Motivation determines multiple aspects of behavior, including action selection and energization of behavior. Several components of the underlying neural systems have been examined closely, but the ...specific role of the different neuromodulatory systems in motivation remains unclear. Here, we compare directly the activity of dopaminergic neurons from the substantia nigra pars compacta and noradrenergic neurons from the locus coeruleus in monkeys performing a task manipulating the reward/effort trade-off. Consistent with previous reports, dopaminergic neurons encoded the expected reward, but we found that they also anticipated the upcoming effort cost in connection with its negative influence on action selection. Conversely, the firing of noradrenergic neurons increased with both pupil dilation and effort production in relation to the energization of behavior. Therefore, this work underlines the contribution of dopamine to effort-based decision making and uncovers a specific role of noradrenaline in energizing behavior to face challenges.
The trade-off between effort and reward is one of the main determinants of behavior, and its alteration is at the heart of major disorders such as depression or Parkinson's disease. Monoaminergic ...neuromodulators are thought to play a key role in this trade-off, but their relative contribution remains unclear. Rhesus monkeys (Macaca mulatta) performed a choice task requiring a trade-off between the volume of fluid reward and the amount of force to be exerted on a grip. In line with a causal role of noradrenaline in effort, decreasing noradrenaline levels with systemic clonidine injections (0.01 mg/kg) decreased exerted force and enhanced the weight of upcoming force on choices, without any effect on reward sensitivity. Using computational modeling, we showed that a single variable ("effort") could capture the amount of resources necessary for action and control both choices (as a variable for decision) and force production (as a driving force). Critically, the multiple effects of noradrenaline manipulation on behavior could be captured by a specific modulation of this single variable. Thus, our data strongly support noradrenaline's implication in effort processing.
Behavioral studies in both human and animals generally converge to the dogma that multisensory integration improves reaction times (RTs) in comparison to unimodal stimulation. These multisensory ...effects depend on diverse conditions among which the most studied were the spatial and temporal congruences. Further, most of the studies are using relatively simple stimuli while in everyday life, we are confronted to a large variety of complex stimulations constantly changing our attentional focus over time, a modality switch that can impact on stimuli detection. In the present study, we examined the potential sources of the variability in reaction times and multisensory gains with respect to the intrinsic features of a large set of natural stimuli.
Rhesus macaque monkeys and human subjects performed a simple audio-visual stimulus detection task in which a large collection of unimodal and bimodal natural stimuli with semantic specificities was presented at different saliencies. Although we were able to reproduce the well-established redundant signal effect, we failed to reveal a systematic violation of the race model which is considered to demonstrate multisensory integration. In both monkeys and human species, our study revealed a large range of multisensory gains, with negative and positive values. While modality switch has clear effects on reaction times, one of the main causes of the variability of multisensory gains appeared to be linked to the intrinsic physical parameters of the stimuli.
Based on the variability of multisensory benefits, our results suggest that the neuronal mechanisms responsible of the redundant effect (interactions vs. integration) are highly dependent on the stimulus complexity suggesting different implications of uni- and multisensory brain regions. Further, in a simple detection task, the semantic values of individual stimuli tend to have no significant impact on task performances, an effect which is probably present in more cognitive tasks.
Introduction
While several theories have highlighted the importance of the noradrenergic system for behavioral flexibility, a number of recent studies have also shown a role for noradrenaline in ...motivation, particularly in effort processing. Here, we designed a novel sequential cost/benefit decision task to test the causal influence of noradrenaline on these two functions in rhesus monkeys.
Methods
We manipulated noradrenaline using clonidine, an alpha-2 noradrenergic receptor agonist, which reduces central noradrenaline levels and examined how this manipulation influenced performance on the task.
Results
Clonidine had two specific and distinct effects: first, it decreased choice variability, without affecting the cost/benefit trade-off; and second, it reduced force production, without modulating the willingness to work.
Conclusions
Together, these results support an overarching role for noradrenaline in facing challenging situations in two complementary ways: by modulating behavioral volatility, which would facilitate adaptation depending on the lability of the environment, and by modulating the mobilization of resources to face immediate challenges.
Objective
Hair greying (i.e. canitie) is a physiological process occurring with the loss of melanin production and deposition within the hair shafts. Many studies reported the oxidation as the main ...biological process underlying this defect of pigmentation. Even though the overall appearance and biomechanical properties of hairs are reported to be altered with greying, there is a lack of information about molecular modifications occurring in grey hair shafts.
The aim of this study was thus to investigate the molecular signature and associated changes occurring in greying hair shafts by confocal Raman microspectroscopy.
Methods
This study was conducted on pigmented, intermediate (i.e. grey) and unpigmented hairs taken from 29 volunteers. Confocal Raman microspectroscopy measurements were acquired directly on hair shafts.
Results
Automatic classification of Raman spectra revealed 5 groups displaying significant differences. Hence, the analysis of the molecular signature highlighted the existence of 3 sub‐groups within grey hair: light, medium and dark intermediate. Among molecular markers altered in the course of greying, this study identified for the first time a gradual modification of lipid conformation (trans/gauche ratio) and protein secondary structure (α‐helix/β‐sheet ratio), referring respectively to an alteration of barrier function and biomechanical properties of greying hair.
Conclusion
This study thus reports for the first time a highly specific molecular signature as well as molecular modifications within grey hair shaft.
Résumé
Objectif
Le grisonnement du cheveu (i.e. canitie) est un processus physiologique correspondant à l'altération de la production et du dépôt des pigments de mélanine au sein de la tige pilaire. De nombreuses études identifient l'oxydation en tant que principal phénomène à l'origine de ce défaut de pigmentation. L’apparence globale et les propriétés biomécaniques des cheveux grisonnants sont également rapportées comme étant altérées. Cependant, il existe un manque d'information concernant les modifications moléculaires ayant lieu dans la tige pilaire grisonnante. Le but de cette étude était donc d'investiguer par microspectroscopie confocale Raman la signature moléculaire de la tige pilaire grisonnante ainsi que les changements biologiques associés.
Méthodes
Cette étude a été réalisée sur des cheveux pigmentés, intermédiaires (i.e. gris) et non pigmentés, prélevés sur 29 volontaires. Les mesures par microspectroscopie Raman confocale ont directement été acquises sur la tige pilaire.
Résultats
Une classification automatique des spectres Raman a permis de révéler 5 groupes présentant des différences significatives. Ainsi, l'analyse de la signature moléculaire spectrale identifie 3 sous‐groupes au sein des cheveux gris : intermédiaires clairs, moyens et foncés. Parmi les marqueurs moléculaires altérés au cours du grisonnement, cette étude identifie pour la première fois une modification graduelle de la conformation des lipides (ratio trans /gauche) et de la structure secondaire des protéines (ratio hélice α/feuillets β). Ces marqueurs correspondent respectivement à l'altération de la fonction barrière et des propriétés biomécaniques des cheveux gris.
Conclusion
Cette étude met en évidence pour la première fois une signature moléculaire extrêmement précise ainsi que des modifications moléculaires en lien avec le grisonnement de la tige pilaire.
Raman spectra acquired on pigmented, intermediate and unpigmented hair. (a) Dendrogram showing the hierarchical cluster analysis (HCA) of Raman spectra acquired on hair ex vivo. (b) Mean Raman spectra representative of each group previously determined by HCA. (c) Zoom on Raman spectral region (Raman band center : 1,580 cm‐1 corresponding to the vibration of the ring νC–C) analyzed to investigate melanin content. (d) Quantification of melanin content in each group. Statistical analyses according to Student’s t test compared to pigmented hair (with ***: p < 0.001)
Appropriate gaze interaction is essential for primate social life. Prior studies have suggested the involvement of the amygdala in processing eye cues but its role in gaze behavior during live social ...exchanges remains unknown. We recorded the activity of neurons in the amygdala of two monkeys as they engaged in spontaneous visual interactions. We showed that monkeys adjust their oculomotor behavior and actively seek to interact with each other through mutual gaze. During fixations on the eye region, some amygdala neurons responded with short latency and more strongly to mutual than non-reciprocal gaze (averted gaze). Other neurons responded with long latency and were more strongly modulated by active, self-terminated mutual gaze fixations than by passively terminated ones. These results suggest that the amygdala not only participates to the evaluation of eye contact, but also plays a role in the timing of fixations which is crucial for adaptive social interactions through gaze.
•We investigate the role of the amygdala in social gaze during live interaction.•A social interactive task allows to capture dynamics of spontaneous gaze behavior.•We show new functional features of amygdala neurons during live social interactions.•Amygdala encodes the monitoring of other's gaze and the regulation of one's own gaze.
Significance Promotion of remyelination has become a new therapeutic avenue to prevent neuronal degeneration and promote recovery in white matter diseases, such as multiple sclerosis (MS). To date ...most of these strategies have been developed in short-lived rodent models of demyelination, which spontaneously repair. Well-defined nonhuman primate models closer to man would allow us to efficiently advance therapeutic approaches. Here we present a nonhuman primate model of optic nerve demyelination that recapitulates several features of MS lesions. The model leads to failed remyelination, associated with progressive axonal degeneration and visual dysfunction, thus providing the missing link to translate emerging preclinical therapies to the clinic for myelin disorders such as MS.
Background
Line‐field confocal optical coherence tomography (LC‐OCT) is an imaging technique providing non‐invasive “optical biopsies” with an isotropic spatial resolution of ∼1 μm and deep ...penetration until the dermis. Analysis of obtained images is classically performed by experts, thus requiring long and fastidious training and giving operator‐dependent results. In this study, the objective was to develop a new automated method to score the quality of the dermal matrix precisely, quickly, and directly from in vivo LC‐OCT images. Once validated, this new automated method was applied to assess photo‐aging‐related changes in the quality of the dermal matrix.
Materials and methods
LC‐OCT measurements were conducted on the face of 57 healthy Caucasian volunteers. The quality of the dermal matrix was scored by experts trained to evaluate the fibers’ state according to four grades. In parallel, these images were used to develop the deep learning model by adapting a MobileNetv3‐Small architecture. Once validated, this model was applied to the study of dermal matrix changes on a panel of 36 healthy Caucasian females, divided into three groups according to their age and photo‐exposition.
Results
The deep learning model was trained and tested on a set of 15 993 images. Calculated on the test data set, the accuracy score was 0.83. As expected, when applied to different volunteer groups, the model shows greater and deeper alteration of the dermal matrix for old and photoexposed subjects.
Conclusions
In conclusion, we have developed a new method that automatically scores the quality of the dermal matrix on in vivo LC‐OCT images. This accurate model could be used for further investigations, both in the dermatological and cosmetic fields.
Motivation determines multiple aspects of behavior, including action selection and energization of behavior. Several components of the underlying neural systems have been examined closely, but the ...specific role of the different neuromodulatory systems in motivation remains unclear. Here, we compare directly the activity of dopaminergic neurons from the substantia nigra pars compacta and noradrenergic neurons from the locus coeruleus in monkeys performing a task manipulating the reward/effort trade-off. Consistent with previous reports, dopaminergic neurons encoded the expected reward, but we found that they also anticipated the upcoming effort cost in connection with its negative influence on action selection. Conversely, the firing of noradrenergic neurons increased with both pupil dilation and effort production in relation to the energization of behavior. Therefore, this work underlines the contribution of dopamine to effort-based decision making and uncovers a specific role of noradrenaline in energizing behavior to face challenges.
Ocular saccades bringing the gaze toward the straight-ahead direction (centripetal) exhibit higher dynamics than those steering the gaze away (centrifugal). This is generally explained by oculomotor ...determinants: centripetal saccades are more efficient because they pull the eyes back toward their primary orbital position. However, visual determinants might also be invoked: elements located straight-ahead trigger saccades more efficiently because they receive a privileged visual processing. Here, we addressed this issue by using both pro- and anti-saccade tasks in order to dissociate the centripetal/centrifugal directions of the saccades, from the straight-ahead/eccentric locations of the visual elements triggering those saccades. Twenty participants underwent alternating blocks of pro- and anti-saccades during which eye movements were recorded binocularly at 1 kHz. The results confirm that centripetal saccades are always executed faster than centrifugal ones, irrespective of whether the visual elements have straight-ahead or eccentric locations. However, by contrast, saccades triggered by elements located straight-ahead are consistently initiated more rapidly than those evoked by eccentric elements, irrespective of their centripetal or centrifugal direction. Importantly, this double dissociation reveals that the higher dynamics of centripetal pro-saccades stem from both oculomotor and visual determinants, which act respectively on the execution and initiation of ocular saccades.
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