Foveation, the ability to focus on a point for clear vision, is crucial for reading smoothly and tracking moving objects. Research shows that unstable foveation disrupts reading by causing more frequent eye movements. However, it’s unclear if this also affects smooth tracking of moving targets in slow readers. This study therefore investigates the link between foveation during reading and the tracking of moving targets, in a large group of participants displaying variable reading speeds in a virtual reality environment. Our analysis shows that slower readers have more intrusive fixational eye movements characterized by greater spatial and temporal variability during reading. Additionally, these readers display less efficient tracking of moving targets. Interestingly, the rate and spatial variability of catch-up saccades during object tracking correlates with fixational eye movement rates and spatial variability during reading. Our findings thus demonstrate that poor foveation stability in slow readers also affects other eye movement activities, such as during object tracking. We conclude with a discussion on the limitations of virtual reality-based reading assessment and the shared mechanisms of foveal stabilization, which might be altered under conditions of reading impairment.

Remifentanil is routinely administered in human neurosurgery whilst its use in non-human primates is not described. Here we described a new remifentanil-propofol total intravenous anesthesia (TIVA) for macaque neurosurgery and we compared it retrospectively to fentanyl-propofol anesthesia. Twelve anesthesias were performed (F=6; R=6). After premedication, anesthesia was induced with 3 mcg/kg fentanyl (F) or 3 mcg/kg remifentanil (R) intravenously (IV) and maintained through propofol and fentanyl [0.17 ± 0.01 mcg/kg/min after induction and 0.13 ± 0.01 mcg/kg/min during maintenance] or remifentanil [0.1 ± 0.02 mcg/kg/min after induction and 0.16 ± 0.05 mcg/kg/min during maintenance] constant-rate-infusion (CRI), respectively. Tracheal intubation in R was characterized by apnea, absence of laryngeal reaction, and cough compared to F. The mean propofol rate administered in F [0.3 ± 0.1 at start to 0.2± 0.1 mg/kg/min for maintenance] was significantly higher than in R [0.17 ± 0.1 at start to 0.16 ± 0.01 mg/kg/min for maintenance].The cardiovascular and respiratory parameters did not differ significantly between the two groups. Extubation time was shorter in R compared to F [8 (6– 10) and 18 (14– 22) minutes respectively]. Finally, the new remifentanil-propofol TIVA proved to be a beneficial refinement for macaque neurosurgery, providing smoother intubation, cardiovascular stability, lower propofol requirements and faster recovery.

Background: The use of Rhesus macaques in vision research is crucial due to their visual system's similarity to humans. While invasive techniques have been the norm, there has been a shift towards non-invasive methods, such as facemasks and head molds, to enhance animal welfare and address ethical concerns. New Method: We present a non-invasive, 3D-printed chinrest with infrared sensors, adapted from canine research, allowing for accurate eye movement measurements and voluntary animal participation in experiments. Results: The chinrest method showed a 16% and 28% increase in average trial numbers for Monkey 1 and Monkey 2, respectively, compared to the traditional headpost method. The engagement was high, with monkeys performing over 500 trials per session and initiating a new trial after an average intertrial interval of approximately 1 second. The hit rate improved by about 10% for Monkey 1 in the chinrest condition, and the fixation precision, measured by the standard deviation of gaze positions, was significantly better in the chinrest condition, with Monkey 1 showing a reduction in fixation imprecision from 0.26 degrees to 0.17 degrees in the X-axis. Comparison with Existing Methods: The chinrest approach showed significant improvements in trial engagement and reduction in aborted trials due to fixation breaks, indicating less stress and potentially improved data quality compared to previous non-invasive methods. Conclusions: The chinrest method offers a significant advancement in primate cognitive testing by allowing for precise data collection while addressing animal welfare concerns, possibly leading to better scientific outcomes and a paradigm shift in primate research methodologies.

Developing optogenetic methods for research in non-human primates (NHP) is important for translational neuroscience and for delineating brain function with unprecedented specificity. Here we assess, in macaque monkeys, the selectivity by which optogenetic stimulation of the primary visual cortex (V1) drives the local laminar and widespread cortical connectivity related to visual perception. Towards this end, we transfected neurons with light-sensitive channelrhodopsin in dorsal V1. fMRI revealed that optogenetic stimulation of V1 using blue light at 40 Hz increased functional activity in the visual association cortex, including areas V2/V3, V4, motion-sensitive area MT and frontal eye fields, although nonspecific heating and eye movement contributions to this effect could not be ruled out. Neurophysiology and immunohistochemistry analyses confirmed optogenetic modulation of spiking activity and opsin expression with the strongest expression in layer 4-B in V1. Stimulating this pathway during a perceptual decision task effectively elicited a phosphene percept in the receptive field of the stimulated neurons in one monkey. Taken together, our findings demonstrate the great potential of optogenetic methods to drive the large-scale cortical circuits of the primate brain with high functional and spatial specificity.

In the adult visual system, topographic reorganization of the primary visual cortex (V1) after retinal lesions has been extensively investigated. In contrast, the plasticity of higher order extrastriate areas following retinal lesions is less well studied. Here, we used fMRI to study reorganization of visual areas V2/V3 following the induction of permanent, binocular, homonymous retinal lesions in 4 adult macaque monkeys. We found that the great majority of voxels that did not show visual modulation on the day of the lesion in the V2/V3 lesion projection zone (LPZ) demonstrated significant visual modulations 2 weeks later, and the mean modulation strength remained approximately stable thereafter for the duration of our observations (4-5 months). The distribution of eccentricities of visually modulated voxels inside the V2/V3 LPZ spanned a wider range post-lesion than pre-lesion, suggesting that neurons inside the LPZ reorganize by receiving input either from the foveal or the peripheral border of the LPZ, depending on proximity. Overall, we conclude that area V2/V3 of adult rhesus macaques displays a significant capacity for topographic reorganization following retinal lesions markedly exceeding the corresponding capacity of area V1.

Studying higher brain function presents fundamental scientific challenges but has great potential for impactful translation to the clinic, supporting the needs of many patients suffering from conditions that relate to neuronal dysfunction. For many key questions relevant to human neurological conditions and clinical interventions, non-human primates (NHPs) remain the only suitable model organism and the only effective way to study the relationship between brain structure and function with the knowledge and tools currently available. Here we present three exemplary studies of current research yielding important findings that are directly translational to human clinical patients but which would be impossible without NHP studies. Our first example shows how studies of the NHP prefrontal cortex are leading to clinically relevant advances and potential new treatments for human neuropsychiatric disorders such as depression and anxiety. Our second example looks at the relevance of NHP research to our understanding of visual pathways and the visual cortex, leading to visual prostheses that offer treatments for otherwise blind patients. Finally, we consider recent advances in treatments leading to improved recovery of movement and motor control in stroke patients, resulting from our improved understanding of brain stem parallel pathways involved in movement in NHPs. The case for using NHPs in neuroscience research, and the direct benefits to human patients, is strong but has rarely been set out directly. This paper reviews three very different areas of neuroscience research, expressly highlighting the unique insights offered to each by NHP studies and their direct applicability to human clinical conditions.

Neuronal activity in visual area V4 is well known to be modulated by selective attention, and there are reports on V4 lesions leading to attentional deficits. However, it remains unclear whether V4 microstimulation can elicit attentional benefits. To test this hypothesis, we performed local microstimulation in area V4 and explored its spatial and time dynamics in two macaque monkeys performing a visual detection task. Microstimulation was delivered via chronically implanted multi-electrode arrays. We found that microstimulation increases average performance by 35% and reduces luminance detection thresholds by -30%. This benefit critically depends on the onset of microstimulation relative to the stimulus, consistent with known dynamics of endogenous attention. These results show that local microstimulation of V4 can improve behavior and highlight the critical role of V4 for attention.

Natural vision engages a wide range of higher-level regions that integrate visual information over the large-scale brain network. How interareal connectivity reconfigures during the processing of ongoing natural visual scenes and how these dynamic functional changes relate to the underlaying anatomical links between regions is not well understood. Here, we hypothesized that macaque visual brain regions are poly-functional sharing the capacity to change their configuration state depending on the nature of visual input. To address this hypothesis, we reconstructed networks from in-vivo diffusion-weighted imaging (DWI) and functional magnetic resonance imaging (fMRI) data obtained in four alert macaque monkeys viewing naturalistic movie scenes. At first, we characterized network properties and found greater interhemispheric density and greater inter-subject variability in free-viewing networks as compared to structural networks. From the structural connectivity, we then captured modules on which we identified hubs during free-viewing that formed a widespread visuo-saccadic network across frontal (FEF, 46v), parietal (LIP, Tpt), and occipitotemporal modules (MT, V4, TEm), and that excluded primary visual cortex. Inter-subject variability of well-connected hubs reflected subject-specific configurations that largely recruited occipito-parietal and frontal modules. Across the cerebral hemispheres, free-viewing networks showed higher correlations among long-distance brain regions as compared to structural networks. From these findings, we hypothesized that long-distance interareal connectivity could reconfigure depending on the ongoing changes in visual scenes. Testing this hypothesis by applying temporally resolved functional connectivity we observed that many structurally defined areas (such as areas V4, MT/MST and LIP) were poly-functional as they were recruited as hub members of multiple network states that changed during the presentation of scenes containing objects, motion, faces, and actions. We suggest that functional flexibility in macaque macroscale brain networks is required for the efficient interareal communication during active natural vision. To further promote the use of naturalistic free-viewing paradigms and increase the development of macaque neuroimaging resources, we share our datasets in the PRIME-DE consortium.

When a visual stimulus is repeated, average neuronal responses typically decrease, yet they might maintain or even increase their impact through increased synchronization. Previous work has found that many repetitions of a grating lead to increasing gamma-band synchronization. Here we show in awake macaque area V1 that both, repetition-related reductions in firing rate and increases in gamma are specific to the repeated stimulus. These effects showed some persistence on the timescale of minutes. Further, gamma increases were specific to the presented stimulus location. Importantly, repetition effects on gamma and on firing rates generalized to natural images. These findings suggest that gamma-band synchronization subserves the adaptive processing of repeated stimulus encounters, both for generating efficient stimulus responses and possibly for memory formation.

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.

Developing optogenetics in non-human primates (NHPs) is essential for translating its successful implementation in rodents to clinical applications in humans. However, information about how optogenetics influences the primate cortex remains limited. Here, we evaluate how optogenetic stimulation of the primate primary visual cortex (V1) affects local and large-scale network activation concerned with visual perception. To this end we injected an optogenetic construct (AAV9-hSyn-ChR2-eYFP) into the V1 cortex of four macaque monkeys (macaca mulatta) and measured the effects of optogenetic V1 stimulation using functional magnetic resonance imaging (fMRI), laminar electrophysiology, and behavioural assessment. In three macaques, blood-oxygen-dependent (BOLD) fMRI activity could be reliably elicited with optogenetic stimulation in V1 and several connected extrastriate brain areas, including V2/V3, motion-sensitive area MT and the frontal-eye-fields (FEF), in particular when pulsed stimulation at 40 Hz was applied. BOLD modulation was associated with consistent neural spiking activity measured in V1 of two macaques. More detailed analysis revealed strongest neuronal activation in layer 4B and infragranular layers, which tightly reflected the histological expression pattern of the optogenetic construct in V1. Driving this visual network proved sufficient to elicit a visual percept (‘phosphene’) in one macaque during a perceptual choice task. Taken together, our findings reveal the laminar and large-cortical activation pattern related to visual phosphene generation and emphasize the need for further improving optogenetic methods in NHPs as a step towards applications in humans.

The lateral geniculate nucleus (LGN) of the dorsal thalamus is the primary recipient of the two eyes’ outputs. Most LGN neurons are monocular in that they are activated by visual stimulation through only one (dominant) eye. However, there are both intrinsic connections and inputs from binocular structures to the LGN that could provide these neurons with signals originating from the other (non-dominant) eye. Indeed, previous work introducing luminance differences across the eyes or using a single-contrast stimulus showed binocular modulation for single unit activity in anesthetized macaques and multiunit activity in awake macaques. Here, we sought to determine the influence of contrast viewed by both the non-dominant and dominant eyes on LGN single-unit responses in awake macaques. To do this, we adjusted each eye’s signal strength by independently varying the contrast of stimuli presented to the two eyes. Specifically, we recorded LGN single unit spiking activity in two awake macaques while they viewed drifting gratings of varying contrast. We found that LGN neurons of all types [parvocellular (P), magnocellular (M), and koniocellular (K)] were significantly suppressed when stimuli were presented at low contrast to the dominant eye and at high contrast to the non-dominant eye. Further, the inputs of the two eyes showed antagonistic interaction, whereby the magnitude of binocular suppression diminished with high contrast in the dominant eye, or low contrast in the non-dominant eye. These results suggest that the LGN represents a site of precortical binocular processing involved in resolving discrepant contrast differences between the eyes.

Small fixational eye-movements are a fundamental aspect of vision and thought to reflect fine shifts in covert attention during active viewing. While the perceptual benefits of these small eye movements have been demonstrated during a wide range of experimental tasks including during free viewing, their function during reading remains surprisingly unclear. Previous research demonstrated that readers with increased microsaccade rates displayed longer reading speeds. To what extent increased fixational eye movements are, however, specific to reading and might be indicative of reading skill deficits remains, however, unknown. To address this topic, we compared the eye movement scan paths of 13 neurotypical individuals and 13 subjects diagnosed with developmental dyslexia during short story reading and free viewing of natural scenes. We found that during reading only, dyslexics tended to display small eye movements more frequently compared to neurotypicals, though this effect was not significant at the population level, as it could also occur in slow readers not diagnosed as dyslexics. In line with previous research, neurotypical readers had twice as many regressive compared to progressive microsaccades, which did not occur during free viewing. In contrast, dyslexics showed similar amounts of regressive and progressive small fixational eye movements during both reading and free viewing. We also found that participants with smaller fixational saccades from both neurotypical and dyslexic samples displayed reduced reading speeds and lower scores during independent tests of reading skill. Slower readers also displayed greater variability in the landing points and temporal occurrence of their fixational saccades. Both the rate and spatio-temporal variability of fixational saccades were associated with lower phonemic awareness scores. As none of the observed differences between dyslexics and neurotypical readers occurred during control experiments with free viewing, the reported effects appear to be directly related to reading. In summary, our results highlight the predictive value of small saccades for reading skill, but not necessarily for developmental dyslexia.

A growing body of psychophysical research reports theta (3-8 Hz) rhythmic fluctuations in visual perception that are often attributed to an attentional sampling mechanism arising from theta rhythmic neural activity in mid- to high-level cortical association areas. However, it remains unclear to what extent such neuronal theta oscillations might already emerge at early sensory cortex like the primary visual cortex (V1), e.g. from the stimulus filter properties of neurons. To address this question, we recorded multi-unit neural activity from V1 of two macaque monkeys viewing a static visual stimulus with variable sizes, orientations and contrasts. We found that among the visually responsive electrode sites, more than 50 % showed a spectral peak at theta frequencies. Theta power varied with varying basic stimulus properties. Within each of these stimulus property domains (e.g. size), there was usually a single stimulus value that induced the strongest theta activity. In addition to these variations in theta power, the peak frequency of theta oscillations increased with increasing stimulus size and also changed depending on the stimulus position in the visual field. Further analysis confirmed that this neural theta rhythm was indeed stimulus-induced and did not arise from small fixational eye movements (microsaccades). When the monkeys performed a detection task of a target embedded in a theta-generating visual stimulus, reaction times also tended to fluctuate at the same theta frequency as the one observed in the neural activity. The present study shows that a highly stimulus-dependent neuronal theta oscillation can be elicited in V1 that appears to influence the temporal dynamics of visual perception.

Sampling of information is thought to be an important aspect of explorative behaviour. Evidence for it has been gained in behavioural assessments of a variety of overt and covert cognitive domains, including sensation, attention, memory, eye movements and dexterity. A common aspect across many findings is that sampling tends to exhibit a rhythmicity at low frequencies (theta, 4-8 Hz; alpha, 9-12 Hz). Neurophysiological investigations in a wide range of species, including rodents, non-human primates and humans have demonstrated the presence of sampling related neural oscillations in a number of brain areas ranging from early sensory cortex, hippocampus to high-level cognitive areas. However, to assess whether rhythmic sampling represents a general aspect of exploratory behaviour one must critically evaluate the task parameters, and their potential link with neural oscillations. Here we focus on sampling during attentive vision to present an overview on the experimental conditions that are used to investigate rhythmic sampling and associated oscillatory brain activity in this domain. This review aims to (1) provide guidelines to efficiently quantify behavioural rhythms, (2) compare results from human and non-human primate studies and (3) argue that the underlying neural mechanisms of sampling can co-occur in both sensory and high-level areas.

All neuroelectrical, neurochemical, neuromolecular, ionic, etc. processes expressed in physical quantities, are considered, by default, to realize biologically and/or socially expedient information functions. However, scientific experience claims that physical processes ‘are indifferent’ to a person’s biological or/and social existence (Soloviov, 2019). Thus, we are faced with an intriguing question: what makes the neural networks of the brain integrate information (Tononi) biologically and/or socially expediently. The Fig.1 in a high generalized way symbolizes the physical structure of the neural networks of the brain, which provide the information operations of accumulation and integration of information by means of mental phenomena. I insist that subjective value (realized in the limbic region) directs all information processes in the neural networks of the brain to biological (later in evolution, social) expediency. I insist that the perception of information in the human brain occurs by means of subjective value. I insist that the integration of information is determined by means of subjective value. I insist that even the storing information in the brain is controlled by means of subjective value. Further, we will take into account that physical causality presupposes the direction of the cause from the outside towards the body. However, in the case of the brain, the opposite determination may be observed. Here we are talking about the formation of informationally well-endowed motor acts in the brain on the basis of integrated information. Subjective value turns out to be an “indetermined” factor of choice of needed for organization of behavior information inside the continuum of information fixed in the brain (Soloviov, 2019). Thus, the factor of subjective value, operating with information accumulated in the brain, turns out to be a fundamental mechanism for the implementation of causality from within of high level living

Optogenetics has revolutionized neuroscience in small laboratory animals, but its effect on animal models more closely related to humans, such as non-human primates (NHPs), has been mixed. To make evidence-based decisions in primate optogenetics, the scientific community would benefit from a centralized database listing all attempts, successful and unsuccessful, of using optogenetics in the primate brain. We contacted members of the community to ask for their contributions to an open science initiative. As of this writing, 45 laboratories around the world contributed more than 1,000 injection experiments, including precise details regarding their methods and outcomes. Of those entries, more than half had not been published. The resource is free for everyone to consult and contribute to on the Open Science Framework website. Here we review some of the insights from this initial release of the database and discuss methodological considerations to improve the success of optogenetic experiments in NHPs.

BACKGROUND:Neuroscience studies with macaque monkeys may require cranial implants to stabilize the head or gain access to the brain for scientific purposes. Wound management that promotes healing after the cranial implant surgery in non-human primates can be difficult as it is not necessarily possible to cover the wound margins.NEW METHOD:Here, we developed an easily modifiable head cap that protects the sutured skin margins after cranial implant surgery and contributes to wound healing. The protective head cap was developed in response to monkeys picking at sutured skin margins around an implant, complicating healing. The user-friendly protective cap, made from Klarity- R™ Sheet (3.2 mm thick with 36 % or 42 % perforation) is affixed to the implant post-surgically. Once secured and while the monkey is still anesthetized, the plastic sheeting is molded around the implant. The protective head cap restricts the monkey's finger access to its' wound margins while allowing air to circulate to promote wound healing.RESULTS AND COMPARISON WITH EXISTING METHODS:Across two UK primate facilities, the protective head cap promoted wound healing. In monkeys that did not wear the head cap, re-suturing was necessary in ∼30 % of cases. In contrast, none of the monkeys that wore the head cap required re-suturing. The monkeys wearing the head cap also had reduced numbers of days of prescribed antibiotics and analgesia.CONCLUSION:This bespoken, easily adaptable, protective head cap supports postoperative wound healing, and enhances the welfare of monkeys involved in neuroscience research.