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International audience; Visuo-spatial attentional orienting is fundamental to selectively process behaviorally relevant information, depending on both low-level visual attributes of stimuli in the environment and higher-level factors, such as goals, expectations and prior knowledge. Growing evidence suggests an impact of the locus-cœruleus-norepinephrine (LC-NE) system in attentional orienting that depends on taskcontext. Nonetheless, most of previous studies used visual displays encompassing a target and various distractors, often preceded by cues to orient the attentional focus. This emphasizes the contribution of goal-driven processes, at the expense of other factors related to the stimulus content. Here, we aimed to determine the impact of NE on attentional orienting in more naturalistic conditions, using complex images and without any explicit task manipulation. We tested the effects of atomoxetine (ATX) injections, a NE reuptake inhibitor, on four monkeys during free viewing of images belonging to three categories: landscapes, monkey faces and scrambled images. Analyses of the gaze exploration patterns revealed, first, that the monkeys spent more time on each fixation under ATX compared to the control condition, regard less of the image content. Second, we found that, depending on the image content, ATX modulated the impact of low-level visual salience on attentional orienting. This effect correlated with the effect of ATX on the number and duration of fixations. Taken together, our results demonstrate that ATX adjusts the contribution of salience on attentional orienting depending on the image content, indicative of its role in balancing the role of stimulus-driven and top-down control during free viewing of complex stimuli.

International audience; • Atomoxetine decreases reaction time of the most prevalent trials. • Atomoxetine modulates the accumulation rate of sensory information. • Atomoxetine adapts the response strategy to the 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.

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. Electronic supplementary material The online version of this article (10.1007/s00213-019-05336-7) contains supplementary material, which is available to authorized users.

International audience; Although the relative expansion of the frontal cortex in primate evolution is generally accepted, the nature of the human uniqueness, if any, and between-species anatomo-functional comparisons of the frontal areas remain controversial. To provide a novel interpretation of the evolution of primate brains, sulcal morphological variability of the medial frontal cortex was assessed in Old World monkeys (macaque/baboon) and Hominoidea (chimpanzee/ human). We show that both Hominoidea possess a paracingulate sulcus, which was previously thought to be unique to the human brain and linked to higher cognitive functions, such as mentalizing. Also, we show systematic sulcal morphological organization of the medial frontal cortex that can be traced from Old World monkeys to Hominoidea species, demonstrating an evolutionarily conserved organizational principle. These data provide a new framework to compare sulcal morphology, cytoarchitectonic areal distribution, connectivity, and function across the primate order, leading to clear predictions about how other primate brains might be anatomo-functionally organized.

The vestibular system has widespread connections in the central nervous system. Several activation loci following vestibular stimulations have been notably reported in deep, limbic areas that are otherwise difficult to reach and modulate in healthy subjects. Following preliminary evidence, suggesting that such stimulations might affect mood and affective processing, we wondered whether the vestibular system is also involved in motivation. Evolutionary accounts suggest that visuo-vestibular mismatches might have a role in preventing the search for and exploitation of goods that previously resulted in aversive reactions, as they would be a fine warning signal which follows the contact with or ingestion of noxious neurotoxins. The first question was thus whether vestibular stimulation alters sensitivity to reward. Secondly, we sought to assess whether attention is allocated in space differently when cued by highly motivational stimuli, and if this interplay is further modulated by the vestibular system. In order to evaluate both motivational and attentional assets, we administered a Posner-like cueing task to 30 healthy subjects concurrently receiving sham or galvanic vestibular stimulation (GVS; Left-Anodal and Right-Anodal configurations). The participants had to discriminate targets appearing in either exogenously cued or uncued locations (50% validity); cues predicted the amount of points (0, 2, or 10) and thus money that they could earn for a correct response. The results highlight a robust inhibition of return (IOR) (faster responses for invalidly-cued targets) which was not modulated by different levels of reward or GVS. Across all stimulation sessions, rewards exerted a powerful beneficial effect over performance: reaction times were faster when rewards were at stake. However, this effect was largest in sham, but greatly reduced in GVS conditions, most notably with the Right-Anodal configuration. This is the first evidence for a decreased sensitivity to rewards causally induced by a perturbation of the vestibular system. While future studies will shed light on its neural underpinnings and clinical implications, here we argue that GVS could be a safe and promising way to enrich our understanding of reward processes and eventually tackle the management of patients with aberrant sensitivity to rewards.

According to contemporary views, the lateral frontal cortex is organized along a rostro-caudal functional axis with increasingly complex cognitive/behavioral control implemented rostrally, and increasingly detailed motor control implemented caudally. Whether the medial frontal cortex follows the same organization remains to be elucidated. To address this issue, the functional connectivity of the 3 cingulate motor areas (CMAs) in the human brain with the lateral frontal cortex was investigated. First, the CMAs and their representations of hand, tongue, and eye movements were mapped via task-related functional magnetic resonance imaging (fMRI). Second, using resting-state fMRI, their functional connectivity with lateral prefrontal and lateral motor cortical regions of interest (ROIs) were examined. Importantly, the above analyses were conducted at the single-subject level to account for variability in individual cingulate morphology. The results demonstrated a rostro-caudal functional organization of the CMAs in the human brain that parallels that in the lateral frontal cortex: the rostral CMA has stronger functional connectivity with prefrontal regions and weaker connectivity with motor regions; conversely, the more caudal CMAs have weaker prefrontal and stronger motor connectivity. Connectivity patterns of the hand, tongue and eye representations within the CMAs are consistent with that of their parent CMAs. The parallel rostral-to-caudal functional organization observed in the medial and lateral frontal cortex could likely contribute to different hierarchies of cognitive-motor control.

The arbitrary mapping of sensory information onto action forms an important element of the intelligent behavior of primates (also called conditional associative learning). The cortico-basal ganglia-thalamo-cortical loops are thought to play a key role in such behavior. The present research was undertaken to investigate the role of the basal ganglia (BG) in conditional visuo-motor associative learning using three complementary approaches: 1) single-unit recordings in awake monkeys, 2) behavioral testing in patients suffering from Parkinson's disease (a neurodegenerative disease affecting the BG), and 3) functional neuroimaging in healthy subjects. The results of all three studies converge to indicate that the BG are involved in both the acquisition and the retention phases of visuo-motor associations., Avec l'expérience, nous acquérons une panoplie de règles, associations arbitraires entre des stimuli externes et des actes moteurs, qui nous permettent d'adapter notre comportement à l'environnement (apprentissage associatif conditionnel). Ce type d'apprentissage met en jeu les boucles reliant les ganglions de la base (GGB) et le cortex frontal. Ce travail visait à préciser le rôle des GGB dans l'apprentissage de règles visuo-motrices conditionnelles en utilisant plusieurs approches : 1) l'enregistrement de l'activité des neurones du striatum chez le singe éveillé, 2) l'étude chez des patients atteints de la maladie de Parkinson (une pathologie neurodégénérative touchant les GGB) et 3) la neuroimagerie fonctionnelle chez l'homme sain. Les résultats des trois expériences convergent pour indiquer que les GGB sont impliqués à la fois dans l'acquisition et la rétention des associations visuo-motrices.

Pr. Marc Jeannerod, Président Pr. Bioulac, rapporteur Dr. Apicella, rapporteur Pr. Dubois, examinateur Dr. Burnod, examinateur Dr. Driss Boussaoud; The arbitrary mapping of sensory information onto action forms an important element of the intelligent behavior of primates (also called conditional associative learning). The cortico-basal ganglia-thalamo-cortical loops are thought to play a key role in such behavior. The present research was undertaken to investigate the role of the basal ganglia (BG) in conditional visuo-motor associative learning using three complementary approaches: 1) single-unit recordings in awake monkeys, 2) behavioral testing in patients suffering from Parkinson's disease (a neurodegenerative disease affecting the BG), and 3) functional neuroimaging in healthy subjects. The results of all three studies converge to indicate that the BG are involved in both the acquisition and the retention phases of visuo-motor associations.; Avec l'expérience, nous acquérons une panoplie de règles, associations arbitraires entre des stimuli externes et des actes moteurs, qui nous permettent d'adapter notre comportement à l'environnement (apprentissage associatif conditionnel). Ce type d'apprentissage met en jeu les boucles reliant les ganglions de la base (GGB) et le cortex frontal. Ce travail visait à préciser le rôle des GGB dans l'apprentissage de règles visuo-motrices conditionnelles en utilisant plusieurs approches : 1) l'enregistrement de l'activité des neurones du striatum chez le singe éveillé, 2) l'étude chez des patients atteints de la maladie de Parkinson (une pathologie neurodégénérative touchant les GGB) et 3) la neuroimagerie fonctionnelle chez l'homme sain. Les résultats des trois expériences convergent pour indiquer que les GGB sont impliqués à la fois dans l'acquisition et la rétention des associations visuo-motrices.

International audience; This study integrated functional connectivity measures using resting-state fMRI and behavioral data from a single-case observation of patient (PER) one year after right-hemispheric hemorrhage in the intraparietal sulcus and superior parietal lobule (IPS/SPL). PER showed no sign of clinical neglect. Her behavioral performance in the visuo-manual pointing task and in the letter discrimination task under conditions of endogenous and exogenous attentional cueing was compared between the left (affected) and right (unaffected/control) peripheral visual fields. The resting-state fMRI demonstrated an imbalance between the right and left hemispheric frontoparietal functional connectivity within the dorsal attentional and motor networks. Although the frontal and occipital cortices were not structurally damaged, specific fronto-occipital functional connectivity was imbalanced, which was strongly associated with the behavioral changes. First, the activity in the right frontal eye field showed weaker correlations with the activity in the right inferior occipital area compared to the correlation with the activity in the left inferior occipital area. This imbalanced fronto-occipital functional connectivity was accompanied by a specific impairment in endogenous covert attention in the left visual field. Second, the activity within M1 in both hemispheres showed weaker correlations with the activity of the right cuneus compared to the correlation with the activity in the left cuneus. The imbalanced fronto-occipital functional connectivity was associated with the impairment of the reaching movement of the left and right hands towards the left visual field (optic ataxia). Altogether, our results showed that a lesion to the posterior parietal cortex affects the relationship between distal regions underlying the sensorimotor and attentional abilities

International audience; 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.

Somatic inputs originating from bioregulatory processes can guide cognition and behavior. One such bodily signal, mostly overlooked so far, is represented by visuo-vestibular coupling and its alteration, which in extreme cases may result in motion sickness. We argued that the inherently perturbed interoceptive state that follows can be a powerful determinant of human motivated behavior, resulting in a blunted response to appetitive stimuli and an exaggerated response to noxious ones. We sought to assess such differential impact of visuo-vestibular mismatches on value through a task involving conflict monitoring. We therefore administered to 42 healthy participants a modified version of the Flankers task, in which distractors (arrows, pointing in either a congruent or incongruent direction) signaled the availability of monetary incentives (gains, losses, or neutral trials). While performing the task, participants received either galvanic vestibular stimulation (GVS), or sham stimulation. We have found impaired behavioral performances when value, which was attached to task-irrelevant information, was at stake. Gains and losses, interestingly, dissociated, and only the latter caused enhanced interference costs in the task, suggesting that negative incentives may be more effective in capturing human attention than positive ones. Finally, we have found some weak evidence for GVS to further increase the processing of losses, as suggested by even larger interference costs in this condition. Results were, however, overall ambiguous, and suggest that much more research is needed to better understand the link between the vestibular system and motivation.HighlightsVisuo-Vestibular mismatches may be important somatic markers affecting the evaluation of reinforcers;When attached to distractors, value information impairs behavioral performance for the task at hand;Trials in which potential losses were at stake were associated with larger interference costs arising from conflicting information between the target and the flankers;GVS (Right-Anodal) may further increase the interference caused by losses, but the evidence in this respect was ambiguous and inconclusive