Word encoding during sleep

To test whether humans can encode words during sleep we played everyday words to men while they were napping and assessed priming from sleep-played words following waking. Words were presented during non-rapid eye movement (NREM) sleep. Priming was assessed using a semantic and a perceptual priming test. These tests measured differences in the processing of words that had been or had not been played during sleep. Synonyms to sleep-played words were the targets in the semantic priming test that tapped the meaning of sleep-played words. All men responded to sleep-played words by producing up-states in their electroencephalogram. Up-states are NREM sleep-specific phases of briefly increased neuronal excitability. The word-evoked up-states might have promoted word processing during sleep. Yet, the mean performance in the priming tests administered following sleep was at chance level, which suggests that participants as a group failed to show priming following sleep. However, performance in the two priming tests was positively correlated to each other and to the magnitude of the word-evoked up-states. Hence, the larger a participant's word-evoked up-states, the larger his perceptual and semantic priming. Those participants who scored high on all variables must have encoded words during sleep. We conclude that some humans are able to encode words during sleep, but more research is needed to pin down the factors that modulate this ability.

Systematic diagonal and vertical errors in antisaccades and memory-guided saccades

Studies of memory-guided saccades in monkeys show an upward bias, while studies of antisaccades in humans show a diagonal effect, a deviation of endpoints toward the 45° diagonal. To determine if these two different spatial biases are specific to different types of saccades, we studied prosaccades, antisaccades and memory-guided saccades in humans. The diagonal effect occurred not with prosaccades but with antisaccades and memory-guided saccades with long intervals, consistent with hypotheses that it originates in computations of goal location under conditions of uncertainty. There was a small upward bias for memory-guided saccades but not prosaccades or antisaccades. Thus this bias is not a general effect of target uncertainty but a property specific to memory-guided saccades.

Physiological time structure of the tibialis anterior motor activity during sleep in mice, rats and humans

The validation of rodent models for restless legs syndrome (Willis-Ekbom disease) and periodic limb movements during sleep requires knowledge of physiological limb motor activity during sleep in rodents. This study aimed to determine the physiological time structure of tibialis anterior activity during sleep in mice and rats, and compare it with that of healthy humans. Wild-type mice (n = 9) and rats (n = 8) were instrumented with electrodes for recording the electroencephalogram and electromyogram of neck muscles and both tibialis anterior muscles. Healthy human subjects (31 ± 1 years, n = 21) underwent overnight polysomnography. An algorithm for automatic scoring of tibialis anterior electromyogram events of mice and rats during non-rapid eye movement sleep was developed and validated. Visual scoring assisted by this algorithm had inter-rater sensitivity of 92-95% and false-positive rates of 13-19% in mice and rats. The distribution of the time intervals between consecutive tibialis anterior electromyogram events during non-rapid eye movement sleep had a single peak extending up to 10 s in mice, rats and human subjects. The tibialis anterior electromyogram events separated by intervals <10 s mainly occurred in series of two-three events, their occurrence rate in humans being lower than in mice and similar to that in rats. In conclusion, this study proposes reliable rules for scoring tibialis anterior electromyogram events during non-rapid eye movement sleep in mice and rats, demonstrating that their physiological time structure is similar to that of healthy young human subjects. These results strengthen the basis for translational rodent models of periodic limb movements during sleep and restless legs syndrome/Willis-Ekbom disease.

A Vertical Asymmetry in Saccades

Visual exploration of natural scenes imposes demands that differ between the upper and the lower visual hemifield. Yet little is known about how ocular motor performance is affected by the location of visual stimuli or the direction of a behavioural response. We compared saccadic latencies between upper and lower hemifield in a variety of conditions, including short-latency prosaccades, long-latency prosaccades, antisaccades, memory-guided sac- cades and saccades with increased attentional and selection demand. All saccade types, except memory guided saccades, had shorter latencies when saccades were directed to- wards the upper field as compared to downward saccades (p<0.05). This upper field reaction time advantage probably arises in ocular motor rather than visual processing. It may originate in structures involved in motor preparation rather than execution.

Hypothalamic feedforward inhibition of thalamocortical network controls arousal and consciousness.

During non-rapid eye movement (NREM) sleep, synchronous synaptic activity in the thalamocortical network generates predominantly low-frequency oscillations (<4 Hz) that are modulated by inhibitory inputs from the thalamic reticular nucleus (TRN). Whether TRN cells integrate sleep-wake signals from subcortical circuits remains unclear. We found that GABA neurons from the lateral hypothalamus (LHGABA) exert a strong inhibitory control over TRN GABA neurons (TRNGABA). We found that optogenetic activation of this circuit recapitulated state-dependent changes of TRN neuron activity in behaving mice and induced rapid arousal during NREM, but not REM, sleep. During deep anesthesia, activation of this circuit induced sustained cortical arousal. In contrast, optogenetic silencing of LHGABA-TRNGABA transmission increased the duration of NREM sleep and amplitude of delta (1-4 Hz) oscillations. Collectively, these results demonstrate that TRN cells integrate subcortical arousal inputs selectively during NREM sleep and may participate in sleep intensity.

Sleep-Wake Cycle Dysfunction in the TgCRND8 Mouse Model of Alzheimer's Disease: From Early to Advanced Pathological Stages.

In addition to cognitive decline, individuals affected by Alzheimer's disease (AD) can experience important neuropsychiatric symptoms including sleep disturbances. We characterized the sleep-wake cycle in the TgCRND8 mouse model of AD, which overexpresses a mutant human form of amyloid precursor protein resulting in high levels of β-amyloid and plaque formation by 3 months of age. Polysomnographic recordings in freely-moving mice were conducted to study sleep-wake cycle architecture at 3, 7 and 11 months of age and corresponding levels of β-amyloid in brain regions regulating sleep-wake states were measured. At all ages, TgCRND8 mice showed increased wakefulness and reduced non-rapid eye movement (NREM) sleep during the resting and active phases. Increased wakefulness in TgCRND8 mice was accompanied by a shift in the waking power spectrum towards fast frequency oscillations in the beta (14-20 Hz) and low gamma range (20-50 Hz). Given the phenotype of hyperarousal observed in TgCRND8 mice, the role of noradrenergic transmission in the promotion of arousal, and previous work reporting an early disruption of the noradrenergic system in TgCRND8, we tested the effects of the alpha-1-adrenoreceptor antagonist, prazosin, on sleep-wake patterns in TgCRND8 and non-transgenic (NTg) mice. We found that a lower dose (2 mg/kg) of prazosin increased NREM sleep in NTg but not in TgCRND8 mice, whereas a higher dose (5 mg/kg) increased NREM sleep in both genotypes, suggesting altered sensitivity to noradrenergic blockade in TgCRND8 mice. Collectively our results demonstrate that amyloidosis in TgCRND8 mice is associated with sleep-wake cycle dysfunction, characterized by hyperarousal, validating this model as a tool towards understanding the relationship between β-amyloid overproduction and disrupted sleep-wake patterns in AD.

Mathematical modelling of neural processes within the oculomotor system

It is presented a mathematical model of the oculomotor plant, based on experimental data in cats. The system that generates, from the neuronal processes at the motoneuron, the control signals to the eye muscles that moves the eye. In contrast with previous models, that base the eye movement related motoneuron behavior on a first order linear differential equation, non-linear effects are described: A dependency on the eye angular position of the model parameters.

Activation of ventrolateral preoptic neurons by the somnogen prostaglandin D2

Prostaglandin D2 (PGD2) is an extensively studied sleep-promoting substance, but the neuroanatomical basis of PGD2-induced sleep is only partially understood. To determine potential regions involved in this response, we used Fos immunohistochemistry to identify neurons activated by infusion of PGD2 into the subarachnoid space below the rostral basal forebrain. PGD2 increased nonrapid eye movement sleep and induced striking expression of Fos in the ventrolateral preoptic area (VLPO), a cluster of neurons that may promote sleep by inhibiting the tuberomammillary nucleus, the source of the ascending histaminergic arousal system. Fos expression in the VLPO was positively correlated with the preceding amount of sleep and negatively correlated with Fos expression in the tuberomammillary nucleus. PGD2 also increased Fos immunoreactivity in the basal leptomeninges and several regions implicated in autonomic regulation. These observations suggest that PGD2 may induce sleep via leptomeningeal PGD2 receptors with subsequent activation of the VLPO.

Sleep modifies retinal ganglion cell responses in the normal rat

Recordings were obtained from the visual system of rats as they cycled normally between waking (W), slow-wave sleep (SWS), and rapid eye movement (REM) sleep. Responses to flashes delivered by a light-emitting diode attached permanently to the skull were recorded through electrodes implanted on the cornea, in the chiasm, and on the cortex. The chiasm response reveals the temporal order in which the activated ganglion cell population exits the eyeball; as reported, this triphasic event is invariably short in latency (5–10 ms) and around 300 ms in duration, called the histogram. Here we describe the differences in the histograms recorded during W, SWS, and REM. SWS histograms are always larger than W histograms, and an REM histogram can resemble either. In other words, the optic nerve response to a given stimulus is labile; its configuration depends on whether the rat is asleep or awake. We link this physiological information with the anatomical fact that the brain dorsal raphe region, which is known to have a sleep regulatory role, sends fibers to the rat retina and receives fibers from it. At the cortical electrode, the visual cortical response amplitudes also vary, being largest during SWS. This well known phenomenon often is explained by changes taking place at the thalamic level. However, in the rat, the labile cortical response covaries with the labile optic nerve response, which suggests the cortical response enhancement during SWS is determined more by what happens in the retina than by what happens in the thalamus.

Diazepam-induced changes in sleep: Role of the α1 GABAA receptor subtype

Ligands acting at the benzodiazepine (BZ) site of γ-aminobutyric acid type A (GABAA) receptors currently are the most widely used hypnotics. BZs such as diazepam (Dz) potentiate GABAA receptor activation. To determine the GABAA receptor subtypes that mediate the hypnotic action of Dz wild-type mice and mice that harbor Dz-insensitive α1 GABAA receptors [α1 (H101R) mice] were compared. Sleep latency and the amount of sleep after Dz treatment were not affected by the point mutation. An initial reduction of rapid eye movement (REM) sleep also occurred equally in both genotypes. Furthermore, the Dz-induced changes in the sleep and waking electroencephalogram (EEG) spectra, the increase in power density above 21 Hz in non-REM sleep and waking, and the suppression of slow-wave activity (SWA; EEG power in the 0.75- to 4.0-Hz band) in non-REM sleep were present in both genotypes. Surprisingly, these effects were even more pronounced in α1(H101R) mice and sleep continuity was enhanced by Dz only in the mutants. Interestingly, Dz did not affect the initial surge of SWA at the transitions to sleep, indicating that the SWA-generating mechanisms are not impaired by the BZ. We conclude that the REM sleep inhibiting action of Dz and its effect on the EEG spectra in sleep and waking are mediated by GABAA receptors other than α1, i.e., α2, α3, or α5 GABAA receptors. Because α1 GABAA receptors mediate the sedative action of Dz, our results provide evidence that the hypnotic effect of Dz and its EEG “fingerprint” can be dissociated from its sedative action.

Attentional processes associated with victimization history and posttraumatic symptomatology in women exposed to intimate partner violence

Exposure to intimate partner violence (IPV) puts women at risk for severe and chronic physical and mental health consequences, including elevations in IPV-related psychopathology and increased risk for future victimization. Previous research has examined attention as one of the key information processing mechanisms associated with elevated psychopathology and risk for victimization; however, the nature of attentional processing in response to IPV-related information in women exposed to IPV is poorly understood. Therefore, the current study aimed to further understanding of associations between attentional processing, IPV exposure, and related distress using measures of eye movement and subjective interpretations of IPV-related information. A sample of women exposed to IPV (n = 57) viewed sets of negative, positive, and neutral relationship images for 15 s each while having their eye movements monitored and later provided subjective ratings and interpretations of levels of risk and safety in those images. We examined associations of outcome measures with proximal victimization experiences and IPV-related psychopathology (i.e., depression, posttraumatic stress disorder (PTSD), anxiety, and dissociation). Results indicated a bias to attend to negative relationship images relative to positive and neutral images, though this attention bias fluctuated over time and varied as a function of symptomatology such that depression corresponded with increases in attention to negative images over time and PTSD corresponded with decreases in attention to negative images. The general attention bias for negative images appeared to be explained by rumination on and/or difficulty disengaging from negative images, which was related to general elevations in psychopathology as well as exposure to revictimization by different perpetrators. Subjective interpretations and perception of danger cues were related to victimization history and level and type of IPV-related distress. We replicated these procedures with a sample of undergraduate students without IPV histories or related symptomatology (n = 33) and found that the overall attention bias for negative images was not replicated, despite general similarities in patterns of attention over time. Results therefore indicated associations between attentional processing and IPV exposure and related symptomatology. Implications for models of IPV-related psychopathology and attentional processing as well as directions for future study and interventions are discussed.

Influence of experience and training on dental students’ examination performance regarding panoramic images

Physician training has greatly benefitted from insights gained in understanding the manner in which experts search medical images for abnormalities. The aims of this study were to compare the search patterns of 30 fourth-year dental students and 15 certified oral and maxillofacial radiologists (OMRs) over panoramic images and to determine the most robust variables for future studies involving image visualization. Eye tracking was used to capture the eye movement patterns of both subject groups when examining 20 panoramic images classified as normal or abnormal. Abnormal images were further subclassified as having an obvious, intermediate, or subtle abnormality. The images were presented in random order to each participant, and data were collected on duration of the participants’ observations and total distance tracked, time to first eye fixation, and total duration and numbers of fixations on and off the area of interest (AOI). The results showed that the OMRs covered greater distances than the dental students (p<0.001) for normal images. For images of pathosis, the OMRs required less total time (p<0.001), made fewer eye fixations (p<0.01) with fewer saccades (p<0.001) than the students, and required less time before making the first fixation on the AOI (p<0.01). Furthermore, the OMRs covered less distance (p<0.001) than the dental students for obvious pathoses. For investigations of images of pathosis, time to first fixation is a robust parameter in predicting ability. For images with different levels of subtlety of pathoses, the number of fixations, total time spent, and numbers of revisits are important parameters to analyze when comparing observer groups with different levels of experience.

LCD vs. E-ink: An Analysis of the Reading Behavior

Electronic books (e-book) are an interesting option compared to classic paper books. Most e-reading devices of the first generation were based on e-ink technology. With the appearance of the Apple iPad on the market, TFT-LCDs became important in the field of e-reading. Both technologies have advantages and disadvantages but the question remains whether one or the other technology is better for reading. In the present study we analyzed and compared reading behavior when reading on e-inkreader (e-ink displays) and on tablets (TFT-LCDs) as measured by eye-tracking. The results suggest that the reading behavior on tablets is indeed very similar to the reading behavior on e-ink-reader. Participants showed no difference in fixation duration. Significant differences in reading speed and in the proportion of regressive saccades suggest that tablets, under special artificial light conditions, may even provide better legibility.

Influence of experience and training on dental students’ examination performance regarding panoramic images.

Physician training has greatly benefitted from insights gained in understanding the manner in which experts search medical images for abnormalities. The aims of this study were to compare the search patterns of 30 fourth-year dental students and 15 certified oral and maxillofacial radiologists (OMRs) over panoramic images and to determine the most robust variables for future studies involving image visualization. Eye tracking was used to capture the eye movement patterns of both subject groups when examining 20 panoramic images classified as normal or abnormal. Abnormal images were further subclassified as having an obvious, intermediate, or subtle abnormality. The images were presented in random order to each participant, and data were collected on duration of the participants’ observations and total distance tracked, time to first eye fixation, and total duration and numbers of fixations on and off the area of interest (AOI). The results showed that the OMRs covered greater distances than the dental students (p<0.001) for normal images. For images of pathosis, the OMRs required less total time (p<0.001), made fewer eye fixations (p<0.01) with fewer saccades (p<0.001) than the students, and required less time before making the first fixation on the AOI (p<0.01). Furthermore, the OMRs covered less distance (p<0.001) than the dental students for obvious pathoses. For investigations of images of pathosis, time to first fixation is a robust parameter in predicting ability. For images with different levels of subtlety of pathoses, the number of fixations, total time spent, and numbers of revisits are important parameters to analyze when comparing observer groups with different levels of experience.