Modulation of pulvinar connectivity with cortical areas in the control of selective visual attention.

Selective attention mechanisms operate across large-scale cortical networks by amplifying behaviorally relevant sensory information while suppressing interference from distractors. Although it is known that fronto-parietal regions convey information about attentional priorities, it is unclear how such cortical communication is orchestrated. Based on its unique connectivity pattern with the cortex, we hypothesized that the pulvinar, a nucleus of the thalamus, may play a key role in coordinating and modulating remote cortical activity during selective attention. By using a visual task that orthogonally manipulated top-down selection and bottom-up competition during functional MRI, we investigated the modulations induced by task-relevant (spatial cue) and task-irrelevant but salient (distractor) stimuli on functional interactions between the pulvinar, occipito-temporal cortex, and frontoparietal areas involved in selective attention. Pulvinar activity and connectivity were distinctively modulated during the co-occurrence of the cue and salient distractor stimuli, as opposed to the presence of one of these factors alone. Causal modelling analysis further indicated that the pulvinar acted by weighting excitatory signals to cortical areas, predominantly in the presence of both the cue and the distractor. These results converge to support a pivotal role of the pulvinar in integrating top-down and bottom-up signals among distributed networks when confronted with conflicting visual stimuli, and thus contributing to shape priority maps for the guidance of attention.

Functional connectivity fingerprints of the human pulvinar: Decoding its role in cognition.

The pulvinar is the largest thalamic nucleus in the brain and considered as a key structure in sensory processing and attention. Although its anatomy is well known, in particular thanks to studies in non-human primates, its role in perception and cognition remains poorly understood. Here, we used resting-state functional connectivity from a large sample of high-resolution data provided by the Human Connectome Project, combined with a large-scale meta-analysis approach to segregate and characterize the functional organization of the pulvinar nucleus. We identified five clusters per pulvinar with distinct connectivity profiles and determined their respective co-activation patterns. Using the Neurosynth database, we then investigated the functional significance of these co-activation networks. Our results confirm the functional heterogeneity of the pulvinar, revealing clearcut differences across clusters in terms of their connectivity patterns and associated cognitive domains. While the anterior and lateral clusters appear to be involved in action and attention domains, the ventromedial and dorsomedial clusters may preferentially subserve emotional processes and saliency detection. In contrast, the inferior cluster shows less specificity but correlates with perception and memory processes. Collectively, our results suggest that the pulvinar underwrites different components of cognition, supporting a central role in the coordination of cortico-subcortical processes mediated by distributed brain networks.

Boosting Norepinephrine Transmission Triggers Flexible Reconfiguration of Brain Networks at Rest.

The locus coeruleus-norepinephrine (LC-NE) system is thought to act as a reset signal allowing brain network reorganization in response to salient information in the environment. However, no direct evidence of NE-dependent whole-brain reorganization has ever been described. We used resting-state functional magnetic resonance imaging in monkeys to investigate the impact of NE-reuptake inhibition on whole-brain connectivity patterns. We found that boosting NE transmission changes functional connectivity between and within resting-state networks. It modulated the functional connectivity pattern of a brainstem network including the LC region and interactions between associative and sensory-motor networks as well as within sensory-motor networks. Among the observed changes, those involving the fronto-parietal attention network exhibited a unique pattern of uncoupling with other sensory-motor networks and correlation switching from negative to positive with the brainstem network that included the LC nucleus. These findings provide the first empirical evidence of NE-dependent large-scale brain network reorganization and further demonstrate that the fronto-parietal attention network represents a central feature within this reorganization.

Could LC-NE-Dependent Adjustment of Neural Gain Drive Functional Brain Network Reorganization?

The locus coeruleus-norepinephrine (LC-NE) system is thought to act at synaptic, cellular, microcircuit, and network levels to facilitate cognitive functions through at least two different processes, not mutually exclusive. Accordingly, as a reset signal, the LC-NE system could trigger brain network reorganizations in response to salient information in the environment and/or adjust the neural gain within its target regions to optimize behavioral responses. Here, we provide evidence of the co-occurrence of these two mechanisms at the whole-brain level, in resting-state conditions following a pharmacological stimulation of the LC-NE system. We propose that these two mechanisms are interdependent such that the LC-NE-dependent adjustment of the neural gain inferred from the clustering coefficient could drive functional brain network reorganizations through coherence in the gamma rhythm. Via the temporal dynamic of gamma-range band-limited power, the release of NE could adjust the neural gain, promoting interactions only within the neuronal populations whose amplitude envelopes are correlated, thus making it possible to reorganize neuronal ensembles, functional networks, and ultimately, behavioral responses. Thus, our proposal offers a unified framework integrating the putative influence of the LC-NE system on both local- and long-range adjustments of brain dynamics underlying behavioral flexibility.

The helmet head restraint system: a viable solution for resting state fMRI in awake monkeys.

In monkey neuroimaging, head restraint is currently achieved via surgical implants. Eradicating such invasive head restraint from otherwise non-invasive monkey studies could represent a substantial progress in terms of Reduction and Refinement. Two non-invasive helmet-based methods are available but they are used exclusively by the pioneering research groups who designed them. In the absence of independent replication, they have had little impact in replacing the surgical implants. Here, we built a modified version of the helmet system proposed by Srihasam et al. (2010 NeuroImage, 51(1), 267-73) and tested it for resting state fMRI in awake monkeys. Extremely vulnerable to motion artifacts, resting state fMRI represents a decisive test for non-invasive head restraint systems. We compared two monkeys restrained with the helmet to one monkey with a surgically implanted head post using both a seed-based approach and an independent component analysis. Technically, the helmet system proved relatively easy to develop. Scientifically, although it allowed more extensive movements than the head post system, the helmet proved viable for resting state fMRI, in particular when combined with the independent component analysis that deals more effectively with movement-related noise than the seed-based approach. We also discuss the pros and cons of such device in light of the European Union new 2013 regulation on non-human primate research and its firm Reduction and Refinement requests.

Self-Regulation of Attention in Children in a Virtual Classroom Environment: A Feasibility Study.

Attention is a crucial cognitive function that enables us to selectively focus on relevant information from the surrounding world to achieve our goals. Impairments in sustained attention pose challenges, particularly in children with attention deficit hyperactivity disorder, a neurodevelopmental disorder characterized by impulsive and inattentive behavior. While psychostimulant medications are the most effective ADHD treatment, they often yield unwanted side effects, making it crucial to explore non-pharmacological treatments. We propose a groundbreaking protocol that combines electroencephalography-based neurofeedback with virtual reality (VR) as an innovative approach to address attention deficits. By integrating a virtual classroom environment, we aim to enhance the transferability of attentional control skills while simultaneously increasing motivation and interest among children. The present study demonstrates the feasibility of this approach through an initial assessment involving a small group of healthy children, showcasing its potential for future evaluation in ADHD children. Preliminary results indicate high engagement and positive feedback. Pre- and post-protocol assessments via EEG and fMRI recordings suggest changes in attentional function. Further validation is required, but this protocol is a significant advancement in neurofeedback therapy for ADHD. The integration of EEG-NFB and VR presents a novel avenue for enhancing attentional control and addressing behavioral challenges in children with ADHD.

Optic flow selectivity in the macaque parieto-occipital sulcus.

In humans, several neuroimaging studies have demonstrated that passive viewing of optic flow stimuli activates higher-level motion areas, like V6 and the cingulate sulcus visual area (CSv). In macaque, there are few studies on the sensitivity of V6 and CSv to egomotion compatible optic flow. The only fMRI study on this issue revealed selectivity to egomotion compatible optic flow in macaque CSv but not in V6 (Cotterau et al. Cereb Cortex 27(1):330-343, 2017, but see Fan et al. J Neurosci. 35:16303-16314, 2015). Yet, it is unknown whether monkey visual motion areas MT + and V6 display any distinctive fMRI functional profile relative to the optic flow stimulation, as it is the case for the homologous human areas (Pitzalis et al., Cereb Cortex 20(2):411-424, 2010). Here, we described the sensitivity of the monkey brain to two motion stimuli (radial rings and flow fields) originally used in humans to functionally map the motion middle temporal area MT + (Tootell et al. J Neurosci 15: 3215-3230, 1995a; Nature 375:139-141, 1995b) and the motion medial parietal area V6 (Pitzalis et al. 2010), respectively. In both animals, we found regions responding only to optic flow or radial rings stimulation, and regions responding to both stimuli. A region in the parieto-occipital sulcus (likely including V6) was one of the most highly selective area for coherently moving fields of dots, further demonstrating the power of this type of stimulation to activate V6 in both humans and monkeys. We did not find any evidence that putative macaque CSv responds to Flow Fields.

Pulvino-cortical interaction: An integrative role in the control of attention.

Selective attention is a fundamental cognitive function that guides behavior by selecting and prioritizing salient or relevant sensory information of our environment. Despite early evidence and theoretical proposal pointing to an implication of thalamic control in attention, most studies in the past two decades focused on cortical substrates, largely ignoring the contribution of subcortical regions as well as cortico-subcortical interactions. Here, we suggest a key role of the pulvinar in the selection of salient and relevant information via its involvement in priority maps. Prioritization may be achieved through a pulvinar-mediated generation of alpha oscillations, which may then modulate neuronal gain in thalamo-cortical circuits. Such mechanism might orchestrate the synchrony of cortico-cortical interaction, by rendering neural communication more effective, precise and selective. We propose that this theoretical framework will support a timely shift from the prevailing cortico-centric view of cognition to a more integrative perspective of thalamic contributions to attention and executive control processes.

Atomoxetine modulates the relationship between perceptual abilities and response bias.

Elucidation of how neuromodulators influence motivated behaviors is a major challenge of neuroscience research. It has been proposed that the locus-cœruleus-norepinephrine system promotes behavioral flexibility and provides resources required to face challenges in a wide range of cognitive processes. Both theoretical models and computational models suggest that the locus-cœruleus-norepinephrine system tunes neural gain in brain circuits to optimize behavior. However, to the best of our knowledge, empirical proof demonstrating the role of norepinephrine in performance optimization is scarce. Here, we modulated norepinephrine transmission in monkeys performing a Go/No-Go discrimination task using atomoxetine, a norepinephrine-reuptake inhibitor. We tested the optimization hypothesis by assessing perceptual sensitivity, response bias, and their functional relationship within the framework of the signal detection theory. We also manipulated the contingencies of the task (level of stimulus discriminability, target stimulus frequency, and decision outcome values) to modulate the relationship between sensitivity and response bias. We found that atomoxetine increased the subject's perceptual sensitivity to discriminate target stimuli regardless of the task contingency. Atomoxetine also improved the functional relationship between sensitivity and response bias, leading to a closer fit with the optimal strategy in different contexts. In addition, atomoxetine tended to reduce reaction time variability. Taken together, these findings support a role of norepinephrine transmission in optimizing response strategy.

Atomoxetine improves attentional orienting in a predictive context.

The role of norepinephrine (NE) in visuo-spatial attention remains poorly understood. Our goal was to identify the attentional processes influenced by atomoxetine (ATX) injections, a NE-reuptake inhibitor that boosts the level of NE in the brain, and to characterize these influences. We tested the effects of ATX injections, on seven monkeys performing a saccadic cued task in which cues and distractors were used to manipulate spatial attention. We found that when the cue accurately predicted the location of the upcoming cue in 80% of the trials, ATX consistently improved attentional orienting, as measured from reaction times (RTs). These effects were best accounted for by a faster accumulation rate in the valid trials, rather than by a change in the decision threshold. By contrast, the effect of ATX on alerting and distractor interference was more inconsistent. Finally, we also found that, under ATX, RTs to non-cued targets were longer when these were presented separately from cued targets. This suggests that the impact of NE on visuo-spatial attention depends on the context, such that the adaptive changes elicited by the highly informative value of the cues in the most frequent trials were accompanied by a cost in the less frequent trials.

An Open Resource for Non-human Primate Imaging.

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

Social Facilitation of Cognition in Rhesus Monkeys: Audience Vs. Coaction.

Social psychology has long established that the mere presence of a conspecific, be it an active co-performer (coaction effect), or a passive spectator (audience effect) changes behavior in humans. Yet, the process mediating this fundamental social influence has so far eluded us. Brain research and its nonhuman primate animal model, the rhesus macaque, could shed new light on this long debated issue. For this approach to be fruitful, however, we need to improve our patchy knowledge about social presence influence in rhesus macaques. Here, seven adults (two dyads and one triad) performed a simple cognitive task consisting in touching images to obtain food treats, alone vs. in presence of a co-performer or a spectator. As in humans, audience sufficed to enhance performance to the same magnitude as coaction. Effect sizes were however four times larger than those typically reported in humans in similar tasks. Both findings are an encouragement to pursue brain and behavior research in the rhesus macaque to help solve the riddle of social facilitation mechanisms.