Pathway-selective optogenetics reveals the functional anatomy of top-down attentional modulation in the macaque visual cortex.

Spatial attention represents a powerful top-down influence on sensory responses in primate visual cortical areas. The frontal eye field (FEF) has emerged as a key candidate area for the source of this modulation. However, it is unclear whether the FEF exerts its effects via its direct axonal projections to visual areas or indirectly through other brain areas and whether the FEF affects both the enhancement of attended and the suppression of unattended sensory responses. We used pathway-selective optogenetics in rhesus macaques performing a spatial attention task to inhibit the direct input from the FEF to area MT, an area along the dorsal visual pathway specialized for the processing of visual motion information. Our results show that the optogenetic inhibition of the FEF input specifically reduces attentional modulation in MT by about a third without affecting the neurons' sensory response component. We find that the direct FEF-to-MT pathway contributes to both the enhanced processing of target stimuli and the suppression of distractors. The FEF, thus, selectively modulates firing rates in visual area MT, and it does so via its direct axonal projections.

Public controversy and citizens' attitude formation about animal research: A case for scholarship and recommendations on conflicts at the science-society interface.

Activist groups attack animal research and put scientists and their institutions under pressure, whereas scientists often remain silent. We report an interdisciplinary research project driven by a communication science perspective on how citizens respond to news reports about animal research (3 experiments, overall N = 765) and a German science-initiated information platform ("Tierversuche verstehen"; controlled user study, N = 100). Findings demonstrate that a critical journalist perspective within neutral, two-sided news reports (e.g., skeptical expert statements or images of suffering animals) does not affect citizen opinion strongly. Information media provided by scientific institutions seem to be welcomed even by citizens who hold critical prior attitudes. From these results, we develop a set of recommendations for future public communication of animal research that builds on best practices in organizational and crisis communication. These suggestions are intended to empower animal researchers to actively participate in public debate to support citizens' informed attitude formation.

Phase of neural oscillations as a reference frame for attention-based routing in visual cortex.

Selective attention allows the brain to efficiently process the image projected onto the retina, selectively focusing neural processing resources on behaviorally relevant visual information. While previous studies have documented the crucial role of the action potential rate of single neurons in relaying such information, little is known about how the activity of single neurons relative to their neighboring network contributes to the efficient representation of attended stimuli and transmission of this information to downstream areas. Here, we show in the dorsal visual pathway of monkeys (medial superior temporal area) that neurons fire spikes preferentially at a specific phase of the ongoing population beta (∼20 Hz) oscillations of the surrounding local network. This preferred spiking phase shifts towards a later phase when monkeys selectively attend towards (rather than away from) the receptive field of the neuron. This shift of the locking phase is positively correlated with the speed at which animals report a visual change. Furthermore, our computational modeling suggests that neural networks can manipulate the preferred phase of coupling by imposing differential synaptic delays on postsynaptic potentials. This distinction between the locking phase of neurons activated by the spatially attended stimulus vs. that of neurons activated by the unattended stimulus, may enable the neural system to discriminate relevant from irrelevant sensory inputs and consequently filter out distracting stimuli information by aligning the spikes which convey relevant/irrelevant information to distinct phases linked to periods of better/worse perceptual sensitivity for higher cortices. This strategy may be used to reserve the narrow windows of highest perceptual efficacy to the processing of the most behaviorally relevant information, ensuring highly efficient responses to attended sensory events.

Orchestration of saccadic eye-movements by brain rhythms in macaque Frontal Eye Field.

Visual perception has been suggested to operate on temporal 'chunks' of sensory input, rather than on a continuous stream of visual information. Saccadic eye movements impose a natural rhythm on the sensory input, as periods of steady fixation between these rapid eye movements provide distinct temporal segments of information. Ideally, the timing of saccades should be precisely locked to the brain's rhythms of information processing. Here, we investigated such locking of saccades to rhythmic neural activity in rhesus monkeys performing a visual foraging task. We found that saccades are phase-locked to local field potential oscillations (especially, 9-22 Hz) in the Frontal Eye Field, with the phase of oscillations predictive of the saccade onset as early as 100 ms prior to these movements. Our data also indicate a functional role of this phase-locking in determining the direction of saccades. These findings show a tight-and likely important-link between oscillatory brain activity and rhythmic behavior that imposes a rhythmic temporal structure on sensory input, such as saccadic eye movements.

Effect of attention on human direction-discrimination thresholds at iso-eccentric locations in the visual field: A registered report protocol.

Human visual perceptual performance is strongly dependent on a given stimulus' distance from the line of sight, i.e. its eccentricity. In addition, multiple studies have shown a dependence on a stimulus' angular position relative to the fovea. In humans, the resulting spatial profile of perceptual performance (the "performance field") typically shows better performance near the lower vertical meridian, compared to the upper vertical meridian, and better performance near the horizontal meridian compared to the vertical meridian. Predominantly, these variations have been interpreted as sensory inhomogeneities. But it has also been shown that they are modulated by the allocation of spatial attention, either homogeneously elevating performance or compensating for the sensory inhomogeneities. Here, we propose a study protocol for pre-registration to investigate such interactions between sensory and attentional effects. First, we will determine performance fields for time-dependent, dynamic stimuli, namely the direction discrimination of moving random dot patterns. Then, we will establish whether directing focal attention to a particular stimulus location differentially improves thresholds compared to a distributed attention condition.

A Touchscreen-Based, Multiple-Choice Approach to Cognitive Enrichment of Captive Rhesus Macaques (Macaca mulatta).

Research on the psychological and physiological well-being of captive animals has focused on investigating different types of social and structural enrichment. Consequently, cognitive enrichment has been understudied, despite the promising external validity, comparability, and applicability. As we aim to fill this gap, we developed an interactive, multiple-choice interface for cage-mounted touchscreen devices that rhesus monkeys (Macaca mulatta) can freely interact with, from within their home enclosure at the Cognitive Neuroscience Laboratory of the German Primate Center. The multiple-choice interface offers interchangeable activities that animals can choose and switch between. We found that all 16 captive rhesus macaques tested consistently engaged with the multiple-choice interface across 6 weekly sessions, with 11 of them exhibiting clear task preferences, and displaying proficiency in performing the selected tasks. Our approach does not require social separation or dietary restriction and is intended to increase animals' sense of competence and agency by providing them with more control over their environment. Thanks to the high level of automation, our multiple-choice interface can be easily incorporated as a standard cognitive enrichment practice across different facilities and institutes working with captive animals, particularly non-human primates. We believe that the multiple-choice interface is a sustainable, scalable, and pragmatic protocol for enhancing cognitive well-being and animal welfare in captivity.

Human and macaque pairs employ different coordination strategies in a transparent decision game.

Many real-world decisions in social contexts are made while observing a partner's actions. To study dynamic interactions during such decisions, we developed a setup where two agents seated face-to-face to engage in game-theoretical tasks on a shared transparent touchscreen display ('transparent games'). We compared human and macaque pairs in a transparent version of the coordination game 'Bach-or-Stravinsky', which entails a conflict about which of two individually-preferred opposing options to choose to achieve coordination. Most human pairs developed coordinated behavior and adopted dynamic turn-taking to equalize the payoffs. All macaque pairs converged on simpler, static coordination. Remarkably, two animals learned to coordinate dynamically after training with a human confederate. This pair selected the faster agent's preferred option, exhibiting turn-taking behavior that was captured by modeling the visibility of the partner's action before one's own movement. Such competitive turn-taking was unlike the prosocial turn-taking in humans, who equally often initiated switches to and from their preferred option. Thus, the dynamic coordination is not restricted to humans but can occur on the background of different social attitudes and cognitive capacities in rhesus monkeys. Overall, our results illustrate how action visibility promotes the emergence and maintenance of coordination when agents can observe and time their mutual actions.

To live with others is to make concessions. You may want to go to the movies tonight, but your partner may prefer the theatre: reaching a mutually desirable goal ­ that is, spending time together ­ requires adjusting your preferences to theirs. Many other social species also make such decisions, in particular monkeys that live in large groups. Conceptually, these interactions are known as coordination games. In such scenarios, two players must coordinate their actions to attain a coveted reward, but they must also resolve a conflict about who gets the larger share. This makes the joint strategy non-trivial, and different pairs of players might resort to different strategies. In the laboratory, coordination games are often tested in settings which do not allow participants to monitor each other's behaviors as they make these complex choices. In real life, however, individuals making a joint decision can often observe each other and receive immediate feedback. In response, Moeller et al. developed a new way to test coordination games that allows more realistic social interactions. In their setup, two participants face each other and use a shared see-through touchscreen to perform a task. This new design was used to test how humans and macaque monkeys solved a simplified version of the 'Bach or Stravinsky' coordination game, which involves choosing between a red and blue target on the screen. Players in a pair had been trained to 'prefer' opposite colors. In this game, collaboration is beneficial (both individuals get a better prize if they choose the same color) but also creates unfairness (the reward is higher for the participant whose 'favorite' color is selected). When paired up, both humans and monkeys learned to collaborate and to go for the same color (or, in some monkey pairs, the same side of the screen). However, only humans took turns selecting red or blue so that players could alternate getting the highest reward. Monkeys usually settled on one color throughout the game, unless they had learned the 'turn-taking' strategy from a human partner; in that case, the color chosen in each trial was typically determined by the monkey who was the faster to move. These experiments show how monkeys and humans use visual information about their partner's actions to coordinate their choices, paving the way for further decision-making studies that accurately reflect how interactions unfold in real life. Moeller et al. expect that this will help to understand how cooperation and competition emerge in these two species, including how direct face-to-face contact, or lack thereof in some aspects of our modern world, shapes our social behavior.

Home-Enclosure-Based Behavioral and Wireless Neural Recording Setup for Unrestrained Rhesus Macaques.

Electrophysiological studies with behaving nonhuman primates often require the separation of animals from their social group as well as partial movement restraint to perform well-controlled experiments. When the research goal per se does not mandate constraining the animals' movements, there are often still experimental needs imposed by tethered data acquisition. Recent technological advances meanwhile allow wireless neurophysiological recordings at high band-width in limited-size enclosures. Here, we demonstrate wireless neural recordings at single unit resolution from unrestrained rhesus macaques while they performed self-paced, structured visuomotor tasks on our custom-built, stand-alone touchscreen system [eXperimental Behavioral Instrument (XBI)] in their home environment. We were able to successfully characterize neural tuning to task parameters, such as visuo-spatial selectivity during movement planning and execution, as expected from existing findings obtained via setup-based neurophysiology recordings. We conclude that when movement restraint and/or a highly controlled, insulated environment are not necessary for scientific reasons, cage-based wireless neural recordings are a viable option. We propose an approach that allows the animals to engage in a self-paced manner with our XBI device, both for fully automatized training and cognitive testing, as well as neural data acquisition in their familiar environment, maintaining auditory and sometimes visual contact with their conspecifics.

The Dot-Probe Attention Bias Task as a Method to Assess Psychological Well-Being after Anesthesia: A Study with Adult Female Long-Tailed Macaques (Macaca fascicularis).

Understanding the impact routine research and laboratory procedures have on animals is crucial to improving their well-being and to the success and reproducibility of the research they are involved in. Cognitive measures of welfare offer insight into animals' internal psychological state, but require validation. Attention bias - the tendency to attend to one type of information over another - is a cognitive phenomenon documented in humans and animals that is known to be modulated by affective state (i.e., emotions). Hence, changes in attention bias may offer researchers a deeper perspective of their animals' psychological well-being. The dot-probe task is an established method for quantifying attention bias in humans (by measuring reaction time to a dot-probe replacing pairs of stimuli), but has yet to be validated in animals. We developed a dot-probe task for long-tailed macaques (Macaca fascicularis) to determine if the task can detect changes in attention bias following anesthesia, a context known to modulate attention and trigger physiological arousal in macaques. Our task included the following features: stimulus pairs of threatening and neutral facial expressions of conspecifics and their scrambled counterparts, two stimuli durations (100 and 1,000 ms), and counterbalancing of the dot-probe's position on the touchscreen (left and right) and location relative to the threatening stimulus. We tested 8 group-housed adult females on different days relative to being anesthetized (baseline and 1-, 3-, 7-, and 14-days after). At baseline, monkeys were vigilant to threatening content when stimulus pairs were presented for 100 ms, but not 1,000 ms. On the day immediately following anesthesia, we found evidence that attention bias changed to an avoidance of threatening content. Attention bias returned to threat vigilance by the third day postanesthesia and remained so up to the last day of testing (14-days after anesthesia). We also found that attention bias was independent of the type of stimuli pair (i.e., whole face vs. scrambled counterparts), suggesting that the scrambled stimuli retained aspects of the original stimuli. Nevertheless, whole faces were more salient to the monkeys as responses to these trials were generally slower than to scrambled stimulus pairs. Overall, our study suggests it is feasible to detect changes in attention bias following anesthesia using the dot-probe task in nonhuman primates. Our results also reveal important aspects of stimulus preparation and experimental design.

Attention to visual motion suppresses neuronal and behavioral sensitivity in nearby feature space.

BACKGROUND: Feature-based attention prioritizes the processing of the attended feature while strongly suppressing the processing of nearby ones. This creates a non-linearity or "attentional suppressive surround" predicted by the Selective Tuning model of visual attention. However, previously reported effects of feature-based attention on neuronal responses are linear, e.g., feature-similarity gain. Here, we investigated this apparent contradiction by neurophysiological and psychophysical approaches. RESULTS: Responses of motion direction-selective neurons in area MT/MST of monkeys were recorded during a motion task. When attention was allocated to a stimulus moving in the neurons' preferred direction, response tuning curves showed its minimum for directions 60-90° away from the preferred direction, an attentional suppressive surround. This effect was modeled via the interaction of two Gaussian fields representing excitatory narrowly tuned and inhibitory widely tuned inputs into a neuron, with feature-based attention predominantly increasing the gain of inhibitory inputs. We further showed using a motion repulsion paradigm in humans that feature-based attention produces a similar non-linearity on motion discrimination performance. CONCLUSIONS: Our results link the gain modulation of neuronal inputs and tuning curves examined through the feature-similarity gain lens to the attentional impact on neural population responses predicted by the Selective Tuning model, providing a unified framework for the documented effects of feature-based attention on neuronal responses and behavior.

Electrophysiological dataset from macaque visual cortical area MST in response to a novel motion stimulus.

Establishing the cortical neural representation of visual stimuli is a central challenge of systems neuroscience. Publicly available data would allow a broad range of scientific analyses and hypothesis testing, but are rare and largely focused on the early visual system. To address the shortage of open data from higher visual areas, we provide a comprehensive dataset from a neurophysiology study in macaque monkey visual cortex that includes a complete record of extracellular action potential recordings from the extrastriate medial superior temporal (MST) area, behavioral data, and detailed stimulus records. It includes spiking activity of 172 single neurons recorded in 139 sessions from 4 hemispheres of 3 rhesus macaque monkeys. The data was collected across 3 experiments, designed to characterize the response properties of MST neurons to complex motion stimuli. This data can be used to elucidate visual information processing at the level of single neurons in a high-level area of primate visual cortex. Providing open access to this dataset also promotes the 3R-principle of responsible animal research.

Dynamic coupling of oscillatory neural activity and its roles in visual attention.

Oscillatory neural activity is believed to have a central role in information processing in the mammalian brain. While early studies often focussed on the function of individual frequency bands, there is emerging appreciation for the role of simultaneous activity in many distinct frequency bands and the interactions between them in high-level cognitive functions. Here, we focus on the role of cross-frequency coupling (CFC) in visual attention. First, we propose a framework that reconciles previous contrasting findings, showing how CFC could have a functional role on both intra- and interareal scales. Second, we outline how CFC between distinct frequency bands could label different submodalities of sensory information. Overall, our scheme provides a novel perspective of how interfrequency interaction contributes to efficient and dynamic processing of information across the brain.

The development of visual attention in early infancy: Insights from a free-viewing paradigm.

Theories of visual attention suggest a cascading development of subfunctions such as alertness, spatial orientation, attention to object features, and endogenous control. Here, we aimed to track infants' visual developmental steps from a primarily exogenously to more endogenously controlled processing style during their first months of life. In this repeated measures study, 51 infants participated in seven fortnightly assessments at postterm ages of 4-16 weeks. Infants were presented with the same set of static and dynamic paired comparison stimuli in each assessment. Visual behavior was evaluated by a newly introduced scoring scheme. Our results confirmed the suggested visual developmental hierarchy and clearly demonstrated the suitability of our scoring scheme for documenting developmental changes in visual attention during early infancy. Besides the general ontogenetic course of development, we also discuss intra- and interindividual differences which may affect single assessments, and highlight the importance of repeated measurements for reliable evaluation of developmental changes.

Assessing cognitive flexibility in humans and rhesus macaques with visual motion and neutral distractors.

Introduction: Cognitive flexibility is the ability of an individual to make behavioral adjustments in response to internal and/or external changes. While it has been reported in a wide variety of species, established paradigms to assess cognitive flexibility vary between humans and non-human animals, making systematic comparisons difficult to interpret. Methods: We developed a computer-based paradigm to assess cognitive flexibility in humans and non-human primates. Our paradigm (1) uses a classical reversal learning structure in combination with a set-shifting approach (4 stimuli and 3 rules) to assess flexibility at various levels; (2) it employs the use of motion as one of three possible contextual rules; (3) it comprises elements that allow a foraging-like and random interaction, i.e., instances where the animals operate the task without following a strategy, to potentially minimize frustration in favor of a more positive engagement. Results and Discussion: We show that motion can be used as a feature dimension (in addition to commonly used shape and color) to assess cognitive flexibility. Due to the way motion is processed in the primate brain, we argue that this dimension is an ideal candidate in situations where a non-binary rule set is needed and where participants might not be able to fully grasp other visual information of the stimulus (e.g., quantity in Wisconsin Card Sorting Test). All participants in our experiment flexibly shifted to and from motion-based rules as well as color- and shape-based rules, but did so with different proficiencies. Overall, we believe that with such approach it is possible to better characterize the evolution of cognitive flexibility in primates, as well as to develop more efficient tools to diagnose and treat various executive function deficits.

A Deep Learning-Based Approach to Video-Based Eye Tracking for Human Psychophysics.

Real-time gaze tracking provides crucial input to psychophysics studies and neuromarketing applications. Many of the modern eye-tracking solutions are expensive mainly due to the high-end processing hardware specialized for processing infrared-camera pictures. Here, we introduce a deep learning-based approach which uses the video frames of low-cost web cameras. Using DeepLabCut (DLC), an open-source toolbox for extracting points of interest from videos, we obtained facial landmarks critical to gaze location and estimated the point of gaze on a computer screen via a shallow neural network. Tested for three extreme poses, this architecture reached a median error of about one degree of visual angle. Our results contribute to the growing field of deep-learning approaches to eye-tracking, laying the foundation for further investigation by researchers in psychophysics or neuromarketing.

Comparing the influence of stimulus size and contrast on the perception of moving gratings and random dot patterns-A registered report protocol.

Modern accounts of visual motion processing in the primate brain emphasize a hierarchy of different regions within the dorsal visual pathway, especially primary visual cortex (V1) and the middle temporal area (MT). However, recent studies have called the idea of a processing pipeline with fixed contributions to motion perception from each area into doubt. Instead, the role that each area plays appears to depend on properties of the stimulus as well as perceptual history. We propose to test this hypothesis in human subjects by comparing motion perception of two commonly used stimulus types: drifting sinusoidal gratings (DSGs) and random dot patterns (RDPs). To avoid potential biases in our approach we are pre-registering our study. We will compare the effects of size and contrast levels on the perception of the direction of motion for DSGs and RDPs. In addition, based on intriguing results in a pilot study, we will also explore the effects of a post-stimulus mask. Our approach will offer valuable insights into how motion is processed by the visual system and guide further behavioral and neurophysiological research.

Cholinergic manipulations affect sensory responses but not attentional enhancement in macaque MT.

BACKGROUND: Attentional modulation in the visual cortex of primates is characterized by multiplicative changes of sensory responses with changes in the attentional state of the animal. The cholinergic system has been linked to such gain changes in V1. Here, we aim to determine if a similar link exists in macaque area MT. While rhesus monkeys performed a top-down spatial attention task, we locally injected a cholinergic agonist or antagonist and recorded single-cell activity. RESULTS: Although we confirmed cholinergic influences on sensory responses, there was no additional cholinergic effect on the attentional gain changes. Neither a muscarinic blockage nor a local increase in acetylcholine led to a significant change in the magnitude of spatial attention effects on firing rates. CONCLUSIONS: This suggests that the cellular mechanisms of attentional modulation in the extrastriate cortex cannot be directly inferred from those in the primary visual cortex.

Primate extrastriate cortical area MST: a gateway between sensation and cognition.

Primate visual cortex consists of dozens of distinct brain areas, each providing a highly specialized component to the sophisticated task of encoding the incoming sensory information and creating a representation of our visual environment that underlies our perception and action. One such area is the medial superior temporal cortex (MST), a motion-sensitive, direction-selective part of the primate visual cortex. It receives most of its input from the middle temporal (MT) area, but MST cells have larger receptive fields and respond to more complex motion patterns. The finding that MST cells are tuned for optic flow patterns has led to the suggestion that the area plays an important role in the perception of self-motion. This hypothesis has received further support from studies showing that some MST cells also respond selectively to vestibular cues. Furthermore, the area is part of a network that controls the planning and execution of smooth pursuit eye movements and its activity is modulated by cognitive factors, such as attention and working memory. This review of more than 90 studies focuses on providing clarity of the heterogeneous findings on MST in the macaque cortex and its putative homolog in the human cortex. From this analysis of the unique anatomical and functional position in the hierarchy of areas and processing steps in primate visual cortex, MST emerges as a gateway between perception, cognition, and action planning. Given this pivotal role, this area represents an ideal model system for the transition from sensation to cognition.

A neural correlate of visual feature binding in primate lateral prefrontal cortex.

We effortlessly perceive visual objects as unified entities, despite the preferential encoding of their various visual features in separate cortical areas. A 'binding' process is assumed to be required for creating this unified percept, but the underlying neural mechanism and specific brain areas are poorly understood. We investigated 'feature-binding' across two feature dimensions, using a novel stimulus configuration, designed to disambiguate whether a given combination of color and motion direction is perceived as bound or unbound. In the "bound" condition, two behaviorally relevant features (color and motion) belong to the same object, while in the "unbound" condition they belong to different objects. We recorded local field potentials from the lateral prefrontal cortex (lPFC) in macaque monkeys that actively monitored the different stimulus configurations. Our data show a neural representation of visual feature binding especially in the 4-12 Hz frequency band and a transmission of binding information between different lPFC neural subpopulations. This information is linked to the animal's reaction time, suggesting a behavioral relevance of the binding information. Together, our results document the involvement of the prefrontal cortex, targeted by the dorsal and ventral visual streams, in binding visual features from different dimensions, in a process that includes a dynamic modulation of low frequency inter-regional communication.