Saccadic Eye Movement in Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Alzheimer's disease (AD) is the leading cause of dementia, and mild cognitive impairment (MCI) is considered the transitional state to AD dementia (ADD) and other types of dementia, whose symptoms are accompanied by altered eye movement. In this work, we reviewed the existing literature and conducted a meta-analysis to extract relevant eye movement parameters that are significantly altered owing to ADD and MCI. We conducted a systematic review of 35 eligible original publications in saccade paradigms and a meta-analysis of 27 articles with specified task conditions, which used mainly gap and overlap conditions in both prosaccade and antisaccade paradigms. The meta-analysis revealed that prosaccade and antisaccade latencies and frequency of antisaccade errors showed significant alterations for both MCI and ADD. First, both prosaccade and antisaccade paradigms differentiated patients with ADD and MCI from controls, however, antisaccade paradigms was more effective than prosaccade paradigms in distinguishing patients from controls. Second, during prosaccade in the gap and overlap conditions, patients with ADD had significantly longer latencies than patients with MCI, and the trend was similar during antisaccade in the gap condition as patients with ADD had significantly more errors than patients with MCI. The anti-effect magnitude was similar between controls and patients, and the magnitude of the latency of the gap effect varied among healthy controls and MCI and ADD subjects, but the effect size of the latency remained large in both patients. These findings suggest that, using gap effect, anti-effect, and specific choices of saccade paradigms and conditions, distinctions could be made between MCI and ADD patients as well as between patients and controls.

Head and eye movements are each facilitated by the offset of a central fixation point in a virtual gap paradigm.

Eye movements exhibit reduced latencies when the point of fixation is extinguished prior to, or coincident with, the appearance of a peripheral target. Two independent components are responsible for this facilitation. If the offset occurs before target onset, it presents a warning which stimulates response preparation and execution. If offset occurs prior to or coincident with target onset, it triggers the release of fixation-maintenance neurons in the superior colliculus that can delay saccadic responses. While the warning effect facilitates responses regardless of effector, the fixation release effect is thought to be specific to the oculomotor system. Head movements, like saccades, contribute significantly to gaze shifts and may be generated directly by the SC. While head movements have been shown to benefit from the warning effect, it is unknown if, and to what degree, they are affected by the release of fixation-maintenance neurons responsible for inhibiting saccades. To address this issue, we measured head and eye response latencies in a virtual reality-based gap paradigm, turning off the fixation point either 200 ms before (temporal gap condition), coincident with (step condition), or 1000 ms after (temporal overlap/baseline condition) target onset. Our results indicate that head movements, like saccades, are facilitated by both the warning and release components of the gap paradigm. Further, rotational kinematics during gap trials differed significantly from those observed in step and overlap trials (higher, earlier peak velocities). These results are discussed with respect to the theorized structure and organisation of the superior colliculus in humans.

Characteristic Analysis and Structural Design of Hollow-Core Photonic Crystal Fibers with Band Gap Cladding Structures.

Due to their flexible structure and excellent optical characteristics hollow-core photonic crystal fibers (HC-PCFs) are used in many fields, such as active optical devices, communications, and optical fiber sensing. In this paper, to analyze the characteristics of HC-PCFs, we carried out finite element analysis and analyzed the design for the band gap cladding structure of HC-PCFs. First, the characteristics of HC19-1550 and HC-1550-02 in the C-band were simulated. Subsequently, the structural optimization of the seven-cell HC-1550-02 and variations in characteristics of the optimized HC-1550-02 in the wavelength range 1250-1850 nm were investigated. The simulation results revealed that the optimal number of cladding layers is eight, the optimal core radius is 1.8 times the spacing of adjacent air holes, and the optimal-relative thickness of the core quartz-ring is 2.0. In addition, the low confinement loss bandwidth of the optimized structure is 225 nm. Under the transmission bandwidth of the optimized structure, the core optical power is above 98%, the confinement loss is below 9.0 × 10-3 dB/m, the variation range of the effective mode field area does not exceed 10 µm2, and the relative sensitivity is above 0.9570. The designed sensor exhibits an ultra-high relative sensitivity and almost zero confinement loss, making it highly suitable for high-sensitivity gas or liquid sensing.

Subject Filled-gap Effects: A Self-paced Reading Study with Mandarin Learners of English.

This study examined how L1 Mandarin L2 English learners with different L2 proficiency levels processed the syntactic structure of English sentences. Using a self-paced reading paradigm, this study investigated three issues: first, whether Mandarin learners of English were able to predict the syntactic structure, subject filled-gap, in online English sentence reading; second, whether the parser would commit more strongly to the subject gap analysis when there is a longer distance between the filler and the potential gap; third, how L2 proficiency levels would influence this process. The results showed that regardless of their English proficiency levels, Mandarin learners of English were capable to predict a subject filled-gap when processing English sentences. Besides, the subject filled-gap effect was not found in the sentences with adjuncts between the filler and the potential gap. This indicated that L2 learners' predictive ability in syntactic processing did not need to be activated by the increase of processing time or difficulty. Due to the efficiency of sentence processing, there is no need to increase the processing burden for L2 learners.

Single-unit activity in marmoset posterior parietal cortex in a gap saccade task.

Abnormal saccadic eye movements can serve as biomarkers for patients with several neuropsychiatric disorders. The common marmoset (Callithrix jacchus) is becoming increasingly popular as a nonhuman primate model to investigate the cortical mechanisms of saccadic control. Recently, our group demonstrated that microstimulation in the posterior parietal cortex (PPC) of marmosets elicits contralateral saccades. Here we recorded single-unit activity in the PPC of the same two marmosets using chronic microelectrode arrays while the monkeys performed a saccadic task with gap trials (target onset lagged fixation point offset by 200 ms) interleaved with step trials (fixation point disappeared when the peripheral target appeared). Both marmosets showed a gap effect, shorter saccadic reaction times (SRTs) in gap vs. step trials. On average, stronger gap-period responses across the entire neuronal population preceded shorter SRTs on trials with contralateral targets although this correlation was stronger among the 15% "gap neurons," which responded significantly during the gap. We also found 39% "target neurons" with significant saccadic target-related responses, which were stronger in gap trials and correlated with the SRTs better than the remaining neurons. Compared with saccades with relatively long SRTs, short-SRT saccades were preceded by both stronger gap-related and target-related responses in all PPC neurons, regardless of whether such response reached significance. Our findings suggest that the PPC in the marmoset contains an area that is involved in the modulation of saccadic preparation.NEW & NOTEWORTHY As a primate model in systems neuroscience, the marmoset is a great complement to the macaque monkey because of its unique advantages. To identify oculomotor networks in the marmoset, we recorded from the marmoset posterior parietal cortex during a saccadic task and found single-unit activities consistent with a role in saccadic modulation. This finding supports the marmoset as a valuable model for studying oculomotor control.

The role of fixation disengagement in the parallel programming of sequences of saccades.

One of the core mechanisms involved in the control of saccade responses to selected target stimuli is the disengagement from the current fixation location, so that the next saccade can be executed. To carry out everyday visual tasks, we make multiple eye movements that can be programmed in parallel. However, the role of disengagement in the parallel programming of saccades has not been examined. It is well established that the need for disengagement slows down saccadic response time. This may be important in allowing the system to program accurate eye movements and have a role to play in the control of multiple eye movements but as yet this remains untested. Here, we report two experiments that seek to examine whether fixation disengagement reduces saccade latencies when the task completion demands multiple saccade responses. A saccade contingent paradigm was employed and participants were asked to execute saccadic eye movements to a series of seven targets while manipulating when these targets were shown. This both promotes fixation disengagement and controls the extent that parallel programming can occur. We found that trial duration decreased as more targets were made available prior to fixation: this was a result both of a reduction in the number of saccades being executed and in their saccade latencies. This supports the view that even when fixation disengagement is not required, parallel programming of multiple sequential saccadic eye movements is still present. By comparison with previous published data, we demonstrate a substantial speeded of response times in these condition ("a gap effect") and that parallel programming is attenuated in these conditions.

Methods for chair restraint and training of the common marmoset on oculomotor tasks.

The oculomotor system is the most thoroughly understood sensorimotor system in the brain, due in large part to electrophysiological studies carried out in macaque monkeys trained to perform oculomotor tasks. A disadvantage of the macaque model is that many cortical oculomotor areas of interest lie within sulci, making high-density array and laminar recordings impractical. Many techniques of molecular biology developed in rodents, such as optogenetic manipulation of neuronal subtypes, are also limited in this species. The common marmoset ( Callithrix jacchus) possesses a smooth cortex, allowing easy access to frontoparietal oculomotor areas, and may bridge the gap between systems neuroscience in macaques and molecular techniques. Techniques for restraint, training, and neural recording in these animals have been well developed in auditory neuroscience. Those for oculomotor neuroscience, however, remain at a relatively early stage. In this article we provide details of a custom-designed restraint chair for marmosets, a combination head restraint/recording chamber allowing access to cortical oculomotor areas and providing stability suitable for eye movement and neural recordings, as well as a training protocol for oculomotor tasks. We additionally report the results of a psychophysical study in marmosets trained to perform a saccade task using these methods, showing that, as in rhesus and humans, marmosets exhibit a "gap effect," a decrease in reaction time when the fixation stimulus is removed before the onset of a visual saccade target. These results are the first evidence of this effect in marmosets and support the common marmoset model for neurophysiological investigations of oculomotor control. NEW & NOTEWORTHY The ability to carry out neuronal recordings in behaving primates has provided a wealth of information regarding the neural circuits underlying the control of eye movements. Such studies require restraint of the animal within a primate chair, head fixation, methods of acclimating the animals to this restraint, and the use of operant conditioning methods for training on oculomotor tasks. In contrast to the macaque model, relatively few studies have reported in detail methods for use in the common marmoset. In this report we detail custom-designed equipment and methods by which we have used to successfully train head-restrained marmosets to perform basic oculomotor tasks.

The disengagement of visual attention in the gap paradigm across adolescence.

Attentional disengagement is important for successful interaction with our environment. The efficiency of attentional disengagement is commonly assessed using the gap paradigm. There is, however, a sharp contrast between the number of studies applying the gap paradigm to clinical populations and the knowledge about the underlying developmental trajectory of the gap effect. The aim of the present study was, therefore, to investigate attentional disengagement in a group of children aged 9-15. Besides the typically deployed gap and the overlap conditions, we also added a baseline condition in which the fixation point was removed at the moment that the target appeared. This allowed us to reveal the appropriate experimental conditions to unravel possible developmental differences. Correlational analyses showed that the size of the gap effect became smaller with increasing age, but only for the difference between the gap and the overlap conditions. This shows that there is a gradual increase in the capacity to disengage visual attention with increasing age, but that this effect only becomes apparent when the gap and the overlap conditions are compared. The gradual decrease of the gap effect with increasing age provides additional evidence that the attentional system becomes more efficient with increasing age and that this is a gradual process.

Action and perception are temporally coupled by a common mechanism that leads to a timing misperception.

We move our eyes to explore the world, but visual areas determining where to look next (action) are different from those determining what we are seeing (perception). Whether, or how, action and perception are temporally coordinated is not known. The preparation time course of an action (e.g., a saccade) has been widely studied with the gap/overlap paradigm with temporal asynchronies (TA) between peripheral target onset and fixation point offset (gap, synchronous, or overlap). However, whether the subjects perceive the gap or overlap, and when they perceive it, has not been studied. We adapted the gap/overlap paradigm to study the temporal coupling of action and perception. Human subjects made saccades to targets with different TAs with respect to fixation point offset and reported whether they perceived the stimuli as separated by a gap or overlapped in time. Both saccadic and perceptual report reaction times changed in the same way as a function of TA. The TA dependencies of the time change for action and perception were very similar, suggesting a common neural substrate. Unexpectedly, in the perceptual task, subjects misperceived lights overlapping by less than ∼100 ms as separated in time (overlap seen as gap). We present an attention-perception model with a map of prominence in the superior colliculus that modulates the stimulus signal's effectiveness in the action and perception pathways. This common source of modulation determines how competition between stimuli is resolved, causes the TA dependence of action and perception to be the same, and causes the misperception.

On the interplay between pain observation, guilt and shame proneness and honesty.

Seeing others in pain can stimulate powerful socio-emotional responses. Does it also make us more moral? In two laboratory experiments, we examined the interplay between pain observation, self-reported guilt and shame, subjective perceptions of pain intensity, and subsequent honest behavior. Watching a confederate perform a moderately painful (vs. non-painful) task did not affect honest behavior in a subsequent die-roll task. Independent of pain observation, there was a positive relationship between self-reported guilt proneness and shame proneness and honesty. More specifically, individuals who are more prone to feeling guilt -and to a lesser extent shame- behaved more honestly. Furthermore, we found weak support for the hypothesis that greater perceived pain (rather than objective pain) is associated with less cheating. We call for further research in the interconnections between perceived pain, guilt, shame, and moral behavior.

Blue-light effects on saccadic eye movements and attentional disengagement.

People are constantly exposed to high-energy blue light as they spend considerable amounts of time reading and browsing materials on electronic products like computers and cellphones. Recent studies suggest that the stimulation of intrinsically photosensitive retinal ganglion cells (ipRGCs)-a newly discovered type of photoreceptor shown to be particularly sensitive to blue light-activates brain regions related to eye movements and attentional orienting (e.g., frontal eye fields). It remains unclear, however, whether and how blue light affects eye movements and attention behaviorally. We examined this by adopting the gap paradigm in which participants made saccades to a peripheral target as quickly and accurately as possible while the fixation sign vanished (i.e., the gap condition) or remained visible. Participants were exposed to blue and orange light on two separate days. Faster saccade latency under blue light was found across two experiments, and the results indicate that blue light shortened saccade latency when attention and eye movements operate simultaneously. Our findings provide evidence for the blue-light facilitatory effect on eye movements and attentional disengagement, and suggest that blue light can enhance the speed of saccadic eye movements.

Reduced engagement of visual attention in children with autism spectrum disorder.

LAY ABSTRACT: Limited eye contact and difficulty tracking where others are looking are common in people with autism spectrum disorder. It is unclear, however, whether these are specifically social differences; it is possible that they are a result of broader alterations in engaging and disengaging visual attention. We used eye-tracking technology with children with autism spectrum disorder (n = 35) and typical development (n = 32), showing them both social and nonsocial imaging to test their visual attention. Children with autism spectrum disorder had a significant difference in how long it took them to look from an image in the middle to one on the side, depending on whether the middle image stayed on the screen or flashed off before the one on the side appeared. This difference was present for both social and nonsocial images, and was related to cognitive ability for only the children with autism spectrum disorder. Our findings suggest that children with autism spectrum disorder have differences in general processes of engaging visual attention that are not specifically social in nature, and that these processes may relate to cognitive ability in autism spectrum disorder. Affected processes of visual engagement in autism spectrum disorder may contribute to symptoms like reduced eye contact, but social-specific symptoms of autism spectrum disorder likely do not stem from reduced visual engagement alone.

The Disengagement of Visual Attention: An Eye-Tracking Study of Cognitive Impairment, Ethnicity and Age.

Various studies have shown that Alzheimer's disease (AD) is associated with an impairment of inhibitory control, although we do not have a comprehensive understanding of the associated cognitive processes. The ability to engage and disengage attention is a crucial cognitive operation of inhibitory control and can be readily investigated using the "gap effect" in a saccadic eye movement paradigm. In previous work, various demographic factors were confounded; therefore, here, we examine separately the effects of cognitive impairment in Alzheimer's disease, ethnicity/culture and age. This study included young (N = 44) and old (N = 96) European participants, AD (N = 32), mildly cognitively impaired participants (MCI: N = 47) and South Asian older adults (N = 94). A clear reduction in the mean reaction times was detected in all the participant groups in the gap condition compared to the overlap condition, confirming the effect. Importantly, this effect was also preserved in participants with MCI and AD. A strong effect of age was also evident, revealing a slowing in the disengagement of attention during the natural process of ageing.

Saccade latency bias toward temporal hemifield: Evidence for role of retinotectal tract in mediating reflexive saccades.

The superior colliculus (SC) plays a critical role in mediating reflexive eye movements. Under optimal conditions, for example including a temporal 'gap' of 200 ms after fixation offset and prior to target onset, it is possible to isolate a population of 'express saccades' with very short latencies between 80 and 120 ms. Ablation of the SC abolishes express saccades in monkeys. However, it remains to be established whether express saccade generation is dependent upon visual afferents transmitting direct retinal projections to SC via the retinotectal tract (RTT). In nineteen healthy human participants, we used a gap paradigm to investigate whether express saccades demonstrate shorter latencies to targets in the temporal hemifield, a marker for RTT function. A population of predominantly reflexive saccades (with latencies between 70 and 150 ms) was isolated in which latencies toward temporal hemifield targets were shown to be shorter than toward nasal hemifield targets. The advantages for reflexive saccades toward temporal hemifield targets suggest that visual efferents from the retina to the superior colliculus contribute to generating reflexively triggered saccades.

Investigation of mode assignment on YVO4 crystal in high temperature region by polarized Raman spectroscopy and first principles calculations.

Polarized Raman spectra for 11 modes in the YVO4 crystal were measured in the temperature range from room temperature to 473K, and the mode assignment on Raman modes was analyzed using the first-principles calculations. We found that the calculated frequency values are in good agreement with the experimental ones. The large difference of the temperature line broadening between two peaks (380cm-1 and 891cm-1) of A1g mode has been reported and it is thought to be due to band gap effect in PDOS.

Nonspecific effects of gap paradigm on swallowing.

OBJECTIVE: Analogous to the gap paradigm in experiments for saccadic eye movements with very short reaction times, we hypothesized that the initiation of oropharyngeal swallowing movements guided by visual cues are encouraged under experimental conditions using a similar gap paradigm. METHODS: A red visual cue indicating to hold a bolus in the mouth and a blue one indicating to swallow the bolus were sequentially provided on a computer display to 11 healthy participants. The gap period between these cues varied from 0 to 800ms. Swallowing kinetics and kinematics were recorded using surface electromyography and a laser displacement sensor, respectively. RESULTS: In comparison with the no-gap paradigm, the delay from the onset of muscle activities to initiation of movement significantly decreased with a 100- (p<0.01) and 200-ms (p<0.005) gap period. With other gap periods, no significant change was detected in the delay. CONCLUSIONS: Initiation of visually guided swallowing was enhanced by a gap paradigm of 100-200ms. Wrist flexion was boosted in a similar manner. Thus, the gap effect may be a generalized warning effect. SIGNIFICANCE: Our findings might provide insights into the contribution of the basal ganglia to volitional swallowing.

Reduced visual disengagement but intact phasic alerting in young children with autism.

Children with autism may have difficulties with visual disengagement-that is, inhibiting current fixations and orienting to new stimuli in the periphery. These difficulties may limit these children's ability to flexibly monitor the environment, regulate their internal states, and interact with others. In typical development, visual disengagement is influenced by a phasic alerting network that increases the processing speed of the visual system after salient events. The role of the phasic alerting effect in the putative atypical disengagement performance in autism spectrum disorder (ASD) is not known. Here, we compared visual disengagement in six-year-old children with autism (N = 18) and typically developing children (N = 17) matched for age and nonverbal IQ. We manipulated phasic alerting during a visual disengagement task by adding spatially nonpredictive sounds shortly before the onset of the visual peripheral targets. Children with ASD showed evidence of delayed disengagement compared to the control group. Sounds facilitated visual disengagement similarly in both groups, suggesting typical modulation by phasic alerting in ASD in the context of this task. These results support the view that atypical visual disengagement in ASD is related to other factors than atypicalities in the alerting network. Autism Res 2017, 10: 539-545. © 2016 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.

Synergetic SERS Enhancement in a Metal-Like/Metal Double-Shell Structure for Sensitive and Stable Application.

Because of either thermal/chemical instability or high optical loss in noble metal nanostructures, searching for alternative plasmonic materials is becoming more and more urgent, considering the practical biosensing applications under various extreme conditions. In this work, titanium nitride (TiN), a low-loss metal-like material with both excellent thermal and excellent chemical stabilities, was proposed to composite with Ag hollow nanosphere (HNS) nanostructures as an effective surface-enhanced Raman scattering (SERS) substrate to realize both highly sensitive and highly stable molecular detection. Because of the multiple-mode local surface plasmon resonance around the spherical composite nanospheres and the "gap effect" derived from the ultrasmall nanogaps within the precisely controlled plasmonic arrays, an intensively enhanced local field was successfully induced on this SERS substrate. Combined with the unique charge transferring process between Ag and TiN, a synergistically enhanced SERS sensitivity involving both physical and chemical mechanisms was achieved. Especially, with the isolation of TiN, a time-durable Raman detection on these TiN-Ag HNS arrays was accomplished, showing great potential for practical applications.

Effects of extraordinary snowfall on traffic safety.

Snowfall affects traffic safety by causing changes in roadway surface and visibility that result in crashes, spinouts, and breakdowns. Using data collected at a site that regularly receives nearly 1000 cm of snow during the snow season, this study examines the impact of snowfall quantity, gap between snow events, and weather conditions on crash and incident frequencies. Estimation results from regression analysis show that snowfall severity significantly impacts crashes and incidents but the impact diminishes marginally with each additional centimeter of snow. Gap has a significant fixed effect on crashes but its impact on incidents varies significantly across observations. The effect of the mixed precipitation condition is smaller in comparison to an all-snow condition. These results will help inform policy for snow removal and traffic enforcement in areas of high snowfall.

Using eye tracking to test for individual differences in attention to attractive faces.

We assessed individual differences in visual attention toward faces in relation to their attractiveness via saccadic reaction times. Motivated by the aim to understand individual differences in attention to faces, we tested three hypotheses: (a) Attractive faces hold or capture attention more effectively than less attractive faces; (b) men show a stronger bias toward attractive opposite-sex faces than women; and (c) blue-eyed men show a stronger bias toward blue-eyed than brown-eyed feminine faces. The latter test was included because prior research suggested a high effect size. Our data supported hypotheses (a) and (b) but not (c). By conducting separate tests for disengagement of attention and attention capture, we found that individual differences exist at distinct stages of attentional processing but these differences are of varying robustness and importance. In our conclusion, we also advocate the use of linear mixed effects models as the most appropriate statistical approach for studying inter-individual differences in visual attention with naturalistic stimuli.