Biology subjects

Silani, G.

Publications and source records attributed to Silani, G..

9 recordsLinked to original sources

bioRxiv2026

Opioids modulate Curiosity-Driven Exploration in Music

Curiosity, a key driver of exploration and learning, is reinforced by reward-related neurochemical systems, yet the role of the opioidergic system in modulating this behavior remains unclear. Music, as a highly rewarding stimulus, offers a unique context to investigate the neurochemical basis of curiosity, particularly the unexplored role of opioids in music-driven exploration. To fill this gap, we performed a double-blind within-subject pharmacological design, in which 26 participants received, in two different sessions, either a placebo or the opioid antagonist naltrexone. During each session, participants engaged in a music exploration/exploitation trade-off paradigm designed to assess their willingness to pay for exploring unfamiliar electronic music. Using logistic regression mixed-effects models, we found that while naltrexone did not affect overall curiosity ratings, it significantly reduced exploratory behavior in states of heightened curiosity. These findings suggest that the opioidergic system plays a critical role in regulating the relationship between curiosity and exploration, particularly in the context of novel and rewarding stimuli like music. Overall, the present research provides new and compelling evidence on the important relationship between curiosity and exploration and its regulation with the opioidergic neurotransmitter subsystem. Significance StatementThe present research aimed to advance our understanding of the neurochemical mechanisms underlying curiosity and information seeking. In our study, we employed a pharmacological design to examine the role of the opioidergic system in music-related exploration. Using a novel music exploration/exploitation paradigm, we found that while naltrexone, an opioid antagonist, did not affect baseline curiosity ratings, it markedly reduced exploratory behavior during high-curiosity states in the presence of potential monetary losses. These results provide new evidence that opioidergic modulation plays a critical role in regulating curiosity-driven exploration. This new evidence might be relevant in the future for better understanding how neurochemical systems shape learning, motivation, and affective responses in complex cognitive domains such as music.

neuroscience↗

bioRxiv2023

Effects of dopamine and opioid receptor antagonism on the neural processing of social and non-social rewards

Rewards are a broad category of stimuli inducing approach behavior to aid survival. Extensive evidence from animal research has shown that wanting (the motivation to pursue a reward) and liking (the pleasure associated with its consumption) are mostly regulated by dopaminergic and opioidergic activity in dedicated brain areas. However, less is known about the neuroanatomy of dopaminergic and opioidergic regulation of reward processing in humans, especially when considering different types of rewards (i.e., social and non-social). To fill this gap of knowledge, we combined dopaminergic and opioidergic antagonism (via amisulpride and naltrexone administration) with functional neuroimaging to investigate the neurochemical and neuroanatomical bases of wanting and liking of matched non-social (food) and social (interpersonal touch) rewards, using a randomized, between-subject, placebo-controlled, double-blind design. While at the behavioral level no drug effect was observed, brain activity was modulated by the administered compounds. In particular, opioid antagonism, compared to placebo, was associated with reduced activity in the medial orbitofrontal cortex during consumption of the most valued social and non-social rewards. Dopamine antagonism, however, had no clear effects on brain activity in response to rewards anticipation. These findings provide insights into the neurobiology of human reward processing and suggest a similar opioidergic regulation of the neural responses to social and non-social reward consumption.

neuroscience↗

bioRxiv2022

Effects of dopamine D2 and opioid receptor antagonism on the trade-off between model-based and model-free behavior in healthy volunteers

Our daily behaviour requires a flexible arbitration between actions we do out of habit and actions that are directed towards a specific goal. Drugs that target opioid and dopamine receptors are notorious for inducing maladaptive habitual drug consumption, yet how the opioidergic and dopaminergic neurotransmitter systems contribute to the arbitration between habitual and goal-directed behaviour is poorly understood. By combining pharmacological challenges with a well-established decision-making task and a novel computational model, we show that the administration of the D2 dopamine receptor antagonist amisulpride led to an increase in goal-directed or model-based relative to habitual or model-free behaviour, whereas the non-selective opioid receptor antagonist naltrexone had no appreciable effect. These findings highlight the distinct functional contributions of dopamine and opioid receptors to goal-directed and habitual behaviour and support the notion that D2 receptor antagonists promote stabilisation of goal-relevant information.

neuroscience↗

bioRxiv2021

Emotional ego- and altercentric biases in high-functioning autism spectrum disorder: Behavioral and neurophysiological evidence

Self-other distinction is a crucial aspect of social cognition, as it allows us to differentiate our own mental and emotional states from those of others. Research suggests that this ability might be impaired in individuals with autism spectrum disorder (ASD), but convincing evidence of self-other distinction deficits in the emotional domain is lacking. Here we aimed at evaluating emotional self-other distinction abilities in adults with and without ASD, in two behavioral pilot studies and one fMRI study. By using a newly developed virtual ball-tossing game that induced simultaneous positive and negative emotional states in each participant and another person, we were able to measure emotional egocentric and altercentric biases (namely the tendency to ascribe self-/other-related emotions to others/ourselves, respectively). Despite no behavioral differences, individuals with ASD showed decreased activation 1) in the right temporoparietal junction (rTPJ) during active overcoming of the emotional egocentric bias vs. passive game viewing, and 2) in the right supramarginal gyrus (rSMG) during ego-vs. altercentric biases, compared to neurotypical participants. These results suggest a different recruitment of these two regions in ASD when dealing with conflicting emotional states of oneself and another person. Furthermore, they highlight the importance of considering different control conditions when interpreting the involvement of rTPJ and rSMG during self-other distinction processes.

neuroscience↗

bioRxiv2021

Enhanced negative response to stress following morphine administration increases wanting of social reward

Animal research suggests a central role of the -opioid receptor (MOR) system in regulating affiliative behaviors and in mediating the stress-buffering function of social contact. However, the neurochemistry of stress-related social contact seeking in humans is still poorly understood. In a randomized, double-blind, between-subject design, healthy female volunteers (N = 80) received either 10 mg of the -opioid agonist morphine sulfate, or a placebo. Following a standardized psychosocial stress induction, participants engaged in a social reward task, in which the motivation to obtain skin-to-skin social touch and the hedonic reactions elicited by such touch were assessed. Morphine prevented the increase of salivary cortisol typically observed following acute stress exposure. Notably, this altered HPA axis responsivity was associated with increased negative affect in response to psychosocial stress, and with enhanced subjective wanting of highly rewarding social contact. These findings provide novel evidence on the effect of exogenous opioids administration on the reactions to psychosocial stress and point to a state-dependent regulation of social motivation.

neuroscience↗

bioRxiv2020

Neural correlates of interpersonal space permeability and flexibility in autism spectrum disorder

Previous research indicates that the size of interpersonal space at which the other is perceived as intrusive (permeability) and the ability to adapt interpersonal distance based on contextual factors (flexibility) are altered in Autism Spectrum Disorder (ASD). However, the neurophysiological basis of these alterations remains poorly understood. To fill this gap, we used fMRI and assessed interpersonal space preferences of individuals with ASD before and after engaging in cooperative and non-cooperative social interactions. Compared to matched controls, ASDs showed lower comfort in response to an approaching confederate, indicating preference for larger interpersonal space in autism (altered permeability). This preference was accompanied by reduced activity in bilateral dorsal intraparietal sulcus (dIPS) and left fusiform face area (FFA), regions previously shown to be involved in interpersonal space regulation. Furthermore, we observed differences in effective connectivity among dIPS, FFA, and amygdala in ASDs compared to controls, depending on the level of experienced comfort. No differences between groups were observed in interpersonal space regulation after an experienced social interaction (flexibility). Taken together, the present findings suggest that a dysregulation of the activity and connectivity of brain areas involved in interpersonal space processing may contribute to avoidance of physical proximity and social impairments in ASD.

neuroscience↗

bioRxiv2020

Beyond sharing unpleasant affect - evidence for pain-specific opioidergic modulation of empathy for pain

The neural mechanisms underpinning empathy for pain are still a matter of debate. One of the major questions is whether empathy-related pain responses indicate domain-general vs. pain-specific affective responses. Using fMRI and psychopharmacological experiments, we investigated if placebo analgesia reduces first-hand and empathic experiences of affective touch, and compared them to the effects on pain. Placebo analgesia also affected the first-hand and empathic experience of unpleasant touch, implicating domain-general effects. However, and in contrast to pain and pain empathy, administering an opioid antagonist did not block these effects. Moreover, placebo analgesia reduced neural activity related to both modalities in the bilateral insular cortex, while it specifically modulated activity in the anterior midcingulate cortex for pain and pain empathy. These findings provide causal evidence that one of the major neurochemical systems for pain regulation is involved in pain empathy, and crucially substantiate the role of shared representations in empathy.

neuroscience↗

bioRxiv2019

Dopaminergic and opioidergic regulation of implicit and explicit wanting and liking of social and nonsocial rewards

The observation of animal hedonic orofacial and behavioral reactions has played a fundamental role for the identification of a dopaminergic motivational, and an opioidergic hedonic component of reward. Translation to humans remains difficult, however, as human research has struggled to adopt a similar operationalization of reward. Here, we investigated the neurochemical basis of hedonic facial and behavioral reactions to different types of rewards in healthy adult volunteers, by pharmacologically reducing dopaminergic and opiodergic receptor-specific action. Subjective ratings, physical effort, and facial reactions to matched primary social (affective touch) and nonsocial (food) rewards were assessed. Both drugs resulted in reduced physical effort and increased negative facial reactions during reward anticipation, but only opioidergic manipulation caused reduced positive facial reactions during reward consumption. This suggest that facial reactions during anticipated and experienced pleasure rely on partly different neurochemical systems, providing novel evidence in support of existing theoretical models of reward.

neuroscience↗

bioRxiv2019

Age-related changes in human emotional egocentricity: evidence from multi-level neuroimaging

Emotional egocentric bias (EEB) occurs when, due to a partial failure in self-other distinction, empathy for anothers emotions is influenced by our own emotional state. Recent studies have demonstrated that this bias is higher in children, adolescents and older adults than in young adults. In the latter, overcoming emotional egocentrism has been associated with significant activity in the right supramarginal gyrus (rSMG), as well as increased connectivity between rSGM and somatosensory and visual cortices. Investigations on the neural correlates of EEB in adolescents and older adults are missing. We filled this gap, by asking female participants from three different age groups (adolescents, young adults and older adults, N=92) to perform a well-validated EEB task (Silani et al., 2013) in an MRI scanner. A multi-level analysis approach of MRI data including functional segregation, effective connectivity and structural analyses was adopted. Results revealed higher EEB in older compared to young adults and a comparable EEB in adolescents and young adults. Age-related differences in EEB were associated with differences in task-related rSMG connectivity with somatosensory cortices, especially with S2, which acted as a partial mediator between age and EEB. These findings provide further evidence for the crucial role of the rSMG in self-other distinction in the emotional domain, and suggest that the age-related decline in overcoming EEB is best explained by changes in rSMG connectivity rather than decreased regional activity in that area. This advocates a more systematic investigation of task-related connectivity in studies on aging and life-span development of social-cognitive phenomena.\n\nSignificance StatementEmpathy comprises both the ability to identify and share anothers emotional state, and the ability to disentangle ones own from the others emotional state. When self- and other-related emotions are conflicting, empathy might be negatively influenced by egocentric tendencies. This phenomenon is referred to as emotional egocentric bias (EEB), with previous research showing that its extent changes across the life-span. Here, we provide evidence that age-related differences in EEB are mainly associated with age-related changes in rSMG effective connectivity, and in particular that higher EEB in older adults is associated to lower rSMG effective connectivity with somatosensory cortices. These findings suggest the importance, particularly in aging, of intact functional connectivity for optimal socio-cognitive functioning.

neuroscience↗