Biology subjects

Rodriguez-Fornells, A.

Publications and source records attributed to Rodriguez-Fornells, A..

13 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↗

bioRxiv2026

Characterizing reward sensitivity to natural singing: an individual differences approach

Singing is an innate human behaviour present across cultures and the lifespan. Despite lacking direct biological advantages, its ubiquity suggests that it is intrinsically rewarding. This research aimed to investigate the underlying factors that explain variability in sensitivity to deriving reward and enjoyment from natural singing in the general population. In Study 1 (n = 606), an initial pool of items describing daily, non-professional singing behaviours were administered to an international adult sample. Exploratory factor analysis revealed a unidimensional structure of 20 items with acceptable model fit, organized into five facets representing distinct domains of singing-related rewards: 1) pleasure and emotional evocation, 2) social singing reward, 3) singing frequency, 4) mood regulation through singing, and 5) inattentional singing during routine tasks. In Study 2 (n = 430), confirmatory factor analysis in a new sample supported this structure. When both samples were combined (n = 1036), the unidimensional model defined by these five facets showed acceptable to excellent goodness-of-fit indices, supporting the conceptualization of singing reward as a multidimensional construct with differentiated facets. This led to the Barcelona-Aarhus Natural Singing Engagement Questionnaire (BANSEQ), which demonstrated excellent reliability ( = .94) and population-level stability. Study 3 (n = 1036) tested the convergent validity of BANSEQ with measures of music reward and engagement and identified sociodemographic and psychological correlates across the five facets of singing reward. Overall, these findings characterize the sources of individual differences in the hedonic experience of natural singing and propose BANSEQ as a robust psychometric tool for its assessment in the general population.

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bioRxiv2025

Brain function in language and associated networks in non- or minimally verbal children

Language is universal in humans, develops robustly in infancy, and is rarely absent entirely in aphasia following strokes. Non- or minimally verbal children, in whom language has not developed by school-age in either production or comprehension, thus provide an unparalleled window into the human brain when it is deprived of language function. Yet insights from functional MRI are absent. Here we report results from a first study of intrinsic connectivity in 9 non- or minimally verbal children with autism spectrum disorder (nvASD) scanned under sedation with propofol along with 8 typically developing children (scanned awake), using resting-state (rs) fMRI. We targeted both functional (FC) and anatomically constrained, generative effective connectivity (GEC) in the speech and language networks, the insula and associated networks, and the hippocampus. Identical analyses were applied to an independent rsMRI dataset of healthy adults scanned both under propofol and while awake, to evaluate sedation confounds. NvASDs compared to their neurotypical peers showed a widespread pattern of hypoconnectivity in auditory speech perception, frontotemporal, and semantic processing regions, which extended further to the insula, and the hippocampus. GEC results selectively replicated these patterns, which correlated with autism diagnostic observation schedule (ADOS) behavioral scores within the nvASD group. This hypoconnectivity pattern extended neither to the adults scanned under propofol, nor to the visual cortex used as control region in nvASD, suggesting that this pattern of results could not be explained by sedation. Together, this first evidence from intrinsic connectivity reveals a broad pattern of underconnectivity across key cognitive networks, which provides a neural correlate for the significant breakdown of language-related cognitive functions in this population.

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bioRxiv2025

Functionally Relevant and Reliable Brain Stimulation Targets for Enhancement of Novel Word-Learning

Linking word-forms and their meanings is central to language learning. Transcranial direct current stimulation (tDCS), has shown potential to enhance this process, but with variable effects. This study aimed to (1) identify reliable and functionally relevant tDCS target brain regions to enhance novel-word learning and (2) assess test-retest reliability (TRR) of behavioral and imaging outcomes. Twenty healthy individuals completed two functional magnetic resonance imaging (fMRI) sessions using parallel task versions. Participants learned picture-pseudoword associations across six learning blocks. Behavioral learning was analyzed using linear-mixed-models. Whole-brain and region-of-interest (ROI) analyses examined learning-related activity changes and their behavioral relevance. TRR was assessed using intraclass correlation coefficients (ICCs). Participants successfully acquired the novel-word forms, indexed by increased accuracy and faster latency across stages. Behavioral outcomes showed good-to-excellent TRR. The task elicited robust language-learning related activity and activity changes across stages were correlated with learning success. Task-related activity was variable, but voxels within significant clusters ([~]81%) and most ROIs showed moderate-to-excellent consistency. Power analyses confirmed a sufficient sample size for detecting the reported ICCs. Current modeling suggested that focal-tDCS can induce neurophysiologically relevant electrical field strength in the identified target regions. Hence, we identified accessible, reliable and functionally relevant cortical targets for enhancing novel-word learning. TRR results support the usefulness of the paradigm for future concurrent tDCS-fMRI research. Our study also outlines a general path towards optimization of brain stimulation studies by implementing an empirically informed approach for selecting reliable and relevant target regions and implementation of reliable experimental and imaging paradigms.

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bioRxiv2025

Satiety does not abolish Pavlovian-to-instrumental transfer but accelerates devaluation in humans

Environmental cues that predict palatable food can robustly drive behavior, override satiety signals and promote maladaptive eating habits. However, conventional human paradigms often fail to capture the dynamic interplay between hunger, satiety, and cue-induced behavioral actions. To address this, we built a novel automated dispenser synchronized with task events and integrated into an adapted human Pavlovian-to-instrumental transfer (PIT) paradigm to deliver real, consumable food rewards in real time--allowing participants to eat online and thereby induce satiation or sustain hunger. In one experiment, we manipulated food rewards by varying portion size and consumption timing. Large portions consumed immediately induced rapid satiation, whereas small, trial-by-trial portions kept participants non-satiated; correspondingly, large portions accelerated devaluation of the food reward--evidenced by a pronounced decline in instrumental responding--while small portions sustained cue-driven behavior over time. In a subsequent experiment, small, immediately consumed food rewards (which kept participants non-satiated) were directly compared with real-time monetary rewards. Although both reward types initially invigorated behavior, the motivational impact of monetary rewards declined quicker, suggesting that the absence of physiological feedback renders secondary reinforcers more vulnerable to rapid devaluation. These findings suggest that satiety accelerates, rather than abolishes, the influence of food-associated cues. The distinct temporal dynamics observed for food and monetary outcomes underscore the importance of real-time ingestion in human PIT paradigms, offering new insights into the mechanisms by which physiological states modulate cue-driven devaluation.

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bioRxiv2025

The effects of reliable social feedback on language learning: insights from EEG and pupillometry

Language learning is often a social process, and social feedback may play a motivational role. We examined the neurophysiological correlates of word learning with feedback varying in reliability and social content. Participants associated novel auditory words with objects and received social (video clips) or symbolic (static images) feedback. In a forced-choice task, participants learned to associate novel auditory words with known objects and received feedback that was either Social Reliable (correct), Social Unreliable (random), or Symbolic Reliable (correct). Post-training behavioral performance was better for words learned with social and symbolic reliable feedback. Stimulus-preceding negativity (SPN) and late positive complex (LPC) ERP amplitudes, as well as pupil dilation, showed differences as a function of feedback reliability and social content. In the reliable conditions, before feedback, SPN amplitude grew as learning progressed, likely due to the expectation of receiving positive feedback. During feedback, LPC amplitude for positive feedback diminished as learning progressed but not for negative feedback, which was likely consistently used for context updating. These effects were not observed for unreliable feedback, probably because its value was not used for updating information. Pupillometry results corroborated these findings, showing greater dilation for negative vs positive feedback in reliable conditions. Finally, when feedback was social, processing was associated with more frontal activation and behavioral performance was closely correlated with both ERP and pupillometry results. Overall, our findings show differential processing of feedback depending on its informational and social content, advancing our understanding of how social and cognitive processes interact to shape word learning.

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bioRxiv2025

Alpha and beta desynchronization during consolidation of newly learned words

While a growing body of literature exists on initial word-to-meaning mapping and retrieval of fully lexicalized words, our understanding on the consolidation that occurs between these two stages remains limited. The current study investigated the neural correlates of retrieving newly learned word meanings using oscillatory brain dynamics. Participants learned to associate new words with unknown objects and performed overt and covert naming tasks during the first and last days of a five-day training period. Behavioral results showed improved overt naming on Day 5 compared to Day 1. Selecting only words that were successfully produced in the overt naming task, we examined oscillatory activity associated with word retrieval while participants produced new words covertly, both pre- (Day 1) and post (Day 5) learning. The results showed a robust alpha (8-12 Hz) and lower beta (13-25 Hz) power decrease during covert naming after learning. We hypothesize that this alpha-beta power decrease indexes successful word retrieval following consolidation.

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bioRxiv2024

Dopamine dynamics in chronic pain: music-induced sex-dependent behavioral effects in mice

1Chronic pain is a debilitating disease that is usually comorbid to anxiety and depression. Current treatment approaches primarily rely on analgesics, but they often neglect emotional aspects. Non-pharmacological interventions have been incorporated into clinics to provide a more comprehensive management of chronic pain. Among these interventions, listening to music is a well-accepted and cost-effective option. However, the underlying mechanisms of music-mediated pain relief remain insufficiently understood. Here, our aim was to evaluate the effects of music exposure in an animal model of chronic pain. First, we injected mice with the inflammatory agent complete Freunds adjuvant (CFA) into the hind paw and housed them for 14 days with background music during their active period (Mozart K.205, overnight), or silence. The impact of music exposure on nociception and anxiety-like and depression-like behaviors was evaluated through different paradigms, including the hot plate, Von Frey, elevated plus maze, splash, and tail suspension tests. Additionally, we investigated whether music influences dopamine dynamics in the nucleus accumbens (NAcc), a pivotal region involved in pain processing, anhedonia, and reward. Our findings indicate that music exposure prevents the decreased NAcc activity observed in CFA-injected mice, linking with a sex-dependent reduction of allodynia, anxiety- and depression-like behaviors. Thus, females were more sensitive to music exposure. Collectively, our findings provide compelling evidence for the integration of music listening as a non-pharmacological intervention in chronic pain conditions. Moreover, the observed impact on the NAcc suggests its potential as a therapeutic target for addressing chronic pain and its associated symptoms.

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bioRxiv2022

Tactile attention modulates occipital alpha oscillations in early blindness

Alpha oscillatory activity is thought to contribute to the cueing of visual attention through the engagement of task-relevant occipital regions. In early blindness, occipital alpha oscillations are systematically reduced, suggesting that occipital alpha depends on visual experience. However, it is still unknown if alpha activity could serve attentional cueing in non-visual modalities in blind people, especially considering previous research that showed the recruitment of the occipital cortex for non-visual processing. To test this idea, we used electroencephalography to answer whether alpha oscillations reflected a differential recruitment of task-relevant regions between expected and unexpected conditions in two (texture and shape discrimination) haptic tasks. As expected, time frequency analyses showed that alpha suppression in parieto-occipital sites was significantly reduced in early blind individuals. The source reconstruction analysis revealed that group differences originated in the middle occipital cortex. In that region, expected trials evoked higher alpha desynchronization than unexpected trials in the EB group only. Our results support the role of alpha rhythms in the recruitment of occipital areas also in early blind participants, and for the first time we show that even if posterior alpha activity is reduced in blindness, it is however sensitive to task-dependent factors. Our findings therefore suggest that occipital alpha activity may be involved in tactile attention in blind individuals, maintaining the function proposed for visual attention in sighted population but switched to the tactile modality. Altogether, our results indicate that attention-dependent modulation of alpha oscillatory activity does not depend on visual experience. SIGNIFICANCE STATEMENTAre posterior alpha oscillations and their role in attention dependent on visual experience? Our results show that tactile attention can modulate posterior alpha activity in blind (but not sighted) individuals through the engagement of occipital regions, suggesting that in early blindness, alpha oscillations maintain their proposed role in visual attention but subserve tactile processing. Our findings bring a new understanding to the role that alpha oscillatory activity plays in blindness, contrasting with the view supporting that alpha activity is rather task unspecific.

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bioRxiv2021

Entering into a self-regulated learning mode prevents detrimental effect of feedback removal on memory

Recently, we provided causal evidence that self-regulated dopamine signaling enhanced long-term memory formation in the absence of any external feedback or reward (Ripolles et al., 2016, 2018) if a congruent meaning inferred from semantic context (DA-dependent learning), while DA-signals were absent if no congruent meaning could be inferred (DA-independent learning). Here, we investigated the interaction of self-regulated learning with externally-regulated DA-signalling by providing external performance feedback in the first or second half of trials. We found that removing feedback during DA-dependent learning lowered subsequent recognition rates a day later, whereas recognition remained high in the group which received feedback only in the second half. In contrast, feedback modestly enhanced recognition rates for both groups for DA-independent learning. Our findings suggest that external reinforcers can selectively impair DA-dependent memories if internal DA-dependent processes are not already established and highlights the relevance of self-regulated learning in education to support stable memory formation.

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bioRxiv2020

Neural signatures of predictive language processing in Parkinson's disease with and without mild cognitive impairment

Cognitive deficits are common in Parkinsons disease (PD), with some PD patients meeting criteria for mild cognitive impairment (MCI). An unaddressed question is whether linguistic prediction is preserved in PD. This ability is nowadays deemed crucial in achieving fast and efficient comprehension, and it may be negatively impacted by cognitive deterioration. To fill this gap of knowledge, we used event-related potentials (ERPs) to evaluate mechanisms of linguistic prediction in a sample of PD patients (on dopamine compensation) with and without MCI. To this end, participants read sentence contexts that were predictive or not about a sentence-final word. The final word appeared after 1 second, matching or mismatching the prediction. The introduction of the interval allowed to capture neural responses both before and after sentence-final words, reflecting semantic anticipation and processing. PD patients with normal cognition (N = 58) showed ERP responses comparable to those of matched controls. Specifically, in predictive contexts, a slow negative potential developed prior to sentence-final words, reflecting semantic anticipation. Later, expected words elicited reduced N400 responses (compared to unexpected words), indicating facilitated semantic processing. Besides, PD patients with MCI (N = 20) showed a prolongation of the N400 congruency effect (compared to matched PD patients without MCI), indicating that further cognitive decline impacts semantic processing. Finally, lower verbal fluency scores correlated with prolonged N400 congruency effects and with reduced pre-word differences in all PD patients (N = 78). This relevantly points to a role of deficits in temporal-dependent mechanisms in PD, besides prototypical frontal dysfunction, in altered semantic anticipation and semantic processing during sentence comprehension.

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bioRxiv2020

Dopaminergic signalling modulates reward-driven music memory consolidation

Previously, we provided causal evidence for a dopamine-dependent effect of intrinsic reward on memory during self-regulated learning (Ripolles et al., 2016; Ripolles et al., 2018). Here, we further investigated the dopamine-dependent link between reward and memory by focusing on one of the most iconic abstract rewards in humans: music. Twenty-nine healthy participants listened to unfamiliar excerpts--which had to be remembered following a consolidation period--after the intake of a dopaminergic antagonist, a dopaminergic precursor, and a placebo across three separated sessions. The intervention modulated the pleasantness experienced during music-listening and memory recognition of the presented songs (i.e., lower with the antagonist, higher with the precursor) in individuals with higher sensitivity to musical reward. Our work highlights the flexibility of the human dopaminergic system, which is able to enhance memory formation not only through explicit and/or primary reinforcers but also via intrinsic, abstract, or aesthetic rewards of different natures.

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bioRxiv2018

Intrinsically regulated learning is modulated by synaptic dopamine availability

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; Ripolles 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 behavioural sessions of our 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 bidirectionally modulated behavioral measures of both learning and pleasantness, inducing memory benefits after 24 hours 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 dopamine sensitivity drastically alters learning success.

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