Motoyasu Honma

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.

Sleep dissolves illusion: sleep withstands learning of visuo-tactile-proprioceptive integration induced by repeated days of rubber hand illusion training.

Multisensory integration is a key factor in establishing bodily self-consciousness and in adapting humans to novel environments. The rubber hand illusion paradigm, in which humans can immediately perceive illusory ownership to an artificial hand, is a traditional technique for investigating multisensory integration and the feeling of illusory ownership. However, the long-term learning properties of the rubber hand illusion have not been previously investigated. Moreover, although sleep contributes to various aspects of cognition, including learning and memory, its influence on illusory learning of the artificial hand has not yet been assessed. We determined the effects of daily repetitive training and sleep on learning visuo-tactile-proprioceptive sensory integration and illusory ownership in healthy adult participants by using the traditional rubber hand illusion paradigm. Subjective ownership of the rubber hand, proprioceptive drift, and galvanic skin response were measured to assess learning indexes. Subjective ownership was maintained and proprioceptive drift increased with daily training. Proprioceptive drift, but not subjective ownership, was significantly attenuated after sleep. A significantly greater reduction in galvanic skin response was observed after wakefulness compared to after sleep. Our results suggest that although repetitive rubber hand illusion training facilitates multisensory integration and physiological habituation of a multisensory incongruent environment, sleep corrects illusional integration and habituation based on experiences in a multisensory incongruent environment. These findings may increase our understanding of adaptive neural processes to novel environments, specifically, bodily self-consciousness and sleep-dependent neuroplasticity.

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.

Neuroticism relates to daytime wakefulness and sleep devaluation via high neurophysiological efficiency in the bilateral prefrontal cortex: a preliminary study.

Higher wake promotion against sleep drive boosts cognitive processing, but it also seems to increase the risk of insomnia by reinforcing an obsession with sleep in neurotic patients. To explore whether a personality trait of neuroticism simultaneously facilitates wake-promoting ability and sleep devaluation via a common regional prefrontal function under a sleep-restricted condition, working memory tasks were administered to 49 healthy humans after a 2-h sleep restriction. Higher wake-promoting ability demonstrated in a high-load task was correlated with lower bilateral prefrontal activation, as measured by near-infrared spectroscopy. Structural equation modeling revealed that neuroticism predicts sleep devaluation and wake-promoting ability via left and right regional prefrontal efficiency, respectively. Our results indicate that neuroticism-related neural efficiency increases resilience to sleepiness, but decreases sleep satisfaction.

Disturbances in equilibrium function after major earthquake

Major earthquakes were followed by a large number of aftershocks and significant outbreaks of dizziness occurred over a large area. However it is unclear why major earthquake causes dizziness. We conducted an intergroup trial on equilibrium dysfunction and psychological states associated with equilibrium dysfunction in individuals exposed to repetitive aftershocks versus those who were rarely exposed. Greater equilibrium dysfunction was observed in the aftershock-exposed group under conditions without visual compensation. Equilibrium dysfunction in the aftershock-exposed group appears to have arisen from disturbance of the inner ear, as well as individual vulnerability to state anxiety enhanced by repetitive exposure to aftershocks. We indicate potential effects of autonomic stress on equilibrium function after major earthquake. Our findings may contribute to risk management of psychological and physical health after major earthquakes with aftershocks, and allow development of a new empirical approach to disaster care after such events.

Dysfunctional counting of mental time in Parkinson's disease.

Patients with Parkinson’s disease (PD) often underestimate time intervals, however it remains unclear why they underestimate rather than overestimate them. The current study examined time underestimation and counting in patients with PD, in relation to dopamine transporter (DaT) located on presynaptic nerve endings in the striatum. Nineteen non-dementia patients with PD and 20 age- and sex-matched healthy controls performed two time estimation tasks to produce or reproduce time intervals with counting in the head, to examine dysfunctional time counting processing. They also performed tapping tasks to measure cycles of counting with 1 s interval with time estimation. Compared to controls, patients underestimated time intervals above 10 s on time production not reproduction tasks, and the underestimation correlated with fast counting on the tapping task. Furthermore, striatal DaT protein levels strongly correlated with underestimation of time intervals. These findings suggest that distortion of time intervals is guided by cumulative output of fast cycle counting and that this is linked with striatal DaT protein deficit.

Memory suppression trades prolonged fear and sleep-dependent fear plasticity for the avoidance of current fear

Sleep deprivation immediately following an aversive event reduces fear by preventing memory consolidation during homeostatic sleep. This suggests that acute insomnia might act prophylactically against the development of posttraumatic stress disorder (PTSD) even though it is also a possible risk factor for PTSD. We examined total sleep deprivation and memory suppression to evaluate the effects of these interventions on subsequent aversive memory formation and fear conditioning. Active suppression of aversive memory impaired retention of event memory. However, although the remembered fear was more reduced in sleep-deprived than sleep-control subjects, suppressed fear increased, and seemed to abandon the sleep-dependent plasticity of fear. Active memory suppression, which provides a psychological model for Freuds ego defense mechanism, enhances fear and casts doubt on the potential of acute insomnia as a prophylactic measure against PTSD. Our findings bring into question the role of sleep in aversive-memory consolidation in clinical PTSD pathophysiology.

Hyper-volume of eye-contact perception and social anxiety traits.

Eye-contact facilitates effective interpersonal exchange during social interactions, but can be a considerable source of anxiety for individuals with social phobia. However, the relationship between the fundamental spatial range of eye-contact perception and psychiatric traits is, to date, unknown. In this study, I analyzed the eye-contact spatial response bias and the associated pupil response, and how they relate to traits of social interaction disorders. In a face-to-face situation, 21 pairs of subjects were randomly assigned to be either viewers or perceivers. The viewer was instructed to gaze either at the perceivers eyes, or at a predetermined point, and the perceiver was asked to indicate whether eye-contact had been established or not. I found that the perceptual volume is much larger than the actual volume of eye-contact, and that the subjective judgment of eye-contact elicited greater pupil dilation in the perceiver. Furthermore, the relationship between behavioral performance and social anxiety traits was identified. These findings provide new indications that internal traits related to lower social anxiety are potentially related to a restriction of spatial response bias for eye-contact.

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.