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Contains fulltext : 217200.pdf (Publisher’s version ) (Closed access) Nonhuman primate neuroimaging is on the cusp of a transformation, much in the same way its human counterpart was in 2010, when the Human Connectome Project was launched to accelerate progress. Inspired by an open data-sharing initiative, the global community recently met and, in this article, breaks through obstacles to define its ambitions. 4 p.

Rhesus macaques ( Macaca mulatta) used in behavioural neuroscience are often required to complete cognitively complex tasks, for which a high level of motivation is essential. To induce motivation, researchers may implement fluid-restriction protocols, whereby freely available water is limited, such that fluid can be used as a reward in the laboratory. A variety of different rewards and schedules are used, but there exists a lack of data assessing their effectiveness. In this study, we aimed to quantify fluid preference in rhesus macaques and to use these preferences to compare the motivational quality of different reward schedules: the monkey's previous reward (i.e. the fluid used to reward them in past studies), their new preferred reward, a variable schedule of previous and preferred reward, and a choice between the previous and preferred rewards. We found that it may be possible to reduce the level of restriction if an adequately motivating preferred reward is identified, but that this is dependent on the animal. Each monkey responded differently to both the fluid-preference assessments and to the different reward schedules. As such, monkeys should not be subject to ‘blanket’ protocols but should be assessed individually to maintain adequate scientific data collection at the least severe level of fluid restriction.

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. ispartof: NEURON vol:108 issue:6 ispartof: location:United States status: published

The timing and accuracy of perceptual decision making is exquisitely sensitive to fluctuations in arousal. Although extensive research has highlighted the role of neural evidence accumulation in forming decisions, our understanding of how arousal impacts these processes remains limited. Here we isolated electrophysiological signatures of evidence accumulation alongside signals reflecting target selection, attentional engagement and motor output and examined their modulation as a function of both tonic and phasic arousal, indexed by baseline and task-evoked pupil diameter, respectively. For both pupillometric measures, the relationship with reaction time was best described by a second-order, U-shaped, polynomial. Additionally, the two pupil measures were predictive of a unique set of EEG signatures that together represent multiple information processing steps of perceptual decision-making, including evidence accumulation. Finally, we found that behavioural variability associated with fluctuations in both tonic and phasic arousal was largely mediated by variability in evidence accumulation.

Summary 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., Highlights • Openly shared, large non-human primate neuroimaging data resource • Multiple imaging modalities contributed from investigators around the world • Quality assessments of the dataset • Discussed pitfalls and challenges in analyzing the non-human primate MRI data, The PRIMatE Data Exchange (PRIME-DE) consortium is an open science resource for the neuroimaging community aiming to facilitate efforts to map the non-human primate connectome. It aggregates and shares anatomical, functional, and diffusion MRI datasets from laboratories throughout the world.

Attention affects neuronal processing and improves behavioural performance. In extrastriate visual cortex these effects have been explained by normalization models, which assume that attention influences the circuit that mediates surround suppression. While normalization models have been able to explain attentional effects, their validity has rarely been tested against alternative models. Here we investigate how attention and surround/mask stimuli affect neuronal firing rates and orientation tuning in macaque V1. Surround/mask stimuli provide an estimate to what extent V1 neurons are affected by normalization, which was compared against effects of spatial top down attention. For some attention/surround effect comparisons, the strength of attentional modulation was correlated with the strength of surround modulation, suggesting that attention and surround/mask stimulation (i.e. normalization) might use a common mechanism. To explore this in detail, we fitted multiplicative and additive models of attention to our data. In one class of models, attention contributed to normalization mechanisms, whereas in a different class of models it did not. Model selection based on Akaike's and on Bayesian information criteria demonstrated that in most cells the effects of attention were best described by models where attention did not contribute to normalization mechanisms. This demonstrates that attentional influences on neuronal responses in primary visual cortex often bypass normalization mechanisms.

Macaques are often motivated to perform in neuroscientific experiments by implementing fluid restriction protocols. Daily access to water is controlled and the monkeys are rewarded with droplets of fluid for performing correct trials in the laboratory. Although these protocols are widely used and highly effective, it is important from a 3Rs perspective to investigate refinements that may help to lessen the severity of the fluid restriction applied. We assessed the use of social stimuli (images of conspecifics) as rewards for four rhesus macaques performing simple cognitive tasks. We found that individual preferences for images of male faces, female perinea and control stimuli could be identified in each monkey. However, using preferred images did not translate into effective motivators on a trial-by-trial basis: animals preferred fluid rewards, even when fluid restriction was relaxed. There was no difference in the monkeys' performance of a task when using greyscale versus colour images. Based on our findings, we cannot recommend the use of social stimuli, in this form, as a refinement to current fluid restriction protocols. We discuss the potential alternatives and possibilities for future research.

Muscarinic signaling affects attention, action selection, learning, and memory through multiple signaling cascades, which act at different timescales and which alter ion channels in cell type–specific manners. The effects of muscarinic signaling differ between cortical layers and between brain areas. Muscarinic signaling adds flexibility to the processing mode of neuronal networks, thereby supporting processing according to task demands. This review outlines possible scenarios to describe how it contributes to cellular mechanisms of attention and how it affects channeling of information in different neuronal circuits.

Summary Attention improves perception by affecting different aspects of the neuronal code. It enhances firing rates, it reduces firing rate variability and noise correlations of neurons, and it alters the strength of oscillatory activity. Attention-induced rate enhancement in striate cortex requires cholinergic mechanisms. The neuropharmacological mechanisms responsible for attention-induced variance and noise correlation reduction or those supporting changes in oscillatory activity are unknown. We show that ionotropic glutamatergic receptor activation is required for attention-induced rate variance, noise correlation, and LFP gamma power reduction in macaque V1, but not for attention-induced rate modulations. NMDA receptors mediate attention-induced variance reduction and attention-induced noise correlation reduction. Our results demonstrate that attention improves sensory processing by a variety of mechanisms that are dissociable at the receptor level., Highlights • NMDA receptors aid variance and covariance reduction • Cholinergic and NMDA receptors serve different functions in attentional modulation • Attention affects second-order statistics of neuronal activity in V1 • NMDA and AMPA receptor blockade oppositely affect V1 gamma frequency oscillations, Attention improves neuronal processing by increasing response strength and fidelity. Herrero et al. show that NMDA receptor availability is selectively required for increased response fidelity. The study isolates attentional mechanisms at the receptor level.

The functional magnetic resonance imaging (fMRI) blood oxygenation level-dependent (BOLD) signal is regularly used to assign neuronal activity to cognitive function. Recent analyses have shown that the local field potential (LFP) gamma power is a better predictor of the fMRI BOLD signal than spiking activity. However, LFP gamma power and spiking activity are usually correlated, clouding the analysis of the neural basis of the BOLD signal. We show that changes in LFP gamma power and spiking activity in the primary visual cortex (V1) of the awake primate can be dissociated by using grating and plaid pattern stimuli, which differentially engage surround suppression and cross-orientation inhibition/facilitation within and between cortical columns. Grating presentation yielded substantial V1 LFP gamma frequency oscillations and significant multi-unit activity. Plaid pattern presentation significantly reduced the LFP gamma power while increasing population multi-unit activity. The fMRI BOLD activity followed the LFP gamma power changes, not the multi-unit activity. Inference of neuronal activity from the fMRI BOLD signal thus requires detailed a priori knowledge of how different stimuli or tasks activate the cortical network.

Attention increases our ability to detect behaviorally relevant stimuli. At the neuronal level this is supported by increased firing rates of neurons representing the attended object. In primary visual cortex an attention-mediated activity increase depends on the presence of the neuromodulator acetylcholine. Using a spiking network model of visual cortex we have investigated how acetylcholine interacts with biased feedback to enable attentional processing. Although acetylcholine affects cortical processing in a multitude of manners, we restricted our analysis to four of its main established actions. These were (i) a reduction in firing rate adaptation by reduction in M-currents (muscarinic), (ii) an increase in thalamocortical synaptic efficacy by nicotinic presynaptic receptors, (iii) a reduction in lateral interactions by muscarinic presynaptic receptors, and (iv) an increase in inhibitory drive by muscarinic receptors located on inhibitory interneurons. We found that acetylcholine contributes to feedback-mediated attentional modulation, mostly by reducing intracortical interactions and also to some extent by increasing the inhibitory drive. These findings help explain why acetylcholine is necessary for top‐down-driven attentional modulation, and suggest a close interdependence of cholinergic and feedback drive in mediating cognitive function.

Summary Rhythmic activity of neuronal ensembles has been proposed to play an important role in cognitive functions such as attention, perception, and memory. Here we investigate whether rhythmic activity in V1 of the macaque monkey (macaca mulatta) is affected by top-down visual attention. We measured the local field potential (LFP) and V1 spiking activity while monkeys performed an attention-demanding detection task. We show that gamma oscillations were strongly modulated by the stimulus and by attention. Stimuli that engaged inhibitory mechanisms induced the largest gamma LFP oscillations and the largest spike field coherence. Directing attention toward a visual stimulus at the receptive field of the recorded neurons decreased LFP gamma power and gamma spike field coherence. This decrease could reflect an attention-mediated reduction of surround inhibition. Changes in synchrony in V1 would thus be a byproduct of reduced inhibitory drive, rather than a mechanism that directly aids perceptual processing., Highlights ► Gamma synchronization in V1 depends on activation of normalization mechanisms ► Attention reduces strength of LFP gamma synchronization in V1 ► Attention reduces spike field coherence in V1 ► Increased gamma spike field coherence in is not a universal mechanism of attention

The visual system encodes the features of visual stimuli as well as their behavioral relevance. Stimuli with a high luminance contrast evoke more activity in the visual cortex than stimuli with a low contrast. At the same time, attended stimuli evoke more activity than nonattended stimuli. There is a debate about how visual features and attention jointly determine neuronal activity in the visual cortex. Some studies suggested that attention increases apparent contrast (Reynolds et al., 2000), others that attention amplifies responses by a constant factor (Williford and Maunsell, 2006), and yet others that attention and contrast have largely additive effects (Buracas and Boynton, 2007; Thiele et al., 2009). The influence of attention on contrast sensitivity differs between neurons, raising the possibility that attention and contrast could be coded conjointly in a population of neurons. Here we investigate this possibility by recording neuronal activity at multiple sites in the primary visual cortex of macaque monkeys using multielectrode recording techniques and support vector machines to decode attended stimuli as well as stimulus contrast. We find that many, but not all, V1 neurons are influenced by attention and that the effects of attention and contrast are additive on average. Stimulus contrast can be decoded from neuronal responses not strongly modulated by attention, whereas the attended stimulus can be decoded as the difference in activity of cells that are influenced by attention and cells that are not. The success of the approach suggests that visual attention and stimulus contrast are represented by largely separable codes. Copyright © 2010 the authors.

Attention is a rich psychological and neurobiological construct that influences almost all aspects of cognitive behaviour. It enables enhanced processing of behaviourally relevant stimuli at the expense of irrelevant stimuli. At the cellular level, rhythmic synchronization at local and long-range spatial scales complements the attention-induced firing rate changes of neurons. The former is hypothesized to enable efficient communication between neuronal ensembles tuned to spatial and featural aspects of the attended stimulus. Recent modelling studies suggest that the rhythmic synchronization in the gamma range may be mediated by a fine balance between N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate postsynaptic currents, whereas other studies have highlighted the possible contribution of the neuromodulator acetylcholine. This review summarizes some recent modelling and experimental studies investigating mechanisms of attention in sensory areas and discusses possibilities of how glutamatergic and cholinergic systems could contribute to increased processing abilities at the cellular and network level during states of top-down attention.

Attention can selectively enhance neuronal responses and exclude external noise, but the neuronal computations that underlie these effects remain unknown. At the neuronal level, noise exclusion might result in altered spatial integration properties. We tested this proposal by recording neuronal activity and length tuning in neurons of the primary visual cortex of the macaque when attention was directed toward or away from stimuli presented in each neuron's classical receptive field. For cells with central-parafoveal receptive fields, attention reduced spatial integration, as demonstrated by a reduction in preferred stimulus length and in the size of the spatial summation area. Conversely, in cells that represented more peripheral locations, attention increased spatial integration by increasing the cell's summation area. This previously unknown dichotomy between central and peripheral vision could support accurate analysis of attended foveal objects and target selection for impending eye movements to peripheral objects.

In normal vision, visual scenes are predictable, as they are both spatially and temporally redundant. Evidence suggests that the visual system may use the spatio-temporal regularities of the external world, available in the retinal signal, to extract information from the visual environment and better reconstruct current and future stimuli. We studied this by recording neuronal responses of primary visual cortex (area V1) in anaesthetized and paralysed macaques during the presentation of dynamic sequences of bars, in which spatio-temporal regularities and local information were independently manipulated. Most V1 neurons were significantly modulated by events prior to and distant from stimulation of their classical receptive fields (CRFs); many were more strongly tuned to prior and distant events than they were to CRFs bars; and several showed tuning to prior information without any CRF stimulation. Hence, V1 neurons do not simply analyse local contours, but impute local features to the visual world, on the basis of prior knowledge of a visual world in which useful information can be distributed widely in space and time.

We develop new data-robust lower-bound methods to quantify the information carried by the timing of spikes emitted by neuronal populations. These methods have better sampling properties and are tighter than previous bounds based on neglecting correlation in the noise entropy. Our new lower bounds are precise also in the presence of strongly correlated firing. They are not precise only if correlations are strongly stimulus modulated over a long time range. Under conditions typical of many neurophysiological experiments, these techniques permit precise information estimates to be made even with data samples that are three orders of magnitude smaller than the size of the response space.

Spatial and temporal regularities commonly exist in natural visual scenes. The knowledge of the probability structure of these regularities is likely to be informative for an efficient visual system. Here we explored how manipulating the spatio–temporal prior probability of stimuli affects human orientation perception. Stimulus sequences comprised four collinear bars (predictors) which appeared successively towards the foveal region, followed by a target bar with the same or different orientation. Subjects' orientation perception of the foveal target was biased towards the orientation of the predictors when presented in a highly ordered and predictable sequence. The discrimination thresholds were significantly elevated in proportion to increasing prior probabilities of the predictors. Breaking this sequence, by randomising presentation order or presentation duration, decreased the thresholds. These psychophysical observations are consistent with a Bayesian model, suggesting that a predictable spatio–temporal stimulus structure and an increased probability of collinear trials are associated with the increasing prior expectation of collinear events. Our results suggest that statistical spatio–temporal stimulus regularities are effectively integrated by human visual cortex over a range of spatial and temporal positions, thereby systematically affecting perception.

This work examined the mechanisms underlying auditory motion processing in the auditory cortex of awake monkeys using functional magnetic resonance imaging (fMRI). We tested to what extent auditory motion analysis can be explained by the linear combination of static spatial mechanisms, spectrotemporal processes, and their interaction. We found that the posterior auditory cortex, including A1 and the surrounding caudal belt and parabelt, is involved in auditory motion analysis. Static spatial and spectrotemporal processes were able to fully explain motion-induced activation in most parts of the auditory cortex, including A1, but not in circumscribed regions of the posterior belt and parabelt cortex. We show that in these regions motion-specific processes contribute to the activation, providing the first demonstration that auditory motion is not simply deduced from changes in static spatial location. These results demonstrate that parallel mechanisms for motion and static spatial analysis coexist within the auditory dorsal stream., Author summary Motion is a fundamental dimension of acoustic and visual stimuli that is critical for animals to interact with their environment. Yet, surprisingly, we still do not understand the basic mechanisms in the brain that underlie perception of auditory motion. For the last 30 y, this research field has been hampered by unsuccessful attempts to answer a simple but fundamental question: is auditory motion perception deduced from processing individual static sounds, or are there mechanisms in the auditory domain dedicated to detecting motion? Here we report the discovery of specific motion detectors located in the auditory cortex of primates. We demonstrate that these auditory motion detectors are close to the well-known visual motion detectors. Both types of detectors are likely to be crucial for the planning of limb and eye movement. This study addresses a fundamental issue in neuroscience and sheds new light on the brain mechanisms underlying the essential aspects of our ability to navigate the world.

Natural sounds are characterized by their spectral content and the modulation of energy over time. Using functional magnetic resonance imaging in awake macaques, we observed topographical representations of these spectral and temporal dimensions in a single structure, the inferior colliculus, the principal auditory nucleus in the midbrain. These representations are organized as a map with two approximately perpendicular axes: one representing increasing temporal rate and the other increasing spectral frequency.

'Stimulus roving' refers to a paradigm in which the properties of the stimuli to be discriminated vary from trial to trial, rather than being kept constant throughout a block of trials. Rhesus monkeys have previously been shown to improve their contrast discrimination performance on a non-roving task, in which they had to report the contrast of a test stimulus relative to that of a fixed-contrast sample stimulus. Human psychophysics studies indicate that roving stimuli yield little or no perceptual learning. Here, we investigate how stimulus roving influences perceptual learning in macaque monkeys and how the addition of flankers alters performance under roving conditions. Animals were initially trained on a contrast discrimination task under non-roving conditions until their performance levels stabilized. The introduction of roving contrast conditions resulted in a pronounced drop in performance, which suggested that subjects initially failed to heed the sample contrast and performed the task using an internal memory reference. With training, significant improvements occurred, demonstrating that learning is possible under roving conditions. To investigate the notion of flanker-induced perceptual learning, flanker stimuli (30% fixed-contrast iso-oriented collinear gratings) were presented jointly with central (roving) stimuli. Presentation of flanker stimuli yielded substantial performance improvements in one subject, but deteriorations in the other. Finally, after the removal of flankers, performance levels returned to their pre-flanker state in both subjects, indicating that the flanker-induced changes were contingent upon the continued presentation of flankers.

Pitch is an auditory percept critical to the perception of music and speech, and for these harmonic sounds, pitch is closely related to the repetition rate of the acoustic wave. This paper reports a test of the assumption that non-human primates and especially rhesus monkeys perceive the pitch of these harmonic sounds much as humans do. A new procedure was developed to train macaques to discriminate the pitch of harmonic sounds and thereby demonstrate that the lower limit for pitch perception in macaques is close to 30 Hz, as it is in humans. Moreover, when the phases of successive harmonics are alternated to cause a pseudo-doubling of the repetition rate, the lower pitch boundary in macaques decreases substantially, as it does in humans. The results suggest that both species use neural firing times to discriminate pitch, at least for sounds with relatively low repetition rates.

A variety of psychophysical and neurophysiological studies suggest that chromatic motion perception in the primate brain may be performed outside the classical motion processing pathway. We addressed this provocative proposal directly by assessing the sensitivity of neurons in motion area MT to moving colored stimuli while simultaneously determining perceptual sensitivity in nonhuman primate observers. The results of these studies demonstrate a strong correspondence between neuronal and perceptual measures. Our findings testify that area MT is indeed a principal component of the neuronal substrate for color-based motion processing.

Brain areas at higher levels of cortical organization are thought to be more involved in decision processes than are earlier, i.e. lower, sensory areas. Hence, neuronal activity correlated with decisions should vary with an area’s position in the cortical hierarchy. To test this proposal, we investigated whether a change in neuronal activity during error trials depends in a systematic way on cortical hierarchical position. While macaque monkeys discriminated the direction of moving visual stimuli, the activity of direction-selective neurons was recorded in four extrastriate visual areas: V3A, the middle temporal area, the middle superior temporal area and the posterior part of the superior temporal polysensory area. Neuronal activity was significantly reduced in all areas when the monkeys made errors in judging the direction of stimuli moving in the preferred direction with low and intermediate luminance contrast. The amount of activity reduction was » 50% in all of the visual areas. Thus, the activity on error trials is reduced in early visual processing, independent of the hierarchy in the dorsal visual pathway. The activity reduction depended on stimulus contrast and the direction of the decision relative to the stimulus motion. It was profound and significant in all areas at low stimulus contrast. However, it was nonsignificant at high stimulus contrast. Our data suggest that activity reduction on error trials is due to lack of attention in association with stimulus expectation.

One adult monkey (Macaca fascicularis) was investigated psychophysically and electrophysiologically after at least 5 years of late onset esotropic macrostrabismus (squint angle 52 deg). Behavioural tests revealed normal monocular visual and visuomotor functions. No indications of deep amblyopia or oculomotor asymmetry were found. The monkey used the left or right eye alternately at about equal frequencies. Single unit recordings from area V1 disclosed a normal ocular dominance distribution. Most V1 neurons from both hemispheres received binocular input. Thus, discordant visual information from corresponding retinal locations of the two eyes converged onto the cortical neurons. No evidence for anomalous retinal correspondence was found. Diplopia and confusion must therefore be avoided by suppression of vision through one eye to allow stable, unambiguous perception. Possible suppression was investigated by stimulating a neuron through the same eye when it was actively used for fixation in one set of trials, and when it was not used for fixation in another set of trials. Significant differences in these two stimulus conditions were found in 2039 neurons from area V1 and in 1134 motion sensitive neurons recorded in the middle superior temporal area (MT). The normalized population activity in V1 and MT was higher if cells were stimulated through the fixating eye. The data are discussed with respect to possible suppressive mechanisms helping to prevent double vision in strabismus and in binocular rivalry. © 1997 Elsevier Science Ltd. All rights reserved.

Rhesus monkeys underwent training in a contrast discrimination task, in which grating stimuli were presented at parafoveal and peripheral visual field locations. Subjects had to compare a sample stimulus that had a fixed contrast of 30% to a test stimulus that varied in contrast from trial to trial. Extensive practice yielded improvements in contrast discrimination that were observed across the full range of test stimulus contrasts. These improvements occurred across multiple sessions, as well as across trials within individual sessions. The finer the contrast discriminations required, the longer it took for subjects to improve. Improvements in psychophysical performance resulted in the steepening of psychometric functions and/or shifts in the point of subjective equality towards the contrast of the sample stimulus. Enhancement in discrimination was especially pronounced around the contrast level of the sample stimulus, to which the subject was consistently exposed. The changes resulted in increased accuracy overall, lower discrimination thresholds, and faster response times. Partial transfer of learning, from vertically oriented training stimuli to horizontally oriented testing stimuli, was observed, while transfer to stimuli with different spatial frequencies was less pronounced. The results demonstrate the existence of perceptual learning in the contrast domain, whereby learning affects multiple performance-related psychophysical metrics.

SINGLE units in the middle temporal area (MT), the middle superior temporal area (MST) and the upper part of the superior temporal polysensory area (STP p ) of the monkey's brain were recorded during the discrimination of direction of visual motion near contrast threshold. In addition to stimulus-related decisions the monkeys often made stimulus-independent decisions while stimuli were well below detection threshold (contrast

Rhesus macaques are an important model in behavioral neuroscience due to their advanced cognitive abilities. To motivate animals to engage in complex tasks, fluid rewards, in conjunction with fluid control protocols, are often used. The impact of these protocols on animal welfare is controversial. We compared two fluid control protocols against a protocol providing free access to water and evaluated the impacts on physiological states of hydration, behavioral measures of welfare, and scientific output. Blood physiology did not significantly differ between any of the protocols, and urine measures were indicative of well functioning, healthy kidneys. Changes in behaviors were limited, the main one being an increase in motivation to drink on the stricter fluid control protocol, and improved task performance early in the week. Overall, fluid control protocols had little measurable impact on the welfare of rhesus macaques while ensuring that scientific data of high quality could be obtained.

The brain continuously adapts its processing machinery to behavioural demands. To achieve this, it rapidly modulates the operating mode of cortical circuits, controlling the way that information is transformed and routed. This article will focus on two experimental approaches by which the control of cortical information processing has been investigated: the study of state-dependent cortical processing in rodents and attention in the primate visual system. Both processes involve a modulation of low-frequency activity fluctuations and spiking correlation, and are mediated by common receptor systems. We suggest that selective attention involves processes that are similar to state change, and that operate at a local columnar level to enhance the representation of otherwise non-salient features while suppressing internally generated activity patterns.

The perceptual salience and visibility of image elements is influenced by other elements in their vicinity. The perceptual effect of image elements on an adjacent target element depends on their relative orientation. Collinear flanking elements usually improve sensitivity for the target element, whereas orthogonal elements have a weaker effect. It is believed that the collinear flankers exert these effects through lateral interactions between neurons in the primary visual cortex (area V1), but the precise mechanisms underlying these contextual interactions remain unknown. Here, we directly examined this question by recording the effects of flankers on the responses of V1 neurons at parafoveal representations while monkeys performed a fixation task or a contrast detection task. We found, unexpectedly, that collinear flankers reduce the monkeys' perceptual sensitivity for a central target element. This behavioral effect was explained by a flanker-induced increase in the activity of V1 neurons in the absence of the central target stimulus, which reduced the amplitude of the target response. Our results indicate that the dominant effect of collinear flankers in parafoveal vision is suppression and suggest that these suppressive effects are caused by a decrease in the dynamic range of neurons coding the central target. Copyright © 2010 the authors.

Previous studies have proposed a variety of mechanisms by which attention influences neuronal activity. Here we investigated the mechanisms of attention in the striate cortex of monkeys performing a spatial or an object-based attention task at various stimulus contrasts and compared neuronal contrast response functions with and without attention. Our data are best described by an “additive” interaction: The influence of attention on the neuronal response is relatively independent of the stimulus contrast, at least when the stimulus has enough contrast to become visible. This shows that attention adds to the neuronal responses in a largely contrast invariant manner. These data support recent functional magnetic resonance imaging studies and suggest that feedback from higher areas exerts a constant attentional drive that is mostly task not stimulus driven.

Attention can selectively enhance neuronal responses and exclude external noise. To investigate these effects and their neuronal mechanisms we investigated spatial integration and the underlying neuronal mechanisms in primary visual cortex. We found evidence for spatial filtering mechanisms, whereby attention reduced spatial integration in macaque V1 neurons. To study possible mechanisms of this effect, we measured length tuning in V1 in the presence and absence of externally applied acetylcholine. The effects of acetylcholine application and attention in V1 were largely similar. Acetylcholine reduced spatial integration by reducing the neuron’s summation area. Thus, attention can alter perceptual and neuronal spatial integration, and acetylcholine may contribute to these task dependent receptive field dynamics.

Neurons in primary visual cortex exhibit well documented centre-surround receptive field organization, whereby the centre is dominated by excitatory influences and the surround is generally dominated by inhibitory influences. These effects have largely been established by measuring the output of neurons, i.e. their spiking activity. How excitation and inhibition are reflected in the local field potential (LFP) is little understood. As this can bear on the interpretation of human fMRI BOLD data and on our understanding of the mechanisms of local field potential oscillations, we measured spatial integration and centre-surround properties in single- and multiunit recordings of V1 in the awake fixating macaque monkey, and compared these to spectral power in different frequency bands of simultaneously recorded LFPs. We quantified centre-surround organization by determining the size of the summation and suppression area in spiking activity as well as in different frequency bands of the LFP, with the main focus on the gamma band. Gratings extending beyond the summation area usually inhibited spiking activity while the LFP gamma-band activity increased monotonically for all grating sizes. This increase was maximal for stimuli infringing upon the near classical receptive field surround, where suppression started to dominate spiking activity. Thus, suppressive influences in primary cortex can be inferred from spiking activity, but they also seem to affect specific features of gamma-band LFP activity.

Sensation, memories, and predictions contribute to choices in everyday life, and their relative impact should change with task constraints. To investigate how the impact from sensory cortex on decision making varies with task constraints we trained macaque monkeys in a direction discrimination task where they could maximize reward by waiting for sensory visual information early in a trial, while focusing on memory and reward prediction as a trial progressed. The task constraints caused animals to indicate decisions in complete absence of visual motion stimuli (stimulus independent decisions), as 25% of the trials were 'no stimulus' trials. On 'no stimulus' trials reward delivery depended on the current decision in relation to the decision history. Stimulus independent decisions occurred during an epoch when a stimulus could in principle have been presented, or afterwards when stimuli could not occur anymore. Stimulus independent decisions were significantly different during these two periods. Reward exploitation was more efficient late in the trial, but it was not associated with systematic activity changes in directionally selective neurons in area MT. Conversely, systematic changes of neuronal activity and firing rate correlation in directionally selective middle temporal area (MT) neurons were restricted to a short time period before early decisions. Changing task constraints in the course of a single trial thus determines how neurons in sensory areas contribute to decision making.

Attention is often regarded as a mechanism by which attended objects become perceptually more salient, akin to increasing their contrast. We demonstrate that attention is better described as a mechanism by which task relevant information impacts on ongoing processing, while excluding task irrelevant information. We asked subjects to judge the orientation of a target relative to a reference, in a single and dual task setting. The target orientation percept was systematically influenced by the presentation of prior spatio-temporal context. We found that the sign of the context influence depended on target contrast, but its strength depended on the level of attention devoted to the task. Thus the effects of attention and contrast were fundamentally different; contrast influenced the sign of contextual interactions, while attention suppressed these interactions irrespective of their sign.

Our ability to perceive, attend, and memorize depends on bidirectional information exchange between hierarchically organized brain areas. Areas lower in the hierarchy send information through feedforward connections to higher areas. Higher areas modulate the activity in lower areas by means of feedback connections, and thereby influence the local processing as well as the information they receive. Although this scheme is well accepted, the exact role of feedforward and feedback connections in cognition is still poorly understood, let alone the mechanisms by which they mediate their effects. A report by Self et al. (1) in PNAS sheds light on the mechanisms involved. They delineate the different receptor types that contribute to feedforward and to feedback processing. They recorded neuronal activity from macaque primary visual cortex (V1) while animals performed a figure-ground detection task. V1 neurons in awake animals show differential activity depending on whether they represent the figure (2, 3) or whether they represent the background, even if the image within their receptive field is identical under both conditions. This differential activity is known as figure-ground modulation, and it depends …

Increased rhythmic brain activity in the high frequency range and decreased rhythmic activity in the low frequency range is a hallmark of cognitive function and ability. A novel study links these findings to the cholinergic theory of attention, demonstrating that attention-induced rebalancing of brain rhythms is augmented by acetylcholine.

While several previous psychophysical and neurophysiological studies have demonstrated chromatic (red/green) input to motion processing, the nature of this input is still a matter of debate. In particular, recent controversy has developed regarding whether chromatic motion processing relies on lower-level processes [J. Neurosci. 14 (1994) 4854; 19 (1999) 6571] versus higher-level, attention- or salience-based mechanisms [Science 257 (1992) 1563; Proc. Natl. Acad. Sci. 96 (1999a) 8289; 96 (1999b) 15374]. In this study, we investigated the degree to which chromatic motion is influenced by attentional mechanisms by employing a dual-task paradigm, which allowed us to compare the strength of chromatic motion under conditions of poor versus full attention. Here, we found that for equiluminant red/green gratings, chromatic motion processing is as robust in poor, as in full, attention conditions. This lack of an attentional effect suggests that chromatic motion processing must rely, at least in part, on lower-level (i.e., preattentive) motion mechanisms. For non-equiluminant (e.g., red brighter than green) gratings, however, attention significantly modulates chromatic motion strength. Possible explanations for this latter result are discussed in the context of inherent salience differences between the bright-red and dim-green stripes of the heterochromatic grating. 2002 Elsevier Science Ltd. All rights reserved.

Cholinergic neurons in the basal forebrain enable alert and attending brain states. A study now shows how basal forebrain activity increases coding abilities of cortical neurons and at what stages these changes occur.

The dorsal pathway of the primate brain, especially the middle temporal area (MT or V5) and the superior middle temporal area (MST or V5a), is strongly involved in motion detection. The relation between neural firing rates and psychophysical performance has led to the assumption that the neural code used by these areas consists of the relative discharge rates of neuronal populations. As an additional neural code, temporal correlation of neural activity has been suggested. Our study addresses the involvement of such a code in awake monkeys performing a motion discrimination task.We found significant temporal correlations between simultaneously recorded pairs of units in areas MT and MST and other extrastriate cortical areas. Units recorded from the same electrode were more frequently synchronized than units recorded from different electrodes placed within the same or different cortical areas. Activity synchronization was present in the expectation period before stimulus presentation and could not be inducedde novoby the stimulus. Rather, we found a contrast-dependent reduction of correlation strength on stimulus onset. Correlation strength did not vary systematically with stimulus directions. We conclude that under the conditions of this study, temporal decorrelation of MT and MST neurons could be used to detect the stimulus, but synchronization does not convey specific information about its direction of motion and therefore is unlikely to contribute to performance in our direction discrimination task. Activity synchronization in the period before stimulus onset could be related to attentive expectation.

The objective of this study was to investigate whether a representation of auditory space in the superior colliculus (SC) of the echolocating megachiropteran bat (Rousettus aegyptiacus) exists. Additionally the subcortical auditory connectivity of the SC was investigated. A total of 207 units were recorded in five awake animals while presenting acoustic stimuli (white noise, clicks, and pure tones) at different positions in space. Six units responded to acoustic stimulation. Three of these located within the superficial layers and one located in the intermediate layers were classified as omnidirectional units. Two units were located within the deep layers. One was classified as a hemifield unit, and the other as a frontal unit. All units responded phasically to acoustic stimulation with a latency of 4-150 ms. None of them could be activated by visual stimuli. We further examined the interaction of paired auditory and visual stimulation in 116 visually responsive units. Responses to visual stimulation were markedly altered by acoustic stimulation in 5 units. The influence of the acoustic stimuli was temporally and spatially restricted, and resulted either in a reduction or an elevation of unit responsiveness. Horseradish peroxidase was injected into the SC of eight animals to investigate the auditory subcortical connectivity of the SC. Retrograde labeling in auditory structures was rare compared with labeling found in nonauditory structures (e.g., retina, substantia nigra, parabigeminal nucleus). In auditory structures retrograde labeling was found mainly in the external nucleus of the inferior colliculus and in the nucleus of the brachium of the inferior colliculus. To a lesser extent it was found in the nucleus sagulum and in the area medial to the lemniscal nuclei. In one case the dorsal nucleus of the lateral lemniscus and the anterolateral periolivary nucleus were labeled. Our results reveal only a sparse auditory input into the SC of the flying fox, R. aegyptiacus. On the basis of single-unit recordings, we did not find an elaborate representation of auditory space as it is described for several other species. The existence of auditory and bimodal neurones, in combination with their response properties, nonetheless indicate that there might be a representation of auditory space in the SC of R. aegyptiacus.

Direction-selective neurons from the middle temporal area (MT) and the middle superior temporal area (MST) were recorded while a monkey performed a direction discrimination task. Stimuli consisted of evenly spaced bars moving in one of the four cardinal directions. Monkey's reaction time, single-cell latency, and direction selectivity were calculated when stimuli of 53%, 24%, and 4% contrast were presented, and the monkey indicated a correct decision. Mean reaction time was 359±77 ms at 53% contrast, 391±107 ms at 24% contrast, and 582±374 ms at 4% contrast. Most neurons exhibiting direction selective responses at 53% contrast was also active at 24% contrast (MT, 99%; MST, 88%). The number of neurons still exhibiting stimulus-related activity at 4% contrast dramatically decreased (MT to 28%; MST to 41%). Shortest latencies were found at high contrast level (53% contrast; MT, 29 ms; population mean, 76±40 ms; MST, 35 ms; population mean, 77±27 ms). Single cell and population latency increased at lower contrast (4% contrast: MT minimum, 86 ms; population mean, 180±76 ms; MST minimum, 97 ms; population mean, 205±56 ms). This indicates that the mean increase in latency at the single-cell level only partially reflects the increase in reaction time (mean reaction time increased by 223 ms, while mean single-cell latency increased by ∼100 ms in MT and MST). We therefore calculated the normalised population response at different contrast levels. The maximal population activity was always found at the highest contrast level and this was set to 1. In MT it took 75 – 80 ms from stimulus onset until half maximal activity (0.5) was reached at 53% contrast. To reach 0.5 took 85 – 90 ms at 24% contrast and 205 – 210 ms at 4% contrast. For MST the respective values were 85 ms (53% contrast), 90 ms (24% contrast) and 255 ms (4%) contrast. Thus the time to reach half the maximal population activity much better reflects the reaction time than the mean of the latencies calculated from single cells.

Non-human-primate fMRI is becoming increasingly recognised as the missing link between the widely applied methods of human imaging and intracortical animal electrophysiology. A crucial requirement for the optimal application of this method is the precise knowledge of the time course of the Blood Oxygenation Level Dependent (BOLD) signal. We mapped the BOLD signal time course in the inferior colliculus (IC), medial geniculate body (MGB) and in tonotopically defined fields in the auditory cortex of two macaques. The results show little differences in the BOLD-signal time courses within the auditory pathway. However, we observed systematic differences in the magnitude of the change in the BOLD signal with significantly stronger signal changes in field A1 of the auditory cortex compared to field R. The measured time course of the signal was in good agreement with similar studies in human auditory cortex but showed considerable differences to data reported from macaque visual cortex. Consistent with the studies in humans we measured a peak in the BOLD response around 4 s after the onset of 2-s broadband noise stimuli while previous studies recorded from the primary visual cortex of the same species reported the earliest peaks to short visual stimuli several seconds later. The comparison of our results with previous studies does not support differences in haemodynamic responses within the auditory system between human and non-human primates. Furthermore, the data will aid optimal design of future auditory fMRI studies in non-human primates.