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Pallavicini, C.

Publications and source records attributed to Pallavicini, C..

At least 19 recordsLinked to original sources

Serotonergic psychedelics delay resting state neurovascular coupling dynamics

Psychedelics are increasingly explored as tools to investigate consciousness and cognition, and as potential treatments for mood disorders. While neuroimaging has been central to characterizing their mechanisms of action, the interpretation of these studies may be confounded by the neurovascular effects elicited by these drugs. Here, we investigated the modulation of resting state neurovascular coupling by the serotonergic psychedelics LSD and DMT. Applying a blind deconvolution algorithm to blood-oxygen-level-dependent (BOLD) signals, we found that both drugs increased the estimated hemodynamic delays in regions overlapping with the distribution of serotonin receptors implicated in psychedelic action and vascular regulation. Deconvolution enhanced the detection of psychedelic-induced changes in whole-brain functional connectivity, suggesting that vascular effects obscure connectivity changes instead of generating spurious results. Finally, a biophysical whole-brain model linked these effects to increased flow-dependent feedback and slower dissipation of the vasoactive drive. These findings underscore the need to account for vascular effects in future psychedelic neuroimaging studies.

neuroscience↗

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↗

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↗

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↗

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↗

Spatial layout of visual specialization is shaped by competing default mode and sensory networks

Understanding how the brain encodes information started with a map but turned into a maze: paths multiplied; boundaries blurred. Neurons tuned to specific features are not confined to single regions, but distributed across the cortex. Retinotopy, once thought limited to early visual areas, now appears in over 20 cortical regions--from the tip of the occipital cortex to the shore of the lateral frontal cortex. To describe and understand these complex mosaics of functional specialization, we focus on the spatial influences that shape their emergence across the cortical sheet. To this end, we developed Spatial Component Decomposition (SCD), a sparse dictionary learning framework that locates sources of spatial influence without relying on prior assumptions from systems neuroscience. Applied to MRI data capturing retinotopic maps, SCD reveals a dominant linear gradient extending over 60 mm from V1 and covering all the known posterior visual areas. Yet, it also revealed systematic competition from other primary sensory areas and default mode transmodal hubs. These suppressive influences shape the cortical embedding of visual information, even during purely visual tasks. Our results suggest that functional specialization emerges from spatial competition between representational systems--not just from feedforward inputs.

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↗

The intrinsic cortical geometry of reading

How does the brain support the complex processes that allow us to read? Using predictive modeling we establish that visual and association cortex are closer together in individuals with stronger oral reading ability. These findings indicate that large-scale cortical geometry provides a scaffold that supports the coordinated processing required to read.

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↗

DMT induces a transient destabilization of whole-brain dynamics

The transition towards the brain state induced by psychedelic drugs is frequently neglected in favor of a static description of their acute effects. We used a time-dependent whole-brain model to reproduce large-scale brain dynamics measured with fMRI from 15 volunteers under 20 mg intravenous N,N-Dimethyltryptamine (DMT), a short-acting psychedelic. To capture its transient effects, we parametrized the proximity to a global bifurcation using a pharmacokinetic equation. Simulated perturbations revealed a transient of heightened reactivity concentrated in fronto-parietal regions and visual cortices, correlated with serotonin 5HT2a receptor density, the primary target of psychedelics. These advances suggest a mechanism to explain key features of the psychedelic state and also predicts that the temporal evolution of these features aligns with pharmacokinetics. Our results contribute to understanding how psychedelics introduce a transient where minimal perturbations can achieve a maximal effect, shedding light on how short psychedelic episodes may extend an overarching influence over time.

neuroscience↗

A Comparative Machine Learning Study of Connectivity-Based Biomarkers of Schizophrenia

Functional connectivity holds promise as a biomarker of psychiatric disorders. Yet, its high dimensionality, combined with small sample sizes in clinical research, increases the risk of overfitting when the aim is prediction. Recently, low-dimensional representations of the connectome such as macroscale cortical gradients and gradient dispersion have been proposed, with studies noting consistent gradient and dispersion differences in psychiatric conditions. However, it is unknown which of these derived measures has the highest predictive capacity and how they compare to raw connectivity. Our study evaluates which connectome features -- functional connectivity, gradients, or gradient dispersion -- best identify schizophrenia. Figure 1 summarizes this work. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=41 SRC="FIGDIR/small/573898v1_fig1.gif" ALT="Figure 1"> View larger version (15K): org.highwire.dtl.DTLVardef@12c0fdorg.highwire.dtl.DTLVardef@13c4702org.highwire.dtl.DTLVardef@59f8d7org.highwire.dtl.DTLVardef@e00f56_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1.C_FLOATNO Overview of the methods and main outcome of the paper. Schematic images: Flaticon.com. NC: neurotypical controls, SCZ: patients with schizophrenia. C_FIG Surprisingly, our findings indicate that functional connectivity outperforms its low-dimensional derivatives such as cortical gradients and gradient dispersion in identifying schizophrenia. Additionally, we demonstrated that the edges which contribute the most to classification performance are the ones connecting primary sensory regions.

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↗

Low-dimensional organization of global brain states of reduced consciousness

Brain states are frequently represented using a unidimensional scale measuring the richness of subjective experience (level of consciousness). This description assumes a mapping between the high-dimensional space of whole-brain configurations and the trajectories of brain states associated with changes in consciousness, yet this mapping and its properties remain unknown. We combined whole-brain modelling, data augmentation and deep learning for dimensionality reduction to determine a mapping representing states of consciousness in a low-dimensional space, where distances parallel similarities between states. An orderly trajectory from wakefulness to brain injured patients is revealed in a latent space whose coordinates represent metrics related to functional modularity and structure-function coupling, both increasing alongside loss of consciousness. Finally, we investigated the effects of model perturbations, providing geometrical interpretation for the stability and reversibility of states. We conclude that conscious awareness depends on functional patterns encoded as a low-dimensional trajectory within the vast space of brain configurations.

neuroscience↗

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↗

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↗

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↗

Unifying turbulent dynamics framework distinguishes different brain states

Recently, significant advances have been made by identifying the levels of synchronicity of the underlying dynamics of a given brain state. This research has demonstrated that unconscious dynamics tend to be more synchronous than those found in conscious states, which are more asynchronous. Here we go beyond this dichotomy to demonstrate that the different brain states are always underpinned by spatiotemporal chaos but with dissociable turbulent dynamics. We investigated human neuroimaging data from different brain states (resting state, meditation, deep sleep, and disorders of consciousness after coma) and were able to distinguish between them using complementary model-free and model-based measures of turbulent information transmission. Our model-free approach used recent advances describing a measure of information cascade across spatial scales using tools from turbulence theory. Complementarily, our model-based approach used exhaustive in silico perturbations of whole-brain models fitted to the empirical neuroimaging data, which allowed us to study the information encoding capabilities of the brain states. Overall, the current framework demonstrates that different levels of turbulent dynamics are fundamental for describing and differentiating between brain states.

neuroscience↗

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↗