Healthy new born babies give the first cry and nurse themselves on mother’s breasts at the beginning of their lives. Grown-up’s mouth supports healthy lifestyle to enjoy eating, talking and laughing. When the last moment comes, leaving the last words to say good-bye helps their love ones and themselves rest in peace. Mouth works to take nutrition by eating meals, to reach to understand each other by talking, to express emotion ; delight, anger, sorrow and pleasure. The mouth supports their life from the birth until the end of their life as a human. According to Penfield’s brain mapping, sense and move of mouth occupies 1/ 3 of whole brain field. From the discrimination distance between two points on the body surface, mouth is one of the most sensitive parts of the body such like hands. Recently, it is drawing attention that the oral health can be threatening to general health. Periodontitis, a gingival inflammation, leads to several health problems such as endocarditis, diabetes, premature delivery and a low birth-weight infant, by spreading oral bacteria or inflammatory cytokines through peripheral blood circulation. Erroneous swallowing of filthy saliva also develops aspiration pneumonia. Responding to these problems, it is recommended the establishment of team medical care including dentist and dental hygienist, the promotion of perioperative oral health management and oral health care of elderly. The distance between dental care and medical care are getting closer. This article introduces the importance of oral function by showing some references of oral health from the dentist’s point of view.

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Excessive alcohol use is the third leading cause of preventable deaths after smoking and obesity and is implicated in many physical and mental complications. One such complication, alcohol-related dementia(ARD)is brought about by direct or indirect ethanol intoxication, and coexisting nutritional deficiency, liver disease, cerebrovascular disease and traumatic brain injury. While the concept of ARD is multifactorial and includes all cognitive deficits in alcoholics, the central clinical manifestations are exemplified by Korsakoff's syndrome(KS), a persistent neuropsychiatric syndrome characterized by amnesia and disorientation that is caused by thiamine deficiency along with excessive alcohol consumption. A 3-dimensional MRI method for voxel-based morphometry demonstrates that the parahippocampal/ hippocampal atrophy is specific to KS and the thalamus atrophy and the third ventricle enlargement were more severe in patients with KS than in cognitively normal alcoholics. This review also shows late-onset ARD which occurs in alcoholics over 60 years old, and which has been underestimated and underdiagnosed. These older alcoholics have high prevalence of lacunar infarcts and deep white matter lesions on the brain, which is associated not only with their cognitive decline, but also with their frailty, leading to high morbidity and mortality ratio. ARD is potentially reversible. However, the severity of alcohol dependence, age, and concomitant nutritional, physical and environmental factors can all have an impact on the outcome. Therefore, people with ARD benefit from comprehensive approach to lifestyle factors so that they can minimizes preventable risks, maintains health status and overcomes chronic diseases. Nursing home placement may be an appropriate treatment option for some refractory, long-term alcoholics with dementia.

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Posttraumatic stress disorder(PTSD)is an anxiety disorder that may develop following exposure to a highly traumatic event. Although exposure-based cognitive behavior therapy is commonly used to treat PTSD, additional treatments, such as pharmacological agents, are needed to make the therapy more effective. Accordingly, many researchers have proposed to animal models to study the neurobiological mechanisms underlying PTSD. In the first pat of this paper, we explain Pavlovian fear conditioning and conditioned place preference which are typically used to measure aversive and euphoric emotional memories respectively. The second part explains stress-induced enhancement of conditioned fear in rats as a useful animal model of PTSD.

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Alzheimer’s disease(AD)was described first over 100 years ago. Todays, AD is the most common type of dementia in the elderly worldwide. About 35.6 million of patients suffer from dementia in the world and more than 60 million people are estimated to develop in the next 20 years, indicating that one patient will occur every 4 seconds. The prevalence and incidence of AD increase along with age but all aged person will not develop the disease. So, AD might be affected by genetic factors as well as non-genetic determinants including ageing. As many neurodegenerative diseases, AD is also composed of familial and sporadic AD. The rare familial AD is caused by mutations in the specific genes. Three causative genes were identified in the early-onset autosomal dominantly inherited AD. Sporadic late-onset AD(LOAD)risk is strongly influenced by genetic factors such as the presence of the apolipoprotein E ε4 allele(APOE4). About a half of LOAD does not carry APOE4 and the remaining etiology appears much more complex and includes a number of genetic and environmental factors. Copy number variations such as APP duplication and other genomic regions as well as the genetic mutations of the risk genes are supposed to be susceptible to AD. AD is pathologically characterized by amyloid β peptide(Aβ)deposition in the extracellular fields and neurofibrillary tangles consisted of highly phosphorylated microtubule-associated protein tau in neurons. The amyloid plaques are detected by PIB-PET imaging. APOE4 carriers significantly correlate with PIB-PET positive and decrease in CSF Aβ level. If the underlying variants in the risk genes and copy number variations are detected, the correlations with endophenotypes might be better addressed. I review the relationship of the phenotype and genotype by discussing the new findings and implications for clinical diagnosis and treatments.

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The necessity for the welfare policy over intellectual disability(ID)was claimed for in the United States 50 years or more ago, and the concept of the developmental disorder/ disability appeared for the first time. The term of “neurodevelopmental disorders” has been introduced in May, 2013 in the diagnostic and statistical manual of mental disorders 5th edition(DSM-5). The range of deficits varies from very specific limitations of learning e. g. developmental dyslexia(DD)to global impairment of social skills or intelligence(ID), and these developmental disorders frequently co-occur, for example, many children with attention deficit hyperactivity disorder(ADHD)also have a specific learning disorder. We conducted a phonological manipulation task to extract phonological processing skills in healthy adults, typically developing children, and DD children in Japan. During phonological manipulation, several brain regions are found to participate, such as the left inferior and middle frontal gyri, left superior temporal gyrus, and bilateral basal ganglia in a functional magnetic resonance imaging study. Children with DD showed hyperactivity in the basal ganglia compared with the two other groups, which reflects inefficient phonological processing. Hypoactivity in the left superior temporal gyrus was also found. The present study provided initial findings for phonological manipulation in dyslexic Japanese children.

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Event-related potentials include P300 reflect various cognitive functions. Studies of ERPs in children, based on a task relevant oddball paradigm, reveal a decrease in the latency of P300 with increasing age. This developmental change could be related to maturation phenomena in cognitive processes. Squires et al. delineated P3a and P3b components in P300. In our study, no task-relevant P300, likely corresponds to P3a(passive attention), whereas conventional P300 corresponds to P3b(active attention). These findings indicate a developmental difference between the P3a and P3b potentials. The development of fundamental cognitive function like passive attention reaches the adult level at an earlier age than the cognitive like active attention. In order to objectively evaluate auditory spatial perception of patients with mental retardation, the P300(P3b)event-related potentials and key-press reaction times of auditory stimuli with Doppler effect were compered with mild mental retarded patients and age-matched healthy normal children. P300 latency in mental retarded children did not delay more than that in normal children. However, key-press reaction time in mental retarded children delayed significantly more than that in normal children. We suggested that the combination of P300 latency and key-press reaction time was more useful to evaluate the auditory spatial cognitive function in children.

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54 We have studied the frontal lobe functions in normal children and patients with developmental disorders. The major components of frontal lobe functions are considered to be behavior inhibition, working memory, and executive function. We evaluated the effect of emotional autonomic response on behavior inhibition using sympathetic skin response. Normal children showed obvious autonomic responses to visual aversive stimuli, while the patients with conduct disorder showed no response. We also studied the developmental role of emotion during decision making. In the reinforcement learning task, the emotional autonomic response appeared specifically during reword/ punishment judgements in adults, whereas children did not show such an organized response. Furthermore, we studied the developmental changes of working memory using saccade eye movements. In normal children, significant correlations were observed between saccade latency, accuracy, error rates and age. Significant difference existed between normal children and patients with developmental disorders. Finally, we evaluated the developmental changes of executive functions which depend upon contextual reasoning. Two neurally distinct cognitive selection mechanisms involve the prefrontal lobes : those based on internal representation(context dependent)and those involving exploratory processing of novelsituations(contextindependent),usingcognitivebiastask. Thenormalchildrenshowed context independent responses, while adolescents and adults showed context dependent responses, suggesting that the locus of frontal cortical control shifts right to left as cognitive contextual reasoning develops. These findings suggest that emotional autonomic response is a critical requirement for behavior inhibition and decision making of future outcomes, and that the frontal lobe function is also critical for the temporal organization of cognitive processes.

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The function of recognizing faces has an important role in our daily social life. Evaluating the mechanism and the way it develops is very important for helping and educating children with difficulties in recognizing faces so that they can eventually recognize social information. Conversely, investigating the pathological conditions in people who have difficulties in facial recognition helps us to clarify the normal mechanism of facial recognition. th In this manuscript, based on a presentation at a symposium of the 18 meeting of the Japanese Society of Cognitive Neuroscience, the mechanism of facial recognition in adults, postnatal development of facial recognition and clinical phenotypes of diseases associated with difficulties in facial recognition are discussed.

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Several clinical trials designed for Alzheimer’s disease treatment were reported such as tramiprosate (inhibitor of Aβ aggregation), NSAIDs(tarenflurbil)and γ-secretase inhibitors(semagacertat). However, these trials were halted because of no clinical improvements. Based on the amyloid cascade theory, immunotherapy might be effective for the treatment of Alzheimer’s disease. Several clinical trials using anti-Aβ antibody(passive immunization)failed to ameliorate cognitive functions such as ADAS-cog or DAD despite of Aβ clearance in the bran and decreases in CSF T-tau/P-tau. These data indicated that the therapeutic time windows for administration of antibodies should be in the period between preclinical AD and mild cognitive impairment. NIA(National Institute on Aging)and AA(Alzheimer’s Association)proposed the new criteria of probable AD, MCI and preclinical AD. New clinical trials for amyloid PET positive, non-demented old persons and for preclinical patients of autosomal dominant Alzheimer’s disease are planned. Early diagnosis using amyloid imaging, early treatment by Aβ vaccine might be effective in prophylactic therapy of Alzheimer’s disease in the future.

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Although studies of attention-deficit/ hyperactivity disorder(AD/ HD)animal models are in progress, currently proposed models remain incomplete. Therefore, new animal models are needed to address these limitations. In this study, we examined whether Nagase Analubuminemic Rats(NAR), which have no remarkable physiological abnormalities, could be a suitable animal model of AD/ HD. We evaluated hyperactivity(open field travel distance), impulsiveness(time spent in open arm of an elevated minus maze), and attention(spontaneous alternation using a Y-maze)of a wild-type of NAR in comparison with the control Sprague-Dawley(SD)rat. Results showed that NAR were significantly more hyperactive(p < 0.001)and had higher impulsiveness(p < 0.001), and attention deficit(p < 0. 05)than SD rats. In addition, concentrations of dopamine, noradrenaline, 5-hydroxytryptamine(5-HT), and 5-hydroxyindole acetic acid in the prefrontal cortex of NARs were significantly decreased compared with those in SD rats. Furthermore, the concentration of 5-HT in the NARs was lower compared with that in SD rats, in the cerebellum. These results suggest that the NAR become a reliable animal model for behavioral and neurochemical phenotypes of AD/ HD.

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