psychiatric disorders. The fact that either overexpression (Dys1A-Tg) or underexpression (Sandy) of dysbindin-1 leads to behavioral alterations in mice highlights the functional importance of dysbindin-1 in vivo.

Autism spectrum disorder is a neurodevelopmental disorder characterized by impairments in social interactions, reduced verbal communication abilities, stereotyped repetitive behaviors, and restricted interests. It is a complex condition caused by genetic and environmental factors; the high heritability of this disorder supports the presence of a significant genetic contribution. Many studies have suggested that copy-number variants contribute to the etiology of autism spectrum disorder. Recently, copy-number variants of the nephronophthisis 1 gene have been reported in patients with autism spectrum disorder. To the best of our knowledge, only six autism spectrum disorder cases with duplications of the nephronophthisis 1 gene have been reported. These patients exhibited intellectual dysfunction, including verbal dysfunction in one patient, below-average verbal intellectual ability in one patient, and intellectual disability in four patients. In this study, we identified nephronophthisis 1 duplications in two unrelated Japanese patients with autism spectrum disorder using a high-resolution single-nucleotide polymorphism array. This report is the first to describe a nephronophthisis 1 duplication in an autism spectrum disorder patient with an average verbal intelligence quotient and an average performance intelligence quotient. However, the second autism spectrum disorder patient with a nephronophthisis 1 duplication had a below-average performance intelligence quotient. Neither patient exhibited physical dysfunction, motor developmental delay, or neurological abnormalities. This study supports the clinical observation of nephronophthisis 1 duplication in autism spectrum disorder cases and might contribute to our understanding of the clinical phenotype that arises from this duplication.