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Bruno, N.

Publications and source records attributed to Bruno, N..

9 recordsLinked to original sources

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↗

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↗

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↗

Time-resolved neural and experience dynamics of medium- and high-dose DMT

N,N-Dimethyltryptamine (DMT) is a fast-acting psychedelic drug that induces a radical reorganisation of conscious contents and brain dynamics. However, our understanding of how brain dynamics support psychedelic-induced conscious states remains unclear. We therefore present a repeated-measures dose-dependent study of the subjective and neural dynamics induced through DMT under naturalistic conditions. Nineteen participants received either a 20mg or 40mg dose of freebase DMT across two sessions in a blinded, counterbalanced order. Electroencephalography (EEG) data and time-resolved measures of subjective experience (Temporal Experience Tracing) were collected. Both doses of DMT induced rapid changes in experience dimensions, with the 40mg dose inducing more extreme visual hallucinations and emotionally intense experiences. Strikingly, lempel-ziv complexity, previously hailed as a robust phenomenological correlate within the psychedelic-state, was the least strongly associated neural marker. These findings suggest that the relationship between neural complexity and phenomenology in psychedelic states is less clear than originally hypothesised.

neuroscience↗

Perception - action dissociations depend on factors that affect multisensory processing

Behavioral perception-action dissociations are widely used to test models of high-level vision, but debates concerning their interpretation have underestimated the role of multisensory mechanisms in such tests. Sensorimotor tasks engage multisensory processing in fundamentally different ways in comparison to perceptual tasks, and these differences can modulate the effects of illusion in specific ways in accord with the features of the experimental task. To test this idea, we compared perception and action using a well-understood size-contrast effect, the Uznadze illusion, and manipulated both unimodal and crossmodal stimulation as well as conditions that are known to favor or hinder multisensory integration. Results demonstrate that varying such conditions can cause a visual task to be affected by the illusion, or remain fully unaffected, whereas a visuomotor task can be affected by the illusion, remain immune from the illusion, or, unexpectedly, even show a robust reverse effect. Thus, similar or dissociable effects on perception and action can be observed depending on factors that are known to affect multisensory processing.These findings provide a novel perspective on a long standing debate in behavioral cognitive neuroscience.

neuroscience↗

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↗

Distinct Electrophysiological Signatures of Intentional and Unintentional Mind-Wandering Revealed by Low-Frequency EEG Markers

Mind-wandering is typically characterized by the common experience wherein attention veers off into thoughts unrelated to the task at hand. Recent research highlights the intentionality dimension of mind-wandering as a key predictor of adverse functional outcomes with intentional and unintentional task-unrelated thought (TUT) differentially linked to neural, behavioral, clinical, and functional correlates. We here aimed to elucidate the electrophysiological underpinnings of intentional and unintentional TUT by systematically examining the individual and collective discriminative power of a large set of EEG markers to distinguish between attentional states. Univariate and multivariate analyses were conducted on 54 predefined markers belonging to four conceptual families: ERP, spectral, information theory and connectivity measures, extracted from scalp EEG recordings prior to multidimensional reports of ongoing thought from participants performing a sustained attention task. We report here that on-task, intentional and unintentional TUT exhibit distinct electrophysiological signatures in the low frequency range. More specifically, increased features of the theta frequency range were found to be most discriminative between on-task and off-task states, while features within the alpha band were characteristic of intentional TUT when compared to unintentional TUT. This result is theoretically well aligned with contemporary accounts describing alpha activity as an index of internally oriented attention and a potential mechanism to shield internal processes from sensory input. Our study verifies the validity of the intentionality dimension of mind-wandering and represents a step forward towards real-time detection and mitigation of maladaptive mind-wandering.

neuroscience↗

Activation of the Crtc2/Creb1 transcriptional network in skeletal muscle enhances weight loss during intermittent fasting

The Creb-Regulated Transcriptional Coactivator (Crtc) family of transcriptional coregulators drive Creb1-mediated transcription effects on metabolism in many tissues, but the in vivo effects of Crtc2/Creb1 transcription on skeletal muscle metabolism are not known. Skeletal muscle-specific overexpression of Crtc2 (Crtc 2 mice) induced greater mitochondrial activity, metabolic flux capacity for both carbohydrates and fats, improved glucose tolerance and insulin sensitivity, and increased oxidative capacity, supported by upregulation of key metabolic genes. Crtc2 overexpression led to greater weight loss during alternate day fasting (ADF), selective loss of fat rather than lean mass, supported by maintenance of higher energy expenditure during the fast. ADF downregulated most of the mitochondrial electron transport genes, and other regulators of mitochondrial function, that were substantially reversed by Crtc2-driven transcription. Glucocorticoids acted with AMPK to drive atrophy and mitophagy, which was reversed by Crtc2/Creb1 signaling. Crtc2/Creb1-mediated signaling coordinates metabolic adaptations in skeletal muscle that explain how Crtc2/Creb1 regulates metabolism and weight loss.

physiology↗

Chemical Systems Biology Reveals Mechanisms of Dissociated Glucocorticoid Receptor Signaling

Glucocorticoids display remarkable anti-inflammatory activity, but their use is limited by on-target adverse effects including insulin resistance and skeletal muscle atrophy. We used a chemical systems biology approach, Ligand Class Analysis (LCA), to examine ligands designed to modulate glucocorticoid receptor activity through distinct structural mechanisms. These ligands displayed diverse activity profiles, providing the variance required to identify target genes and coregulator interactions that were highly predictive of their effects on myocyte glucose disposal and protein balance. Their anti-inflammatory effects were linked to glucose disposal but not muscle atrophy. This approach also predicted selective modulation in vivo, identifying compounds that were muscle sparing or anabolic for protein balance and mitochondrial potential. LCA defined the mechanistic links between the ligand-receptor interface and ligand-driven physiological outcomes, a general approach that can be applied to any ligand-regulated allosteric signaling system.

pharmacology and toxicology↗