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T Sawaguchi

Publications and source records attributed to T Sawaguchi.

At least 37 records · Page 2Linked to original sources
PubMed2001

Prefrontal cortical representation of visuospatial working memory in monkeys examined by local inactivation with muscimol.

In primates, dorsolateral areas of the prefrontal cortex (PFC) play a major role in visuospatial working memory. To examine the functional organization of the PFC for representing visuospatial working memory, we produced reversible local inactivation, with the local injection of muscimol (5 microg, 1 microl), at various sites (n = 100) in the dorsolateral PFC of monkeys and observed the behavioral consequences in an oculomotor delayed-response task that required memory-guided saccades for locations throughout both visual fields. At 82 sites, the local injection of muscimol induced deficits in memory-guided saccades to a few specific, usually contralateral, target locations that varied with the location of the injection site. Such deficits depended on the delay length, and longer delays were associated with larger deficits in memory-guided saccades. The injection sites and affected spatial locations of the target showed a gross topographical relationship. No deficits appeared for a control task in which the subject was required to make a visually guided saccade to a visible target. These findings suggest that a specific site in the dorsolateral PFC is responsible for the working memory process for a specific visuospatial coordinate to guide goal-directed behavior. Further, memoranda for specific visuospatial coordinates appear to be represented in a topographical memory map within the dorsolateral PFC to represent visuospatial working memory processes.

Animals↗
PubMed2000

The role of D1-dopamine receptors in working memory-guided movements mediated by frontal cortical areas.

Like the striatum, the frontal motor cortices receive dopaminergic fibers from midbrain dopamine cells and contain high levels of dopamine receptors. Among frontal cortical areas, the dorsolateral PFC (PFd1) and the dorsal premotor cortex (PMd) have strong neural connections and play a major role for working memory-guided directional movements. To reveal the role of dopamine in this cognitive motor function, dopamine antagonists (SCH23390 for D1 receptors and sulpiride for D2 receptors) were applied locally or iontophoretically to the PFd1 and PMd in monkeys that performed delayed-response tasks with memory-guided directional movements. Applications of SCH23390, but not sulpiride, to these areas had significant effects at both the behavioral and neuronal levels. In the PFd1 and at the behavioral level, local injections of SCH23390 induced specific errors for memory-guided saccades, whereas it had no effects on visually guided saccades. In the PMd, local injections of SCH23390 induced directional errors and increased reaction time and movement time in memory-guided reaching movements. At the neuron level, iontophoretic applications of SCH23390 attenuated directional tuning of neurons of the PFd1 and PMd, which showed directional activities during the delay-and/or response-period(s). These findings suggest that the activation of D1-dopamine receptors in these frontal cortical areas plays a facilitating role in a series of neuronal processes of working memory-guided directional movements; the working memory process for guiding motor act in the PFd1 and preparation/control of directional manual movements in the PMd. In addition, our findings may provide insight into symptoms of schizophrenia and Parkinson's disease; the dysfunction of D1-dopamine receptors in the PMd1 and PMd may contribute to some symptoms, such as bradyphrenia and bradykinesia, in these disorders.

Journal Article↗
PubMed2000

Factors influencing the determination of arousal thresholds in infants - a review.

Objective: To review the major confounding factors that influence the determination of arousal thresholds in infants.Review of confounding factors: The determination of arousal thresholds in infants measures their arousability from sleep. The evaluation is influenced by various conditions. The infant's arousability is decreased by maternal factors, such as exposure to cigarette smoke, alcohol, illegal drugs or medications during gestation or breastfeeding. The levels of arousal thresholds also depend on the age of the infant and on experimental conditions, such as previous sleep deprivation, type of arousal challenges, time of administration of the arousal challenge, sleep stage, body position, room temperature, use of a pacifier, bed sharing, or type of feeding. In addition, spontaneous arousals can occur and modify the infant's response to external arousal challenges.Conclusions: Factors known to modify infants' arousability from sleep should be controlled during studies designed to determine arousal thresholds.

Journal Article↗
PubMed2000

The epidemiological study on registered cases of sudden infant death syndrome (SIDS) in Tokyo: examination of the effect of autopsy on diagnosis of SIDS and the mortality statistics in Japan.

In the United States and most of European countries, a diagnosis of sudden infant death syndrome (SIDS) may be given only after an autopsy has been performed. Under the new definition of SIDS in Japan, an autopsy is now mandatory for the diagnosis of SIDS. However, according to the official records on autopsies, the proportion of autopsy for sudden infant death in Japan is still low (less than 30%). If a physician suspects SIDS from a review of the patient's medical history and medical findings, he can write 'suspected SIDS' as the cause of death on the death certificate without performing an autopsy. Such a clinical diagnosis is entered in the Vital Statistics section by the Japanese Ministry of Health and Welfare. In this report, a comparative epidemiological survey of registered cases of SIDS--after autopsy and with no autopsy--was carried out by examining the data from the death certificates registered by the Japanese Ministry of Health and Welfare (vital statistics in Tokyo from January 1979 to December 1996). There were 369 cases of SIDS registered in Tokyo. We found 247 diagnosed after autopsy (66.9%) and 122 with no autopsy (33.1%). The following epidemiological variables were used: address of the deceased (a specific area in Tokyo), sex, year of death, time of death, month of death, age at death, occupation of householders, and place of death. There were epidemiological differences at the 0.05 significance level between registered cases diagnosed after autopsy and those diagnosed without autopsies, as follows: year (P=0.016) and place of death (P=0.037). In addition, there were slight epidemiological differences at the 0.10 significance level between registered cases diagnosed after autopsy and with no autopsy, as follows: month of death (P=0.076) and age at death (P=0.082). This suggests that the quality of diagnosis of SIDS is not completely guaranteed. With respect to the area of residence, the incidence of SIDS is high in those areas where autopsy is performed frequently. In Tokyo, the medical examiner system is enforced only in the urban area and there is a possibility that SIDS is being underdiagnosed in the rural area of the Metropolitan Tokyo. It is likely that the diagnosis of SIDS without autopsy will influence the quality of SIDS diagnoses. The administrative inadequacy in the autopsy system in Japan should be corrected to improve the accuracy of SIDS diagnosis.

Age Factors↗
PubMed2000

Post-mortem analysis of apoptotic changes associated with human skin bruises.

The estimation of the age of skin bruises is of importance in forensic medicine, especially in child abuse cases. Time-dependent changes in bruise colour and/or associated histological features have been used with a limited degree of success. An increased rate of apoptosis in the injured tissue has been considered as a novel time-dependent marker of cell death, by injury inflicted in a rat model. The object of the present study was to apply the TUNEL method of DNA end labelling to identify and enumerate apoptotic cells in bruised and normal skin in order to study the relationship of apoptotic cell density with the age of the bruise. A commercially available DNA end labelling kit, TUNEL method, was standardised, validated and used for this purpose. Twenty unselected post-mortem cases with bruises due to a variety of causes were studied. The apoptotic cells stained with TUNEL reaction were counted in 10 high power fields in the epidermis, as well as in the dermis of formaldehyde-fixed paraffin-embedded skin specimens. The mean positive cell densities (+/- 1 S.E.) were compared with respect to the age of the bruise. In the epidermis, the mean apoptotic cell count was statistically significantly greater in the bruised skin compared to normal skin in 2- to 6-day-old bruises; whilst in the dermis the same was true in 3- to 8-day-old bruises. The overall findings suggest that there is a quiescent period prior to the increase in the apoptotic cell activity that is seen following skin bruising. This is so provided the post-mortem skin samples were collected within a lapse of 6 days or less between the time of death and formalin fixation and paraffin embedding to avoid the bias made by the difference of length of post-mortem interval.

Adult↗
PubMed2000

Application of electrophoresis technology to DNA analysis.

We used the variable number tandem repeat (VNTR) polymorphism and the ten short tandem repeat (STR) polymorphisms to study a number of disputed paternity cases in the Japanese population. For the determination of VNTR locus (D1S80) and the ten STR loci (vWA, F13B, TH01, TPOX, CSF1PO, F13A01, LPL, D3S1744, D12S1090, D18S849) we used polymerase chain reaction (PCR) amplification and the vertical polyacrylamide gel electrophoresis technique followed by SYBR green I staining. The irregular repeats were analyzed by sequencing from bands of vertical polyacrylamide gel electrophoresis using the latest gene analyzing equipment, the ABI PRISM 310 Genetic Analyzer. The probable genotypes of the deceased putative father were deduced by Komatu's method from the genotypes of the widow and the genotypes of their children. The calculation of paternity probability used the Essen-Moller formula and Bayes's theorem. Calculated in eleven loci, the distinguishing probabilities (DP) and the mean exclusion chance (MEC) were 0.9999 and 0.9989, respectively. Therefore, information obtained from eleven DNA polymorphisms is enough to determine paternity plausibility.

DNA↗
PubMed2000

Parallel visuospatial and audiospatial working memory processes in the monkey dorsolateral prefrontal cortex.

The dorsolateral area of the prefrontal cortex (PFC) in primates is involved in visuospatial working memory, but the cellular basis of spatial working memory for auditory information is poorly understood. Here we examined dorsolateral PFC neurons using visual and auditory oculomotor delayed-response tasks. We found that the dorsolateral PFC contains two groups of neurons, each showing directional delay-period activity depending on the location of the visual or auditory cue, suggesting that parallel neuronal processes for visual and auditory spatial working memory occur in the dorsolateral PFC.

Action Potentials↗
PubMed1999

Properties of delay-period neuronal activity in the monkey dorsolateral prefrontal cortex during a spatial delayed matching-to-sample task.

The dorsolateral prefrontal cortex (PFC) has been implicated in visuospatial memory, and its cellular basis has been extensively studied with the delayed-response paradigm in monkeys. However, using this paradigm, it is difficult to dissociate neuronal activities related to visuospatial memory from those related to motor preparation, and few studies have provided evidence for the involvement of PFC neurons in visuospatial memory of a sensory cue, rather than in motor preparation. To extend this finding, we examined neuronal activities in the dorsolateral PFC while a rhesus monkey performed a spatial delayed matching-to-sample (SDMTS) task, which allows us to adequately access visuospatial memory independent of any sensorimotor components. The SDMTS task required the subject to make a lever-holding NOGO response or a lever-releasing GO response when a visuospatial matching cue (white spot, one of four peripheral locations, 15 degrees in eccentricity) matched or did not match a sample cue (physically the same as the matching cue) that had been presented prior to a delay period (3 s). Thus, the SDMTS task requires the subject to remember visuospatial information regarding the sample cue location during the delay period and is suitable for accessing visuospatial memory independent of any sensorimotor components, such as motor preparation, for directed movements. Of a total of 385 task-related neurons, 184 showed a sustained increase in activity during the delay period ("delay-period activity"). Most of these neurons (n = 165/184, 90%) showed positional delay-period activity, i.e., delay-period activity where the magnitude differed significantly with the position of the sample cue. This activity appears to be involved in visuospatial memory and to form a "memory field." To quantitatively examine the properties of positional delay-period activity, we introduced a tuning index (TI) and a discriminative index (DI), which represent the sharpness of tuning and the discriminative ability, respectively, of positional delay-period activity. Both TI and DI varied among neurons with positional delay-period activity and were closely related to the time from the onset of the sample cue to the onset of positional delay-period activity; positional delay-period activity with sharper tuning and a greater discriminative ability had a slower onset. Furthermore, at the population level, both TI and DI were increased during the delay period in the neuronal population with a high DI value. These results extend previous findings to suggest that integrative, convergent processes of neuronal activities for increasing the accuracy of visuospatial memory may occur in the dorsolateral PFC. Thus, a critical role of the dorsolateral PFC in visuospatial memory may be to sharpen it to guide behaviors/decisions requiring accurate visuospatial memory.

Animals↗
PubMed1999

hOGG1 Ser326Cys polymorphism and lung cancer susceptibility.

The human homologue of the yeast OGG1 gene, hOGG1, has been cloned, and its genetic structure has been determined. Several polymorphisms in the hOGG1 gene were detected in the Japanese populations, and among them, the Ser-Cys polymorphism at codon 326 has been shown to have a functional difference in complementation of mutant Escherichia coli that is defective in the repair of 8-hydroxyguanine. Activity in the repair of 8-hydroxyguanine is greater in hOGG1-Ser326 protein than in hOGG1(326) protein. Because many environmental carcinogens produce 8-hydroxyguanine residue and mismatching to this modified base potentially causes oncogenic mutations, the capacity to repair these lesions can be involved in cancer susceptibility in human beings. We, therefore, examined allele distributions of the Ser326Cys polymorphism in a case-control study of male lung cancer in Okinawa. The analyses based on 241 cases and 197 hospital controls disclosed the following findings. (a) Those with the Cys/Cys genotype were at an increased risk of squamous cell carcinoma and nonadenocarcinoma compared to those with the Ser/Cys and those with the Ser/Ser genotypes combined. The odds ratios adjusted for age and smoking history were 3.01 (95% confidence interval, 1.33-6.83) and 2.18 (95% confidence interval, 1.05-4.54), respectively. (b) The odds ratios for other histological subtypes of lung cancer or those in total were not significant. Those for Cys/Cys or Ser/Cys genotype against Ser/Ser did not reach statistical significance in any cell type. (c) The distributions of this polymorphism varied for different populations (Chinese, Japanese, Micronesians, Melanesians, Hungarians, and Australian Caucasians), with much less prevalence of Cys allele in the latter three populations. Although our sample size was limited, these results indicate that the Ser326Cys variant may be related to squamous cell lung cancer susceptibility. The Cys/Cys genotype appears to be more susceptible to squamous cell carcinoma, although the risk is less than that previously reported to be associated with the CYP1A1 gene. Further studies are needed to assess the importance of the interpopulation variation to cancer susceptibility.

Adult↗
PubMed1998

Is the incidence of SIDS increasing in Asia?

The incidence of SIDS in western countries has decreased since the late 1980s after active SIDS prevention campaigns. By contrast, both Taiwan and Japan have reported an increase in incidences. In this report data from England, Wales, Scotland, Northern Ireland, Japan and Hong Kong are analysed. Regression coefficient and linearity of regression tests were used to determine if there was any significant increase or decrease in post-neonatal mortality (PNNM), SIDS mortality and mortality among infants 1-5 months old. A statistically significant decrease in SIDS was recognized in England, Wales, Scotland and Northern Ireland, whereas statistically significant increases were noted for Japan and Hong Kong. However in Japan and Hong Kong both the PNNM and mortality of infants between 1-5 months in age fell significantly, suggesting that the increased SIDS rates could be due to a change in diagnostic labelling. Further study will be required to determine whether this increase in the incidence of SIDS is genuine or only an artifact.

Asia↗
PubMed1998

Monkey prefrontal neuronal activity coding the forthcoming saccade in an oculomotor delayed matching-to-sample task.

To determine the role of the dorsolateral prefrontal cortex (PFC) in the selection of memory-guided saccadic eye movements, we recorded the activities of PFC neurons while macaque monkeys performed an oculomotor delayed matching-to-sample task. The task was designed to dissociate motor factors from visual factors in the selection and retention of the direction of the forthcoming saccade during delay periods after the visual cue but before the GO signal was presented. While the monkey fixated on a central fixation spot (FX period, 1 s), a sample cue (1 of 4 geometric figures) and a matching cue composed of two geometric figures were presented in succession (SC and MC periods, respectively, 0.5 s) with a brief delay (D1 period, 1 or 1.5 s). After another delay (D2 period, 1.5 s), the monkey made a saccade (GO period, <0.5 s) toward one of four locations (the goal) that had been indicated by the combination of the sample and matching cues in the MC period. We recorded the activities of 224 neurons in the periprincipal sulcal area of 3 hemispheres of 2 monkeys. Sixty-five neurons (29%) showed a significant increase in activity during the D2 period. Some of these also responded during other phases of the task (SC period, n = 32; D1, 22; MC, 53; GO, 47). Some of the activity during the D2(52/65, 80%) and GO (40/47, 85%) periods was associated with the direction of the forthcoming saccade ("direction selective"). Although most MC-period activities of D2 neurons were direction selective (38/53, 73%), a fraction of them (14/38) was also affected by both saccade direction and matching cue pattern. To compare quantitatively the contribution of motor (saccade direction) and visual (matching-cue pattern) factors to the activity of D2 neurons, we calculated directional and visual dependency indices (DDI and VDI) for each of the three periods (MC, D2, and GO). In both the D2 and GO periods, D2 neurons with high DDI values and low VDI values predominated. In the MC period, however, there was no significant difference between the distributions of DDI and VDI values. These findings suggest that PFC neurons store the direction of memory-guided saccades during a delay period before eye movement and that the same neurons may be involved in the decision-making process that underlies the selection of the saccade direction during the MC period.

Animals↗