A Model of Prefrontal Cortex Dopaminergic Modulation during the Delayed Alternation Task

International audienceWorking memory performance is modulated by the level of dopamine (DA) D1 receptors stimulation in the prefrontal cortex (PFC). This modulation is exerted at different time scales. Injection of D1 agonists/antagonists exerts a long-lasting influence (several minutes or hours) on PFC pyramidal neurons. In contrast, during performance of a cognitive task, the duration of the postsynaptic effect of phasic DA release is short lasting. The functional relationships of these two time scales of DA modulation remain poorly understood. Here we propose a model that combines these two time scales of DA modulation on a prefrontal neural network. The model links the cellular and behavioral levels during performance of the delayed alternation task. The network, which represents the activity of deep-layer pyramidal neurons with intrinsic neuro-nal properties, exhibits two stable states of activity that can be switched on and off by excitatory inputs from long-distance cortical areas arriving in superficial layers. These stable states allow PFC neurons to maintain representations during the delay period. The role of an increase of DA receptors stimulation is to restrict inputs arriving on the prefrontal network. The model explains how the level of working memory performance follows an inverted U-shape with an increased stimulation of DA D1 receptors. The model predicts that (1) D1 receptor agonists increase perseverations, (2) D1 antagonists increase distractability, and (3) the duration of the postsynaptic effect of phasic DA release in the PFC is adjusted to the delay period of the task. These results show how the precise duration of the postsynaptic effect of phasic DA release influences behavioral performance during a simple cognitive task

A causal role for right temporo-parietal junction in signaling moral conflict

International audienceThe right temporo-parietal junction (rTPJ) has been proposed to play a key role in guiding human altruistic behavior, but its precise functional contribution to altruism remains unclear. We aimed to disentangle three possible functions of the rTPJ for human altruism, namely: implementing the motivation to help, signaling conflicts between moral and material values, or representing social reputation concerns. Our novel donation-decision task consisted of decisions requiring trade-offs of either positive moral values and monetary cost when donating to a good cause, or negative moral values and monetary benefits when sending money to a bad cause. Disrupting the rTPJ using transcranial magnetic stimulation did not change the general motivation to give or to react to social reputation cues, but specifically reduced the behavioral impact of moral-material conflicts. These findings reveal that signaling moral-material conflict is a core rTPJ mechanism that may contribute to a variety of human moral behaviors

Processing of primary and secondary rewards: A quantitative meta-analysis and review of human functional neuroimaging studies

One fundamental question concerning brain reward mechanisms is to determine how reward-related activity is influenced by the nature of rewards. Here, we review the neuroimaging literature and explicitly assess to what extent the representations of primary and secondary rewards overlap in the human brain. To achieve this goal, we performed an activation likelihood estimation (ALE) meta-analysis of 87 studies (1452 subjects) comparing the brain responses to monetary, erotic and food reward outcomes. Those three rewards robustly engaged a common brain network including the ventromedial prefrontal cortex, ventral striatum, amygdala, anterior insula and mediodorsal thalamus, although with some variations in the intensity and location of peak activity. Money-specific responses were further observed in the most anterior portion of the orbitofrontal cortex, supporting the idea that abstract secondary rewards are represented in evolutionary more recent brain regions. In contrast, food and erotic (i.e. primary) rewards were more strongly represented in the anterior insula, while erotic stimuli elicited particularly robust responses in the amygdala. Together, these results indicate that the computation of experienced reward value does not only recruit a core "reward system" but also reward type-dependent brain structures

Testosterone causes both prosocial and antisocial status-enhancing behaviors in human males

Although popular discussion of testosterone’s influence on males often centers on aggression and antisocial behavior, contemporary theorists have proposed that it instead enhances behaviors involved in obtaining and maintaining a high social status. Two central distinguishing but untested predictions of this theory are that testosterone selectively increases status-relevant aggressive behaviors, such as responses to provocation, but that it also promotes nonaggressive behaviors, such as generosity toward others, when they are appropriate for increasing status. Here, we tested these hypotheses in healthy young males by injecting testosterone enanthate or a placebo in a double-blind, between-subjects, randomized design (n = 40). Participants played a version of the Ultimatum Game that was modified so that, having accepted or rejected an offer from the proposer, participants then had the opportunity to punish or reward the proposer at a proportionate cost to themselves. We found that participants treated with testosterone were more likely to punish the proposer and that higher testosterone levels were specifically associated with increased punishment of proposers who made unfair offers, indicating that testosterone indeed potentiates aggressive responses to provocation. Furthermore, when participants administered testosterone received large offers, they were more likely to reward the proposer and also chose rewards of greater magnitude. This increased generosity in the absence of provocation indicates that testosterone can also cause prosocial behaviors that are appropriate for increasing status. These findings are inconsistent with a simple relationship between testosterone and aggression and provide causal evidence for a more complex role for testosterone in driving status-enhancing behaviors in males

DC-SIGN Is the Major Mycobacterium tuberculosis Receptor on Human Dendritic Cells

Early interactions between lung dendritic cells (LDCs) and Mycobacterium tuberculosis, the etiological agent of tuberculosis, are thought to be critical for mounting a protective anti-mycobacterial immune response and for determining the outcome of infection. However, these interactions are poorly understood, at least at the molecular level. Here we show that M. tuberculosis enters human monocyte-derived DCs after binding to the recently identified lectin DC-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN). By contrast, complement receptor (CR)3 and mannose receptor (MR), which are the main M. tuberculosis receptors on macrophages (Mφs), appeared to play a minor role, if any, in mycobacterial binding to DCs. The mycobacteria-specific lipoglycan lipoarabinomannan (LAM) was identified as a key ligand of DC-SIGN. Freshly isolated human LDCs were found to express DC-SIGN, and M. tuberculosis–derived material was detected in CD14−HLA-DR+DC-SIGN+ cells in lymph nodes (LNs) from patients with tuberculosis. Thus, as for human immunodeficiency virus (HIV), which is captured by the same receptor, DC-SIGN–mediated entry of M. tuberculosis in DCs in vivo is likely to influence bacterial persistence and host immunity

Differences in Cortical Structure and Functional MRI Connectivity in High Functioning Autism

Autism spectrum disorders (ASD) represent a complex group of neurodevelopmental conditions characterized by deficits in communication and social behaviors. We examined the functional connectivity (FC) of the default mode network (DMN) and its relation to multimodal morphometry to investigate superregional, system-level alterations in a group of 22 adolescents and young adults with high-functioning autism compared to age-, and intelligence quotient-matched 29 healthy controls. The main findings were that ASD patients had gray matter (GM) reduction, decreased cortical thickness and larger cortical surface areas in several brain regions, including the cingulate, temporal lobes, and amygdala, as well as increased gyrification in regions associated with encoding visual memories and areas of the sensorimotor component of the DMN, more pronounced in the left hemisphere. Moreover, patients with ASD had decreased connectivity between the posterior cingulate cortex, and areas of the executive control component of the DMN and increased FC between the anteromedial prefrontal cortex and areas of the sensorimotor component of the DMN. Reduced cortical thickness in the right inferior frontal lobe correlated with higher social impairment according to the scores of the Autism Diagnostic Interview-Revised (ADI-R). Reduced cortical thickness in left frontal regions, as well as an increased cortical thickness in the right temporal pole and posterior cingulate, were associated with worse scores on the communication domain of the ADI-R. We found no association between scores on the restrictive and repetitive behaviors domain of ADI-R with structural measures or FC. The combination of these structural and connectivity abnormalities may help to explain some of the core behaviors in high-functioning ASD and need to be investigated further

Diplomazia creativa al servizio di strategie di nicchia di una piccola potenza

In the year marking the centenary since the foundation of the Azerbaijani Diplomatic Service, Baku’s foreign policy is increasingly characterised by a broader understanding of diplomacy, shaped by the gradual yet steady expansion of both areas and the tools for intervention. Guided by the attempt to develop a ‘niche strategy’ aiming at safeguarding and promoting Azerbaijani national interest, the Humanitarian Diplomacy emerges as a privileged field for Baku to adopt a pro-active and creative foreign policy. Building upon the debate around the interests behind the aid-providing activities of traditional and emerging donors, the article aims at introducing the motivations and the aims behind Azerbaijani aid policy. In particular, it aims at demonstrating that Baku’s Humanitarian Diplomacy aims chiefly at achieving immaterial benefits, having to do with international prestige and with the construction and international projection of a Good International Citizenship