Hirokuni Tagaya

Time estimation during sleep relates to the amount of slow wave sleep in humans

Humans have the ability to estimate the amount of time that has elapsed during sleep (time estimation ability; TEA) that enables a subset of individuals to wake up at a predetermined time without referring to a watch or alarm clock. Although previous studies have indicated sleep structure as a key factor that might influence TEA during sleep, which sleep parameters could affect the TEA has not been clarified. We carried out an experimental study in which 20 healthy volunteers participated in six time estimation trials during the 9-h nighttime sleep (NS) experiment or daytime sleep (DS) experiment. The time estimation ratio (TER, ratio of the subjective estimated time interval to actual time interval) decreased significantly from the first to the sixth trial in both the NS and DS experiments. TER correlated positively with slow wave sleep (SWS) in both experiments, suggesting that SWS was a determining factor in accurate time estimation, irrespective of circadian phase they slept. No other sleep parameters showed steady influence on TEA. The present findings demonstrate that longer period of SWS is associated with the longer sleep time they subjectively experienced during sleep.

Neuropsychological Detection of the Early Stage of Amnestic Mild Cognitive Impairment without Objective Memory Impairment

Aim: We investigate the assessment method to detect the early stage of amnestic mild cognitive impairment (aMCI) using Wechsler Memory Scale – Revised (WMS-R) and Wechsler Adult Intelligence Scale – Third Edition (WAIS-III). Methods: Three groups (normal group, aMCI group, and early aMCI group), controlled for age and years of education, underwent brain 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET), WAIS-III, WMS-R, and other tests. The early aMCI group does not fulfill the clinical diagnostic criteria of aMCI because patients do not have objective memory impairment, but their clinical symptoms and results of 18F-FDG PET indicate that they should be included in the category of aMCI. Results: The discrepancy of scores between Verbal IQ and General Memory had the highest accuracy in discriminating between normal and early aMCI groups. Conclusion: The cutoff point determined in this study is useful to detect an early stage of aMCI, which may be distinguished from aMCI using the current criteria.

Amygdala-centred functional connectivity affects daily cortisol concentrations: a putative link with anxiety

The amygdala plays a critical role in emotion. Its functional coupling with the hippocampus and ventromedial prefrontal cortex extending to a portion of the anterior cingulate cortex (ACC) is implicated in anxiogenesis and hypothalamic-pituitary-adrenal (HPA) system regulation. However, it remains unclear how amygdala-centred functional connectivity (FC) affects anxiety and cortisol concentrations in everyday life. Here, we investigate the relationship between daily cortisol concentrations (dCOR) and amygdala-centred FC during emotional processing in forty-one healthy humans. FC analyses revealed that higher dCOR predicted strengthened amygdala-centred FC with the hippocampus and cerebellum, but inhibited FC with the supramarginal gyrus and a perigenual part of the ACC (pgACC) when processing fearful faces (vs. neutral faces). Notably, the strength of amygdala-hippocampus FC mediated the positive relationship between cortisol and anxiety, specifically when the effect of amygdala-pgACC FC, a presumptive neural indicator of emotional control, was taken into account. Individuals with diminished connectivity between the amygdala and pgACC during fear-related processing might be more vulnerable to anxiogenesis as it pertains to greater circulating cortisol levels in everyday life. Individual functional patterns of amygdala-hippocampal-pgACC connectivity might provide a key to understand the complicate link between cortisol and anxiety-related behaviors.

Does neurocognitive function affect cognitive bias toward an emotional stimulus? Association between general attentional ability and attentional bias toward threat

Background: Although poorer cognitive performance has been found to be associated with anxiety, it remains unclear whether neurocognitive function affects biased cognitive processing toward emotional information. We investigated whether general cognitive function evaluated with a standard neuropsychological test predicts biased cognition, focusing on attentional bias toward threat. Methods: One hundred and five healthy young adults completed a dot-probe task measuring attentional bias and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) measuring general cognitive function, which consists of five domains: immediate memory, visuospatial/constructional, language, attention, and delayed memory. Stepwise multiple regression analysis was performed to examine the relationship between attentional bias and cognitive function. Results: The attentional domain was the best predictor of attentional bias toward threat (β = −0.26, p = 0.006). Within the attentional domain, digit symbol coding was negatively correlated with attentional bias (r = −0.28, p = 0.005). Conclusions: The present study provides the first evidence that general attentional ability, which was assessed with a standard neuropsychological test, affects attentional bias toward threatening information. Individual cognitive profiles might be important for the measurement and modification of cognitive biases.

Cognitive dysfunction in patients with very mild Alzheimer's disease and amnestic mild cognitive impairment showing hemispheric asymmetries of hypometabolism on ¹⁸F-FDG PET.

We investigated cognitive dysfunction in patients with Alzheimers disease (AD) and amnestic mild cognitive impairment (aMCI) who present hemispheric asymmetries of cerebral metabolic rate of glucose (CMRglc) decrease on 18F‐fluorodeoxyglucose positron emission tomography.

Intelligence or years of education: which is better correlated with memory function in normal elderly Japanese subjects?

Background:u2002 We compared differences in intelligence and memory function between normal elderly Japanese subjects with more years of education and those with fewer years of education. We also investigated clinical and neuropsychological factors that are strongly correlated with memory function.

Higher cortisol levels at diurnal trough predict greater attentional bias towards threat in healthy young adults

BACKGROUNDnAttentional bias (AB), selective information processing towards threat, can exacerbate anxiety and depression. Despite growing interest, physiological determinants of AB are yet to be understood. We examined whether stress hormone cortisol and its diurnal variation pattern contribute to AB.nnnMETHODSnEighty-seven healthy young adults underwent assessments for AB, anxious personality traits, depressive symptoms, and attentional function. Salivary cortisol was collected at three time points daily (at awakening, 30 min after awakening, and bedtime) for 2 consecutive days. We performed: (1) multiple regression analysis to examine the relationships between AB and the other measures and (2) analysis of variance (ANOVA) between groups with different cortisol variation patterns for the other measures.nnnRESULTSnMultiple regression analysis revealed that higher cortisol levels at bedtime (p<0.001), an anxious personality trait (p=0.011), and years of education (p=0.036) were included in the optimal model to predict AB (adjusted R(2)=0.234, p<0.001). ANOVA further demonstrated significant mean differences in AB and depressive symptoms; individuals with blunted cortisol variation exhibited significantly greater AB and depression than those with moderate variation (p=0.037 and p=0.009, respectively).nnnLIMITATIONSnNeuropsychological assessment focused on attention and cortisol measurement at three time points daily.nnnCONCLUSIONSnWe showed that higher cortisol levels at bedtime and blunted cortisol variation are associated with greater AB. Individuals who have higher cortisol levels at diurnal trough might be at risk of clinical anxiety or depression but could also derive more benefits from the attentional-bias-modification program.

The functional activity and effective connectivity of pulvinar are modulated by individual differences in threat-related attentional bias.

The pulvinar is important in selective attention, particularly to visual stimuli under the focus of attention. However, the pulvinar is assumed to process emotional stimuli even outside the focus of attention, because of its tight connection with the amygdala. We therefore investigated how unattended emotional stimuli affect the pulvinar and its effective connectivity (EC) while considering individual differences in selective attention. fMRI in 41 healthy human subjects revealed that the amygdala, but not the pulvinar, more strongly responded to unattended fearful faces than to unattended neutral faces (UFu2009>u2009UN), although we observed greater EC from the pulvinar to the amygdala. Interestingly, individuals with biased attention toward threat (i.e., attentional bias) showed significantly increased activity (UFu2009>u2009UN) and reduced grey matter volume in the pulvinar. These individuals also exhibited stronger EC from the pulvinar to the attention-related frontoparietal network (FPN), whereas individuals with greater attentional control showed more enhanced EC from the pulvinar to the amygdala, but not the FPN (UFu2009>u2009UN). The pulvinar may filter unattended emotional stimuli whose sensitivity depends on individual threat-related attentional bias. The connectivity patterns of the pulvinar may thus be determined based on individual differences in threat-related attentional bias and attentional control.

Effects of zolpidem/triazolam on cognitive performance 12 hours after acute administration

OBJECTIVEnMost previous studies have concluded that decreased cognitive function and performance due to ultra-short acting hypnotics do not persist after 6-9xa0h post-administration. This study examined the effects of ultra-short acting hypnotics on cognitive function and performance 12xa0h after administration, ie, a time considered sufficient for the effects of hypnotics to disappear.nnnMETHODSnThirteen healthy young male volunteers (mean age, 23.4xa0±xa03.2 years) participated in this study. Participants attended three sessions of polysomnography (PSG) recording preceded by oral administration of placebo for the first session, and 5xa0mg zolpidem or 0.25xa0mg triazolam for the second and third sessions, in a double-blinded, randomized manner at intervals of at least five days. A cognitive test battery was administered following each session, consisting of a psychomotor vigilance task (PVT), which reflects alertness and sleepiness, digit symbol substitution test (DSST), which reflects attention and working memory function, and assessment of subjective sleepiness and mental condition using a visual analog scale (VAS).nnnRESULTS AND CONCLUSIONSnThe administration of hypnotics significantly increased total sleep time, sleep efficiency, and sleep stages 2 and 4, and significantly decreased wake after sleep onset and sleep stage 1. PVT parameters were not affected by the administration of hypnotics, but DSST score was significantly lower, and subjective alertness, vigor, and sadness significantly deteriorated, after administration. In conclusion, while objective sleepiness disappeared 12xa0h after the administration of ultra-short acting hypnotics, their effects to decrease cognitive function persisted even after 12xa0h post-administration.

Cytosolic Genomic DNA functions as a Natural Antisense

Stress conditions such as UV irradiation, exposure to genotoxic agents, stalled DNA replication, and even tumors trigger the release of cytosolic genomic DNA (cgDNA). Classically, cgDNA induces interferon response via its binding to proteins such as STING. In this study, we found previously reported cgDNA (cg721) exists in the cytosol of the mouse cell lines, cultured under no stress conditions. The overexpression of cg721 suppressed the complementary RNA expression using strand selection and knockdown of DNA/RNA hybrid R-loop removing enzyme RNase H and three prime repair exonuclease 1 TREX1 increased the expression levels of cg721 and thus, inhibited the target Naa40 transcript, as well as protein expression, with a phenotypic effect. In addition, cgDNA was incorporated into extracellular vesicles (EVs), and the EV-derived cg721 inhibited gene expression of the acceptor cells. Thus, our findings suggest that cg721 functions as a natural antisense DNA and play a role in cell-to-cell gene regulation once it secreted outside the cell as EVs.