Biology subjects

de la Fuente, L. A.

Publications and source records attributed to de la Fuente, L. A..

13 recordsLinked to original sources

bioRxiv2026

Multimodal autonomic arousal tracks dose-dependent affective dynamics during the acute effects of DMT

Serotonergic psychedelics induce altered states of consciousness characterised by profound changes in emotional experience. Although psychedelics modulate autonomic arousal, sympathetic engagement during their affective effects remains poorly characterised. We recorded cardiac, electrodermal, and respiratory activity in 19 participants following inhalation of 20 or 40 mg of freebase N,N-dimethyltryptamine (DMT) under a semi-naturalistic blinded design, alongside time-resolved retrospective phenomenological reports. DMT induced robust increases across all autonomic markers, integrated into a multimodal index that selectively tracked subjective emotional intensity. Dose-dependent divergence followed modality-specific profiles: heart rate and respiratory differences emerged within the first 2 min post-inhalation, whereas electrodermal activity diverged only during the later phase, with higher doses showing prolonged autonomic engagement. DMT thus produces a transient sympathetic activation co-varying with emotional arousal, followed by gradual disengagement accompanied by pleasantness and bliss. By combining time- and cost-effective peripheral physiological measures with time-resolved phenomenological reports, this work contributes to the objective characterisation of psychedelic-induced affective states and provides a methodological basis for future biomarker research in clinical applications.

neuroscience↗

bioRxiv2026

Decoding the phenomenology of spontaneous thought using large language-model ratings on verbal retrospective free reports

AO_SCPLOWBSTRACTC_SCPLOWSpontaneous thoughts constitute most of everyday inner experience, yet long-standing methodological challenges obscure a thorough exploration of their content and neurophysiological underpinnings. Traditional approaches relying on thought probes impose strict constraints on phenomenological reports, whereas online verbal reports disrupt the natural flow of experience while interfering neural signals with motor artifacts. Here, we designed and tested an alternative approach to assess the neural basis of spontaneous thoughts combining delayed verbal retrospective free reports (RFR) with automated phenomenological ratings generated by large language models (LLMs). Twenty-two participants performed an eyes-closed free-thinking task, providing reports that were evaluated along ten phenomenological dimensions by four state-of-the-art LLMs and a panel of human raters. Machine-learning models (ML) were then trained to decode LLM-derived ratings from EEG spectral, complexity, and connectivity features. Our analyses showed that inter-rater agreement among LLMs exceeded that of human raters whereas ML models achieved above-chance accuracy for the prediction of emotional valence. These findings provide support for the use of LLMs for a scalable phenomenological annotation of spontaneous thoughts and suggest that their affective dimensions can be decoded from concurrent EEG activity.

neuroscience↗

bioRxiv2026

Disrupted Emotional Neural Synchrony in Schizophrenia Revealed by Intersubject Correlation of Naturalistic fMRI

BackgroundSchizophrenia is marked by impairments in emotional processing and social cognition, yet traditional neuroimaging paradigms often lack the ecological validity to capture these deficits in real-world contexts. MethodsIn this study, we used intersubject correlation (ISC) analysis of functional MRI data to examine shared neural representations of naturalistic visual narratives in individuals with schizophrenia and healthy controls. Participants viewed short films designed to evoke happy, sad, and emotionally neutral responses, allowing us to compare how synchronized brain activity varied with emotional content across and within groups. ResultsHealthy controls showed greater ISC in regions associated with affective salience, emotion recognition, and social understanding, including the amygdala, insula, and temporal cortices. In contrast, participants with schizophrenia displayed higher synchrony in visual, subcortical, and frontal areas, suggesting a reliance on perceptual and executive systems. To isolate the effects of emotion from general visual processing, we compared ISC during emotional clips relative to neutral videos. This revealed significantly reduced synchrony in the bilateral amygdala in patients, highlighting a core dysfunction in affective engagement. Interestingly, neutral stimuli elicited unexpectedly strong synchronization in frontal and limbic regions in the schizophrenia group, possibly reflecting altered salience attribution to ambiguous or emotionally ambiguous content. ConclusionsThese results point to a functional reorganization of affective processing in schizophrenia, where impaired limbic recruitment is accompanied by compensatory engagement of perceptual and cognitive control networks. ISC during naturalistic stimulation emerges as a powerful tool for capturing subtle disruptions in shared emotional experience in psychiatric populations.

neuroscience↗

bioRxiv2025

A Naturalistic Study on the Combined Neural and Psychological Effects of Psilocybin and Compassion Focused Imagery

Psilocybin is a classic psychedelic drug known to alter subjective experience and elicit long-term psychological changes, enhancing cognitive flexibility and reducing rigid self-related beliefs. Combined with compassion motivational primes that involve generating mental representations of compassion, it may increase the potential for activating the care-affiliative motivational systems, linked to several important biopsychosocial processes underpinning social safeness, social connection and mental wellbeing. We investigated the synergetic effects of psilocybin and compassion imagery with self-reported questionnaires and functional resonance imaging data (fMRI) in a sample of 105 participants. Participants were primed with either attention to breathing or a short compassion focused imagery prime. We found a long-term synergetic effect of compassion imagery and psilocybin on cognitive absorption, as well as changes relative to baseline self-compassion and decentering. Based on functional interactions between attentional, executive and default mode networks, fMRI-based classifiers detected participant engagement in compassion focused imagery before psilocybin intake and distinguished compassion imagery vs. attention to breathing priming only the high dose of psilocybin. Our results support the potential for synergistic effects from combinations of psilocybin and compassion-based interventions to induce long-term psychological changes, reshaping the functional organization of large-scale brain networks. Future confirmatory studies of our exploratory analyses should be conducted to determine whether the combination of psilocybin and compassion-based practices promotes increases in caring and contemplative abilities, enhanced psychological flexibility and well-being.

neuroscience↗

bioRxiv2025

Psilocybin-induced modulation of visual salience processing

Psychedelic compounds significantly reshape conscious perception, yet the implications of these alterations for complex visual-guided behaviors remain poorly understood. We investigated how psilocybin modulates visual salience processing during natural scene perception. Twenty-three participants completed eye-tracking tasks under self-blinded low and high doses of psilocybin, in a naturalistic design with experimental conditions unknown to participants and researchers. Subjects viewed natural scenes while their gaze patterns were recorded and analyzed in relation to normative computational saliency maps generated using a deep learning model of visual attention. Results revealed increased fixation on salient image regions and reduced inter-fixation distance under the high-dose condition, suggesting heightened sensitivity to visual salience and more localized gaze behavior. The Shannon entropy of fixations on high-saliency regions indicated a more exploratory and less predictable visual scanning of the images. Complementary EEG recordings showed broadband spectral power reductions and increased Lempel-Ziv complexity, with delta power negatively correlating with salience metrics. These findings suggest psilocybin enhances bottom-up attentional control while weakening top-down modulation, consistent with theoretical models positing facilitated bottom-up information flow under the acute effect of psychedelics.

neuroscience↗

bioRxiv2023

Acute effects of psilocybin on the dynamics of gaze fixations during visual aesthetic perception

RationaleSerotonergic psychedelics are remarkable for their capacity to induce variable yet reproducible modifications to human consciousness The most salient acute effects of these compounds include perceptual alterations, predominantly in the visual domain, yet to date these alterations have been mostly documented only by subjective reports. ObjectivesWe used eye-tracking to quantify the effects of low vs. high doses of psilocybin mushrooms on the eye movements that underlie the exploration of complex visual stimuli, focusing on the particular case of aesthetic perception. ResultsFollowing a double-blind placebo-controlled design under semi-naturalistic conditions, we demonstrated that high doses of psilocybin result in a more local visual exploration of paintings, and thus in a less entropic fixation probability distribution. Participants reported heightened emotional response and state of flow under the high dose condition. ConclusionsThese findings are consistent with an effect of psilocybin on gaze fixation mediated by altered perception of low-level visual information, such as textures, shapes and colors. Our work also highlights the possibility of investigating psychedelics by addressing their effect on behavior under complex naturalistic conditions, which contributes to maintaining subject engagement while also increasing the ecological validity of the findings.

animal behavior and cognition↗

bioRxiv2022

Masked target visibility is selectively impaired by 20 Hz transcranial alternating current stimulation

It has been proposed that both conscious and unconscious perception are associated with a feedforward sweep of oscillatory activity in the gamma band (>40 Hz), while conscious perception also requires recurrent feedback via beta band (~20 Hz) oscillations. To investigate the causal relationship between these oscillations and (un)conscious visual perception, we assessed the effect of transcranial alternating current stimulation (tACS) in the gamma (40 Hz) and beta (20 Hz) bands on the objective and subjective visibility of targets in a metacontrast backward masking task. We expected that 40hz-tACS would affect both the correct categorization of the target (i.e. objective visibility) and the reports of conscious perception (i.e. subjective visibility). Moreover, we expected that 20Hz-tACS would selectively affect the subjective visibility. Our results showed that target visibility was selectively compromised by 20Hz-tACS but, in contrast to our hypothesis, this effect was specific to objective visibility. Although the power of local beta oscillations increased after 20Hz-tACS, inter-areal beta synchrony could have nevertheless been impaired, a possibility that should be investigated in the future by means of source reconstructed high density electroencephalography recordings. In summary, we provided evidence supporting that 20Hz-tACS is capable of modulating target visibility, suggesting a possible a causal link between synchrony in this frequency band and visual perception. Future studies could build upon this result by investigating other forms of stimulation and other model organisms, further contributing to our knowledge of how conscious access causally depends on brain oscillations.

neuroscience↗

bioRxiv2022

Natural language signatures of psilocybin microdosing

Serotonergic psychedelics are being studied as novel treatments for mental health disorders and as facilitators of improved well-being, mental function and creativity. Recent studies have found mixed results concerning the effects of low doses of psychedelics ("microdosing") on these domains. However, microdosing is generally investigated using instruments designed to assess larger doses of psychedelics, which might lack sensitivity and specificity for this purpose. Following a double-blind and placebo-controlled experimental design, we explored natural language as a resource to identify speech produced under the acute effects of psilocybin microdoses, focusing on variables known to be affected by higher doses: verbosity, semantic variability and sentiment scores. Except for semantic variability, these metrics presented significant differences between a typical active microdose of 0.5 g of psilocybin mushrooms and an inactive placebo condition. Moreover, machine learning classifiers trained using these metrics were capable of distinguishing between conditions with high accuracy (AUC{approx}0.8). Our results constitute first proof that low doses of serotonergic psychedelics can be identified from unconstrained natural speech, with potential for widely applicable, affordable, and ecologically valid monitoring of microdosing schedules.

pharmacology and toxicology↗

bioRxiv2021

Microevidence for microdosing with psilocybin mushrooms: a double-blind placebo-controlled study of subjective effects, behavior, creativity, perception, cognition, and brain activity

The use of low sub-hallucinogenic doses of psychedelics ("microdosing") has gained popularity in recent years. Although anecdotal reports claim multiple benefits associated with this practice, the lack of placebo-controlled studies limits our knowledge of microdosing and its effects. Moreover, research conducted in laboratory settings might fail to capture the motivation of individuals engaged in microdosing protocols. We recruited 34 individuals planning to microdose with psilocybin mushrooms (Psilocybe cubensis), one of the materials most frequently used for this purpose. Following a double-blind placebo-controlled design, we investigated the effects of 0.5 g dried mushrooms on subjective experience, behavior, creativity, perception, cognition, and brain activity. The reported acute effects were significantly more intense for the active dose compared to the placebo, which could be explained by unblinding. For the other measurements, we observed either null effects or a trend towards cognitive impairment and, in the case of EEG, towards reduced theta band spectral power. Our findings support the possibility that expectation effects underlie at least some of the anecdotal benefits attributed to microdosing with psilocybin mushrooms.

neuroscience↗

bioRxiv2021

Temporal irreversibility of neural dynamics as a signature of consciousness

Even though the fundamental laws of physics are the same when the direction of time is inverted, dissipative systems evolve in the preferred temporal direction indicated by the thermodynamic arrow of time. The fundamental nature of this temporal asymmetry led us to hypothesize its presence in the neural activity evoked by conscious perception of the physical world, and thus its covariance with the level of conscious awareness. Inspired by recent developments in stochastic thermodynamics, we implemented a data-driven and model-free deep learning framework to decode the temporal inversion of electrocorticography signals acquired from non-human primates. Brain activity time series recorded during conscious wakefulness could be distinguished from their inverted counterparts with high accuracy, both using frequency and phase information. However, classification accuracy was reduced for data acquired during deep sleep and under ketamine-induced anesthesia; moreover, the predictions obtained from multiple independent neural networks were less consistent for sleep and anesthesia than for conscious wakefulness. Finally, the analysis of feature importance scores highlighted transitions between slow ({approx}20 Hz) and fast frequencies (> 40 Hz) as the main contributors to the temporal asymmetry observed during conscious wakefulness. Our results show that a preferred temporal direction is simultaneously manifest in the neural activity evoked by conscious mentation and in the phenomenology of the passage of time, establishing common ground to tackle the relationship between brain and subjective experience.

neuroscience↗

bioRxiv2021

Baseline power of theta oscillations predicts mystical-type experiences induced by DMT

N,N-Dimethyltryptamine (DMT) is a classic psychedelic capable of inducing short-lasting but profound changes in consciousness. As with other psychedelics, the experience induced by DMT strongly depends upon contextual factors, yet the neurobiological determinants of this variability remain unknown. We combined wireless electroencephalography and source imaging to map changes in neural oscillations elicited by inhaled DMT. Furthermore, we found that the power of frontal and temporal theta oscillations was inversely correlated with scales indexing feelings of unity and transcendence, which are an integral part of the phenomenology of mystical-type experiences. Finally, we established the robustness of these results using a machine learning model for regression trained and tested following a cross-validation procedure. Our results are consistent with the observation that the state of mind prior to consuming a psychedelic drug influences the ensuing subjective experience of the user. We also suggest that priming subjects to reduce their theta power before administration of a serotonergic psychedelic could enhance the likelihood of inducing mystical-type experiences, leading to sustained positive effects in well-being and improving the outcome of therapeutic interventions.

neuroscience↗

bioRxiv2020

Neural and subjective effects of inhaled DMT in natural settings

BackgroundN,N-Dimethyltryptamine (DMT) is a short acting psychedelic tryptamine found naturally in many plants and animals. Few studies to date addressed the neural and psychological effects of DMT alone, either administered intravenously or inhaled in freebase form, and none conducted in natural settings. AimsOur primary aim was to study the acute effects of inhaled DMT in natural settings, focusing on questions tuned to the advantages of conducting field research, including the effects of contextual factors (i.e. "set" and "setting"), the possibility of studying a comparatively large number of subjects, and the relaxed mental state of participants consuming DMT in familiar and comfortable settings. MethodsWe combined state-of-the-art wireless electroencephalography (EEG) with psychometric questionnaires to study the neural and subjective effects of naturalistic DMT use in 35 healthy and experienced participants. ResultsWe observed that DMT significantly decreased the power of alpha (8-12 Hz) oscillations throughout all scalp locations, while simultaneously increasing power of delta (1-4 Hz) and gamma (30-40 Hz) oscillations. Gamma power increases correlated with subjective reports indicative of mystical-type experiences. DMT also increased/decreased global synchrony and metastability in the gamma/alpha band, and resulted in widespread increases in signal complexity. ConclusionsOur results are consistent with previous studies of psychedelic action in the human brain, while at the same time suggesting potential EEG markers of mystical-type experiences in natural settings, thus highlighting the importance of investigating these compounds in the contexts where they are naturally consumed.

neuroscience↗

bioRxiv2019

Over eight hundred cannabis strains characterized by the relationship between their psychoactive effects, perceptual profiles, and chemical compositions

BackgroundCommercially available cannabis strains have multiplied in recent years as a consequence of regional changes in legislation for medicinal and recreational use. Lack of a standardized system to label plants and seeds hinders the consistent identification of particular strains with their elicited psychoactive effects. The objective of this work was to leverage information extracted from large databases to improve the identification and characterization of cannabis strains.\n\nMethodsWe analyzed a large publicly available dataset where users freely reported their experiences with cannabis strains, including different subjective effects and flavour associations. This analysis was complemented with information on the chemical composition of a subset of the strains. Both supervised and unsupervised machine learning algorithms were applied to classify strains based on self-reported and objective features.\n\nResultsMetrics of strain similarity based on self-reported effect and flavour tags allowed machine learning classification into three major clusters corresponding to Cannabis sativa, Cannabis indica, and hybrids. Synergy between terpene and cannabinoid content was suggested by significative correlations between psychoactive effect and flavour tags. The use of predefined tags was validated by applying semantic analysis tools to unstructured written reviews, also providing breed-specific topics consistent with their purported medicinal and subjective effects. While cannabinoid content was variable even within individual strains, terpene profiles matched the perceptual characterizations made by the users and could be used to predict associations between different psychoactive effects.\n\nConclusionsOur work represents the first data-driven synthesis of self-reported and chemical information in a large number of cannabis strains. Since terpene content is robustly inherited and less influenced by environmental factors, flavour perception could represent a reliable marker to predict the psychoactive effects of cannabis. Our novel methodology contributes to meet the demands for reliable strain classification and characterization in the context of an ever-growing market for medicinal and recreational cannabis.

neuroscience↗