Robust Coding of Eye Position in Posterior Parietal Cortex despite Context-Dependent Tuning.

Neurons in posterior parietal cortex (PPC) encode many aspects of the sensory world (e.g., scene structure), the posture of the body, and plans for action. For a downstream computation, however, only some of these dimensions are relevant; the rest are "nuisance variables" because their influence on neural activity changes with sensory and behavioral context, potentially corrupting the read-out of relevant information. Here we show that a key postural variable for vision (eye position) is represented robustly in male macaque PPC across a range of contexts, although the tuning of single neurons depended strongly on context. Contexts were defined by different stages of a visually guided reaching task, including (1) a visually sparse epoch, (2) a visually rich epoch, (3) a "go" epoch in which the reach was cued, and (4) during the reach itself. Eye position was constant within trials but varied across trials in a 3 × 3 grid spanning 24° × 24°. Using demixed principal component analysis of neural spike-counts, we found that the subspace of the population response encoding eye position is orthogonal to that encoding task context. Accordingly, a context-naive (fixed-parameter) decoder was nevertheless able to estimate eye position reliably across contexts. Errors were small given the sample size (∼1.78°) and would likely be even smaller with larger populations. Moreover, they were comparable to that of decoders that were optimized for each context. Our results suggest that population codes in PPC shield encoded signals from crosstalk to support robust sensorimotor transformations across contexts.SIGNIFICANCE STATEMENT Neurons in posterior parietal cortex (PPC) which are sensitive to gaze direction are thought to play a key role in spatial perception and behavior (e.g., reaching, navigation), and provide a potential substrate for brain-controlled prosthetics. Many, however, change their tuning under different sensory and behavioral contexts, raising the prospect that they provide unreliable representations of egocentric space. Here, we analyze the structure of encoding dimensions for gaze direction and context in PPC during different stages of a visually guided reaching task. We use demixed dimensionality reduction and decoding techniques to show that the coding of gaze direction in PPC is mostly invariant to context. This suggests that PPC can provide reliable spatial information across sensory and behavioral contexts.

Visual perturbation of balance suggests impaired motor control but intact visuomotor processing in Parkinson's disease.

Postural instability marks one of the most disabling features of Parkinson's disease (PD), but it only reveals itself after affected brain areas have already been significantly damaged. Thus there is a need to detect deviations in balance and postural control before visible symptoms occur. In this study, we visually perturbed balance in the anterior-posterior direction using sinusoidal oscillations of a moving room in virtual reality at different frequencies. We tested three groups: individuals with PD under dopaminergic medication, an age-matched control group, and a group of young healthy adults. We tracked their center of pressure and their full-body motion, from which we also extracted the center of mass. We investigated sway amplitudes and applied newly introduced phase-locking analyses to investigate responses across participants' bodies. Patients exhibited significantly higher sway amplitudes as compared with the control subjects. However, their sway was phase locked to the visual motion like that of age-matched and young healthy adults. Furthermore, all groups successfully compensated for the visual perturbation by phase locking their sway to the stimulus. As frequency of the perturbation increased, distribution of phase locking (PL) across the body revealed a shift of the highest PL values from the upper body toward the hip region for young healthy adults, which could not be observed in patients and elderly healthy adults. Our findings suggest an impaired motor control, but intact visuomotor processing in early stages of PD, while less flexibility to adapt postural strategy to different perturbations revealed to be an effect of age rather than disease.NEW & NOTEWORTHY A better understanding of visuomotor control in Parkinson's disease (PD) potentially serves as a tool for earlier diagnosis, which is crucial for improving patient's quality of life. In our study, we assess body sway responses to visual perturbations of the balance control system in patients with early-to-mid stage PD, using motion tracking along with recently established phase-locking techniques. Our findings suggest patients at this stage have an impaired muscular stability but intact visuomotor control.

Inter-trial phase coherence of visually evoked postural responses in virtual reality.

Vision plays a central role in maintaining balance. When humans perceive their body as moving, they trigger counter movements. This results in body sway, which has typically been investigated by measuring the body's center of pressure (COP). Here, we aimed to induce visually evoked postural responses (VEPR) by simulating self-motion in virtual reality (VR) using a sinusoidally oscillating "moving room" paradigm. Ten healthy subjects participated in the experiment. Stimulation consisted of a 3D-cloud of random dots, presented through a VR headset, which oscillated sinusoidally in the anterior-posterior direction at different frequencies. We used a force platform to measure subjects' COP over time and quantified the resulting trajectory by wavelet analyses including inter-trial phase coherence (ITPC). Subjects exhibited significant coupling of their COP to the respective stimulus. Even when spectral analysis of postural sway showed only small responses in the expected frequency bands (power), ITPC revealed an almost constant strength of coupling to the stimulus within but also across subjects and presented frequencies. Remarkably, ITPC even revealed a strong phase coupling to stimulation at 1.5 Hz, which exceeds the frequency range that has generally been attributed to the coupling of human postural sway to an oscillatory visual scenery. These findings suggest phase-locking to be an essential feature of visuomotor control.

Eye-position signals in the dorsal visual system are accurate and precise on short timescales.

Eye-position signals (EPS) are found throughout the primate visual system and are thought to provide a mechanism for representing spatial locations in a manner that is robust to changes in eye position. It remains unknown, however, whether cortical EPS (also known as "gain fields") have the necessary spatial and temporal characteristics to fulfill their purported computational roles. To quantify these EPS, we combined single-unit recordings in four dorsal visual areas of behaving rhesus macaques (lateral intraparietal area, ventral intraparietal area, middle temporal area, and the medial superior temporal area) with likelihood-based population-decoding techniques. The decoders used knowledge of spiking statistics to estimate eye position during fixation from a set of observed spike counts across neurons. Importantly, these samples were short in duration (100 ms) and from individual trials to mimic the real-time estimation problem faced by the brain. The results suggest that cortical EPS provide an accurate and precise representation of eye position, albeit with unequal signal fidelity across brain areas and a modest underestimation of eye eccentricity. The underestimation of eye eccentricity predicted a pattern of mislocalization that matches the errors made by human observers. In addition, we found that eccentric eye positions were associated with enhanced precision relative to the primary eye position. This predicts that positions in visual space should be represented more reliably during eccentric gaze than while looking straight ahead. Together, these results suggest that cortical eye-position signals provide a useable head-centered representation of visual space on timescales that are compatible with the duration of a typical ocular fixation.

Intrasaccadic suppression is dominated by reduced detector gain.

Human vision requires fast eye movements (saccades). Each saccade causes a self-induced motion signal, but we are not aware of this potentially jarring visual input. Among the theorized causes of this phenomenon is a decrease in visual sensitivity before (presaccadic suppression) and during (intrasaccadic suppression) saccades. We investigated intrasaccadic suppression using a perceptual template model (PTM) relating visual detection to different signal-processing stages. One stage changes the gain on the detector's input; another increases uncertainty about the stimulus, allowing more noise into the detector; and other stages inject noise into the detector in a stimulus-dependent or -independent manner. By quantifying intrasaccadic suppression of flashed horizontal gratings at varying external noise levels, we obtained threshold-versus-noise (TVN) data, allowing us to fit the PTM. We tested if any of the PTM parameters changed significantly between the fixation and saccade models and could therefore account for intrasaccadic suppression. We found that the dominant contribution to intrasaccadic suppression was a reduction in the gain of the visual detector. We discuss how our study differs from previous ones that have pointed to uncertainty as an underlying cause of intrasaccadic suppression and how the equivalent noise approach provides a framework for comparing the disparate neural correlates of saccadic suppression.

Linc2function: A Comprehensive Pipeline and Webserver for Long Non-Coding RNA (lncRNA) Identification and Functional Predictions Using Deep Learning Approaches.

Long non-coding RNAs (lncRNAs), comprising a significant portion of the human transcriptome, serve as vital regulators of cellular processes and potential disease biomarkers. However, the function of most lncRNAs remains unknown, and furthermore, existing approaches have focused on gene-level investigation. Our work emphasizes the importance of transcript-level annotation to uncover the roles of specific transcript isoforms. We propose that understanding the mechanisms of lncRNA in pathological processes requires solving their structural motifs and interactomes. A complete lncRNA annotation first involves discriminating them from their coding counterparts and then predicting their functional motifs and target bio-molecules. Current in silico methods mainly perform primary-sequence-based discrimination using a reference model, limiting their comprehensiveness and generalizability. We demonstrate that integrating secondary structure and interactome information, in addition to using transcript sequence, enables a comprehensive functional annotation. Annotating lncRNA for newly sequenced species is challenging due to inconsistencies in functional annotations, specialized computational techniques, limited accessibility to source code, and the shortcomings of reference-based methods for cross-species predictions. To address these challenges, we developed a pipeline for identifying and annotating transcript sequences at the isoform level. We demonstrate the effectiveness of the pipeline by comprehensively annotating the lncRNA associated with two specific disease groups. The source code of our pipeline is available under the MIT licensefor local use by researchers to make new predictions using the pre-trained models or to re-train models on new sequence datasets. Non-technical users can access the pipeline through a web server setup.

Summation of visual motion across eye movements reflects a nonspatial decision mechanism.

Human vision remains perceptually stable even though retinal inputs change rapidly with each eye movement. Although the neural basis of visual stability remains unknown, a recent psychophysical study pointed to the existence of visual feature-representations anchored in environmental rather than retinal coordinates (e.g., "spatiotopic" receptive fields; Melcher and Morrone, 2003). In that study, sensitivity to a moving stimulus presented after a saccadic eye movement was enhanced when preceded by another moving stimulus at the same spatial location before the saccade. The finding is consistent with spatiotopic sensory integration, but it could also have arisen from a probabilistic improvement in performance due to the presence of more than one motion signal for the perceptual decision. Here we show that this statistical advantage accounts completely for summation effects in this task. We first demonstrate that measurements of summation are confounded by noise related to an observer's uncertainty about motion onset times. When this uncertainty is minimized, comparable summation is observed regardless of whether two motion signals occupy the same or different locations in space, and whether they contain the same or opposite directions of motion. These results are incompatible with the tuning properties of motion-sensitive sensory neurons and provide no evidence for a spatiotopic representation of visual motion. Instead, summation in this context reflects a decision mechanism that uses abstract representations of sensory events to optimize choice behavior.

Weighted integration of visual position information.

The ability to localize visual objects is a fundamental component of human behavior and requires the integration of position information from object components. The retinal eccentricity of a stimulus and the locus of spatial attention can affect object localization, but it is unclear whether these factors alter the global localization of the object, the localization of object components, or both. We used psychophysical methods in humans to quantify behavioral responses in a centroid estimation task. Subjects located the centroid of briefly presented random dot patterns (RDPs). A peripheral cue was used to bias attention toward one side of the display. We found that although subjects were able to localize centroid positions reliably, they typically had a bias toward the fovea and a shift toward the locus of attention. We compared quantitative models that explain these effects either as biased global localization of the RDPs or as anisotropic integration of weighted dot component positions. A model that allowed retinal eccentricity and spatial attention to alter the weights assigned to individual dot positions best explained subjects' performance. These results show that global position perception depends on both the retinal eccentricity of stimulus components and their positions relative to the current locus of attention.

Multi-segment phase coupling to oscillatory visual drive.

BACKGROUND: It has been shown that humans adapt their postural sway to oscillatory, visually simulated self-motion. However, little is still known about the way individual body segments contribute to this adjustment of body sway and how this contribution varies with different environmental conditions. RESEARCH QUESTION: How do the centre of pressure (COP) and individual body segments phase-lock to a sinusoidal visual drive depending on the frequency of stimulation? METHODS: In this study, we introduce phase coupling as a method for assessing full body motion in response to visual stimuli presented in virtual reality (VR). 12 participants (mean age: 31 ±â€¯9 years) stood inside a virtual tunnel which oscillated sinusoidally in the anterior-posterior direction at a frequency of 0.2 Hz, 0.8 Hz or 1.2 Hz. Primary outcome measures were the trajectories of their COP as well as of 25 body segments obtained by a motion tracking system. RESULTS: Subjects significantly coupled the phase of their COP and body segments to the visual drive. Our analysis yielded significant phase coupling of the COP to the stimulus for all tested frequencies. The phase coupling of body segments revealed a shift in postural response as a function of frequency. At the low frequency of 0.2 Hz, we found strong and significant phase coupling homogeneously distributed across the body. At the higher frequencies of 0.8 Hz and 1.2 Hz, however, overall phase coupling became weaker and was centred around the lower torso and hip segments. SIGNIFICANCE: Information on how the visual percept of self-motion affects balance control is crucial for understanding visuomotor processing in health and disease. Our setup and methods constitute a reliable tool for assessing perturbed balance control, which can be utilized in future clinical trials.

A Stable Visual World in Primate Primary Visual Cortex.

Humans and other primates rely on eye movements to explore visual scenes and to track moving objects. As a result, the image that is projected onto the retina-and propagated throughout the visual cortical hierarchy-is almost constantly changing and makes little sense without taking into account the momentary direction of gaze. How is this achieved in the visual system? Here, we show that in primary visual cortex (V1), the earliest stage of cortical vision, neural representations carry an embedded "eye tracker" that signals the direction of gaze associated with each image. Using chronically implanted multi-electrode arrays, we recorded the activity of neurons in area V1 of macaque monkeys during tasks requiring fast (exploratory) and slow (pursuit) eye movements. Neurons were stimulated with flickering, full-field luminance noise at all times. As in previous studies, we observed neurons that were sensitive to gaze direction during fixation, despite comparable stimulation of their receptive fields. We trained a decoder to translate neural activity into metric estimates of gaze direction. This decoded signal tracked the eye accurately not only during fixation but also during fast and slow eye movements. After a fast eye movement, the eye-position signal arrived in V1 at approximately the same time at which the new visual information arrived from the retina. Using simulations, we show that this V1 eye-position signal could be used to take into account the sensory consequences of eye movements and map the fleeting positions of objects on the retina onto their stable position in the world.

Short-Term Attractive Tilt Aftereffects Predicted by a Recurrent Network Model of Primary Visual Cortex.

Adaptation is a multi-faceted phenomenon that is of interest in terms of both its function and its potential to reveal underlying neural processing. Many behavioral studies have shown that after exposure to an oriented adapter the perceived orientation of a subsequent test is repulsed away from the orientation of the adapter. This is the well-known Tilt Aftereffect (TAE). Recently, we showed that the dynamics of recurrently connected networks may contribute substantially to the neural changes induced by adaptation, especially on short time scales. Here we extended the network model and made the novel behavioral prediction that the TAE should be attractive, not repulsive, on a time scale of a few 100 ms. Our experiments, using a novel adaptation protocol that specifically targeted adaptation on a short time scale, confirmed this prediction. These results support our hypothesis that recurrent network dynamics may contribute to short-term adaptation. More broadly, they show that understanding the neural processing of visual inputs that change on the time scale of a typical fixation requires a detailed analysis of not only the intrinsic properties of neurons, but also the slow and complex dynamics that emerge from their recurrent connectivity. We argue that this is but one example of how even simple recurrent networks can underlie surprisingly complex information processing, and are involved in rudimentary forms of memory, spatio-temporal integration, and signal amplification.

Metacognitive monitoring and control in visual change detection: Implications for situation awareness and cognitive control.

Metacognitive monitoring and control of situation awareness (SA) are important for a range of safety-critical roles (e.g., air traffic control, military command and control). We examined the factors affecting these processes using a visual change detection task that included representative tactical displays. SA was assessed by asking novice observers to detect changes to a tactical display. Metacognitive monitoring was assessed by asking observers to estimate the probability that they would correctly detect a change, either after study of the display and before the change (judgement of learning; JOL) or after the change and detection response (judgement of performance; JOP). In Experiment 1, observers failed to detect some changes to the display, indicating imperfect SA, but JOPs were reasonably well calibrated to objective performance. Experiment 2 examined JOLs and JOPs in two task contexts: with study-time limits imposed by the task or with self-pacing to meet specified performance targets. JOPs were well calibrated in both conditions as were JOLs for high performance targets. In summary, observers had limited SA, but good insight about their performance and learning for high performance targets and allocated study time appropriately.

Adaptation without Plasticity.

Sensory adaptation is a phenomenon in which neurons are affected not only by their immediate input but also by the sequence of preceding inputs. In visual cortex, for example, neurons shift their preferred orientation after exposure to an oriented stimulus. This adaptation is traditionally attributed to plasticity. We show that a recurrent network generates tuning curve shifts observed in cat and macaque visual cortex, even when all synaptic weights and intrinsic properties in the model are fixed. This demonstrates that, in a recurrent network, adaptation on timescales of hundreds of milliseconds does not require plasticity. Given the ubiquity of recurrent connections, this phenomenon likely contributes to responses observed across cortex and shows that plasticity cannot be inferred solely from changes in tuning on these timescales. More broadly, our findings show that recurrent connections can endow a network with a powerful mechanism to store and integrate recent contextual information.

The Dorsal Visual System Predicts Future and Remembers Past Eye Position.

Eye movements are essential to primate vision but introduce potentially disruptive displacements of the retinal image. To maintain stable vision, the brain is thought to rely on neurons that carry both visual signals and information about the current direction of gaze in their firing rates. We have shown previously that these neurons provide an accurate representation of eye position during fixation, but whether they are updated fast enough during saccadic eye movements to support real-time vision remains controversial. Here we show that not only do these neurons carry a fast and accurate eye-position signal, but also that they support in parallel a range of time-lagged variants, including predictive and post dictive signals. We recorded extracellular activity in four areas of the macaque dorsal visual cortex during a saccade task, including the lateral and ventral intraparietal areas (LIP, VIP), and the middle temporal (MT) and medial superior temporal (MST) areas. As reported previously, neurons showed tonic eye-position-related activity during fixation. In addition, they showed a variety of transient changes in activity around the time of saccades, including relative suppression, enhancement, and pre-saccadic bursts for one saccade direction over another. We show that a hypothetical neuron that pools this rich population activity through a weighted sum can produce an output that mimics the true spatiotemporal dynamics of the eye. Further, with different pooling weights, this downstream eye position signal (EPS) could be updated long before (<100 ms) or after (<200 ms) an eye movement. The results suggest a flexible coding scheme in which downstream computations have access to past, current, and future eye positions simultaneously, providing a basis for visual stability and delay-free visually-guided behavior.

Amygdala responses to fearful and happy facial expressions under conditions of binocular suppression.

The human amygdala plays a crucial role in processing affective information conveyed by sensory stimuli. Facial expressions of fear and anger, which both signal potential threat to an observer, result in significant increases in amygdala activity, even when the faces are unattended or presented briefly and masked. It has been suggested that afferent signals from the retina travel to the amygdala via separate cortical and subcortical pathways, with the subcortical pathway underlying unconscious processing. Here we exploited the phenomenon of binocular rivalry to induce complete suppression of affective face stimuli presented to one eye. Twelve participants viewed brief, rivalrous visual displays in which a fearful, happy, or neutral face was presented to one eye while a house was presented simultaneously to the other. We used functional magnetic resonance imaging to study activation in the amygdala and extrastriate visual areas for consciously perceived versus suppressed face and house stimuli. Activation within the fusiform and parahippocampal gyri increased significantly for perceived versus suppressed faces and houses, respectively. Amygdala activation increased bilaterally in response to fearful versus neutral faces, regardless of whether the face was perceived consciously or suppressed because of binocular rivalry. Amygdala activity also increased significantly for happy versus neutral faces, but only when the face was suppressed. This activation pattern suggests that the amygdala has a limited capacity to differentiate between specific facial expressions when it must rely on information received via a subcortical route. We suggest that this limited capacity reflects a tradeoff between specificity and speed of processing.

Neuroscience: Tiny Eye Movements Link Vision and Attention.

Eye movements are essential to human vision. A new study shows that the tiny eye movements we make while holding our gaze on a point of interest are associated with brief, attention-like changes in the sensitivity of visual neurons.

The (un)suitability of modern liquid crystal displays (LCDs) for vision research.

Psychophysical and physiological studies of vision have traditionally used cathode ray tube (CRT) monitors to present stimuli. These monitors are no longer easily available, and liquid crystal display (LCD) technology is continually improving; therefore, we characterized a number of LCD monitors to determine if newer models are suitable replacements for CRTs in the laboratory. We compared the spatial and temporal characteristics of a CRT with five LCDs, including monitors designed with vision science in mind (ViewPixx and Display++), "prosumer" gaming monitors, and a consumer-grade LCD. All monitors had sufficient contrast, luminance range and reliability to support basic vision experiments with static images. However, the luminance of all LCDs depended strongly on viewing angle, which in combination with the poor spatial uniformity of all monitors except the VPixx, caused up to 80% drops in effective luminance in the periphery during central fixation. Further, all monitors showed significant spatial dependence, as the luminance of one area was modulated by the luminance of other areas. These spatial imperfections are most pronounced for experiments that use large or peripheral visual stimuli. In the temporal domain, the gaming LCDs were unable to generate reliable luminance patterns; one was unable to reach the requested luminance within a single frame whereas in the other the luminance of one frame affected the luminance of the next frame. The VPixx and Display++ were less affected by these problems, and had good temporal properties provided stimuli were presented for 2 or more frames. Of the consumer-grade and gaming displays tested, and if problems with spatial uniformity are taken into account, the Eizo FG2421 is the most suitable alternative to CRTs. The specialized ViewPixx performed best among all the tested LCDs, followed closely by the Display++; both are good replacements for a CRT, provided their spatial imperfections are considered.

Prismatic adaptation reduces biased temporal order judgements in spatial neglect.

Visuomotor adaptation to rightward-deviating optical-wedge prisms reduces the clinical manifestations of spatial neglect after right hemisphere damage. We investigated whether this beneficial effect of prism adaptation is due to attenuation of the ipsilesional attentional bias that is common in spatial neglect. Five right hemisphere patients performed visual temporal order judgements before and after visuomotor adaptation to 15 degrees rightward-deviating prisms. The magnitude of patients' ipsilesional attentional bias on the temporal order judgement task was significantly reduced following adaptation. By contrast, the temporal order judgements of normal participants did not change following adaptation to either leftward- or rightward-deviating prisms. The findings suggest that prism adaptation helps to rebalance the distribution of spatial attention following right hemisphere damage.

Prism adaptation and spatial attention: a study of visual search in normals and patients with unilateral neglect.

Visuomotor adaptation to a prism-induced lateral displacement of the visual field induces mild perceptual biases in healthy individuals and improves symptoms of unilateral neglect. The present study employed a speeded visual search task to test the hypothesis that prism adaptation induces an adaptive redistribution of selective spatial attention. In Experiment 1, 32 neurologically healthy, right-handed participants were adapted to a 150 prism-induced lateral (left or right) displacement of the visual field. Spatial attention was measured by search time and error-rate in unique-feature ("preattentive") and feature-absent ("serial") visual search tasks, before and after prism adaptation. The single target appeared at different locations within arrays of 12, 24 or 48 items. Contrary to the attentional hypothesis, the pattern of search performance across the display remained unchanged following prism adaptation. In Experiment 2, we tested four patients with unilateral right hemisphere damage on the visual search tasks, before and after adaptation to 15 degrees rightward-displacing prisms. All four patients showed a pathological gradient of spatial attention toward the ipsilesional side prior to adaptation. Consistent with the results from Experiment 1, the gradient in search performance shown by the patients did not change following prism adaptation. Taken together, these findings suggest that the perceptual aftereffects in normals and amelioration of unilateral neglect following prism adaptation are not mediated by an adaptive redistribution of spatial attention.

Dynamics of eye-position signals in the dorsal visual system.

BACKGROUND: Many visual areas of the primate brain contain signals related to the current position of the eyes in the orbit. These cortical eye-position signals are thought to underlie the transformation of retinal input-which changes with every eye movement-into a stable representation of visual space. For this coding scheme to work, such signals would need to be updated fast enough to keep up with the eye during normal exploratory behavior. We examined the dynamics of cortical eye-position signals in four dorsal visual areas of the macaque brain: the lateral and ventral intraparietal areas (LIP; VIP), the middle temporal area (MT), and the medial-superior temporal area (MST). We recorded extracellular activity of single neurons while the animal performed sequences of fixations and saccades in darkness. RESULTS: The data show that eye-position signals are updated predictively, such that the representation shifts in the direction of a saccade prior to (<100 ms) the actual eye movement. Despite this early start, eye-position signals remain inaccurate until shortly after (10-150 ms) the eye movement. By using simulated behavioral experiments, we show that this brief misrepresentation of eye position provides a neural explanation for the psychophysical phenomenon of perisaccadic mislocalization, in which observers misperceive the positions of visual targets flashed around the time of saccadic eye movements. CONCLUSIONS: Together, these results suggest that eye-position signals in the dorsal visual system are updated rapidly across eye movements and play a direct role in perceptual localization, even when they are erroneous.