The role of opioid transmission in music-induced pleasure.

Studies conducted in rodents indicate a crucial role of the opioid circuit in mediating objective hedonic reactions to primary rewards. However, it remains unclear whether opioid transmission is also essential to experience pleasure with more abstract rewards, such as music. We addressed this question using a double-blind within-subject pharmacological design in which opioid levels were up- and downregulated by administering an opioid agonist (oxycodone) and antagonist (naltrexone), respectively, before healthy participants (n = 21) listened to music. Participants also performed a monetary incentive delay (MID) task to control for the effectiveness of the treatment and the specificity of the effects. Our results revealed that the pharmacological intervention did not modulate subjective reports of pleasure, nor the occurrence of chills. On the contrary, psychophysiological (objective) measures of emotional arousal, such as skin conductance responses (SCRs), were bidirectionally modulated in both the music and MID tasks. This modulation specifically occurred during reward consumption, with greater pleasure-related SCR following oxycodone than naltrexone. These findings indicate that opioid transmission does not modulate subjective evaluations but rather affects objective reward-related psychophysiological responses. These findings raise new caveats about the role of the opioidergic system in the modulation of pleasure for more abstract or cognitive forms of rewarding experiences, such as music.

Music engagement is negatively correlated with depressive symptoms during the COVID-19 pandemic via reward-related mechanisms.

The COVID-19 pandemic has deeply affected the mental health of millions of people. We assessed which of many leisure activities correlated with positive mental health outputs, with particular attention to music, which has been reported to be important for coping with the psychological burden of the pandemic. Questionnaire data from about 1000 individuals primarily from Italy, Spain, and the United States during May-June 2020 show that people picked music activities (listening to, playing, singing, etc.) most often as the leisure experiences that helped them the most to cope with psychological distress related with the pandemic. During the pandemic, hours of engagement in music and food-related activities were associated with lower depressive symptoms. The negative correlation between music and depression was mediated by individual differences in sensitivity to reward, whereas the correlation between food-related activities and improved mental health outputs was explained by differences in emotion suppression strategies. Our results, while correlational, suggest that engaging in music activities could be related to improved well-being with the underlying mechanism being related to reward, consistent with neuroscience findings. Our data have practical significance in pointing to effective strategies to cope with mental health issues beyond those related to the COVID-19 pandemic.

The neural basis of effort valuation: A meta-analysis of functional magnetic resonance imaging studies.

Choosing how much effort to expend is critical for everyday decisions. While several neuroimaging studies have examined effort-based decision-making, results have been highly heterogeneous, leaving unclear which brain regions process effort-related costs and integrate them with rewards. We conducted two meta-analyses of functional magnetic resonance imaging data to examine consistent neural correlates of effort demands (23 studies, 15 maps, 549 participants) and net value (15 studies, 11 maps, 428 participants). The pre-supplementary motor area (pre-SMA) scaled positively with pure effort demand, whereas the ventromedial prefrontal cortex (vmPFC) showed the opposite effect. Moreover, regions that have been previously implicated in value integration in other cost domains, such as the vmPFC and ventral striatum, were consistently involved in signaling net value. The opposite response patterns of the pre-SMA and vmPFC imply that they are differentially involved in the representation of effort costs and value integration. These findings provide conclusive evidence that the vmPFC is a central node for net value computation and reveal potential brain targets to treat motivation-related disorders.

Language statistical learning responds to reinforcement learning principles rooted in the striatum.

Statistical learning (SL) is the ability to extract regularities from the environment. In the domain of language, this ability is fundamental in the learning of words and structural rules. In lack of reliable online measures, statistical word and rule learning have been primarily investigated using offline (post-familiarization) tests, which gives limited insights into the dynamics of SL and its neural basis. Here, we capitalize on a novel task that tracks the online SL of simple syntactic structures combined with computational modeling to show that online SL responds to reinforcement learning principles rooted in striatal function. Specifically, we demonstrate-on 2 different cohorts-that a temporal difference model, which relies on prediction errors, accounts for participants' online learning behavior. We then show that the trial-by-trial development of predictions through learning strongly correlates with activity in both ventral and dorsal striatum. Our results thus provide a detailed mechanistic account of language-related SL and an explanation for the oft-cited implication of the striatum in SL tasks. This work, therefore, bridges the long-standing gap between language learning and reinforcement learning phenomena.

Engagement in Music-Related Activities During the COVID-19 Pandemic as a Mirror of Individual Differences in Musical Reward and Coping Strategies.

The COVID-19 pandemic and the measures taken to mitigate its impact (e.g., confinement orders) have affected people's lives in profound ways that would have been unimagable only months before the pandemic began. Media reports from the height of the pandemic's initial international surge frequently highlighted that many people were engaging in music-related activities (from singing and dancing to playing music from balconies and attending virtual concerts) to help them cope with the strain of the pandemic. Our first goal in this study was to investigate changes in music-related habits due to the pandemic. We also investigated whether engagement in distinct music-related activities (singing, listening, dancing, etc.) was associated with individual differences in musical reward, music perception, musical training, or emotional regulation strategies. To do so, we collected detailed (~1 h-long) surveys during the initial peak of shelter-in-place order implementation (May-June 2020) from over a thousand individuals across different Countries in which the pandemic was especially devastating at that time: the USA, Spain, and Italy. Our findings indicate that, on average, people spent more time in music-related activities while under confinement than they had before the pandemic. Notably, this change in behavior was dependent on individual differences in music reward sensitivity, and in emotional regulation strategies. Finally, the type of musical activity with which individuals engaged was further associated with the degree to which they used music as a way to regulate stress, to address the lack of social interaction (especially the individuals more concerned about the risk of contracting the virus), or to cheer themselves up (especially those who were more worried about the pandemic consequences). Identifying which music-related activities have been particularly sought for by the population as a means for coping with such heightened uncertainty and stress, and understanding the individual differences that underlie said propensities are crucial to implementing personalized music-based interventions that aim to reduce stress, anxiety, and depression symptoms.

Dopamine modulations of reward-driven music memory consolidation.

Music listening provides one of the most significant abstract rewards for humans because hearing music activates the dopaminergic mesolimbic system. Given the strong link between reward, dopamine, and memory, we aimed here to investigate the hypothesis that dopamine-dependent musical reward can drive memory improvements. Twenty-nine healthy participants of both sexes provided reward ratings of unfamiliar musical excerpts that had to be remembered following a consolidation period under three separate conditions: after the ingestion of a dopaminergic antagonist, a dopaminergic precursor, or a placebo. Linear mixed modeling of the intervention data showed that the effect of reward on memory-i.e., the greater the reward experienced while listening to the musical excerpts, the better the memory recollection performance-was modulated by both dopaminergic signaling and individual differences in reward processing. Greater pleasure was consistently associated with better memory outcomes in participants with high sensitivity to musical reward, but this effect was lost when dopaminergic signaling was disrupted in participants with average or low musical hedonia. Our work highlights the flexibility of the human dopaminergic system, which can enhance memory formation not only through explicit and/or primary reinforcers but also via abstract and aesthetic rewards such as music.

Unraveling the Temporal Dynamics of Reward Signals in Music-Induced Pleasure with TMS.

Music's ability to induce feelings of pleasure has been the subject of intense neuroscientific research lately. Prior neuroimaging studies have shown that music-induced pleasure engages cortico-striatal circuits related to the anticipation and receipt of biologically relevant rewards/incentives, but these reports are necessarily correlational. Here, we studied both the causal role of this circuitry and its temporal dynamics by applying transcranial magnetic stimulation (TMS) over the left dorsolateral PFC combined with fMRI in 17 male and female participants. Behaviorally, we found that, in accord with previous findings, excitation of fronto-striatal pathways enhanced subjective reports of music-induced pleasure and motivation, whereas inhibition of the same circuitry led to the reduction of both. fMRI activity patterns indicated that these behavioral changes were driven by bidirectional TMS-induced alteration of fronto-striatal function. Specifically, changes in activity in the NAcc predicted modulation of both hedonic and motivational responses, with a dissociation between pre-experiential versus experiential components of musical reward. In addition, TMS-induced changes in the fMRI functional connectivity between the NAcc and frontal and auditory cortices predicted the degree of modulation of hedonic responses. These results indicate that the engagement of cortico-striatal pathways and the NAcc, in particular, is indispensable to experience rewarding feelings from music.SIGNIFICANCE STATEMENT Neuroimaging studies have shown that music-induced pleasure engages cortico-striatal circuits involved in the processing of biologically relevant rewards. Yet, these reports are necessarily correlational. Here, we studied both the causal role of this circuitry and its temporal dynamics by combining brain stimulation over the frontal cortex with functional imaging. Behaviorally, we found that excitation and inhibition of fronto-striatal pathways enhanced and disrupted, respectively, subjective reports of music-induced pleasure and motivation. These changes were associated with changes in NAcc activity and NAcc coupling with frontal and auditory cortices, dissociating between pre-experimental versus experiential components of musical reward. These results indicate that the engagement of cortico-striatal pathways, and the NAcc in particular, is indispensable to experience rewarding feeling from music.

Common and distinct neural correlates of music and food-induced pleasure: A coordinate-based meta-analysis of neuroimaging studies.

Neuroimaging studies have shown that, despite the abstractness of music, it may mimic biologically rewarding stimuli (e.g., food) in its ability to engage the brain's reward circuitry. However, due to the lack of research comparing music and other types of reward, it is unclear to what extent the recruitment of reward-related structures overlaps among domains. To achieve this goal, we performed a coordinate-based meta-analysis of 38 neuroimaging studies (703 subjects) comparing the brain responses specifically to music and food-induced pleasure. Both engaged a common set of brain regions, including the ventromedial prefrontal cortex, ventral striatum, and insula. Yet, comparative analyses indicated a partial dissociation in the engagement of the reward circuitry as a function of the type of reward, as well as additional reward type-specific activations in brain regions related to perception, sensory processing, and learning. These results support the idea that hedonic reactions rely on the engagement of a common reward network, yet through specific routes of access depending on the modality and nature of the reward.

Do Bilinguals Outperform Monolinguals in Switching Tasks? Contrary Evidence for Nonlinguistic and Linguistic Switching Tasks.

The benefits of bilingualism in executive functions are highly debated. Even so, in switching tasks, these effects seem robust, although smaller than initially thought (Gunnerud et al., 2020; Ware et al., 2020). By handling two languages throughout their lifespan, bilinguals appear to train their executive functions and show benefits in nonlinguistic switching tasks compared to monolinguals. Nevertheless, because bilinguals need to control for the interference of another language, they may show a disadvantage when dealing with task-switching paradigms requiring language control, particularly when those are performed in their less dominant language. The present work explored this issue by studying bilingualism's effects on task switching within the visual and language domains. On the one hand, our results show that bilinguals were overall faster and presented reduced switch costs compared to monolinguals when performing perceptual geometric judgments with no time for task preparation. On the other hand, no bilingual advantage was found when a new sample of comparable bilinguals and monolinguals completed a within-language switching task. Our results provide clear evidence favoring the bilingual advantage, yet only when the task imposes greater executive demands and does not involve language control.

Predictability and Uncertainty in the Pleasure of Music: A Reward for Learning?

Music ranks among the greatest human pleasures. It consistently engages the reward system, and converging evidence implies it exploits predictions to do so. Both prediction confirmations and errors are essential for understanding one's environment, and music offers many of each as it manipulates interacting patterns across multiple timescales. Learning models suggest that a balance of these outcomes (i.e., intermediate complexity) optimizes the reduction of uncertainty to rewarding and pleasurable effect. Yet evidence of a similar pattern in music is mixed, hampered by arbitrary measures of complexity. In the present studies, we applied a well-validated information-theoretic model of auditory expectation to systematically measure two key aspects of musical complexity: predictability (operationalized as information content [IC]), and uncertainty (entropy). In Study 1, we evaluated how these properties affect musical preferences in 43 male and female participants; in Study 2, we replicated Study 1 in an independent sample of 27 people and assessed the contribution of veridical predictability by presenting the same stimuli seven times. Both studies revealed significant quadratic effects of IC and entropy on liking that outperformed linear effects, indicating reliable preferences for music of intermediate complexity. An interaction between IC and entropy further suggested preferences for more predictability during more uncertain contexts, which would facilitate uncertainty reduction. Repeating stimuli decreased liking ratings but did not disrupt the preference for intermediate complexity. Together, these findings support long-hypothesized optimal zones of predictability and uncertainty in musical pleasure with formal modeling, relating the pleasure of music listening to the intrinsic reward of learning.SIGNIFICANCE STATEMENT Abstract pleasures, such as music, claim much of our time, energy, and money despite lacking any clear adaptive benefits like food or shelter. Yet as music manipulates patterns of melody, rhythm, and more, it proficiently exploits our expectations. Given the importance of anticipating and adapting to our ever-changing environments, making and evaluating uncertain predictions can have strong emotional effects. Accordingly, we present evidence that listeners consistently prefer music of intermediate predictive complexity, and that preferences shift toward expected musical outcomes in more uncertain contexts. These results are consistent with theories that emphasize the intrinsic reward of learning, both by updating inaccurate predictions and validating accurate ones, which is optimal in environments that present manageable predictive challenges (i.e., reducible uncertainty).

White Matter Microstructure Reflects Individual Differences in Music Reward Sensitivity.

People show considerable variability in the degree of pleasure they experience from music. These individual differences in music reward sensitivity are driven by variability in functional connectivity between the nucleus accumbens (NAcc), a key structure of the reward system, and the right superior temporal gyrus (STG). However, it is unknown whether a neuroanatomical basis exists for this variability. We used diffusion tensor imaging and probabilistic tractography to study the relationship between music reward sensitivity and white matter microstructure connecting these two regions via the orbitofrontal cortex (OFC) in 38 healthy human participants (24 females and 14 males). We found that right axial diffusivity (AD) in the STG-OFC connectivity inversely correlated with music reward sensitivity. Additionally, right mean diffusivity and left AD in the NAcc-OFC tract also showed an inverse correlation. Further, AD in this tract also correlated with previously acquired BOLD activity during music listening, but not for a control monetary reward task in the NAcc. Finally, we used mediation analysis to show that AD in the NAcc-OFC tract explains the influence of NAcc activation during a music task on music reward sensitivity. Overall, our results provide further support for the idea that the exchange of information among perceptual, integrative, and reward systems is important for musical pleasure, and that individual differences in the structure of the relevant anatomical connectivity influences the degree to which people are able to derive such pleasure.SIGNIFICANCE STATEMENT Music is one of the most important sources of pleasure for many people, but at the same time there are important individual differences in the sensitivity to musical reward. Previous studies have revealed the critical involvement of the functional connectivity between perceptual and subcortical brain areas in the enjoyment of music. However, it is unknown whether individual differences in music sensitivity might arise from variability in the structural connectivity among these areas. Here we show that structural connectivity between supratemporal and orbitofrontal cortices, and between orbitofrontal and nucleus accumbens, predict individual differences in sensibility to music reward. These results provide evidence for the critical involvement of the interaction between the subcortical reward system and higher-order cortical areas in music-induced pleasure.

Brain oscillatory activity of skill and chance gamblers during a slot machine game.

Gambling behavior presents a broad variety of individual differences, with a continuum ranging from nongamblers to pathological gamblers. The reward network has been proposed to be critical in gambling behavior, but little is known about the behavioral and neural mechanisms underlying individual differences that depend on gambling preference. The main goals of the present study were to explore brain oscillatory responses to gambling outcomes in regular gamblers and to assess differences between strategic gamblers, nonstrategic gamblers, and nongamblers. In all, 54 healthy volunteers participated in the study. Electroencephalography was recorded while participants were playing a slot machine task that delivered win, near-miss, and full-miss outcomes. Behaviorally, regular gamblers selected a larger percentage of risky bets, especially when they could select the image to play. The time-frequency results showed larger oscillatory theta power increases to near-misses and increased beta power to win outcomes for regular gamblers, as compared to nongamblers. Moreover, theta oscillatory activity after wins was only increased in nonstrategic gamblers, revealing differences between the two groups of gamblers. The present results reveal differences between regular gamblers and nongamblers in both their behavioral and neural responses to gambling outcomes. Moreover, the results suggest that different brain oscillatory mechanisms might underlie the studied gambling profiles, which might have implications for both basic and clinical studies.

The contribution of striatal pseudo-reward prediction errors to value-based decision-making.

Most studies that have investigated the brain mechanisms underlying learning have focused on the ability to learn simple stimulus-response associations. However, in everyday life, outcomes are often obtained through complex behavioral patterns involving a series of actions. Parallel learning systems might be important to reduce the complexity of the learning problem in such scenarios, as proposed in the framework of hierarchical reinforcement learning (HRL). The key feature of HRL is the decomposition of complex sets of action into subgoals. These subgoals are associated with the computation of pseudo-reward prediction errors (PRPEs), which allow the reinforcement of actions that led to a subgoal before the final goal itself is achieved. Here we wanted to test the hypothesis that, despite not carrying any rewarding value per se, pseudo-rewards might generate a bias in choice behavior in the absence of any advantage. Second, we also hypothesized that this bias might be related to the strength of PRPE striatal representations. In order to test these ideas, we developed a novel decision-making paradigm to assess reward prediction errors (RPEs) and PRPEs in two studies (fMRI study: n = 20; behavioral study: n = 19). Our results show that the participants developed a preference for the most pseudo-rewarding option throughout the task, even though it did not lead to more monetary rewards. fMRI analyses revealed that this preference was predicted by individual differences in the relative striatal sensitivity to PRPEs vs RPEs. Together, our results indicate that pseudo-rewards generate learning signals in the striatum and subsequently bias choice behavior despite their lack of association with actual reward.

Musical reward prediction errors engage the nucleus accumbens and motivate learning.

Enjoying music reliably ranks among life's greatest pleasures. Like many hedonic experiences, it engages several reward-related brain areas, with activity in the nucleus accumbens (NAc) most consistently reflecting the listener's subjective response. Converging evidence suggests that this activity arises from musical "reward prediction errors" (RPEs) that signal the difference between expected and perceived musical events, but this hypothesis has not been directly tested. In the present fMRI experiment, we assessed whether music could elicit formally modeled RPEs in the NAc by applying a well-established decision-making protocol designed and validated for studying RPEs. In the scanner, participants chose between arbitrary cues that probabilistically led to dissonant or consonant music, and learned to make choices associated with the consonance, which they preferred. We modeled regressors of trial-by-trial RPEs, finding that NAc activity tracked musically elicited RPEs, to an extent that explained variance in the individual learning rates. These results demonstrate that music can act as a reward, driving learning and eliciting RPEs in the NAc, a hub of reward- and music enjoyment-related activity.

Dopamine modulates the reward experiences elicited by music.

Understanding how the brain translates a structured sequence of sounds, such as music, into a pleasant and rewarding experience is a fascinating question which may be crucial to better understand the processing of abstract rewards in humans. Previous neuroimaging findings point to a challenging role of the dopaminergic system in music-evoked pleasure. However, there is a lack of direct evidence showing that dopamine function is causally related to the pleasure we experience from music. We addressed this problem through a double blind within-subject pharmacological design in which we directly manipulated dopaminergic synaptic availability while healthy participants (n = 27) were engaged in music listening. We orally administrated to each participant a dopamine precursor (levodopa), a dopamine antagonist (risperidone), and a placebo (lactose) in three different sessions. We demonstrate that levodopa and risperidone led to opposite effects in measures of musical pleasure and motivation: while the dopamine precursor levodopa, compared with placebo, increased the hedonic experience and music-related motivational responses, risperidone led to a reduction of both. This study shows a causal role of dopamine in musical pleasure and indicates that dopaminergic transmission might play different or additive roles than the ones postulated in affective processing so far, particularly in abstract cognitive activities.

Intrinsically regulated learning is modulated by synaptic dopamine signaling.

We recently provided evidence that an intrinsic reward-related signal-triggered by successful learning in absence of any external feedback-modulated the entrance of new information into long-term memory via the activation of the dopaminergic midbrain, hippocampus, and ventral striatum (the SN/VTA-Hippocampal loop; Ripollés et al., 2016). Here, we used a double-blind, within-subject randomized pharmacological intervention to test whether this learning process is indeed dopamine-dependent. A group of healthy individuals completed three behavioral sessions of a language-learning task after the intake of different pharmacological treatments: a dopaminergic precursor, a dopamine receptor antagonist or a placebo. Results show that the pharmacological intervention modulated behavioral measures of both learning and pleasantness, inducing memory benefits after 24 hr only for those participants with a high sensitivity to reward. These results provide causal evidence for a dopamine-dependent mechanism instrumental in intrinsically regulated learning and further suggest that subject-specific reward sensitivity drastically alters learning success.

The impact of visual art and emotional sounds in specific musical anhedonia.

A small percentage of healthy individuals do not find music pleasurable, a condition known as specific musical anhedonia. These individuals have no impairment in music perception which might account for their anhedonia; their sensitivity to primary and secondary rewards is also preserved, and they do not show generalized depression. However, it is still unclear whether this condition is entirely specific to music, or rather reflects a more general deficit in experiencing pleasure, either from aesthetic rewards in general, or in response to other types of emotional sounds. The aim of this study is to determine whether individuals with specific musical anhedonia also show blunted emotional responses from other aesthetic rewards or emotional acoustic stimuli different than music. In two tasks designed to assess sensitivity to visual art and emotional sounds, we tested 13 individuals previously identified as specific musical anhedonics, together with two more groups with average (musical hedonic, HDN) and high (musical hyperhedonics, HHDN) sensitivity to experience reward from music. Differences among groups in skin conductance response and behavioral measures in response to pleasantness were analyzed in both tasks. Notably, specific musical anhedonics showed similar hedonic reactions, both behaviorally and physiologically, as the HDN control group in both tasks. These findings suggest that music hedonic sensitivity might be distinct from other human abstract reward processing and from an individual's ability to experience emotion from emotional sounds. The present results highlight the possible existence of specific neural pathways involved in the capacity to experience reward in music-related activities.

Modulating musical reward sensitivity up and down with transcranial magnetic stimulation.

Humans have the unique capacity to experience pleasure from aesthetic stimuli, such as art and music. Recent neuroimaging findings with music have led to a model in which mesolimbic striatal circuits interact with cortical systems to generate expectancies leading to pleasure 1,2 . However, neuroimaging approaches are correlational. Here, we provide causal evidence for the model by combining transcranial magnetic stimulation over the left dorsolateral prefrontal cortex to directly modulate fronto-striatal function 3 bidirectionally together with measures of pleasure and motivation during music listening. Our results show that perceived pleasure, psychophysiological measures of emotional arousal, and the monetary value assigned to music, are all significantly increased by exciting fronto-striatal pathways, whereas inhibition of this system leads to decreases in all of these variables compared with sham stimulation. These findings support the hypothesis that fronto-striatal function causally mediates both the affective responses and motivational aspects of music-induced reward, and provide insights into how aesthetic responses emerge in the human brain.

Unraveling the Role of the Hippocampus in Reversal Learning.

Research in reversal learning has mainly focused on the functional role of dopamine and striatal structures in driving behavior on the basis of classic reinforcement learning mechanisms. However, recent evidence indicates that, beyond classic reinforcement learning adaptations, individuals may also learn the inherent task structure and anticipate the occurrence of reversals. A candidate structure to support such task representation is the hippocampus, which might create a flexible representation of the environment that can be adaptively applied to goal-directed behavior. To investigate the functional role of the hippocampus in the implementation of anticipatory strategies in reversal learning, we first studied, in 20 healthy individuals (11 women), whether the gray matter anatomy and volume of the hippocampus were related to anticipatory strategies in a reversal learning task. Second, we tested 20 refractory temporal lobe epileptic patients (11 women) with unilateral hippocampal sclerosis, who served as a hippocampal lesion model. Our results indicate that healthy participants were able to learn the task structure and use it to guide their behavior and optimize their performance. Participants' ability to adopt anticipatory strategies correlated with the gray matter volume of the hippocampus. In contrast, hippocampal patients were unable to grasp the higher-order structure of the task with the same success than controls. Present results indicate that the hippocampus is necessary to respond in an appropriately flexible manner to high-order environments, and disruptions in this structure can render behavior habitual and inflexible.SIGNIFICANCE STATEMENT Understanding the neural substrates involved in reversal learning has provoked a great deal of interest in the last years. Studies with nonhuman primates have shown that, through repetition, individuals are able to anticipate the occurrence of reversals and, thus, adjust their behavior accordingly. The present investigation is devoted to know the role of the hippocampus in such strategies. Importantly, our findings evidence that the hippocampus is necessary to anticipate the occurrence of reversals, and disruptions in this structure can render behavior habitual and inflexible.