Active vision at the foveal scale in the primate superior colliculus.

The primate superior colliculus (SC) has recently been shown to possess both a large foveal representation as well as a varied visual processing repertoire. This structure is also known to contribute to eye movement generation. Here, we describe our current understanding of how SC visual and movement-related signals interact within the realm of small eye movements associated with the foveal scale of visuomotor behavior. Within the SC's foveal representation, there is a full spectrum of visual, visual-motor, and motor-related discharge for fixational eye movements. Moreover, a substantial number of neurons only emit movement-related discharge when microsaccades are visually guided, but not when similar movements are generated toward a blank. This represents a particularly striking example of integrating vision and action at the foveal scale. Beyond that, SC visual responses themselves are strongly modulated, and in multiple ways, by the occurrence of small eye movements. Intriguingly, this impact can extend to eccentricities well beyond the fovea, causing both sensitivity enhancement and suppression in the periphery. Because of large foveal magnification of neural tissue, such long-range eccentricity effects are neurally warped into smaller differences in anatomical space, providing a structural means for linking peripheral and foveal visual modulations around fixational eye movements. Finally, even the retinal-image visual flows associated with tiny fixational eye movements are signaled fairly faithfully by peripheral SC neurons with relatively large receptive fields. These results demonstrate how studying active vision at the foveal scale represents an opportunity for understanding primate vision during natural behaviors involving ever-present foveating eye movements.NEW & NOTEWORTHY The primate superior colliculus (SC) is ideally suited for active vision at the foveal scale: it enables detailed foveal visual analysis by accurately driving small eye movements, and it also possesses a visual processing machinery that is sensitive to active eye movement behavior. Studying active vision at the foveal scale in the primate SC is informative for broader aspects of active perception, including the overt and covert processing of peripheral extra-foveal visual scene locations.

Properties of visually guided saccadic behavior and bottom-up attention in marmoset, macaque, and human.

Saccades are stereotypic behaviors whose investigation improves our understanding of how primate brains implement precise motor control. Furthermore, saccades offer an important window into the cognitive and attentional state of the brain. Historically, saccade studies have largely relied on macaques. However, the cortical network giving rise to the saccadic command is difficult to study in macaques because relevant cortical areas lie in deep sulci and are difficult to access. Recently, a New World monkey. the marmoset, has garnered attention as an alternative to macaques because of advantages including its smooth cortical surface. However, adoption of the marmoset for oculomotor research has been limited due to a lack of in-depth descriptions of marmoset saccade kinematics and their ability to perform psychophysical tasks. Here, we directly compare free-viewing and visually guided behavior of marmoset, macaque, and human engaged in identical tasks under similar conditions. In the video free-viewing task, all species exhibited qualitatively similar saccade kinematics up to 25° in amplitude although with different parameters. Furthermore, the conventional bottom-up saliency model predicted gaze targets at similar rates for all species. We further verified their visually guided behavior by training them with step and gap saccade tasks. In the step paradigm, marmosets did not show shorter saccade reaction time for upward saccades whereas macaques and humans did. In the gap paradigm, all species showed similar gap effect and express saccades. Our results suggest that the marmoset can serve as a model for oculomotor, attentional, and cognitive research while we need to be aware of their difference from macaque or human.NEW & NOTEWORTHY We directly compared the results of a video free-viewing task and visually guided saccade tasks (step and gap) among three different species: marmoset, macaque, and human. We found that all species exhibit qualitatively similar saccadic kinematics and saliency-driven saccadic behavior albeit with different parameters. Our results suggest that the marmoset possesses similar neural mechanisms to macaque and human for saccadic control, and it is an appropriate model to study neural mechanisms for active vision and attention.

Visual feature tuning of superior colliculus neural reafferent responses after fixational microsaccades.

The primate superior colliculus (SC) is causally involved in microsaccade generation. Moreover, visually responsive SC neurons across this structure's topographic map, even at peripheral eccentricities much larger than the tiny microsaccade amplitudes, exhibit significant modulations of evoked response sensitivity when stimuli appear perimicrosaccadically. However, during natural viewing, visual stimuli are normally stably present in the environment and are only shifted on the retina by eye movements. Here we investigated this scenario for the case of microsaccades, asking whether and how SC neurons respond to microsaccade-induced image jitter. We recorded neural activity from two male rhesus macaque monkeys. Within the response field (RF) of a neuron, there was a stable stimulus consisting of a grating of one of three possible spatial frequencies. The grating was stable on the display, but microsaccades periodically jittered the retinotopic RF location over it. We observed clear short-latency visual reafferent responses after microsaccades. These responses were weaker, but earlier (relative to new fixation onset after microsaccade end), than responses to sudden stimulus onsets without microsaccades. The reafferent responses clearly depended on microsaccade amplitude as well as microsaccade direction relative to grating orientation. Our results indicate that one way for microsaccades to influence vision is through modulating how the spatio-temporal landscape of SC visual neural activity represents stable stimuli in the environment. Such representation depends on the specific pattern of temporal luminance modulations expected from the relative relationship between eye movement vector (size and direction) on one hand and spatial visual pattern layout on the other.NEW & NOTEWORTHY Despite being diminutive, microsaccades still jitter retinal images. We investigated how such jitter affects superior colliculus (SC) activity. We found that SC neurons exhibit short-latency visual reafferent bursts after microsaccades. These bursts reflect not only the spatial luminance profiles of visual patterns but also how such profiles are shifted by eye movement size and direction. These results indicate that the SC continuously represents visual patterns, even as they are jittered by the smallest possible saccades.

Intelligent system to predict intradialytic hypotension in chronic hemodialysis.

BACKGROUND: Intradialytic hypotension (IDH) is a serious complication and a major risk factor of increased mortality during hemodialysis (HD). However, predicting the occurrence of intradialytic blood pressure (BP) fluctuations clinically is difficult. This study aimed to develop an intelligent system with capability of predicting IDH. METHODS: In developing and training the prediction models in the intelligent system, we used a database of 653 HD outpatients who underwent 55,516 HD treatment sessions, resulting in 285,705 valid BP records. We built models to predict IDH at the next BP check by applying time-dependent logistic regression analyses. RESULTS: Our results showed the sensitivity of 86% and specificity of 81% for both nadir systolic BP (SBP) of <90 mmHg and <100 mmHg, suggesting good performance of our prediction models. We obtained similar results in validating via test data and data of newly enrolled patients (new-patient data), which is important for simulating prospective situations wherein dialysis staff are unfamiliar with new patients. This compensates for the retrospective nature of the BP records used in our study. CONCLUSION: The use of this validated intelligent system can identify patients who are at risk of IDH in advance, which may facilitate well-timed personalized management and intervention.

A neural locus for spatial-frequency specific saccadic suppression in visual-motor neurons of the primate superior colliculus.

Saccades cause rapid retinal-image shifts that go perceptually unnoticed several times per second. The mechanisms for saccadic suppression have been controversial, in part because of sparse understanding of neural substrates. In this study we uncovered an unexpectedly specific neural locus for spatial frequency-specific saccadic suppression in the superior colliculus (SC). We first developed a sensitive behavioral measure of suppression in two macaque monkeys, demonstrating selectivity to low spatial frequencies similar to that observed in earlier behavioral studies. We then investigated visual responses in either purely visual SC neurons or anatomically deeper visual motor neurons, which are also involved in saccade generation commands. Surprisingly, visual motor neurons showed the strongest visual suppression, and the suppression was dependent on spatial frequency, as in behavior. Most importantly, suppression selectivity for spatial frequency in visual motor neurons was highly predictive of behavioral suppression effects in each individual animal, with our recorded population explaining up to ~74% of behavioral variance even on completely different experimental sessions. Visual SC neurons had mild suppression, which was unselective for spatial frequency and thus only explained up to ~48% of behavioral variance. In terms of spatial frequency-specific saccadic suppression, our results run contrary to predictions that may be associated with a hypothesized SC saccadic suppression mechanism, in which a motor command in the visual motor and motor neurons is first relayed to the more superficial purely visual neurons, to suppress them and to then potentially be fed back to cortex. Instead, an extraretinal modulatory signal mediating spatial-frequency-specific suppression may already be established in visual motor neurons.NEW & NOTEWORTHY Saccades, which repeatedly realign the line of sight, introduce spurious signals in retinal images that normally go unnoticed. In part, this happens because of perisaccadic suppression of visual sensitivity, which is known to depend on spatial frequency. We discovered that a specific subtype of superior colliculus (SC) neurons demonstrates spatial-frequency-dependent suppression. Curiously, it is the neurons that help mediate the saccadic command itself that exhibit such suppression, and not the purely visual ones.

Sequential hemifield gating of α- and ß-behavioral performance oscillations after microsaccades.

Microsaccades are tiny saccades that occur during gaze fixation. Even though visual processing has been shown to be strongly modulated close to the time of microsaccades, both at central and peripheral eccentricities, it is not clear how these eye movements might influence longer term fluctuations in brain activity and behavior. Here we found that visual processing is significantly affected and, in a rhythmic manner, even several hundreds of milliseconds after a microsaccade. Human visual detection efficiency, as measured by reaction time, exhibited coherent rhythmic oscillations in the α- and ß-frequency bands for up to ~650-700 ms after a microsaccade. Surprisingly, the oscillations were sequentially pulsed across visual hemifields relative to microsaccade direction, first occurring in the same hemifield as the movement vector for ~400 ms and then the opposite. Such pulsing also affected perceptual detection performance. Our results suggest that visual processing is subject to long-lasting oscillations that are phase locked to microsaccade generation, and that these oscillations are dependent on microsaccade direction.NEW & NOTEWORTHY We investigated long-term microsaccadic influences on visual processing and found rhythmic oscillations in behavioral performance at α- and ß-frequencies (~8-20 Hz). These oscillations were pulsed at a much lower frequency across visual hemifields, first occurring in the same hemifield as the microsaccade direction vector for ~400 ms before switching to the opposite hemifield for a similar interval. Our results suggest that saccades temporally organize visual processing and that such organization can sequentially switch hemifields.

Alteration of the microsaccadic velocity-amplitude main sequence relationship after visual transients: implications for models of saccade control.

Microsaccades occur during gaze fixation to correct for miniscule foveal motor errors. The mechanisms governing such fine oculomotor control are still not fully understood. In this study, we explored microsaccade control by analyzing the impacts of transient visual stimuli on these movements' kinematics. We found that such kinematics can be altered in systematic ways depending on the timing and spatial geometry of visual transients relative to the movement goals. In two male rhesus macaques, we presented peripheral or foveal visual transients during an otherwise stable period of fixation. Such transients resulted in well-known reductions in microsaccade frequency, and our goal was to investigate whether microsaccade kinematics would additionally be altered. We found that both microsaccade timing and amplitude were modulated by the visual transients, and in predictable manners by these transients' timing and geometry. Interestingly, modulations in the peak velocity of the same movements were not proportional to the observed amplitude modulations, suggesting a violation of the well-known "main sequence" relationship between microsaccade amplitude and peak velocity. We hypothesize that visual stimulation during movement preparation affects not only the saccadic "Go" system driving eye movements but also a "Pause" system inhibiting them. If the Pause system happens to be already turned off despite the new visual input, movement kinematics can be altered by the readout of additional visually evoked spikes in the Go system coding for the flash location. Our results demonstrate precise control over individual microscopic saccades and provide testable hypotheses for mechanisms of saccade control in general.NEW & NOTEWORTHY Microsaccadic eye movements play an important role in several aspects of visual perception and cognition. However, the mechanisms for microsaccade control are still not fully understood. We found that microsaccade kinematics can be altered in a systematic manner by visual transients, revealing a previously unappreciated and exquisite level of control by the oculomotor system of even the smallest saccades. Our results suggest precise temporal interaction between visual, motor, and inhibitory signals in microsaccade control.

Postmicrosaccadic enhancement of slow eye movements.

Active sensation poses unique challenges to sensory systems because moving the sensor necessarily alters the input sensory stream. Sensory input quality is additionally compromised if the sensor moves rapidly, as during rapid eye movements, making the period immediately after the movement critical for recovering reliable sensation. Here, we studied this immediate postmovement interval for the case of microsaccades during fixation, which rapidly jitter the "sensor" exactly when it is being voluntarily stabilized to maintain clear vision. We characterized retinal-image slip in monkeys immediately after microsaccades by analyzing postmovement ocular drifts. We observed enhanced ocular drifts by up to ~28% relative to premicrosaccade levels, and for up to ~50 ms after movement end. Moreover, we used a technique to trigger full-field image motion contingent on real-time microsaccade detection, and we used the initial ocular following response to this motion as a proxy for changes in early visual motion processing caused by microsaccades. When the full-field image motion started during microsaccades, ocular following was strongly suppressed, consistent with detrimental retinal effects of the movements. However, when the motion started after microsaccades, there was up to ~73% increase in ocular following speed, suggesting an enhanced motion sensitivity. These results suggest that the interface between even the smallest possible saccades and "fixation" includes a period of faster than usual image slip, as well as an enhanced responsiveness to image motion, and that both of these phenomena need to be considered when interpreting the pervasive neural and perceptual modulations frequently observed around the time of microsaccades.

Visual Functions of the Primate Superior Colliculus.

The superior colliculus (SC) is a subcortical brain structure that is relevant for sensation, cognition, and action. In nonhuman primates, a rich history of studies has provided unprecedented detail about this structure's role in controlling orienting behaviors; as a result, the primate SC has become primarily regarded as a motor control structure. However, as in other species, the primate SC is also a highly visual structure: A fraction of its inputs is retinal and complemented by inputs from visual cortical areas, including the primary visual cortex. Motivated by this, recent investigations are revealing the rich visual pattern analysis capabilities of the primate SC, placing this structure in an ideal position to guide orienting movements. The anatomical proximity of the primate SC to both early visual inputs and final motor control apparatuses, as well as its ascending feedback projections to the cortex, affirms an important role for this structure in active perception.

Harnessing a New Co-Host System and Low Concentration of New TADF Emitters Equipped with Trifluoromethyl- and Cyano-Substituted Benzene as Core for High-Efficiency Blue OLEDs.

A strategic approach combining a new co-host system and low concentration of new thermally activated delayed fluorescence (TADF) emitters to make efficient blue TADF organic light-emitting diode (OLED) was developed. The benchmark TADF molecule, 4CzIPN, was adopted as a probe to examine the feasibility of a co-host composing of a hole transporter SimCP and an electron transporter oCF3-T2T. As a result, a sky blue device with 1 wt % 4CzIPN doped in SimCP:oCF3-T2T co-host exhibited 100% energy transfer and achieved a high external quantum efficiency (EQE) up to 26.1%. Importantly, this device showed a limited efficiency rolloff with an EQE of 24% at 1000 cd m-2. To further shift the emission toward blue, three new TADF molecules, 4CzIPN-CF3, 3CzIPN-H-CF3, and 3CzIPN-CF3, modified either by lowering the electron-withdrawing ability of the acceptor group or by reducing the number of carbazole donors of 4CzIPN, have been synthesized and characterized. Among them, 4CzIPN-CF3 and 3CzIPN-H-CF3 display hypsochromic shift emissions compared to that of 4CzIPN. These new compounds were then explored for their potential applications as TADF emitters. Blue TADF OLEDs with 1 wt % of 4CzIPN-CF3 and 3CzIPN-H-CF3 dispersed in SimCP:oCF3-T2T co-host achieved EQEs of 23.1 and 16.5% and retained high EQEs of 20.9 and 14.7% at 1000 cd m-2, respectively.

The Foveal Visual Representation of the Primate Superior Colliculus.

A defining feature of the primate visual system is its foveated nature. Processing of foveal retinal input is important not only for high-quality visual scene analysis but also for ensuring precise, albeit tiny, gaze shifts during high-acuity visual tasks. The representations of foveal retinal input in the primate lateral geniculate nucleus and early visual cortices have been characterized. However, how such representations translate into precise eye movements remains unclear. Here, we document functional and structural properties of the foveal visual representation of the midbrain superior colliculus. We show that the superior colliculus, classically associated with extra-foveal spatial representations needed for gaze shifts, is highly sensitive to visual input impinging on the fovea. The superior colliculus also represents such input in an orderly and very specific manner, and it magnifies the representation of foveal images in neural tissue as much as the primary visual cortex does. The primate superior colliculus contains a high-fidelity visual representation, with large foveal magnification, perfectly suited for active visuomotor control and perception.

Texture-Map-Based Branch-Collaborative Network for Oral Cancer Detection.

The paper proposes an innovative deep convolutional neural network (DCNN) combined with texture map for detecting cancerous regions and marking the ROI in a single model automatically. The proposed DCNN model contains two collaborative branches, namely an upper branch to perform oral cancer detection, and a lower branch to perform semantic segmentation and ROI marking. With the upper branch the network model extracts the cancerous regions, and the lower branch makes the cancerous regions more precision. To make the features in the cancerous more regular, the network model extracts the texture images from the input image. A sliding window is then applied to compute the standard deviation values of the texture image. Finally, the standard deviation values are used to construct a texture map, which is partitioned into multiple patches and used as the input data to the deep convolutional network model. The method proposed by this paper is called texture-map-based branch-collaborative network. In the experimental result, the average sensitivity and specificity of detection are up to 0.9687 and 0.7129, respectively based on wavelet transform. And the average sensitivity and specificity of detection are up to 0.9314 and 0.9475, respectively based on Gabor filter.

Orientation and Contrast Tuning Properties and Temporal Flicker Fusion Characteristics of Primate Superior Colliculus Neurons.

The primate superior colliculus is traditionally studied from the perspectives of gaze control, target selection, and selective attention. However, this structure is also visually responsive, and it is the primary visual structure in several species. Thus, understanding the visual tuning properties of the primate superior colliculus is important, especially given that the superior colliculus is part of an alternative visual pathway running in parallel to the predominant geniculo-cortical pathway. In recent previous studies, we have characterized receptive field organization and spatial frequency tuning properties in the primate (rhesus macaque) superior colliculus. Here, we explored additional aspects like orientation tuning, putative center-surround interactions, and temporal frequency tuning characteristics of visually-responsive superior colliculus neurons. We found that orientation tuning exists in the primate superior colliculus, but that such tuning is relatively moderate in strength. We also used stimuli of different sizes to explore contrast sensitivity and center-surround interactions. We found that stimulus size within a visual receptive field primarily affects the slope of contrast sensitivity curves without altering maximal firing rate. Additionally, sustained firing rates, long after stimulus onset, strongly depend on stimulus size, and this is also reflected in local field potentials. This suggests the presence of inhibitory interactions within and around classical receptive fields. Finally, primate superior colliculus neurons exhibit temporal frequency tuning for frequencies lower than 30 Hz, with critical flicker fusion frequencies of <20 Hz. These results support the hypothesis that the primate superior colliculus might contribute to visual performance, likely by mediating coarse, but rapid, object detection and identification capabilities for the purpose of facilitating or inhibiting orienting responses. Such mediation may be particularly amplified in blindsight subjects who lose portions of their primary visual cortex and therefore rely on alternative visual pathways including the pathway through the superior colliculus.

Spatial frequency sensitivity in macaque midbrain.

Visual brain areas exhibit tuning characteristics well suited for image statistics present in our natural environment. However, visual sensation is an active process, and if there are any brain areas that ought to be particularly in tune with natural scene statistics, it would be sensory-motor areas critical for guiding behavior. Here we found that the rhesus macaque superior colliculus, a structure instrumental for rapid visual exploration with saccades, detects low spatial frequencies, which are the most prevalent in natural scenes, much more rapidly than high spatial frequencies. Importantly, this accelerated detection happens independently of whether a neuron is more or less sensitive to low spatial frequencies to begin with. At the population level, the superior colliculus additionally over-represents low spatial frequencies in neural response sensitivity, even at near-foveal eccentricities. Thus, the superior colliculus possesses both temporal and response gain mechanisms for efficient gaze realignment in low-spatial-frequency-dominated natural environments.

Two-channel autofluorescence analysis for oral cancer.

We created a two-channel autofluorescence test to detect oral cancer. The wavelengths 375 and 460 nm, with filters of 479 and 525 nm, were designed to excite and detect reduced-form nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) autofluorescence. Patients with oral cancer or with precancerous lesions, and a control group with healthy oral mucosae, were enrolled. The lesion in the autofluorescent image was the region of interest. The average intensity and heterogeneity of the NADH and FAD were calculated. The redox ratio [(NADH)/(NADH + FAD)] was also computed. A quadratic discriminant analysis (QDA) was used to compute boundaries based on sensitivity and specificity. We analyzed 49 oral cancer lesions, 34 precancerous lesions, and 77 healthy oral mucosae. A boundary (sensitivity: 0.974 and specificity: 0.898) between the oral cancer lesions and healthy oral mucosae was validated. Oral cancer and precancerous lesions were also differentiated from healthy oral mucosae (sensitivity: 0.919 and specificity: 0.755). The two-channel autofluorescence detection device and analyses of the intensity and heterogeneity of NADH, and of FAD, and the redox ratio combined with a QDA classifier can differentiate oral cancer and precancerous lesions from healthy oral mucosae.

Meglitinides increase the risk of hypoglycemia in diabetic patients with advanced chronic kidney disease: a nationwide, population-based study.

The safety of short-acting meglitinides in diabetic patients with advanced chronic kidney disease (CKD) has not been widely reported. Diabetic patients with advanced CKD who had a serum creatinine level of > 6 mg/dL a hematocrit level of ≦ 28% and received erythropoiesis-stimulating agent treatment between 2000 and 2010, were included in this nationwide study in Taiwan. The outcomes of interest were defined as hypoglycemia and long-term mortality. The risks of hypoglycemia and death were analyzed using Cox proportional hazards models, with end-stage renal disease and anti-diabetic drugs as time-dependent variables. Fresh users and matched non-users of meglitinides (both n = 2,793) were analyzed. The use of meglitinides increased the risk of hypoglycemia (HR, 1.94, p<0.001), as did other anti-diabetic agents. Concomitant use of meglitinide and insuilin will incresase the hypoglycemic risk. (HR, 1.69, p=0.018) Moreover, it was not the use of meglitinides, but the presence of hypoglycemia that predicted mortality. The function curve showed an insignificant trend towards increased hypoglycemic risk in patients aged > 62 and ≤ 33 years from the generalized additive model. This study suggests that the use of short-acting meglitinides could be associated with increased risk of hypoglycemia in diabetic patients with advanced CKD, especially in patients aged > 62 and ≤ 33 years. Meglitinide combined with insulin will increase hypoglycemia in patients with advanced CKD.

Sharper, Stronger, Faster Upper Visual Field Representation in Primate Superior Colliculus.

Visually guided behavior in three-dimensional environments entails handling immensely different sensory and motor conditions across retinotopic visual field locations: peri-personal ("near") space is predominantly viewed through the lower retinotopic visual field (LVF), whereas extra-personal ("far") space encompasses the upper visual field (UVF). Thus, when, say, driving a car, orienting toward the instrument cluster below eye level is different from scanning an upcoming intersection, even with similarly sized eye movements. However, an overwhelming assumption about visuomotor circuits for eye-movement exploration, like those in the primate superior colliculus (SC), is that they represent visual space in a purely symmetric fashion across the horizontal meridian. Motivated by ecological constraints on visual exploration of far space, containing small UVF retinal-image features, here we found a large, multi-faceted difference in the SC's representation of the UVF versus LVF. Receptive fields are smaller, more finely tuned to image spatial structure, and more sensitive to image contrast for neurons representing the UVF. Stronger UVF responses also occur faster. Analysis of putative synaptic activity revealed a particularly categorical change when the horizontal meridian is crossed, and our observations correctly predicted novel eye-movement effects. Despite its appearance as a continuous layered sheet of neural tissue, the SC contains functional discontinuities between UVF and LVF representations, paralleling a physical discontinuity present in cortical visual areas. Our results motivate the recasting of structure-function relationships in the visual system from an ecological perspective, and also exemplify strong coherence between brain-circuit organization for visually guided exploration and the nature of the three-dimensional environment in which we function.