Kenichi Kuriyama

Circadian fluctuation of time perception in healthy human subjects

Previous studies suggested that various psychophysiological factors have influences on human time perception. In particular, working memory loads, time of day, body temperature, and mood were known as important modifiers of time perception. The purpose of this study is to elucidate factors affecting the short-term time perception under controlled condition. Fourteen healthy young male adults participated in this study. Time perception sessions (TPS) were conducted 4 times at 0900, 1300, 1700 and 2100 h. The TPS consisted of five 10-s time production trials under five different conditions (control trial, those with reward, and 3 different dual-load working memory tasks). Subjective status was assessed using visual analogue scales (VAS). To verify a participants vigilance state, an alpha attenuation coefficient (AAC) was calculated. Two-way repeated measures ANOVA for produced time revealed a significant main effect of session, but no effect of task or interaction. Although produced time was not correlated with AACs or VAS scores, there was a significant negative correlation between produced time and core body temperature. These results suggest that human short-term time perception may be more influenced by circadian rhythm than working memory load or psychophysiological status.

Sleep Accelerates the Improvement in Working Memory Performance

Working memory (WM) performance, which is an important factor for determining problem-solving and reasoning ability, has been firmly believed to be constant. However, recent findings have demonstrated that WM performance has the potential to be improved by repetitive training. Although various skills are reported to be improved by sleep, the beneficial effect of sleep on WM performance has not been clarified. Here, we show that improvement in WM performance is facilitated by posttraining naturalistic sleep. A spatial variant of the n-back WM task was performed by 29 healthy young adults who were assigned randomly to three different experimental groups that had different time schedules of repetitive n-back WM task sessions, with or without intervening sleep. Intergroup and intersession comparisons of WM performance (accuracy and response time) profiles showed that n-back accuracy after posttraining sleep was significantly improved compared with that after the same period of wakefulness, independent of sleep timing, subjects vigilance level, or circadian influences. On the other hand, response time was not influenced by sleep or repetitive training schedules. The present study indicates that improvement in n-back accuracy, which could reflect WM capacity, essentially benefits from posttraining sleep.

D-cycloserine facilitates procedural learning but not declarative learning in healthy humans: A randomized controlled trial of the effect of D-cycloserine and valproic acid on overnight properties in the performance of non-emotional memory tasks

Although D-cycloserine (DCS), a partial agonist of the N-methyl-d-aspartate (NMDA) receptor, and valproic acid (VPA), a histone deacetylase inhibitor, have been investigated for their roles in the facilitation of emotional learning, the effects on non-emotional declarative and procedural learning have not been clarified. We performed a randomized, blind, placebo-controlled, 4-arm clinical trial to determine the effects of DCS and VPA on the overnight properties of declarative and procedural learning in 60 healthy adults. Subjects were orally administrated a placebo, 100 mg DCS, 400 mg VPA, or a combination of 100 mg DCS and 400 mg VPA before they performed declarative and procedural learning tasks. Subjects then had their performance retested the following day. We observed that DCS facilitated procedural but not declarative learning and that VPA did not contribute to learning. Surprisingly, however, VPA attenuated the enhancement effect of DCS when coadministered with it. These results suggest that DCS acts as an enhancer of hippocampus-independent learning and that VPA may have an extinguishing pharmacological effect on excitatory post-synaptic action potentials that NMDA receptors regulate within procedural learning.

Right Prefrontal Activity Reflects the Ability to Overcome Sleepiness during Working Memory Tasks: A Functional Near-Infrared Spectroscopy Study

It has been speculated that humans have an inherent ability to overcome sleepiness that counteracts homeostatic sleep pressure. However, it remains unclear which cortical substrate activities are involved in the ability to overcome sleepiness during the execution of cognitive tasks. Here we sought to confirm that this ability to overcome sleepiness in task execution improves performance on cognitive tasks, showing activation of neural substrates in the frontal cortex, by using a modified n-back (2- and 0-back) working memory task and functional near-infrared spectroscopy. The change in alertness was just correlated with performances on the 2-back task. Activity in the right prefrontal cortex changed depending on alertness changes on the 2- and 0-back tasks independently, which indicates that activity in this region clearly reflects the ability to overcome sleepiness; it may contribute to the function of providing sufficient activity to meet the task load demands. This study reveals characteristics of the ability to overcome sleepiness during the n-back working memory task which goes beyond the attention-control function traditionally proposed.

Time estimation during nocturnal sleep in human subjects

It has been postulated that time estimation during nocturnal sleep in humans can be explained by an interval timing clock inside the brain. However, no systematic investigations have been carried out with respect to how the human brain perceives the passage of time during sleep. The brain mechanisms of over- or underestimation of time spent in sleep have not yet been clarified. Here, we carried out an experimental study in which 11 healthy volunteers participated in time estimation trials scheduled six times during 9 h nocturnal sleep periods, under carefully controlled conditions. The time estimation ratio (TER: a ratio of subjective passage of time to actual time interval) decreased significantly from the first to the sixth trial. Individual TER was positively correlated with slow wave sleep prior to the trial, while it was negatively correlated with REM sleep. Our results indicate that the human brain has an ability to estimate the passage of time during nocturnal sleep without referring to time cues, and that the accuracy of this function fluctuates from overestimation in the early hours of sleep to underestimation in the last hours of sleep.

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.

An N-methyl-D-aspartate receptor agonist facilitates sleep-independent synaptic plasticity associated with working memory capacity enhancement.

Working memory (WM) capacity improvement is impacted by sleep, and possibly by N-methyl-D-aspartate (NMDA) agonists such as D-cycloserine (DCS), which also affects procedural skill performance. However, the mechanisms behind these relationships are not well understood. In order to investigate the neural basis underlying relationships between WM skill learning and sleep, DCS, and both sleep and DCS together, we evaluated training-retest performances in the n-back task among healthy subjects who were given either a placebo or DCS before the task training, and then followed task training sessions either with wakefulness or sleep. DCS facilitated WM capacity enhancement only occurring after a period of wakefulness, rather than sleep, indicating that WM capacity enhancement is affected by a cellular heterogeneity in synaptic plasticity between time spent awake and time spent asleep. These findings may contribute to development, anti-aging processes, and rehabilitation of higher cognition.

Perceptual and not physical eye contact elicits pupillary dilation.

Eye contact is important to share communication during social interactions. However, how accurately humans can perceive the gaze direction of others toward themselves and whether pupils dilate when humans consciously or unconsciously perceive own eyes are looked by others remain unclear. In this study, we examined the relationship between the explicit perception of looking into each others eyes and the implicit physiological response of pupillary dilation by using an original face-to-face method. We found that humans do not correctly detect the gaze direction of others. Furthermore, ones pupils dilated when one gazed at others eyes. Awareness of others gaze on ones eyes, rather than the actual focusing of others gaze on ones eyes, enhanced pupillary dilation. Therefore, physiological responses are caused not when people actually look into each others gaze, but when the consciousness of others gaze is activated, which suggests that eye contact often involves one-way communication.

Diurnal fluctuations in subjective sleep time in humans

Humans have the ability to estimate the passage of time in the absence of external time cues. In this study, we subjected 22 healthy males (aged 21.8±1.9 years) to a 40-min nap trial followed by 80min of wakefulness repeated over 28h, and investigated the relationship between various sleep parameters and the discrepancy (ΔST) of time estimation ability (TEA) during sleep, defined by the difference between actual sleep time (ST) and subjective sleep time (sub-ST) in each nap interval. Both ST and sub-ST were significant diurnal fluctuations with the peak in the early morning (9h after dim-light melatonin onset time, 2h after nadir time of core body temperature rhythm), and subjective sleep duration was estimated to be longer than actual times in all nap intervals (sub-ST>ST). There were significant diurnal fluctuations in discrepancy (sub-ST-ST) of TEA during sleep, and the degree of discrepancy correlated positively with increase in the amount of REM sleep and decrease in the amount of slow-wave sleep. These findings suggest that human TEA operates at a certain level of discrepancy during sleep, and that this discrepancy might be related to the biological clock and its associated sleep architecture.

Effects of sex differences and regulation of the sleep-wake cycle on aversive memory encoding.

Formation of aversive memories sometimes involves a pathogenic cognitive process that could lead to the development of posttraumatic stress disorder (PTSD). Here, we explore chronobiological aspects of shifts in aversive memory encoding abilities around habitual sleep onset periods (SOPs). Thirty university students, who were randomly assigned to one of two groups, watched a suspenseful movie for 2 h, beginning either 3h prior to their habitual sleep onset periods (pre-SOP group) or 1h after their habitual sleep onset periods (post-SOP group). Recognition accuracy was tested 15 min after the movie finished and again 10h after the movie finished, after a sleep period. Overall recognition accuracy was higher in the post-SOP women than in the pre-SOP women, while that in the pre-SOP men was higher than that in the post-SOP men. The recognition accuracy gap (aversive-neutral) was significantly greater in the post-SOP women than in the pre-SOP women throughout both recognition sessions, while there was a non-significant group difference for men. These findings suggest that habitual SOP is a watershed in womens ability to learn to identify aversive events. Women more correctly encode aversive episodes post-SOP than pre-SOP, which could contribute to high PTSD prevalence in women.