An integrative, multiscale view on neural theories of consciousness.

How is conscious experience related to material brain processes? A variety of theories aiming to answer this age-old question have emerged from the recent surge in consciousness research, and some are now hotly debated. Although most researchers have so far focused on the development and validation of their preferred theory in relative isolation, this article, written by a group of scientists representing different theories, takes an alternative approach. Noting that various theories often try to explain different aspects or mechanistic levels of consciousness, we argue that the theories do not necessarily contradict each other. Instead, several of them may converge on fundamental neuronal mechanisms and be partly compatible and complementary, so that multiple theories can simultaneously contribute to our understanding. Here, we consider unifying, integration-oriented approaches that have so far been largely neglected, seeking to combine valuable elements from various theories.

A framework and resource for global collaboration in non-human primate neuroscience.

As science and technology evolve, there is an increasing need for promotion of international scientific exchange. Collaborations, while offering substantial opportunities for scientists and benefit to society, also present challenges for those working with animal models, such as non-human primates (NHPs). Diversity in regulation of animal research is sometimes mistaken for the absence of common international welfare standards. Here, the ethical and regulatory protocols for 13 countries that have guidelines in place for biomedical research involving NHPs were assessed with a focus on neuroscience. Review of the variability and similarity in trans-national NHP welfare regulations extended to countries in Asia, Europe and North America. A tabulated resource was established to advance solution-oriented discussions and scientific collaborations across borders. Our aim is to better inform the public and other stakeholders. Through cooperative efforts to identify and analyze information with reference to evidence-based discussion, the proposed key ingredients may help to shape and support a more informed, open framework. This framework and resource can be expanded further for biomedical research in other countries.

Inversion of pop-out for a distracting feature dimension in monkey visual cortex.

During visual search, it is important to reduce the interference of distracting objects in the scene. The neuronal responses elicited by the search target stimulus are typically enhanced. However, it is equally important to suppress the representations of distracting stimuli, especially if they are salient and capture attention. We trained monkeys to make an eye movement to a unique "pop-out" shape stimulus among an array of distracting stimuli. One of these distractors had a salient color that varied across trials and differed from the color of the other stimuli, causing it to also pop-out. The monkeys were able to select the pop-out shape target with high accuracy and actively avoided the pop-out color distractor. This behavioral pattern was reflected in the activity of neurons in area V4. Responses to the shape targets were enhanced, while the activity evoked by the pop-out color distractor was only briefly enhanced, directly followed by a sustained period of pronounced suppression. These behavioral and neuronal results demonstrate a cortical selection mechanism that rapidly inverts a pop-out signal to "pop-in" for an entire feature dimension thereby facilitating goal-directed visual search in the presence of salient distractors.

Population receptive fields in nonhuman primates from whole-brain fMRI and large-scale neurophysiology in visual cortex.

Population receptive field (pRF) modeling is a popular fMRI method to map the retinotopic organization of the human brain. While fMRI-based pRF maps are qualitatively similar to invasively recorded single-cell receptive fields in animals, it remains unclear what neuronal signal they represent. We addressed this question in awake nonhuman primates comparing whole-brain fMRI and large-scale neurophysiological recordings in areas V1 and V4 of the visual cortex. We examined the fits of several pRF models based on the fMRI blood-oxygen-level-dependent (BOLD) signal, multi-unit spiking activity (MUA), and local field potential (LFP) power in different frequency bands. We found that pRFs derived from BOLD-fMRI were most similar to MUA-pRFs in V1 and V4, while pRFs based on LFP gamma power also gave a good approximation. fMRI-based pRFs thus reliably reflect neuronal receptive field properties in the primate brain. In addition to our results in V1 and V4, the whole-brain fMRI measurements revealed retinotopic tuning in many other cortical and subcortical areas with a consistent increase in pRF size with increasing eccentricity, as well as a retinotopically specific deactivation of default mode network nodes similar to previous observations in humans.

Combining brain perturbation and neuroimaging in non-human primates.

Brain perturbation studies allow detailed causal inferences of behavioral and neural processes. Because the combination of brain perturbation methods and neural measurement techniques is inherently challenging, research in humans has predominantly focused on non-invasive, indirect brain perturbations, or neurological lesion studies. Non-human primates have been indispensable as a neurobiological system that is highly similar to humans while simultaneously being more experimentally tractable, allowing visualization of the functional and structural impact of systematic brain perturbation. This review considers the state of the art in non-human primate brain perturbation with a focus on approaches that can be combined with neuroimaging. We consider both non-reversible (lesions) and reversible or temporary perturbations such as electrical, pharmacological, optical, optogenetic, chemogenetic, pathway-selective, and ultrasound based interference methods. Method-specific considerations from the research and development community are offered to facilitate research in this field and support further innovations. We conclude by identifying novel avenues for further research and innovation and by highlighting the clinical translational potential of the methods.

A collaborative resource platform for non-human primate neuroimaging.

Neuroimaging non-human primates (NHPs) is a growing, yet highly specialized field of neuroscience. Resources that were primarily developed for human neuroimaging often need to be significantly adapted for use with NHPs or other animals, which has led to an abundance of custom, in-house solutions. In recent years, the global NHP neuroimaging community has made significant efforts to transform the field towards more open and collaborative practices. Here we present the PRIMatE Resource Exchange (PRIME-RE), a new collaborative online platform for NHP neuroimaging. PRIME-RE is a dynamic community-driven hub for the exchange of practical knowledge, specialized analytical tools, and open data repositories, specifically related to NHP neuroimaging. PRIME-RE caters to both researchers and developers who are either new to the field, looking to stay abreast of the latest developments, or seeking to collaboratively advance the field .

An Open Resource for Non-human Primate Imaging.

Non-human primate neuroimaging is a rapidly growing area of research that promises to transform and scale translational and cross-species comparative neuroscience. Unfortunately, the technological and methodological advances of the past two decades have outpaced the accrual of data, which is particularly challenging given the relatively few centers that have the necessary facilities and capabilities. The PRIMatE Data Exchange (PRIME-DE) addresses this challenge by aggregating independently acquired non-human primate magnetic resonance imaging (MRI) datasets and openly sharing them via the International Neuroimaging Data-sharing Initiative (INDI). Here, we present the rationale, design, and procedures for the PRIME-DE consortium, as well as the initial release, consisting of 25 independent data collections aggregated across 22 sites (total = 217 non-human primates). We also outline the unique pitfalls and challenges that should be considered in the analysis of non-human primate MRI datasets, including providing automated quality assessment of the contributed datasets.

Mind Reading and Writing: The Future of Neurotechnology.

Recent advances in neuroscience and technology have made it possible to record from large assemblies of neurons and to decode their activity to extract information. At the same time, available methods to stimulate the brain and influence ongoing processing are also rapidly expanding. These developments pave the way for advanced neurotechnological applications that directly read from, and write to, the human brain. While such technologies are still primarily used in restricted therapeutic contexts, this may change in the future once their performance has improved and they become more widely applicable. Here, we provide an overview of methods to interface with the brain, speculate about potential applications, and discuss important issues associated with a neurotechnologically assisted future.

Working memory accuracy for multiple targets is driven by reward expectation and stimulus contrast with different time-courses.

The richness of sensory input dictates that the brain must prioritize and select information for further processing and storage in working memory. Stimulus salience and reward expectations influence this prioritization but their relative contributions and underlying mechanisms are poorly understood. Here we investigate how the quality of working memory for multiple stimuli is determined by priority during encoding and later memory phases. Selective attention could, for instance, act as the primary gating mechanism when stimuli are still visible. Alternatively, observers might still be able to shift priorities across memories during maintenance or retrieval. To distinguish between these possibilities, we investigated how and when reward cues determine working memory accuracy and found that they were only effective during memory encoding. Previously learned, but currently non-predictive, color-reward associations had a similar influence, which gradually weakened without reinforcement. Finally, we show that bottom-up salience, manipulated through varying stimulus contrast, influences memory accuracy during encoding with a fundamentally different time-course than top-down reward cues. While reward-based effects required long stimulus presentation, the influence of contrast was strongest with brief presentations. Our results demonstrate how memory resources are distributed over memory targets and implicates selective attention as a main gating mechanism between sensory and memory systems.

Interocularly merged face percepts eliminate binocular rivalry.

Faces are important visual objects for humans and other social animals. A complex network of specialized brain areas is involved in the recognition and interpretation of faces. This network needs to strike a balance between being sensitive enough to distinguish between different faces with similar features, and being tolerant of low-level visual changes so that a given face is stably perceived as a particular individual. Such stability may require feedback from higher brain regions down to the level where details are represented. Here, we describe a phenomenon in which interocular competition between face features is stabilized and eliminated when observers attend high-level face characteristics. Two different face images presented to the individual eyes do not cause the perceptual fluctuations that are typically observed in binocular rivalry. Instead, they merge into a stable percept of an intermediate face that combines features from both eyes' images. The stability of the intermediate face percept depends on the observer attending holistic face properties such as identity or gender. It disappears when observers explicitly attend facial features, suggesting a crucial role of top-down stabilizing feedback from high-level areas that represent holistic faces back to lower processing levels where detailed face features compete for conscious representation.

Distinct Feedforward and Feedback Effects of Microstimulation in Visual Cortex Reveal Neural Mechanisms of Texture Segregation.

The visual cortex is hierarchically organized, with low-level areas coding for simple features and higher areas for complex ones. Feedforward and feedback connections propagate information between areas in opposite directions, but their functional roles are only partially understood. We used electrical microstimulation to perturb the propagation of neuronal activity between areas V1 and V4 in monkeys performing a texture-segregation task. In both areas, microstimulation locally caused a brief phase of excitation, followed by inhibition. Both these effects propagated faithfully in the feedforward direction from V1 to V4. Stimulation of V4, however, caused little V1 excitation, but it did yield a delayed suppression during the late phase of visually driven activity. This suppression was pronounced for the V1 figure representation and weaker for background representations. Our results reveal functional differences between feedforward and feedback processing in texture segregation and suggest a specific modulating role for feedback connections in perceptual organization.

3D printing and modelling of customized implants and surgical guides for non-human primates.

BACKGROUND: Primate neurobiologists use chronically implanted devices such as pedestals for head stabilization and chambers to gain access to the brain and study its activity. Such implants are skull-mounted, and made from a hard, durable material, such as titanium. NEW METHOD: Here, we present a low-cost method of creating customized 3D-printed cranial implants that are tailored to the anatomy of individual animals. We performed pre-surgical computed tomography (CT) and magnetic resonance (MR) scans to generate three-dimensional (3D) models of the skull and brain. We then used 3D modelling software to design implantable head posts, chambers, and a pedestal anchorage base, as well as craniotomy guides to aid us during surgery. Prototypes were made from plastic or resin, while implants were 3D-printed in titanium. The implants underwent post-processing and received a coating of osteocompatible material to promote bone integration. RESULTS: Their tailored fit greatly facilitated surgical implantation, and eliminated the gap between the implant and the bone. To date, our implants remain robust and well-integrated with the skull. COMPARISON WITH EXISTING METHOD(S): Commercial-off-the-shelf solutions typically come with a uniform, flat base, preventing them from sitting flush against the curved surface of the skull. This leaves gaps for fluid and tissue ingress, increasing the risk of microbial infection and tissue inflammation, as well as implant loss. CONCLUSIONS: The use of 3D printing technology enabled us to quickly and affordably create unique, complex designs, avoiding the constraints levied by traditional production methods, thereby boosting experimental success and improving the wellbeing of the animals.

The Distributed Nature of Working Memory.

Studies in humans and non-human primates have provided evidence for storage of working memory contents in multiple regions ranging from sensory to parietal and prefrontal cortex. We discuss potential explanations for these distributed representations: (i) features in sensory regions versus prefrontal cortex differ in the level of abstractness and generalizability; and (ii) features in prefrontal cortex reflect representations that are transformed for guidance of upcoming behavioral actions. We propose that the propensity to produce persistent activity is a general feature of cortical networks. Future studies may have to shift focus from asking where working memory can be observed in the brain to how a range of specialized brain areas together transform sensory information into a delayed behavioral response.

Intermittent stimulus presentation stabilizes neuronal responses in macaque area MT.

Repeated stimulation impacts neuronal responses. Here we show how response characteristics of sensory neurons in macaque visual cortex are influenced by the duration of the interruptions during intermittent stimulus presentation. Besides effects on response magnitude consistent with neuronal adaptation, the response variability was also systematically influenced. Spike rate variability in motion-sensitive area MT decreased when interruption durations were systematically increased from 250 to 2,000 ms. Activity fluctuations between subsequent trials and Fano factors over full response sequences were both lower with longer interruptions, while spike timing patterns became more regular. These variability changes partially depended on the response magnitude, but another significant effect that was uncorrelated with adaptation-induced changes in response magnitude was also present. Reduced response variability was furthermore accompanied by changes in spike-field coherence, pointing to the possibility that reduced spiking variability results from interactions in the local cortical network. While neuronal response stabilization may be a general effect of repeated sensory stimulation, we discuss its potential link with the phenomenon of perceptual stabilization of ambiguous stimuli as a result of interrupted presentation.

Spike-interval triggered averaging reveals a quasi-periodic spiking alternative for stochastic resonance in catfish electroreceptors.

Catfish detect and identify invisible prey by sensing their ultra-weak electric fields with electroreceptors. Any neuron that deals with small-amplitude input has to overcome sensitivity limitations arising from inherent threshold non-linearities in spike-generation mechanisms. Many sensory cells solve this issue with stochastic resonance, in which a moderate amount of intrinsic noise causes irregular spontaneous spiking activity with a probability that is modulated by the input signal. Here we show that catfish electroreceptors have adopted a fundamentally different strategy. Using a reverse correlation technique in which we take spike interval durations into account, we show that the electroreceptors generate a supra-threshold bias current that results in quasi-periodically produced spikes. In this regime stimuli modulate the interval between successive spikes rather than the instantaneous probability for a spike. This alternative for stochastic resonance combines threshold-free sensitivity for weak stimuli with similar sensitivity for excitations and inhibitions based on single interspike intervals.

Crossmodal duration perception involves perceptual grouping, temporal ventriloquism, and variable internal clock rates.

Here, we investigate how audiovisual context affects perceived event duration with experiments in which observers reported which of two stimuli they perceived as longer. Target events were visual and/or auditory and could be accompanied by nontargets in the other modality. Our results demonstrate that the temporal information conveyed by irrelevant sounds is automatically used when the brain estimates visual durations but that irrelevant visual information does not affect perceived auditory duration (Experiment 1). We further show that auditory influences on subjective visual durations occur only when the temporal characteristics of the stimuli promote perceptual grouping (Experiments 1 and 2). Placed in the context of scalar expectancy theory of time perception, our third and fourth experiments have the implication that audiovisual context can lead both to changes in the rate of an internal clock and to temporal ventriloquism-like effects on perceived on- and offsets. Finally, intramodal grouping of auditory stimuli diminished any crossmodal effects, suggesting a strong preference for intramodal over crossmodal perceptual grouping (Experiment 5).

Spatial summation in macaque parietal area 7a follows a winner-take-all rule.

While neurons in posterior parietal cortex have been found to signal the presence of a salient stimulus among multiple items in a display, spatial summation within their receptive field in the absence of an attentional bias has never been investigated. This information, however, is indispensable when one investigates the mechanisms of spatial attention and competition between multiple visual objects. To examine the spatial summation rule in parietal area 7a neurons, we trained rhesus monkeys to fixate on a central cross while two identical stimuli were briefly displayed in a neuron's receptive field. The response to a pair of dots was compared with the responses to the same dots when they were presented individually. The scaling and power parameters of a generalized summation algorithm varied greatly, both across neurons and across combinations of stimulus locations. However, the averaged response of the recorded population of 7a neurons was consistent with a winner-take-all rule for spatial summation. A control experiment where a monkey covertly attended to both stimuli simultaneously suggests that attention introduces additional competition by facilitating the less optimal stimulus. Thus an averaging stage is introduced between ∼ 200 and 300 ms of the response to a pair of stimuli. In short, the summation algorithm over the population of area 7a neurons carries the signature of a winner-take-all operation, with spatial attention possibly influencing the temporal dynamics of stimulus competition, that is the moment that the "winner" takes "victory" over the "loser" stimulus.