Superior Neuronal Detection of Snakes and Conspecific Faces in the Macaque Medial Prefrontal Cortex.

Snakes and conspecific faces are quickly and efficiently detected in primates. Because the medial prefrontal cortex (mPFC) has been implicated in attentional allocation to biologically relevant stimuli, we hypothesized that it might also be highly responsive to snakes and conspecific faces. In this study, neuronal responses in the monkey mPFC were recorded, while monkeys discriminated 8 categories of visual stimuli. Here, we show that the monkey mPFC neuronal responses to snakes and conspecific faces were unique. First, the ratios of the neurons that responded strongly to snakes and monkey faces were greater than those of the neurons that responded strongly to the other stimuli. Second, mPFC neurons responded stronger and faster to snakes and monkey faces than the other categories of stimuli. Third, neuronal responses to snakes were unaffected by low-pass filtering of the images. Finally, activity patterns of responsive mPFC neurons discriminated snakes from the other stimuli in the second 50 ms period and monkey faces in the third period after stimulus onset. These response features indicate that the mPFC processes fast and coarse visual information of snakes and monkey faces, and support the hypothesis that snakes and social environments have shaped the primate visual system over evolutionary time.

Ingestion of dried-bonito broth (dashi) facilitates PV-parvalbumin-immunoreactive neurons in the brain, and affects emotional behaviors in mice.

OBJECTIVES: Emerging evidence suggests that traditional diets and nutrition have a significant impact on brain development, and could contribute to the promotion of mental health and prevention of psychiatric disorders in children and adolescents. Moreover, deficits in parvalbumin (PV)-immunoreactive and/or GABAergic neurons are closely associated with various psychiatric disorders in children and adolescents. To investigate the possible neural mechanisms of diet involvement in mental health, we analyzed the effects of dried-bonito dashi (Japanese fish broth) (DBD) on PV-immunoreactive neurons and emotional behaviors in young mice. METHODS: Male mice after weaning were fed DBD for 60 days, and tested with a resident-intruder test for aggressiveness and a forced swimming test for depression-like symptoms. After the behavioral testing, PV-immunoreactive neurons in the brain were immunohistochemically analyzed. RESULTS: The results indicated that DBD intake decreased aggressiveness and depression-like symptoms, and increased the densities of PV-immunoreactive neurons in the medial prefrontal cortex (mPFC), amygdala, hippocampus, and superior colliculus. These behavioral changes were correlated with the densities of PV-immunoreactive neurons in the mPFC, amygdala, and hippocampus. However, subdiaphragmatic vagotomy did not affect the effects of DBD on emotional behaviors, although it nonspecifically decreased the densities of PV-immunoreactive neurons. DISCUSSION: The results suggest that DBD might modulate emotional behaviors by promoting PV-immunoreactive and/or GABAergic neuronal activity through parallel routes. The present results highlight a new mechanism for diet involvement in brain functions, and suggest that DBD might have therapeutic potential for the promotion of mental health.

Pulvinar neurons reveal neurobiological evidence of past selection for rapid detection of snakes.

Snakes and their relationships with humans and other primates have attracted broad attention from multiple fields of study, but not, surprisingly, from neuroscience, despite the involvement of the visual system and strong behavioral and physiological evidence that humans and other primates can detect snakes faster than innocuous objects. Here, we report the existence of neurons in the primate medial and dorsolateral pulvinar that respond selectively to visual images of snakes. Compared with three other categories of stimuli (monkey faces, monkey hands, and geometrical shapes), snakes elicited the strongest, fastest responses, and the responses were not reduced by low spatial filtering. These findings integrate neuroscience with evolutionary biology, anthropology, psychology, herpetology, and primatology by identifying a neurobiological basis for primates' heightened visual sensitivity to snakes, and adding a crucial component to the growing evolutionary perspective that snakes have long shaped our primate lineage.

Place-related neuronal activity in the monkey parahippocampal gyrus and hippocampal formation during virtual navigation.

Neuropsychological data in primates demonstrated a pivotal role of the hippocampal formation (HF) and parahippocampal gyrus (PH) in navigation and episodic memory. To investigate the role of HF and PH neurons in environmental scaling in primates, we recorded neuronal activities in the monkey HF and PH during virtual navigation (VN) and pointer translocation (PT) tasks. The monkeys had to navigate within three differently sized virtual spaces with the same spatial cues (VN task) or move a pointer on a screen (PT task) by manipulating a joystick to receive a reward. Of the 234 recorded neurons, 170 and 61 neurons displayed place-related activities in the VN and PT tasks, respectively. Significant differences were observed between the HF and PH neurons. The spatial similarity of place fields between the two different virtual spaces was lower in PH than in HF, while specificities of the neuronal responses to distal spatial cues were higher in PH than in HF. Spatial view information was predominately processed in posterior PH. The spatial scales (place field sizes) of the HF and PH neurons were reduced in the reduced virtual space, as shown in rodent place cells. These results suggest the complementary roles of HF (allocentric representation of landmarks) and PH (representation of the spatial layout of landmarks) in the recognition of a location during navigation.

Subcutaneous edema as a potential cause of catheter failure in older inpatients receiving peripheral parenteral nutrition.

Malnutrition is a common problem among hospitalized older patients. Peripheral parenteral nutrition (PN) can improve patient outcomes but can also lead to complications that affect future treatment. Older inpatients, in particular, are expected to be prone to these catheter-related complications. However, the impact of peripheral PN on older inpatients has been rarely investigated. In the current study, the impact of PN on short peripheral catheters (SPCs) was evaluated by comparing signs and symptoms at the time of catheter removal between 22 patients with PN and 27 without. In addition to external clinical assessment, sonographic investigations of the SPC site were performed. The prevalence of external signs and symptoms of complications was similar between the patients (all P > 0.05). However, subcutaneous edema was found by ultrasound in > 80% of patients with PN, compared with 55.6% of those without PN (P = 0.051). Unlike cases without PN, all patients with PN who presented with external signs and symptoms developed subcutaneous edema (P = 0.022). Multivariate analysis demonstrated that administration of PN was independently associated with subcutaneous edema (adjusted odds ratio = 6.88, 95% confidence interval = 1.083-75.486, P = 0.040). For several decades, phlebitis has been the primary focus of complications related to peripheral PN in clinical settings. However, our results imply that peripheral PN causes subcutaneous edema, which can lead to catheter failure in older inpatients. This study contributes to understanding the etiology of catheter failure during peripheral PN in this population.

Neuronal responses in the nucleus accumbens shell during sexual behavior in male rats.

Previous behavioral studies have indicated that the nucleus accumbens (NAc) shell of a male rat is involved in its sexual behavior; however, no previous studies have investigated neuronal activities in the male rat NAc shell during sexual behavior. To investigate this issue, we recorded single unit activities in the NAc shell of male rats during sexual behavior. Of 123 NAc shell neurons studied, 53, 47, and 40 neurons exhibited significantly changed firing rates at various times during intromission, genital auto-grooming, and sniffing of females, respectively. The two types of NAc shell neurons [putative fast spiking interneurons (pFSIs) and medium spiny neurons (pMSNs)] responded differently during sexual behavior. First, more pFSIs than pMSNs exhibited inhibitory responses to thrusting with intromission and genital grooming, while pFSIs and pMSNs responded similarly to sniffing of females. Second, both pFSIs and pMSNs responded differently to thrusting with and without intromission. Furthermore, NAc shell neuronal activity was significantly different across the different phases of sexual behavior, and the number of NAc shell neurons with delta oscillation, which is related to behavioral inhibition, and high gamma oscillation, which is related to reward perception, increased after ejaculation. Together, our results suggest that the NAc shell is deeply involved in sexual behavior, and changes in NAc shell neuronal activity are related to performance of sexual behavior, encoding cues or contexts related to sexual behavior, reward-related processing, and the inhibition of sexual behavior after ejaculation.

Neuronal responses to face-like stimuli in the monkey pulvinar.

The pulvinar nuclei appear to function as the subcortical visual pathway that bypasses the striate cortex, rapidly processing coarse facial information. We investigated responses from monkey pulvinar neurons during a delayed non-matching-to-sample task, in which monkeys were required to discriminate five categories of visual stimuli [photos of faces with different gaze directions, line drawings of faces, face-like patterns (three dark blobs on a bright oval), eye-like patterns and simple geometric patterns]. Of 401 neurons recorded, 165 neurons responded differentially to the visual stimuli. These visual responses were suppressed by scrambling the images. Although these neurons exhibited a broad response latency distribution, face-like patterns elicited responses with the shortest latencies (approximately 50 ms). Multidimensional scaling analysis indicated that the pulvinar neurons could specifically encode face-like patterns during the first 50-ms period after stimulus onset and classify the stimuli into one of the five different categories during the next 50-ms period. The amount of stimulus information conveyed by the pulvinar neurons and the number of stimulus-differentiating neurons were consistently higher during the second 50-ms period than during the first 50-ms period. These results suggest that responsiveness to face-like patterns during the first 50-ms period might be attributed to ascending inputs from the superior colliculus or the retina, while responsiveness to the five different stimulus categories during the second 50-ms period might be mediated by descending inputs from cortical regions. These findings provide neurophysiological evidence for pulvinar involvement in social cognition and, specifically, rapid coarse facial information processing.

Rearing in enriched environment increases parvalbumin-positive small neurons in the amygdala and decreases anxiety-like behavior of male rats.

BACKGROUND: Early life experiences including physical exercise, sensory stimulation, and social interaction can modulate development of the inhibitory neuronal network and modify various behaviors. In particular, alteration of parvalbumin-expressing neurons, a gamma-aminobutyric acid (GABA)ergic neuronal subpopulation, has been suggested to be associated with psychiatric disorders. Here we investigated whether rearing in enriched environment could modify the expression of parvalbumin-positive neurons in the basolateral amygdala and anxiety-like behavior. RESULTS: Three-week-old male rats were divided into two groups: those reared in an enriched environment (EE rats) and those reared in standard cages (SE rats). After 5 weeks of rearing, the EE rats showed decreased anxiety-like behavior in an open field than the SE rats. Under another anxiogenic situation, in a beam walking test, the EE rats more quickly traversed an elevated narrow beam. Anxiety-like behavior in the open field was significantly and negatively correlated with walking time in the beam-walking test. Immunohistochemical tests revealed that the number of parvalbumin-positive neurons significantly increased in the basolateral amygdala of the EE rats than that of the SE rats, while the number of calbindin-D28k-positive neurons did not change. These parvalbumin-positive neurons had small, rounded soma and co-expressed the glutamate decarboxylase (GAD67). Furthermore, the number of parvalbumin-positive small cells in the basolateral amygdala tended to positively correlate with emergence in the center arena of the open field and negatively correlated with walking time in the beam walking test. CONCLUSION: Rearing in the enriched environment augmented the number of parvalbumin-containing specific inhibitory neuron in the basolateral amygdala, but not that of calbindin-containing neuronal phenotype. Furthermore, the number of parvalbumin-positive small neurons in the basolateral amygdala was negatively correlated with walking time in the beam walking test and tended to be positively correlated with activity in the center arena in the open field test. The results suggest that rearing in the enriched environment augmented parvalbumin-positive specific neurons in the basolateral amygdala, which induced behavioral plasticity that was reflected by a decrease in anxiety-like behavior in anxiogenic situations.

Alpha- and theta-range cortical synchronization and corticomuscular coherence during joystick manipulation in a virtual navigation task.

Previous studies have reported that multiple brain regions are activated during spatial navigation, but it remains unclear how this activation is converted to motor commands for navigation. This study was aimed to investigate synchronization across different brain regions and between cortical areas and muscles during spatial navigation. This synchronization has been suggested to be essential for integrating activity in the multiple brain areas to support higher cognitive functions and for conversion of cortical activity to motor commands. In the present study, the subjects were required to sequentially trace ten checkpoints in a virtual town by manipulating a joystick and to perform this three times while electroencephalograms and electromyograms from the right arm were monitored. Time spent on the task in the third trial was significantly lesser than that in the first trial indicating an improvement in task performance. This repeated learning was associated with an increase in alpha power at the electrodes over the contralateral sensorimotor region and in theta power at the electrodes over the bilateral premotor and frontotemporal regions. Alpha- and theta-range corticocortical coherences between these regions and other brain areas were also increased in the third trial compared to the first trial. Furthermore, alpha- and theta-range corticomuscular coherence was significantly increased in the second and third trials compared to the first trial. These results suggest that alpha- and theta-range synchronous activity across multiple systems is essential for the integrated brain activity required in spatial navigation and for the conversion of this activity to motor commands.

[The role of a molecule associated with drug dependence, shati/nat8l].

Various molecules are involved in drug addiction induced by drugs of abuse. Therefore, the mechanism of drug addiction is still not clear, and it has been a difficulty in the development of preventive and curative drugs for drug dependence. We tried to identify the molecules associated with drug dependence, and found three molecules including shati/nat81. Recently, it has been demonstrated that the substrate for shati/nat81 is aspaltate and shati/nat8l biosynthesizes N-acetylaspartate, which exists abundantly in the mammalian brain. In this study, we investigated the physiological function of shati/nat81 and the role of shati/nat81 in drug dependence. The overexpression of shati/nat81 in the dorsal striatum of mice led to social abnormality and depression-like behavior, and worsened a part of the motor dysfunction induced by Ca2+ channel agonist BAY-K 8644. The overexpression of shati/nat81 in the nucleus accumbens of mice inhibited methamphetamine-induced behavioral and biochemical abnormalities. These findings suggest that the shati/nat81-associated system could play a role in the regulation of mental activity and motor action, and be a new target in the development of therapeutic drugs for drug dependence.

A role for the superior colliculus in the modulation of threat responsiveness in primates: toward the ontogenesis of the social brain.

Defense and social mechanisms in primates seem to share, at least in infancy, common neural substrata.Among these, recent research has implicated the primate superior colliculus (SC) on tasks involving visual detection and recognition of threatening stimuli, such as snakes and faces with emotional expressions. There is also evidence that both kinds of stimuli share specific characteristics and command special attention in the primate visual system. The present review focuses on the role of the SC in these seemingly overlapping functions.We present social behavioral data from capuchin monkeys in which the bilateral lesion of the SC induced a transitory impairment of social behaviors. The findings presented here are compared with previous studies, our own and others, on social behaviors and threat detection. We argue that, although the SC may participate in both systems,its role is more prominent in the detection/recognition of threat. Social interactions more likely depend on larger and more complex neural systems, where the SC may play a key role in early infancy. The implications of these recent findings are discussed under an evolutionary perspective.

Hippocampal neuronal responses during signaled licking of gustatory stimuli in different contexts.

Neuroanatomical studies suggest that hippocampal formation (HF) receives information from all sensory modalities including taste via the parahippocampal cortices. To date, however, no neurophysiological study has reported that HF neurons encode taste information. In the present study, we recorded CA1 HF neurons from freely behaving rats during performance of a visually-guided licking task in two different triangular chambers. When a cue lamp came on, the rats were required to press a bar to trigger a tube to protrude into the chambers for 3 s. During this period, the rats could lick one of six sapid solutions: [0.1M NaCl (salty), 0.3M sucrose (sweet), 0.01 M citric acid (sour), 0.0001 M quinine HCl (bitter), 0.01 M monosodium L-glutamate (MSG, umami), and a mixture of MSG and 0.001 M disodium-5'-inosinate (IMP) (MSG+IMP)], and distilled water. Of a total 285 pyramidal and interneurons, the activity of 173 was correlated with at least one of the events in the task-illumination of cue lamps, bar pressing, or licking the solution. Of these, 137 neurons responded during licking, and responses of 62 of these cells were greater to sapid solutions than to water (taste neurons). Multivariate analyses of the taste neurons suggested that, in the HF, taste quality might be encoded based on hedonic value. Furthermore, the activity of most taste neurons was chamber-specific. These results implicate the HF in guiding appetitive behaviors such as conditioned place preference.

Cerebral hemodynamic responses induced by specific acupuncture sensations during needling at trigger points: a near-infrared spectroscopic study.

Acupuncture stimulation at specific points, or trigger points (TPs), elicits sensations called "de-qi". De-qi sensations relate to the clinical efficacy of the treatment. However, it is neither clear whether de-qi sensations are associated with TPs, nor clear whether acupuncture effects on brain activity are associated with TPs or de-qi. We recorded cerebral hemodynamic responses during acupuncture stimulation at TPs and non-TPs by functional near-infrared spectroscopy. The acupuncture needle was inserted into both TPs and non-TPs within the right extensor muscle in the forearm. Typical acupuncture needle manipulation was conducted eight times for 15 s. The subjects pressed a button if they felt a de-qi sensation. We investigated how hemodynamic responses related to de-qi sensations induced at TPs and non-TPs. We observed that acupuncture stimulations producing de-qi sensations significantly decreased the Oxy-Hb concentration in the supplementary motor area (SMA), pre-supplementary motor area, and anterior dorsomedial prefrontal cortex regardless of the point stimulated. The hemodynamic responses were statistically analyzed using a general linear model and a boxcar function approximating the hemodynamic response. We observed that hemodynamic responses best fit the boxcar function when an onset delay was introduced into the analyses, and that the latency of de-qi sensations correlated with the onset delay of the best-fit function applied to the SMA. Our findings suggest that de-qi sensations favorably predict acupuncture effects on cerebral hemodynamics regardless of the type of site stimulated. Also, the effect of acupuncture stimulation in producing de-qi sensation was partly mediated by the central nervous system including the SMA.

A Prototypical Template for Rapid Face Detection Is Embedded in the Monkey Superior Colliculus.

Human babies respond preferentially to faces or face-like images. It has been proposed that an innate and rapid face detection system is present at birth before the cortical visual pathway is developed in many species, including primates. However, in primates, the visual area responsible for this process is yet to be unraveled. We hypothesized that the superior colliculus (SC) that receives direct and indirect retinal visual inputs may serve as an innate rapid face-detection system in primates. To test this hypothesis, we examined the responsiveness of monkey SC neurons to first-order information of faces required for face detection (basic spatial layout of facial features including eyes, nose, and mouth), by analyzing neuronal responses to line drawing images of: (1) face-like patterns with contours and properly placed facial features; (2) non-face patterns including face contours only; and (3) nonface random patterns with contours and randomly placed face features. Here, we show that SC neurons respond stronger and faster to upright and inverted face-like patterns compared to the responses to nonface patterns, regardless of contrast polarity and contour shapes. Furthermore, SC neurons with central receptive fields (RFs) were more selective to face-like patterns. In addition, the population activity of SC neurons with central RFs can discriminate face-like patterns from nonface patterns as early as 50 ms after the stimulus onset. Our results provide strong neurophysiological evidence for the involvement of the primate SC in face detection and suggest the existence of a broadly tuned template for face detection in the subcortical visual pathway.

Non-invasive electroencephalographical (EEG) recording system in awake monkeys.

BACKGROUND: Human clinical studies reported that several electroencephalographical (EEG) parameters can be used as biomarkers of psychiatric disorders. EEGs recorded from non-human primates (monkeys) is useful for understanding of human pathologies of psychiatric disorders and development of new therapeutic agents. NEW METHODS: In this study, we expand a previous non-invasive head holding system with face masks for awake monkeys to be applied to scalp EEG recording. The new design of a head holding system allows to attach scalp EEG electrodes on the positions comparable to human electrode placement and to present auditory stimuli. RESULTS: With this system, we could record auditory evoked potentials (AEPs) in auditory sensory gating and oddball paradigms, which are often used as biomarkers of psychiatric disorders in animal models and human patients. The recorded AEPs were comparable to previous human clinical data. COMPARISON WITH EXISTING METHODS: Compared with previous non-invasive head holding systems, top, side (cheek and ears), and rear of the head can be open for attachment of EEG electrodes and auditory stimulation in the present system. CONCLUSIONS: The results suggest that the present system is useful in EEG recording from awake monkeys. Furthermore, this system can be applied to eye-tracking and chronic intra-cerebral recording experiments.

Dopamine D1 receptor modulates hippocampal representation plasticity to spatial novelty.

The human hippocampus is critical for learning and memory. In rodents, hippocampal pyramidal neurons fire in a location-specific manner, forming relational representations of environmental cues. The importance of glutamatergic systems in learning and in hippocampal neural synaptic plasticity has been shown. However, the role of dopaminergic systems in the response of hippocampal neural plasticity to novel and familiar spatial stimuli remains unclear. To clarify this important issue, we recorded hippocampal neurons from dopamine D(1) receptor knock-out (D1R-KO) mice and their wild-type (WT) littermates under the manipulation of distinct spatial cues in a familiar and a novel environment. Here we report that in WT mice, the majority of place cells quickly responded to the manipulations of distal and proximal cues in both familiar and novel environments. In contrast, the influence of distal cues on spatial firing in D1R-KO mice was abolished. In the D1R-KO mice, the influence of proximal cues was facilitated in a familiar environment, and in a novel environment most of the place cells were less likely to respond to changes of spatial cues. Our results demonstrate that hippocampal neurons in mice can rapidly and flexibly encode information about space from both distal and proximal cues to cipher a novel environment. This ability is necessary for many types of learning, and lacking D1R can radically alter this learning-related neural activity. We propose that D1R is crucially implicated in encoding spatial information in novel environments, and influences the plasticity of hippocampal representations, which is important in spatial learning and memory.

The direct excitatory effect of IL-1beta on cerebellar Purkinje cell.

Interleukin (IL)-1beta is one of the important proinflammatory cytokines in neural as well as immune systems, and plays a pivotal role in the neuroinflammation. We previously demonstrated that cerebellar IL-1beta is involved in kainate-induced ataxia, i.e., IL-1beta was activated in the cerebellum with systemic administration of kainate, and its type I receptor (IL-1R) was expressed at a soma of cerebellar Purkinje cells. In this study, we examined the effect of IL-1beta on cerebellar Purkinje cell function by recording extracellular neuronal activities in anesthetized mice. Systemic administration of kainate increased the firing rates of cerebellar Purkinje cells in normal mice but showed little effect in IL-1R-knockout (IL-1R-KO) mice. Moreover, microiontophoretic administration of IL-1beta to cerebellar Purkinje cells increased the firing rates promptly in response to IL-1beta. The present results demonstrate that IL-1 system exerts a direct modulatory effect on cerebellar Purkinje cells.

Brain cortical mapping by simultaneous recording of functional near infrared spectroscopy and electroencephalograms from the whole brain during right median nerve stimulation.

To investigate relationships between hemodynamic responses and neural activities in the somatosensory cortices, hemodynamic responses by near infrared spectroscopy (NIRS) and electroencephalograms (EEGs) were recorded simultaneously while subjects received electrical stimulation in the right median nerve. The statistical significance of the hemodynamic responses was evaluated by a general linear model (GLM) with the boxcar design matrix convoluted with Gaussian function. The resulting NIRS and EEGs data were stereotaxically superimposed on the reconstructed brain of each subject. The NIRS data indicated that changes in oxy-hemoglobin concentration increased at the contralateral primary somatosensory (SI) area; responses then spread to the more posterior and ipsilateral somatosensory areas. The EEG data indicated that positive somatosensory evoked potentials peaking at 22 ms latency (P22) were recorded from the contralateral SI area. Comparison of these two sets of data indicated that the distance between the dipoles of P22 and NIRS channels with maximum hemodynamic responses was less than 10 mm, and that the two topographical maps of hemodynamic responses and current source density of P22 were significantly correlated. Furthermore, when onset of the boxcar function was delayed 5-15 s (onset delay), hemodynamic responses in the bilateral parietal association cortices posterior to the SI were more strongly correlated to electrical stimulation. This suggests that GLM analysis with onset delay could reveal the temporal ordering of neural activation in the hierarchical somatosensory pathway, consistent with the neurophysiological data. The present results suggest that simultaneous NIRS and EEG recording is useful for correlating hemodynamic responses to neural activity.

Neural Representation of Overlapping Path Segments and Reward Acquisitions in the Monkey Hippocampus.

Disambiguation of overlapping events is thought to be the hallmark of episodic memory. Recent rodent studies have reported that when navigating overlapping path segments in the different routes place cell activity in the same overlapping path segments were remapped according to different goal locations in different routes. However, it is unknown how hippocampal neurons disambiguate reward delivery in overlapping path segments in different routes. In the present study, we recorded monkey hippocampal neurons during performance of three virtual navigation (VN) tasks in which a monkey alternately navigated two different routes that included overlapping path segments (common central hallway) and acquired rewards in the same locations in overlapping path segments by manipulating a joystick. The results indicated that out of 106 hippocampal neurons, 57 displayed place-related activity (place-related neurons), and 18 neurons showed route-dependent activity in the overlapping path segments, consistent with a hippocampal role in the disambiguation of overlapping path segments. Moreover, 75 neurons showed neural correlates to reward delivery (reward-related neurons), whereas 56 of these 75 reward-related neurons showed route-dependent reward-related activity in the overlapping path segments. The ensemble activity of reward-related neurons represented reward delivery, locations, and routes in the overlapping path segments. In addition, ensemble activity patterns of hippocampal neurons more distinctly represented overlapping path segments than non-overlapping path segments. The present results provide neurophysiological evidence of disambiguation in the monkey hippocampus, consistent with a hippocampal role in episodic memory, and support a recent computational model of "neural differentiation," in which overlapping items are better represented by repeated retrieval with competitive learning.

Non-restorative Sleep Caused by Autonomic and Electroencephalography Parameter Dysfunction Leads to Subjective Fatigue at Wake Time in Shift Workers.

Sleep is a physiological state that plays important role in the recovery of fatigue. However, the relationship between the physiological status of sleep and subjective fatigue remains unknown. In the present study, we hypothesized that the non-recovery of fatigue at wake time due to non-restorative sleep might be ascribed to changes in specific parameters of electroencephalography (EEG) and heart rate variability (HRV) in poor sleepers. Twenty healthy female shift-working nurses participated in the study. Subjective fatigue was assessed using the visual analog scale (VAS) at bedtime and wake time. During sleep on the night between 2 consecutive day shifts, the EEG powers at the frontal pole, HRV based on electrocardiograms, and distal-proximal gradient of skin temperature were recorded and analyzed. The results indicated that the subjects with high fatigue on the VAS at wake time exhibited (1) a decrease in deep non-rapid eye movement (NREM) (stageN3) sleep duration in the first sleep cycle; (2) a decrease in REM latency; (3) a decrease in ultra-slow and delta EEG powers, particularly from 30 to 65 min after sleep onset; (4) a decrease in the total power of HRV, particularly from 0 to 30 min after sleep onset; (5) an increase in the very low frequency component of HRV; and (6) a smaller increase in the distal-proximal gradient of skin temperature, than those of the subjects with low fatigue levels. The correlational and structural equation modeling analyses of these parameters suggested that an initial decrease in the total power of HRV from 0 to 30 min after sleep onset might inhibit the recovery from fatigue during sleep (i.e., increase the VAS score at wake time) via its effects on the ultra-slow and delta powers from 30 to 65 min after sleep onset, stageN3 duration in the first sleep cycle, REM latency, and distal-proximal gradient of skin temperature. These findings suggest an important role of these physiological factors in recovery from fatigue during sleep, and that interventions to modify these physiological factors might ameliorate fatigue at wake time.