BACKGROUND:Neurophysiological studies with awake macaques typically require chronic cranial implants. Headpost and connector-chamber implants are used to allow head stabilization and to house connectors of chronically implanted electrodes, respectively.NEW METHOD:We present long-lasting, modular, cement-free headpost implants made of titanium that consist of two pieces: a baseplate and a top part. The baseplate is implanted first, covered by muscle and skin and allowed to heal and osseointegrate for several weeks to months. The percutaneous part is added in a second, brief surgery. Using a punch tool, a perfectly round skin cut is achieved providing a tight fit around the implant without any sutures. We describe the design, planning and production of manually bent and CNC-milled baseplates. We also developed a remote headposting technique that increases handling safety. Finally, we present a modular, footless connector chamber that is implanted in a similar two-step approach and achieves a minimized footprint on the skull.RESULTS:Twelve adult male macaques were successfully implanted with a headpost and one with the connector chamber. To date, we report no implant failure, great headpost stability and implant condition, in four cases even more than 9 years post-implantation.COMPARISON WITH EXISTING METHODS:The methods presented here build on several related previous methods and provide additional refinements to further increase implant longevity and handling safety.CONCLUSIONS:Optimized implants can remain stable and healthy for at least 9 years and thereby exceed the typical experiment durations. This minimizes implant-related complications and corrective surgeries and thereby significantly improves animal welfare.

The availability of effective vaccines and a high vaccination rate allowed the recent mitigation, or even withdrawal, of many protective measures for containing the SARS CoV-2 pandemic. At the same time, new and highly mutated variants of the virus are found to have significantly higher transmissibility and reduced vaccine efficacy, thus causing high infection rates during the third year of the pandemic. The combination of reduced measures and increased infectivity poses a particular risk for unvaccinated individuals, including animals susceptible to the virus. Among the latter, non-human primates (NHPs) are particularly vulnerable. They serve as important models in various fields of biomedical research and because of their cognitive capabilities, they receive particular attention in animal welfare regulations around the world. Yet, although they played an extraordinarily important role for developing and testing vaccines against SARS-CoV-2, the protection of captive rhesus monkeys against Covid-19 has rarely been discussed. We here report upon twofold mRNA vaccination of a cohort of 19 elderly rhesus monkeys ( Macaca mulatta ) against infection by SARS-CoV-2. All animals were closely monitored on possible side effects of vaccination, and were tested for neutralising antibodies against the virus. The data show that vaccination of rhesus monkeys is a safe and reliable measure to protect these animals against SARS-CoV-2.

Selective visual attention allows the brain to focus on behaviorally relevant information while ignoring irrelevant signals. As a possible mechanism, routing-by-synchronization was proposed: neural populations receiving attended signals align their gamma-rhythmic activity to that of the sending populations, such that incoming spikes arrive at excitability peaks of receiving populations, enhancing signal transfer. Conversely, non-attended signals arrive unaligned to the receiver's oscillation, reducing signal transfer. Therefore, visual signals should be transferred through gamma-rhythmic bursts of information, resulting in a modulation of the stimulus content within the receiving population's activity by its gamma phase and amplitude. To test this prediction, we quantified gamma-phase-dependent stimulus content within neural activity from area V4 of two male macaques performing a visual attention task. For the attended stimulus, we find highest stimulus information content near excitability peaks, an effect that increases with oscillation amplitude, establishing a functional link between selective processing and gamma-activity.SIGNIFICANCE STATEMENT The ability to focus on the behaviorally relevant signals is essential for the brain to cope with the continuous, high-dimensional stream of sensory information it receives. What are the neural mechanisms which allow such selective processing in the visual system? We analyzed data from area V4 and found that the amount of visual signal information content is tightly linked to the phase of local gamma-rhythmic activity, with maximal signal content occurring near peaks of neural excitability. Our investigations provide direct evidence that selective attention relies on rhythmic temporal coordination between visual areas, and establish novel methods for pinpointing pulsed transmission schemes in neural data.

Summary Selective visual attention allows the brain to focus on behaviorally relevant information while ignoring irrelevant signals. As a possible mechanism, routing by synchronization was proposed: neural populations sending attended signals align their gamma-rhythmic activities with receiving populations, such that spikes from the senders arrive at excitability peaks of the receivers, enhancing signal transfer. Conversely, the non-attended signals arrive unaligned to the receiver’s oscillation, reducing signal transfer. Therefore, visual signals should be transferred through periodically pulsed information packages, resulting in a modulation of the stimulus content within the receiver’s activity by its gamma phase and amplitude. To test this prediction, we quantified gamma phase-specific stimulus content within neural activity from area V4 of macaques performing a visual attention task. For the attended stimulus we find enhanced stimulus content reaching its maximum near excitability peaks, with effect magnitude increasing with oscillation amplitude, establishing a functional link between selective processing and gamma activity.

The need for fast and dynamic processing of relevant information imposes high demands onto the flexibility and efficiency of the nervous system. A good example for such flexibility is the attention-dependent selection of relevant sensory information. Studies investigating attentional modulations of neuronal responses to simultaneously arriving input showed that neurons respond, as if only the attended stimulus would be present within their receptive fields (RF). However, attention also improves neuronal representation and behavioral performance, when only one stimulus is present. Thus, attention serves for selecting relevant input and changes the neuronal processing of signals representing selected stimuli, ultimately leading to a more efficient behavioral performance. Here, we tested the hypothesis that attention configures the strength of functional coupling between a local neuronal network's neurons specifically for effective processing of signals representing attended stimuli. This coupling is measured as the strength of γ-synchronization between these neurons. The hypothesis predicts that the pattern of synchronization in local networks should depend on which stimulus is attended. Furthermore, we expect this pattern to be similar for the attended stimulus presented alone or together with irrelevant stimuli in the RF. To test these predictions, we recorded spiking-activity and local field potentials (LFP) with closely spaced electrodes in area V4 of monkeys performing a demanding attention task. Our results show that the γ-band phase coherence (γ-PhC) between spiking-activity and the LFP, as well as the spiking-activity of two groups of neurons, strongly depended on which of the two stimuli in the RF was attended. The γ-PhC was almost identical for the attended stimulus presented either alone or together with a distractor. The functional relevance of dynamic γ-band synchronization is further supported by the observation of strongly degraded γ-PhC before behavioral errors, while firing rates were barely affected. These qualitatively different results point toward a failure of attention-dependent top-down mechanisms to correctly synchronize the local neuronal network in V4, even though this network receives the correctly selected input. These findings support the idea of a flexible, demand-dependent dynamic configuration of local neuronal networks, for performing different functions, even on the same sensory input.

Selective attention allows focusing on only part of the incoming sensory information. Neurons in the extrastriate visual cortex reflect such selective processing when different stimuli are simultaneously present in their large receptive fields. Their spiking response then resembles the response to the attended stimulus when presented in isolation. Unclear is where in the neuronal pathway attention intervenes to achieve such selective signal routing and processing. To investigate this question, we tagged two equivalent visual stimuli by independent broadband luminance noise and used the spectral coherence of these behaviorally irrelevant signals with the field potential of a local neuronal population in male macaque monkeys' area V4 as a measure for their respective causal influences. This new experimental paradigm revealed that signal transmission was considerably weaker for the not-attended stimulus. Furthermore, our results show that attention does not need to modulate responses in the input populations sending signals to V4 to selectively represent a stimulus, nor do they suggest a change of the V4 neurons' output gain depending on their feature similarity with the stimuli. Our results rather imply that selective attention uses a gating mechanism comprising the synaptic "inputs" that transmit signals from upstream areas into the V4 neurons. A minimal model implementing attention-dependent routing by gamma-band synchrony replicated the attentional gating effect and the signals' spectral transfer characteristics. It supports the proposal that selective interareal gamma-band synchrony subserves signal routing and explains our experimental finding that attention selectively gates signals already at the level of afferent synaptic input.SIGNIFICANCE STATEMENT Depending on the behavioral context, the brain needs to channel the flow of information through its networks of massively interconnected neurons. We designed an experiment that allows to causally assess routing of information originating from an attended object. We found that attention "gates" signals at the interplay between afferent fibers and the local neurons. A minimal model demonstrated that coherent gamma-rhythmic activity (∼60 Hz) between local neurons and their afferent-providing input neurons can realize the gating. Importantly, the attended signals did not need to be amplified already in an earlier processing stage, nor did they get amplified by a simple output response modulation. The method provides a useful tool to study mechanisms of dynamic network configuration underlying cognitive processes.

Perception seems so simple.I look out of the window to see houses, trees, people walking past, the sky above, the grass below.I hear birds in the trees, cars going past, the distant sound of an alarm.The world is full of objects that make their presence known to me through my senses -what could be more simple?Yet the efficacy of perceptual experience hides a host of questions for which we do not yet have the answers.Information reaching our senses is generally incomplete, ambiguous, distributed in space and time and not neatly sorted according to its source, so a key function of our perceptual systems is to discover the likely causes of our sensations.Perception as inference or hypothesis testing, formalised in the predictive coding theory, offers an attractive framework for exploring these issues.From this perspective, regularities or patterns provide perceptual systems with some traction, allowing the formation of expectations and a basis for decomposing the world into discrete objects.But in the dynamic world which we inhabit, object representations must be similarly dynamic, and need to form and dissolve, dominate and yield, in a way that facilitates veridical perception.In this talk I will discuss auditory scene analysis in the context of predictive coding using experimental data, exemplar models, and the phenomenon of perceptual multistability.

Receptive fields (RFs) of cortical sensory neurons increase in size along consecutive processing stages. When multiple stimuli are present in a large visual RF, a neuron typically responds to an attended stimulus as if only that stimulus were present. However, the mechanism by which a neuron selectively responds to a subset of its inputs while discarding all others is unknown. Here, we show that neurons can switch between subsets of their afferent inputs by highly specific modulations of interareal gamma-band phase-coherence (PC). We measured local field potentials, single- and multi-unit activity in two male macaque monkeys ( Macaca mulatta ) performing an attention task. Two small stimuli were placed on a screen; the stimuli were driving separate local V1 populations, while both were driving the same local V4 population. In each trial, we cued one of the two stimuli to be attended. We found that gamma-band PC of the local V4 population with multiple subpopulations of its V1 input was differentially modulated. It was high with the input subpopulation representing the attended stimulus, while simultaneously it was very low between the same V4 population and the other input-providing subpopulation representing the irrelevant stimulus. These differential modulations, which depend on stimulus relevance, were also found in the locking of spikes from V4 neurons to the gamma-band oscillations of the V1 input subpopulations. This rapid, highly specific interareal locking provides neurons with a powerful dynamic routing mechanism to select and process only the currently relevant signals.

Work on animals indicates that BOLD is preferentially sensitive to local field potentials, and that it correlates most strongly with gamma band neuronal synchronization. Here we investigate how the BOLD signal in humans performing a cognitive task is related to neuronal synchronization across different frequency bands. We simultaneously recorded EEG and BOLD while subjects engaged in a visual attention task known to induce sustained changes in neuronal synchronization across a wide range of frequencies. Trial-by-trial BOLD fluctuations correlated positively with trial-by-trial fluctuations in high-EEG gamma power (60-80 Hz) and negatively with alpha and beta power. Gamma power on the one hand, and alpha and beta power on the other hand, independently contributed to explaining BOLD variance. These results indicate that the BOLD-gamma coupling observed in animals can be extrapolated to humans performing a task and that neuronal dynamics underlying high- and low-frequency synchronization contribute independently to the BOLD signal.

Neurons receive a vast number of synaptic inputs at the same time. To successfully process a relevant piece of information, a neuron needs to select relevant, while suppressing irrelevant signals. In order to dynamically route a meaningful set of signals through processing pathways, neurons need to have a fast and flexible mechanism to change their effective connectivity. Here, we hypothesize that attention changes effective connectivity by modulating the synchrony between neuronal populations.We investigated whether attention dynamically changes effective connectivity between area V4 neurons and their V1 input. Single unit activity, multi unit activity and local field potentials (LFP) were recorded simultaneously from macaque monkeys’ areas V1 and V4. While maintaining their gaze on a fixation spot, the monkeys had to attend to one of two continuously morphing shapes and respond to reoccurrence of the initial sample shape in the attended stream. Size and position of the shapes were adjusted such that both fitted into a single V4 receptive field (RF) while covering two separate, non-overlapping V1 RFs.We found strong phase-coherence of gamma-band LFPs between the V1 populations responding to the attended stimulus and the V4 population. At the same time, V1 populations responding to the unattended stimulus showed only weak LFP phase-coherence with the V4 population. Furthermore, spike-triggered averages (STAs) of at least 40% of the recording pairs revealed that spikes recorded from area V4 were precisely timed with respect to the phase of the gamma oscillation in the upstream area V1. More importantly, almost all these cases showed an increased effect with attention. These results support the hypothesis that attention induces dynamic changes in the effective connectivity between two anatomically hard-wired neuronal populations by selectively modulating synchrony.

Event-related potentials (ERPs) have been used since the early days of neuroscience to study sensory, perceptual, and cognitive processes. Yet, the electrophysiological phenomena that give rise to ERPs are poorly understood. ERPs become visible after averaging trials that are aligned to an event (e